Aggressive Responses Research Articles

The opposite roles of injustice and cruelty in the internalization of a devaluation: The humiliation paradox revisited.

Cruelty and its link to injustice in contexts of humiliation have not received to date due attention from experimental psychosocial research. Aiming at filling this gap, this paper presents three studies with increasing degrees of experimental control (Ntotal = 1098) that show a dual opponent-process response to being targeted by potentially humiliating actions: while targets appraising more injustice internalize less the devaluation underlying the humiliation experience (thus partially dissolving the so-called "paradox of humiliation", Fernández etal., 2015, Personality and Social Psychology Bulletin, 41, 976), targets appraising more cruelty internalize more a devalued self-view and feel more humiliated. The fine balance between these two closely connected but distinct appraisals is key to understand the internal/subjective experience of targets: seeing themselves mainly as victims of injustice or cruelty will prevent or favour, respectively, their internalization of the devaluation and their feeling humiliated. This opposite pattern also impacts victims' reaction: Both appraisals relate to aggressive responses via anger but while appraising cruelty also paradoxically leads to powerless inertia, appraising injustice (including importantly the injustice of cruelty itself) leads to less powerlessness and more assertive agency. The theoretical and applied implications of approaching the victims of humiliation as victims of both an injustice and a cruelty are discussed.

Effects of Urban Lighting at Night on Daytime Songbird Aggression

Many animals require sleep for daily functions. In spring, songbirds expend a great deal of energy early in the day by singing to attract mates and aggressively protecting territory. Some evidence suggests that artificial lighting at night (ALAN) in the environment of wild birds increases their nighttime activity that, in turn, contributes to sleep loss. This study investigated how ALAN affects northern cardinal (Cardinalis cardinalis) response to experimental aggressive intrusion by conspecifics. The hypothesis tested is that high ALAN near cardinal roosting spots would cause those individuals to have less energy for daytime aggressive behaviors. After selecting known dark and bright urban roosting locations, ALAN was measured at specific sites with active cardinal territories during nighttime hours. Observers returned in the morning to present cardinal territorial songs using standardized call playback protocols. Aggressive behaviors of responding cardinals were recorded and used to quantify aggression intensity. Standard aggression measures included response latency, distance from bird to speaker, number of songs, hops, and flip flops. An aggression index was obtained using factor analysis which confirmed that aggressive responses featured short latency and approach distances, few chips, and many songs, flip flops, and hops. Analysis of variance revealed that cardinals roosting in high ALAN engaged in significantly more aggressive morning responses; directly contradicting predictions and previously published findings. One possible explanation for this result is that high ALAN might improve sleep in cardinals. To test this, autonomous recording units (ARUs) were placed in study locations to record nighttime calling behaviors in high and low ALAN. Insufficient data were obtained to clarify whether nighttime activity was reduced significantly by ALAN exposure. However, results showed that nighttime activity by cardinals is strongly influenced by moonlight, and that determination of the influence of ALAN on nighttime and daytime avian behavior must include measures of lunar illumination.

Bisphenol F-induced precocious genesis of aggressive neurobehavioral response is associated with heightened monoamine oxidase activity and neurodegeneration in zebrafish brain

The production and use of plastics and plastics products has increased dramatically in recent decades. Moreover, their unprotected disposal into ambient life sustaining environment poses a significant health risk. Bisphenol F (BPF) an alternative to bisphenol A (BPA) has been extensively employed for making of plastics. Recent reports have documented the neurotoxic potential of BPF through induction of altered neurochemical profile, microglia-astrocyte-mediated neuroinflammation, oxidative stress, transformed neurobehavioral response, cognitive dysfunction, etc. In the present study, our approach was to understand the underlying mechanism of BPF-persuaded genesis of aggressive neurobehavioral response in zebrafish. The basic findings advocated a temporal transformation in native explorative behaviour and progressive induction of aggressive behavioural response in zebrafish following exposure to BPF. Our neurobehavioral findings supported the argument of oxidative stress-mediated neuromorphological transformation in the periventricular grey zone (PGZ) of the zebrafish brain. In line with earlier reports, our findings also showed that heightened monoamine oxidase (MAO) activity and downregulation in tyrosine hydroxylase expression in the zebrafish brain is associated with the precocious genesis of aggressive neurobehavioral response in zebrafish brain. Our findings also shed light on BPF-instigated apoptotic neuronal death as revealed by augmented chromatin condensation and cleaved caspase-3 expression. Further observation showed that the downregulation of NeuN (a marker of post-mitotic mature neuron) expression provided substantial neurotoxicity, leading to neurodegeneration in the PGZ region of the zebrafish brain. These basic findings grossly advocate that BPF acts as a potent neurotoxicant in transmuting native neurobehavioral response through the induction of oxidative stress, heightened MAO activity and neuromorphological transformation in the zebrafish brain.

