CT-Guided Core Needle Biopsy of Nonspinal Bone Lesions: Comparison of Occult and Visible Bone Lesions.

BACKGROUND. CT guidance may be used for biopsy of indeterminate bone lesions detected by MRI or PET/CT that are not visible (i.e., occult) on CT owing to equipment-, patient-, and operator-related factors. OBJECTIVE. The purpose of this study was to assess diagnostic yield (DY) and diagnostic performance of CT-guided core needle biopsy (CNB) of occult nonspinal bone lesions and to identify the most common benign and malignant diagnoses for occult lesions undergoing CNB. METHODS. This retrospective study included 1033 adult patients who underwent CT-guided nonspinal bone CNB between January 2004 and December 2020. Lesions were classified as occult or visible on CT; biopsies of occult lesions were performed by targeting anatomic landmarks using prebiopsy MRI or PET/CT. Pathologic results of CNB were classified as diagnostic or nondiagnostic to calculate DY of CNB. For nondiagnostic CNBs, final diagnoses were established by subsequent pathologic, clinical, and imaging follow-up. RESULTS. The sample included 70 patients with occult lesions (mean age, 56.8 years; 38 women, 32 men) and 963 patients with visible lesions (mean age, 59.6 years; 475 women, 488 men). Malignancy rate was lower for occult than for visible lesions (42.9% vs 60.9%, p = .004). DY was lower for occult than for visible lesions (37.1% vs 76.9%, p < .001). Diagnostic performance for detecting malignancy on the basis of final diagnoses was lower for occult than for visible lesions in terms of sensitivity (76.7% vs 93.7%, p = .003), specificity (7.9% vs 56.5%, p < .001), and accuracy (38.2% vs 80.0%, p < .001). Final diagnoses among malignant occult and visible lesions included metastasis (frequencies of 63.3% vs 65.4%), leukemia/lymphoma (33.3% vs 11.6%), and myeloma (3.3% vs 10.4%); final diagnoses among benign occult and visible lesions included red marrow (34.2% vs 8.2%), reactive marrow (26.3% vs 11.8%), and fracture (18.4% vs 3.8%). Occult lesions detected by MRI versus PET/CT had lower malignancy rate (39.3% vs 68.0%, p = .03) and lower DY (30.4% vs 60.0%, p = .01). CONCLUSION. At CT-guided CNB, malignancy rate and DY are lower for occult than for visible lesions. Leukemia/lymphoma and red marrow are more common among occult than visible lesions. CLINICAL IMPACT. Understanding these characteristics can help guide radiologists', referring providers', and patients' expectations when CNB of occult bone lesions is requested and performed.

Enhancing Child and Adolescent Psychiatry Recruitment Through a Medical Student Mentorship Network: A Qualitative Study.

OBJECTIVE: There is a shortage of psychiatrists necessary to meet the clinical needs of children and adolescents. Efforts over the past decade to enhance the workforce have had a limited impact. This study sought to identify the critical components of a medical student mentorship network designed to increase recruitment into the subspecialty. METHODS: The authors conducted interviews via synchronized videoconferencing of network site leaders and medical students at 14 schools throughout the USA. In addition, they analyzed verbatim transcripts using a thematic-phenomenological qualitative approach. RESULTS: The authors interviewed thirty-eight program participants during seven focus group sessions: nine program directors and 29 medical students or graduates, a median of five participants per session. They constructed a framework consisting of two overarching domains, comprised of three themes each: (1) life cycle of a subspecialty mentorship network (Origins, Initiation, and Continuity); and (2) next steps to improve the program (Refining goals, Increasing accessibility, and Defining a path forward). CONCLUSION: Preliminary data have already documented the positive impact of participation in this mentorship program on medical student match rates into psychiatry. The qualitative model of this study provides a blueprint to develop, maintain, and optimize this and similar efforts aimed at increasing the child and adolescent psychiatry workforce.

Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder.

The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger's Diagnostic Scale-Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water's relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

PURPOSE: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis. METHODS: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts. RESULTS: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201). CONCLUSION: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.

Expression of immunoreactive inducible nitric oxide synthase in pancreatic islet cells from newly diagnosed and long-term type 1 diabetic donors is heterogeneous and not disease-associated.

Exposure of isolated human islets to proinflammatory cytokines leads to up-regulation of inducible nitric oxide synthase (iNOS), raised NO, and beta cell toxicity. These findings have led to increasing interest in the clinical utility of iNOS blockade to mitigate beta cell destruction in human type 1 diabetes (T1D). However, recent studies show that iNOS-derived NO may also confer beta cell protection. To investigate this dichotomy, we compared islet cell distributions and intensity of iNOS immunostaining in pancreatic sections, co-stained for insulin and glucagon, from new-onset T1D donors (group 1), with non-diabetic autoantibody-negative (group 2), non-diabetic autoantibody-positive (group 3) and long-term diabetic donors (group 4). The cellular origins of iNOS, its frequency and graded intensities in islets and number in peri-islet, intra-islet and exocrine regions were determined. All donors showed iNOS positivity, irrespective of disease and presence of beta cells, had variable labelling intensities, without significant differences in the frequency of iNOS-positive islets among study groups. iNOS was co-localised in selective beta, alpha and other endocrine cells, and in beta cell-negative islets of diabetic donors. The number of peri- and intra-islet iNOS cells was low, being significantly higher in the peri-islet area. Exocrine iNOS cells also remained low, but were much lower in group 1. We demonstrate that iNOS expression in islet cells is variable, heterogeneous and independent of co-existing beta cells. Its distribution and staining intensities in islets and extra-islet areas do not correlate with T1D or its duration. Interventions to inactivate the enzyme to alleviate disease are currently not justified.

TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation.

The activation of the epidermal growth factor receptor (EGFR) is crucial for triggering diverse cellular functions, including cell proliferation, migration, and differentiation, and up-regulation of EGFR expression or activity is a key factor in triggering the development of cancer. Here we show that overexpression of a scaffold protein, tumor necrosis factor receptor (TNF-R)-associated factor 4 (TRAF4), promotes EGF-induced autophosphorylation of EGFR (activation) and downstream signaling, whereas TRAF4 deficiency attenuates EGFR activation and EGF-driven cell proliferation. Using structure-based sequence alignment and NMR spectroscopy, we identified a TRAF4 binding site in the C-terminal half of the juxtamembrane (JM) segment of EGFR, a region known to promote asymmetric dimerization and subsequent activation. Deletion of the TRAF4 binding site led to dramatic defects in EGFR activation and EGF-driven cell proliferation. Specific point mutations in the TRAF4 binding site also resulted in significant attenuation of EGFR activation. Detailed structural examination of the inactive versus active forms of EGFR suggests that TRAF4 binding probably induces a conformational rearrangement of the JM region to promote EGFR dimerization. These results identify a novel mechanism of TRAF4-mediated EGFR activation and signaling.

Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease.

Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament-binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.

Experimental demonstration of the importance of keystone communities for maintaining metacommunity biodiversity and ecosystem functioning.

As local communities within a metacommunity may differ considerably in their contributions to biodiversity and ecosystem functioning, it has been suggested that conservation priority should be given to disproportionately important local communities (i.e., keystone communities). However, we know little about what characterizes a keystone community. Using laboratory protist microcosms as the model system, we examined how the environmental uniqueness and location of a local community affect its contributions to the metacommunities. We found that the removal of local communities with unique environmental conditions, which supported endemic species, reduced regional-scale diversity, qualifying them as regional-scale keystone communities. In addition, the local communities possessing unique environmental conditions had greater impacts on ecosystem functions, including biovolume production and particulate organic matter decomposition. We also found that keystone communities for biovolume production were not keystone for organic matter decomposition, and vice versa. Our study, therefore, demonstrates the important role of keystone communities in maintaining biodiversity and functioning of metacommunities.

Targeted deletion of Insm2 in mice result in reduced insulin secretion and glucose intolerance.

BACKGROUND: Neurogenin3 (Ngn3) and neurogenic differentiation 1 (NeuroD1), two crucial transcriptional factors involved in human diabetes (OMIM: 601724) and islet development, have been previously found to directly target to the E-boxes of the insulinoma-associated 2 (Insm2) gene promoter, thereby activating the expression of Insm2 in insulin-secretion cells. However, little is known about the function of Insm2 in pancreatic islets and glucose metabolisms. METHODS: Homozygous Insm2-/- mice were generated by using the CRISPR-Cas9 method. Glucose-stimulated insulin secretion and islet morphology were analyzed by ELISA and immunostainings. Expression levels of Insm2-associated molecules were measured using quantitative RT-PCR and Western blots. RESULTS: Fasting blood glucose levels of Insm2-/- mice were higher than wild-type counterparts. Insm2-/- mice also showed reduction in glucose tolerance and insulin/C-peptide levels when compared to the wild-type mice. RT-PCR and Western blot analysis revealed that expression of Insm1 was significantly increased in Insm2-/- mice, suggesting a compensatory response of the homolog gene Insm1. Similarly, transcriptional levels of Ngn3 and NeuroD1 were also increased in Insm2-/- mice. Moreover, Insm2-/- female mice showed a significantly decreased reproductive capacity. CONCLUSIONS: Our findings suggest that Insm2 is important in glucose-stimulated insulin secretion and is involved in the development pathway of neuroendocrine tissues which are regulated by the transcription factors Ngn3, NeuroD1 and Insm1.

Clinical and genetic analysis of a rare syndrome associated with neoteny.

PurposeWe describe a novel syndrome in seven female patients with extreme developmental delay and neoteny.MethodsAll patients in this study were female, aged 4 to 23 years, were well below the fifth percentile in height and weight, had failed to develop sexually, and lacked the use of language. Karyotype and array chromosome genomic hybridization analysis failed to identify large-scale structural variations. To further understand the underlying cause of disease in these patients, whole-genome sequencing was performed.ResultsIn five patients, coding de novo mutations (DNMs) were found in five different genes. These genes fell into similar functional categories of transcription regulation and chromatin modification. Comparison to a control population suggested that individuals with neotenic complex syndrome (NCS)-a name that we propose herein-could have an excess of rare inherited variants in genes associated with developmental delay and autism, although the difference was not significant.ConclusionWe describe an extreme form of developmental delay, with the defining characteristic of neoteny. In most patients we identified coding DNMs in a set of genes intolerant of haploinsufficiency; however, it is not clear whether these contributed to NCS. Rare inherited variants may also be associated with NCS, but more samples need to be analyzed to achieve statistical significance.

