tbuckley/cabot-search huggingface dataset:
Chromatin activity identifies differential gene regulation across human ancestries
Authors: Kade P. Pettie, Maxwell Mumbach, Amanda J. Lea, Julien Ayroles, Howard Y. Chang, Maya Kasowski, Hunter B. Fraser
Journal: Genome biology (2024)

Abstract Background Current evidence suggests that cis -regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation. Results To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, we find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, we show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding. Conclusions Overall, our study indicates that some cis -regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This work provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.
ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans
Authors: Hongyu Luo, Linjiang Lao, Kit Sing Au, Hope Northrup, Xiao He, Diane Forget, Marie-Soleil Gauthier, Benoit Coulombe, Isabelle Bourdeau, Wei Shi, Lucia Gagliardi, Maria Candida Barisson Villares Fragoso, Junzheng Peng, Jiangping Wu
Journal: Genome biology (2024)

Abstract Background Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). Results We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination. Conclusions Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.
Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments
Authors: Dong-Xu Wang, Jun-Yu Long, Rui-Zhe Li, Dao-Lin Zhang, Hui Liu, Jingru Liu, Jin-Cheng Tian, Han Li, Jie Liu, Hai-Tao Zhao, Tao Li
Journal: Molecular Cancer (2024)

Abstract Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts ( n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival ( P &lt; 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632–0.850]), progression-free survival ( P = 0.002, HR = 0.669 [95% CI: 0.518–0.864]), durable clinical benefit ( P &lt; 0.001, 54.1% vs. 32.6%), and objective response rate ( P &lt; 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a “hot tumor” phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.
Phase separation as a possible mechanism for dosage sensitivity
Authors: Liang Yang, Jiali Lyu, Xi Li, Gaigai Guo, Xueya Zhou, Taoyu Chen, Yi Lin, Tingting Li
Journal: Genome biology (2024)

Abstract Background Deletion of haploinsufficient genes or duplication of triplosensitive ones results in phenotypic effects in a concentration-dependent manner, and the mechanisms underlying these dosage-sensitive effects remain elusive. Phase separation drives functional compartmentalization of biomolecules in a concentration-dependent manner as well, which suggests a potential link between these two processes, and warrants further systematic investigation. Results Here we provide bioinformatic and experimental evidence to show a close link between phase separation and dosage sensitivity. We first demonstrate that haploinsufficient or triplosensitive gene products exhibit a higher tendency to undergo phase separation. Assessing the well-established dosage-sensitive genes HNRNPK, PAX6, and PQBP1 with experiments, we show that these proteins undergo phase separation. Critically, pathogenic variations in dosage-sensitive genes disturb the phase separation process either through reduced protein levels, or loss of phase-separation-prone regions. Analysis of multi-omics data further demonstrates that loss-of-function genetic perturbations on phase-separating genes cause similar dysfunction phenotypes as dosage-sensitive gene perturbations. In addition, dosage-sensitive scores derived from population genetics data predict phase-separating proteins with much better performance than available sequence-based predictors, further illustrating close ties between these two parameters. Conclusions Together, our study shows that phase separation is functionally linked to dosage sensitivity and provides novel insights for phase-separating protein prediction from the perspective of population genetics data.
Correction to “Analysis of 60 Patients with Relapsed or Refractory T‐cell Acute Lymphoblastic Leukemia and T‐cell Lymphoblastic Lymphoma Treated with <scp>CD7</scp>‐targeted <i>Chimeric Antigen <scp>Receptor‐T</scp></i> Cell Therapy”
Journal: American Journal of Hematology (2024)

In Table 1 of the article, the number of patients for "the group ≤ 14 (n=19), and the group >14 (n= 51)" was incorrect.This should be revised as" the group ≤14 (n = 19), and the group >14 (n = 41)".The correct information regarding this text in Table 1 is shown below.Age, median (range) 19 (2-47) ≤ 14 19 > 14 41We apologize for this error.Thank you very much for your kindness.
Pulmonary toxicity of immune checkpoint immunotherapy
Authors: Mohammad I Ghanbar, Karthik Suresh
Journal: Journal of Clinical Investigation (2024)

Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non-small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.
A systematic review of performance-based assessment studies on cognitive biases in schizophrenia spectrum psychoses and clinical high-risk states: A summary of 40 years of research
Authors: Łukasz Gawęda, Joachim Kowalski, Adrianna Aleksandrowicz, Paulina Bagrowska, Małgorzata Dąbkowska, Renata Pionke-Ubych
Journal: Clinical Psychology Review (2024)
Social and economic interdependence as a basis for peaceful between-group relationships in nonhuman primates and humans
Authors: Cyril C. Grueter
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki asserts that interdependent relationships beyond group boundaries are exceptionally rare among nonhuman mammals. However, rudimentary forms of interdependence can be seen in primate species that form multilevel societies, that is, core social units embedded within higher-level grouping categories. Studies of primate multilevel societies can enrich discussions about the evolutionary origins of peaceful between-group interactions in humans.
The evolution of peace (and war) is driven by an elementary social interaction mechanism
Authors: Ilan Fischer, Shacked Avrashi, Lior Savranevski
Journal: Behavioral and Brain Sciences (2024)

Abstract Here we revise Glowacki's model by proposing a simple and empirically tested mechanism that is applicable to a comprehensive set of social interactions. This parsimonious mechanism accounts for the choice of both cooperative and peaceful alternatives and explains when each choice benefits the interacting parties. It is proposed that this mechanism is key to the evolution of both peace and conflict.
The importance of social rejection as reputational sanction in fostering peace
Authors: Hsuan-Che (Brad) Huang
Journal: Behavioral and Brain Sciences (2024)

Abstract I challenge the idea by Glowacki that “strong sanctions” such as fines, physical punishment, or execution are more effective in promoting peace than “weak punishments” like social rejection. Reviewing evidence that social rejection can have significant social and psychological costs for norm violators, I propose that social rejection can serve as a powerful reputational sanction in fostering peace in society.
A neurological foundation for peaceful negotiations
Authors: Frederick L. Coolidge
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki explored the conditions required for peace and argued its preconditions arose only within the last 100,000 years. The present commentary addresses some major brain changes that occurred only in Homo sapiens within that period of time and the verbal and nonverbal cognitive sequelae of those neurological changes that may have aided the diplomatic negotiations required for peaceful solutions.
Economic games for the study of peace
Authors: Robert Böhm, Simon Columbus
Journal: Behavioral and Brain Sciences (2024)

Abstract Economic games provide models of real-world contexts in which researchers can probe dispositional and structural determinants of intergroup relations. Most intergroup games focus on determinants of aggression between groups and constrain the possibilities for peace. However, paradigms such as the intergroup parochial and universal cooperation game allow for peaceful intergroup relations and can be adapted for the study of peace.
A game of raids: Expanding on a game theoretical approach utilising the prisoner's dilemma and ethnography in situ
Authors: Emily M. L. Jeffries, Sarah E. Wright, Sheina Lew-Levy
Journal: Behavioral and Brain Sciences (2024)

Abstract In this commentary, we set out the specifics of how Glowacki's game theoretical framework for the evolution of peace could be incorporated within broader cultural evolutionary approaches. We outline a formal proposal for prisoner's dilemma games investigating raid-based conflict. We also centre an ethnographic lens to understand the norms surrounding war and peace in intergroup interactions in small-scale communities.
The evolution of (intergroup) peace hinges on how we define groups and peace
Authors: Anne C Pisor, Kristopher M Smith, Jeffrey P Deminchuk
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki defines peace as harmonious relationships between groups maintained without the threat of violence, where groups can be anything from families to nation states. However, defining such contentious concepts like “peace” and “groups” is a difficult task, and we discuss the implications of Glowacki's definitions for understanding intergroup relationships and their evolutionary history.
Creating shared goals and experiences as a pathway to peace
Authors: Stephanie L. Brown, Michael Brown, David Cavallino, Ying-Syun Huang, Qianjing Li, Victor C. Monterroza
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki offers many new directions for understanding and even eliminating the problem of war, especially creating positive interdependencies with out-group members. We develop Glowacki's intriguing proposition that in-group dynamics provide a route to peace by describing a prosocial motivational system, the caregiving system, that aligns individual interests and eliminates the need to use coercion to achieve mutually beneficial outcomes.
Evolution, culture, and the possibility of peace
Authors: Roy F. Baumeister, Brad J. Bushman
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki's work meshes well with our view of human nature as having evolved to use culture to improve survival and reproduction. Peace is a cultural achievement, requiring advances in social organization and control, including leaders who can implement policies to benefit the group, third-party mediation, and intergroup cooperation. Cultural advances shift intergroup interactions from negative-sum (war) to positive-sum (trade).
Capacities for peace, and war, are old and related to <i>Homo</i> construction of worlds and communities
Authors: Agustín Fuentes, Nam Kim, Marc Kissel
Journal: Behavioral and Brain Sciences (2024)