Advances in Understanding Hepatocellular Carcinoma Vasculature: Implications for Diagnosis, Prognostication, and Treatment.

Hepatocellular carcinoma (HCC) progresses through multiple stages of hepatocarcinogenesis, with each stage characterized by specific changes in vascular supply, drainage, and microvascular structure. These vascular changes significantly influence the imaging findings of HCC, enabling non-invasive diagnosis. Vascular changes in HCC are closely related to aggressive histological characteristics and treatment responses. Venous drainage from the tumor toward the portal vein in the surrounding liver facilitates vascular invasion, and the unique microvascular pattern of vessels that encapsulate the tumor cluster (known as a VETC pattern) promotes vascular invasion and metastasis. Systemic treatments for HCC, which are increasingly being used, primarily target angiogenesis and immune checkpoint pathways, which are closely intertwined. By understanding the complex relationship between histopathological vascular changes in hepatocarcinogenesis and their implications for imaging findings, radiologists can enhance the accuracy of imaging diagnosis and improve the prediction of prognosis and treatment response. This, in turn, will ultimately lead to better patient care.

Novel and classical methods similarly describe variation in territory size among males in Neotropical poison frogs with contrasting reproductive and behavioral strategies

Territoriality is a form of social dominance concerning the use of space that ensures the territory owner primary access to critical resources. The territory is defended with visual displays, advertisement calls, physical attacks, or chemical signals. The territory is frequently estimated by mapping locations where an animal is observed engaging in territorial behavior or by tracking. However, these approaches may over- or underestimate the areas defended. Thus, the use of approaches explicitly determining defended areas is critical to properly characterize the territory. Intrusion experiments can elicit a response in territory holders, allowing one to characterize their aggressive responses; however, the aggressive response depends on the species. We describe an approach to experimentally estimate the territory size using playback experiments in a species that exhibits a stereotypical phonotactic response: the nurse frog, Allobates aff. trilineatus and develop a new behavioral index that allows assessing territory size in response to playbacks for a species with non-stereotyped phonotactic response: the endangered Lehmann’s poison frog, Oophaga lehmanni. We conducted 772 playback experiments on 18 males of A. aff. trilineatus, and 222 on nine males of O. lehmanni. We analyzed the results of playback experiments with three different area estimators regularly used to estimate space use and evaluated whether these estimates are correlated. The shape and size of territories varied among individuals and estimators in both species. Although we found that the absolute size of the territory depends on the method used, estimates were strongly correlated, meaning that different estimators similarly describe variation in territory size among males. Choosing an analysis method may not be particularly important for studying the characteristics of territoriality over space and time but using a systematic and standardized experimental approach that also incorporates the particularities of the aggressive response of each species is essential to understand the evolution of space use by poison frogs and other territorial species.

The efficacy of the peace ambassador project: Promoting children’s emotional intelligence to address aggression in the early childhood classroom

This study explored the effect of a social emotional learning programme- the ECE-Peace Ambassador project (ECE-PAP) − on children’s (i) emotional intelligence, (ii) prosocial behaviour, (iii) aggressive behaviour with peers, (iv) and peer exclusion. Employing a quasi-experimental design, ECE-PAP was implemented in 16 schools in Hong Kong. In each school, teachers in one K3 class (4- to 5-year-olds) implemented the programme and a second K3 class served as a control (N=302). Multiple reporters (children, parents, and teachers) provided assessments of children’s emotional competence, social behaviour, aggressive behaviour, and responses to peer aggression the week before the programme, the week after, and three months later. Preliminary analyses showed that at pretest, children in the experimental condition showed lower emotional intelligence and less competent responses to peer aggression than controls. However, these differences disappeared by posttest and remained non-significant at follow-up. Children in the experimental condition showed increases from pre- to posttest in emotional intelligence, emotion labelling, and taking action to stop bullying, and decreases in avoidance and aggressive responses. Implementing the programme over a greater number of weeks was associated with more positive child outcomes. These results suggest that ECE-PAP may be an effective, cost-effective way to address aggressive behaviour in kindergarten classrooms by promoting children’s emotional intelligence and social skills

The Proteogenomics of Prostate Cancer Radioresistance.

Radiation is standard of care in prostate cancer. Yet, we have little understanding of its failure. We demonstrate a new paradigm that radioresistance is fractionation specific and identified POLQ as a radioresistance modulator.

Inflation targeting and output stabilization in an estimated monetary model

This paper studies determinacy conditions in a monetary model with an interest rate rule. In addition to the inflation rate as an argument of the policy rule, we introduce a second argument: output, a case empirically relevant but overlooked in the existing literature on monetary models with flexible prices. Firstly, we estimate a model with money in utility and the production function. We find that an aggressive response to inflation does not necessarily guarantee determinacy anymore. Secondly, we compare monetary policy in the pre-Volcker era and the post-Volcker era. We find that, after the appointment of Paul Volcker, the Federal Reserve started to respond more aggressively to inflation and less aggressively to output. Indeterminacy is pervasive: the equilibrium is indeterminate in both sub-samples. Thirdly, we estimate the impulse response functions. We find that monetary shocks, sunspot inflation shocks, and productivity shocks have long-lasting effects on inflation, output, and interest rates.

Effects of a Brief Separation From the Owner While in the Home Environment: Comparison of Fearful and Control Dogs

ABSTRACT Separation from their owner is stressful for some dogs. Studies examining this phenomenon are usually carried out in novel places. However, given that separation distress can also impact the behavior and welfare of dogs in their home environment, it is critical to study them in this context as well. Our first aim was to evaluate the reactions of dogs to a brief separation from their owner in the home. Secondly, we aimed to examine differences in the reactions of dogs classified as fearful, without (n = 27) and with (n = 17) aggressive responses, as well as controls (n = 28). All dogs were adults, from various breeds and mixes, and lived as pets. Each dog’s behavior was evaluated across three phases: (1) 2 min interaction with owner (baseline), (2) 3 min separation from the owner (alone), and (3) 2 min after the owner returned (owner return). We measured exploration as well as affiliative and stress behaviors. The results show that dogs explored the environment more in phase 1, directed more behaviors toward the door through which the owner had left in phase 2, followed the owner leaving at the end of phase 2, and greeted them when they returned in phase 3. Dogs also spent more time near the owner after their absence in phase 3 than in phase 1. A decrease in exploration triggered by the absence of the owner in phase 2 and a lack of full exploration recovery in phase 3 were observed as possible indicators of stress. No differences were found between fearful dogs and controls. The results indicate that it is possible to evaluate dogs’ reactions to separation from their owner in a more naturalistic context. This could aid in the development of strategies to improve separation-related problems in dogs and thus improve their welfare and quality of life.

What Happens When Parents Find Violence Acceptable? A Case of Violent-Humorous Commercials Targeted at Children

We examine the influence of violent–humorous commercials on children and whether parental mediation can temper children’s aggressive responses to violent–humorous ads. We find that (a) violent–humorous ads lead to higher levels of aggressive affect in children, and (b) violent ads lead to higher levels of aggressive cognition and aggressive affect in children (Study 1). We also find that active parental mediation does not have the intended effect of reducing children’s aggressive responses after they view violent–humorous commercials (Study 1). This effect, which is contradictory to general expectations, occurs because parents are less likely to perceive the violent–humorous (vs. solely violent) ad as violent (Studies 2A and 2B) and, consequently, they show less interest in critically mediating the ad (Study 3). Through this study, for the first time, we show (a) the impact of violent–humorous ads on children (vs. adults); (b) the impact of violent–humorous ads on aggression (beyond attitudes toward ads); and (c) the effect of parents’ violent–humorous ad beliefs on parental mediation. The findings of our study suggest that the humor in a violent–humorous ad appears to trivialize the violence in the ad, with not-so-trivial consequences.