Abstract The capacities required for both peace and war predate 100,000 years ago in the genus Homo are deeply entangled in the modes by which humans physically and perceptually construct their worlds and communities, and may not be sufficiently captured by economic models.
Experimental evidence suggests intergroup relations are, by default, neutral rather than aggressive
Authors: Hirotaka Imada, Nobuhiro Mifune
Journal: Behavioral and Brain Sciences (2024)

Abstract The target article offers a game-theoretical analysis of primitive intergroup aggression (i.e., raiding) and discusses difficulties in achieving peace. We argue the analysis does not capture the actual strategy space, missing out “do-nothing.” Experimental evidence robustly shows people prefer doing nothing against out-group members over cooperating with/attacking them. Thus, the target article overestimates the likelihood of intergroup aggression.
The intertwined nature of peace and war
Authors: Bonaventura Majolo
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki discusses how humans regularly face collective action problems that may result in either peaceful or aggressive between-group interactions. Peace and war probably coevolved in humans. Using a gene–culture evolutionary framework is a powerful way to analyse why, when, and how humans have the capacity to build and maintain long-term peaceful interactions between groups and also to wage deadly wars.
Peace in other primates
Authors: David J. Grüning, Joachim I. Krueger
Journal: Behavioral and Brain Sciences (2024)

Abstract We elaborate on Glowacki's claim that humans are more capable of establishing peace than other mammals. We present three aspects suggesting caution. First, the social capabilities of nonhuman primates should not be underestimated. Second, the effect of these capabilities on peace establishment is nonmonotonous. Third, defining peace by human-centered values introduces a fallacy.
Cultural technologies for peace may have shaped our social cognition
Authors: Amine Sijilmassi, Lou Safra, Nicolas Baumard
Journal: Behavioral and Brain Sciences (2024)

Abstract Peace, the article shows, is achieved by culturally evolved institutions that incentivize positive-sum relationships. We propose that this insight has important consequences for the design of human social cognition. Cues that signal the existence of such institutions should play a prominent role in detecting group membership. We show how this accounts for previous findings and suggest avenues for future research.
NanoIEA: A Nanopatterned Interdigitated Electrode Array‐Based Impedance Assay for Real‐Time Measurement of Aligned Endothelial Cell Barrier Functions (Adv. Healthcare Mater. 2/2024)
Authors: Jong Seob Choi, Hyun Myung Doo, Byunggik Kim, Su Han Lee, Sang‐keun Sung, Gwangjun Go, Allister Suarez, Yeseul Kim, Byung Mook Weon, Byung‐Ok Choi, Hyung Jin Kim, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2024)

Interdigitated Electrodes The work in 2301124 by Deok-Ho Kim and co-workers showcases the development of a nanopatterned interdigitated electrode array (nanoIEA)-based impedance assay, highlighting its application in the quantitative real-time measurement of aligned endothelial cell barrier functions. Additionally, it emphasizes the impact of GSK3 inhibition on enhancing impedance and resistance, underlining the synergistic effects on the cell-cell tightness of aligned endothelial cells through the combined influence of matrix anisotropy and GSK3i treatment.
Multimodal Imaging‐Guided Photoimmunotherapy of Pancreatic Cancer by Organosilica Nanomedicine (Adv. Healthcare Mater. 2/2024)
Authors: Huifeng Zhang, Kun Chen, Kai Guo, Jun Tao, Lina Song, Shuai Ren, Yatong Zhao, Zhaogang Teng, Wenli Qiu, Zhongqiu Wang
Journal: Advanced Healthcare Materials (2024)

Photothermal Therapy In article 2302195, Zhaogang Teng, Wenli Qiu, Zhongqiu Wang, and co-workers develop a multimodal imaging-guided organosilica nanomedicine (DCCGP) for pancreatic cancer photoimmunotherapy. The innovative DCCGP platform combines fluorescence, magnetic resonance, and real-time infrared photothermal imaging, improving diagnostic precision and treatment effectiveness. By integrating photothermal stimulations with the PD-L1-induced ICB effect, it significantly enhances tumor cell elimination, achieving an optimized photoimmunotherapy synergy effect.
Per-Particle Cardiovascular Risk of Lipoprotein(a) vs Non-Lp(a) Apolipoprotein B-Containing Lipoproteins
Authors: Nicholas A. Marston, Giorgio E.M. Melloni, Sabina A. Murphy, Jakub Morze, Frederick K. Kamanu, Patrick T. Ellinor, Christian T. Ruff, Marc S. Sabatine
Journal: Journal of the American College of Cardiology (2024)
Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors
Authors: Ylva Trolle Lagerros, Alessandra Grotta, Sara Freyland, David Grannas, Daniel Peter Andersson
Journal: Journal of the American College of Cardiology (2024)

Phosphodiesterase-5 inhibitor (PDE5i) treatment for erectile dysfunction is associated with lower mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI). There are conflicting results regarding the impact of PDE5i treatment on mortality in conjunction with nitrate medication. The purpose of this study was to investigate the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease treated with nitrate medication. Using the Swedish Patient Register and the Prescribed Drug Register we included men with previous MI or revascularization in 2006-2013 who had 2 dispensed nitrate prescriptions within 6 months. Exposure was defined as at least 2 filled prescriptions of any PDE5i. We performed multivariable Cox proportional hazard regression to estimate HRs with 95% CIs for all-cause, cardiovascular, and noncardiovascular mortality, MI, heart failure, cardiac revascularization, and major cardiovascular events (MACE). In total, 55,777 men were treated with nitrates and 5,710 men with nitrates and a PDE5i. The combined use of PDE5i treatment with nitrates was associated with higher mortality (HR: 1.39; 95% CI: 1.28-1.51), cardiovascular mortality (HR: 1.34; 95% CI: 1.11-1.62), noncardiovascular mortality (HR: 1.40; 95% CI: 1.27-1.54), MI (HR: 1.72; 95% CI: 1.55-1.90), heart failure (HR: 1.67; 95% CI: 1.48-1.90), cardiac revascularization (HR: 1.95; 95% CI: 1.78-2.13), and MACE (HR: 1.70; 95% CI: 1.58-1.83). The use of a PDE5i in combination with nitrate medication in men with stable coronary artery disease may pose an increased hazard for cardiovascular morbidity and mortality. Careful patient-centered consideration before prescribing PDE5is to patients with cardiovascular disease using nitrate medication is warranted.
Anxiety and Depression in Adults With Congenital Heart Disease
Authors: Adrienne H. Kovacs, Koen Luyckx, Corina Thomet, Werner Budts, Junko Enomoto, Maayke A. Sluman, Chun-Wei Lu, Jamie L. Jackson, Paul Khairy, Stephen C. Cook, Shanthi Chidambarathanu, Luis Alday, Mette-Elise Estensen, Mikael Dellborg, Malin Berghammer, Bengt Johansson, Andrew S. Mackie, Samuel Menahem, Maryanne Caruana, Gruschen Veldtman, Alexandra Soufi, Susan M. Jameson, Edward Callus, Shelby Kutty, Erwin Oechslin, Liesbet Van Bulck, Philip Moons
Journal: Journal of the American College of Cardiology (2024)
When Direct Oral Anticoagulants Should Not Be Standard Treatment
Authors: Antoine Bejjani, Candrika D. Khairani, Ali Assi, Gregory Piazza, Parham Sadeghipour, Azita H. Talasaz, John Fanikos, Jean M. Connors, Deborah M. Siegal, Geoffrey D. Barnes, Karlyn A. Martin, Dominick J. Angiolillo, Dawn Kleindorfer, Manuel Monreal, David Jimenez, Saskia Middeldorp, Mitchell S.V. Elkind, Christian T. Ruff, Samuel Z. Goldhaber, Harlan M. Krumholz, Roxana Mehran, Mary Cushman, John W. Eikelboom, Gregory Y.H. Lip, Jeffrey I. Weitz, Renato D. Lopes, Behnood Bikdeli
Journal: Journal of the American College of Cardiology (2024)
Group-structured cultural selection can explain both war and peace
Authors: Sarah Mathew, Matthew Zefferman
Journal: Behavioral and Brain Sciences (2024)

Abstract Glowacki recognizes the importance of norms in enabling war and peace, but does not focus on the cultural evolutionary mechanisms by which these norms are maintained. We highlight how group-structured cultural selection shapes the scale and nature of peaceful intergroup interactions. The mechanistic perspective reveals that there are many more cases of peaceful intergroup relations than the current account implies.