Waterborne atenolol disrupts neurobehavioral and neurochemical responses in adult zebrafish.

Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.

The Influence of Race on Detected and Undetected Sexual Offense Histories: A Comparison of White and Black Men Committed as Sexually Violent Persons.

Understanding the difference between the proportion of sexual offenses that are officially detected versus the total number of sexual crimes that occur has been of interest to decision makers for some time. Previous studies have not considered possible racial differences. More aggressive responses by police and the criminal justice system as well as cultural differences in victim type/reporting rates may result in differences between detection rates of Black versus White men. In the current study (N = 190), we examined the difference between Black (n = 51) and White (n = 139) men committed to a forensic hospital as a Sexually Violent Person on factors that could impact the detected rate. Overall, we found that White men had significantly more total victims, undetected victims, undetected and detected child victims, total male victims, undetected male victims, undetected acquaintance victims, and total (detected and undetected) acquaintance victims than Black men. Black men had significantly more detected adult victims, but this difference did not remain when accounting for undetected victims. We explore reasons for these differences as well as provide recommendations for practice.

The Future of CAR T Therapeutics to Treat Autoimmune Disorders.

The concept of chimeric antigen receptor (CAR) T cell therapy emerged from cancer immunotherapy and has been rapidly adapted and developed for the treatment of autoimmune, especially B-cell-driven, diseases since the first publication of an article featuring a patient with systemic lupus erythematosus in 2021. Phase II studies are about to start, but up to now, only case reports and small series have been published. In contrast to hemato-oncological diseases, where an aggressive response to malignant cells and long-lasting persistence of CAR T cells has been aimed at and observed in many patients, this is not the case with autoimmune diseases but might not be necessary to control disease. Future studies will focus on the optimal target but also on the optimal level of immunogenicity. The latter can be influenced by numerous modulations that affect not only cytokine release but also regulation. In addition, there are potential applications in regulatory cells such as CAR regulatory T cells (Treg). The question of toxicity reduction must also be addressed, as long-term complications such as the potential development of malignant diseases, infections, or cytopenia must be considered even more critically in the area of autoimmune diseases than is the case for patients with oncologic diseases. Alternative antibody-based therapies using the same target (e.g., CD3/CD19 bispecific targeting antibodies) have not been used in these patients and might also be considered in the future. In conclusion, CAR T cell therapy represents a promising therapeutic approach for autoimmune diseases, offering a targeted strategy to modulate immune responses and restore immune tolerance.

A Hybrid Control Framework for Chemical Processes with Long Time Delay: Theory and Experiments.

This paper proposes a hybrid control framework based on internal model concepts, sliding mode control methodology, and fractional-order calculus theory. As a result, a modified Smith predictor (SP) is proposed for nonlinear systems with significant delays. The particular predictive approach enhances the sliding mode control (SMC) controller's transient responses for dead-time processes, and the SMC gives the predictive structure robustness for model mismatches by combining the previous methods with fractional order concepts; the result is a dynamical sliding mode controller. A numerical example is considered to evaluate the performance of the proposed approach, where a step change, external disturbance, and parametric uncertainty test are performed. A real application in the TCLab Arduino kit is presented; the proposed method presented good performance with a little amount of chattering, and in the disturbance rejection case, the overshoot increased with an aggressive response; in both cases, better tuning parameters can improve the process response and the controller action.

Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.

Irritability, a state of excessive reactivity to negative emotional stimuli, is common in individuals with autism spectrum disorder (ASD). Although it has a significant negative impact of patients' disease severity and quality of life, the neural mechanisms underlying irritability in ASD remain largely unclear. We have previously demonstrated that male mice lacking the Coiled-coil and C2 domain containing 1a (Cc2d1a) in forebrain excitatory neurons recapitulate numerous ASD-like behavioral phenotypes, including impaired social behaviors and pronounced repetitive behaviors. Here, using the bottle-brush test (BBT) to trigger and evaluate aggressive and defensive responses, we show that Cc2d1a deletion increases irritability-like behavior in male but not female mice, which is correlated with reduced number of oxytocin (OXT)-expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Intranasal OXT administration or chemogenetic activation of OXT neurons in the PVN rescues irritability-like behavior in Cc2d1a conditional knockout (cKO) mice. Administration of a selective melanocortin receptor 4 agonist, RO27-3225, which potentiates endogenous OXT release, also alleviates irritability-like behavior in Cc2d1a cKO mice, an effect blocked by a specific OXT receptor antagonist, L-368,899. We additionally identify a projection connecting the posterior ventral segment of the medial amygdala (MeApv) and ventromedial nucleus of the ventromedial hypothalamus (VMHvl) for governing irritability-like behavior during the BBT. Chemogenetic suppression of the MeApv-VMHvl pathway alleviates irritability-like behavior in Cc2d1a cKO mice. Together, our study uncovers dysregulation of OXT system in irritability-like behavior in Cc2d1a cKO mice during the BBT and provide translatable insights into the development of OXT-based therapeutics for clinical interventions.

Giorgio Agamben’s Critique of the Covid-19 Response has Little to Do with Biopolitics

ABSTRACT Giorgio Agamben claims that the aggressive coronavirus response in Italy turned the nation’s entire population into formless bare life, which was cast out from meaningful human existence through a sovereign exception. This widely criticised argument appears to stem from Agamben’s radical reinterpretation of biopolitics, a concept popularised by Michel Foucault. Although Agamben is often considered as the second most famous authority on the topic, some have begun to question whether his reinterpretation can operate within the framework set by his predecessor who defines the notion primarily through its life affirming and optimising effects. This has led to an unclear and contested definition of biopolitics, which hinders the notion’s usage as an analytical tool. Agamben’s statements on the pandemic must face similar scrutiny. According to him, life was not optimised during the pandemic. Therefore, Agamben’s critique on the coronavirus response has little to do with the Foucauldian notion of biopolitics, which offers a much sounder way of analysing the Covid crisis.

Concerted monoamine oxidase activity following exposure to di-2-ethylhexyl phthalate is associated with aggressive neurobehavioral response and neurodegeneration in zebrafish brain

Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As DEHP is not chemically bound to the macromolecular polymer of plastics, it can be easily leached out to accumulate in food and environment. Our recent report advocated that exposure to DEHP significantly transformed the innate bottom-dwelling and scototaxis behaviour of zebrafish. Our present study aimed to understand the possible role of DEHP exposure pertaining towards the development of aggressive behaviour and its association with amplified monoamine oxidase activity and neurodegeneration in the zebrafish brain. As heightened monoamine oxidase (MAO) is linked with genesis of aggressive behaviour, our observation also coincides with DEHP-persuaded aggressive neurobehavioral transformation in zebrafish. Our preliminary findings also showed that DEHP epitomized as a prime factor in transforming native explorative behaviour and genesis of aggressive behaviour through oxidative stress induction and changes in the neuromorphology in the periventricular grey zone (PGZ) of the zebrafish brain. With the finding demarcating towards heightened chromatin condensation in the PGZ of zebrafish brain, our further observation by immunohistochemistry showed a profound augmentation in apoptotic cell death marker cleaved caspase 3 (CC3) expression following exposure to DEHP. Our further observation by immunoblotting study also demarcated a temporal augmentation in CC3 and tyrosine hydroxylase expression in the zebrafish brain. Therefore, the gross findings of the present study delineate the idea that chronic exposure to DEHP is associated with MAO-instigated aggressive neurobehavioral transformation and neurodegeneration in the zebrafish brain.

NF1 mutation and TUBB3 amplification in gastric histiocytic sarcoma: a case report and literature review.

Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical courseandpoor response to treatment. Primary gastric histiocytic sarcomais rarerand just reported sporadically.Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical courseandpoor response to treatment. Primary gastric histiocytic sarcomais rarerand just reported sporadically. A case of a 71-year-old female admitted with a one-year history of upper abdominal pain exacerbated after meals. After CT scans revealed a bulged mass atthe lesser curvature of the gastric body, the patient underwent endoscopic submucosal dissection. Microscopically, non-cohesive neoplastic cells diffuselyinfiltrated lamina propria and submucosa, and diffusely expressed LCA, CD4, CD163, CD68 (KP1),CyclinD1, Lysozyme, and Vimentin. PD-L1 (22CS) expression evaluated as CPS 60. The final pathological diagnosis was gastric histiocytic sarcoma.Subsequently, next-generation sequencing identified a nonsense mutation in exon 21 ofNF1gene [c.2446C > T (p.R816*)]andtheTUBB3gene amplification (copy number: 4.55).The patient refused further treatment and died of the tumorhalf a year later. This case broadens the spectrum of differential diagnosis of gastric cancerand emphasizes the value of immunohistochemicaland molecular testsin the accurate diagnosis of histiocytic sarcoma. Furthermore, we performed literature review of 11 cases of gastric histiocytic sarcoma so as to strengthen the understanding of the clinicopathologic features, treatment, and prognosis.

IL-6 knockdown in a model of the human bone marrow, abrogates DNA damage induction in bystander cells post-chemotherapy induced cytokine release syndrome

Following infection or exposure to therapeutic agents, an aggressive immune response may result, termed cytokine storm (CS) or cytokine release syndrome. Here the innate immune system becomes uncontrolled, leading to serious consequences including possible death. Patients surviving CS are at greater risk for de novo tumorigenesis, but it is unclear if any specific cytokines are directly responsible for this outcome. De novo tumorigenesis has been observed in donated cells exposed to CS following haematopoietic stem cell transplant (HSCT).Modelling HSCT, we firstly demonstrated the release of CS levels from the HS-5 human bone marrow stromal cell line, post-exposure to chemotherapy. We then exposed the TK6 lymphoblast cell line to healthy and storm doses of IL-6 and measured increased genotoxicity via the micronucleus assay. During HSCT, haematopoietic cells are exposed to a complex mix of cytokines, so to determine if IL-6 was integral in a chemotherapy-induced bystander effect, we attempted to inhibit IL-6 from HS-5 cells using resatorvid or siRNA, treated with chlorambucil or mitoxantrone, and then co-cultured with bystander TK6 cells. Whilst resatorvid did not reduce IL-6 and did not reduce micronuclei in the bystander TK6 cells, siRNA inhibition reduced IL-6 to healthy in vivo levels, and micronuclei aligned with untreated controls.Our data suggests that exposure to high IL-6 (in the absence of inflammatory cells) has potential to induce genetic damage and may contribute to de novo tumorigenesis post-CS. We suggest that for individuals with a pro-inflammatory profile, anti-IL-6 therapy may be an appropriate intervention to prevent complications post-CS.

Joint-specific rheumatoid arthritis fibroblast-like synoviocyte regulation identified by integration of chromatin access and transcriptional activity.

The mechanisms responsible for the distribution and severity of joint involvement in rheumatoid arthritis (RA) are not known. To explore whether site-specific fibroblast-like synoviocyte (FLS) biology might be associated with location-specific synovitis and explain the predilection for hand (wrist/metacarpal phalangeal joints) involvement in RA, we generated transcriptomic and chromatin accessibility data from FLS to identify the transcription factors and pathways. Networks were constructed by integration of chromatin accessibility and gene expression data. Analysis revealed joint-specific patterns of FLS phenotype, with proliferative, migratory, proinflammatory, and matrix-degrading characteristics observed in resting FLS derived from the hand joints compared with hip or knee. TNF stimulation amplified these differences, with greater enrichment of proinflammatory and proliferative genes in hand FLS compared with hip and knee FLS. Hand FLS also had the greatest expression of markers associated with an "activated" state relative to the "resting" state, with the greatest cytokine and MMP expression in TNF-stimulated hand FLS. Predicted differences in proliferation and migration were biologically validated with hand FLS exhibiting greater migration and cell growth than hip or knee FLS. Distinctive joint-specific FLS biology associated with a more aggressive inflammatory response might contribute to the distribution and severity of joint involvement in RA.