Sex-related difference in food-anticipatory activity of mice.

The expression of food-anticipatory activity (FAA) is induced by restricted feeding (RF), and its entrainment requires food-entrainable oscillators, the neuroanatomical basis of which is currently unclear. Although RF impacts various hormones, sex-related differences in FAA are unclear. 'Here, we report significantly more food-anticipatory wheel-running activity in male than in female mice during RF. In parallel with the sex-related difference in FAA, male and female mice display different food intake and body weight in response to RF. Since gonadal hormones could be involved in the sex-specific difference in FAA, we compared sham and gonadectomized male and female wild-type mice. In gonadectomized mice, the sex difference in FAA was abolished, indicating a role for gonadal hormones in FAA. Further, plasma concentrations of the hormone ghrelin were higher in female than in male mice during ad libitum (AL) feeding, and RF induced a temporal advance in its peak in both sexes. RF also shifted the expression peak of the circadian gene mPer1 in the hippocampus and liver, although no sex difference was found in either the level or the cyclic phase of its expression. Per1(Brdm1) mutant mice were still sexually dimorphic for FAA, but diminished FAA was noted in both male and female Per2(Brdm1) mutant mice. In summary, our results imply that gonadal hormones contribute to the sex difference in FAA, possibly through modulating ghrelin activity.

The copy number variant architecture of psychopathology and cognitive development in the ABCD® study.

Importance: Childhood is a crucial developmental phase for mental health and cognitive function, both of which are commonly affected in patients with psychiatric disorders. This neurodevelopmental trajectory is shaped by a complex interplay of genetic and environmental factors. While common genetic variants account for a large proportion of inherited genetic risk, rare genetic variations, particularly copy number variants (CNVs), play a significant role in the genetic architecture of neurodevelopmental disorders. Despite their importance, the relevance of CNVs to child psychopathology and cognitive function in the general population remains underexplored. Objective: Investigating CNV associations with dimensions of child psychopathology and cognitive functions. Design Setting and Participants: ABCD® study focuses on a cohort of over 11,875 youth aged 9 to 10, recruited from 21 sites in the US, aiming to investigate the role of various factors, including brain, environment, and genetic factors, in the etiology of mental and physical health from middle childhood through early adulthood. Data analysis occurred from April 2023 to April 2024. Main Outcomes and Measures: In this study, we utilized PennCNV and QuantiSNP algorithms to identify duplications and deletions larger than 50Kb across a cohort of 11,088 individuals from the Adolescent Brain Cognitive Development® study. CNVs meeting quality control standards were subjected to a genome-wide association scan to identify regions associated with quantitative measures of broad psychiatric symptom domains and cognitive outcomes. Additionally, a CNV risk score, reflecting the aggregated burden of genetic intolerance to inactivation and dosage sensitivity, was calculated to assess its impact on variability in overall and dimensional child psychiatric and cognitive phenotypes. Results: In a final sample of 8,564 individuals (mean age=9.9 years, 4,532 males) passing quality control, we identified 4,111 individuals carrying 5,760 autosomal CNVs. Our results revealed significant associations between specific CNVs and our phenotypes of interest, psychopathology and cognitive function. For instance, a duplication at 10q26.3 was associated with overall psychopathology, and somatic complaints in particular. Additionally, deletions at 1q12.1, along with duplications at 14q11.2 and 10q26.3, were linked to overall cognitive function, with particular contributions from fluid intelligence (14q11.2), working memory (10q26.3), and reading ability (14q11.2). Moreover, individuals carrying CNVs previously associated with neurodevelopmental disorders exhibited greater impairment in social functioning and cognitive performance across multiple domains, in particular working memory. Notably, a higher deletion CNV risk score was significantly correlated with increased overall psychopathology (especially in dimensions of social functioning, thought disorder, and attention) as well as cognitive impairment across various domains. Conclusions and Relevance: In summary, our findings shed light on the contributions of CNVs to interindividual variability in complex traits related to neurocognitive development and child psychopathology.

A general exposome factor explains individual differences in functional brain network topography and cognition in youth.

Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child's environment ("exposome") and investigate associations with each child's unique, multidimensional pattern of functional brain network organization ("functional topography") and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9-10) and future (ages 11-12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child's exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children's complex, multidimensional environments in cognitive neurodevelopment.

Peripheral Nerve Imaging: Magnetic Resonance and Ultrasound Correlation.

Magnetic resonance (MR) neurography and high-resolution ultrasound are complementary modalities for imaging peripheral nerves. Advances in imaging technology and optimized techniques allow for detailed assessment of nerve anatomy and nerve pathologic condition. Diagnostic accuracy of imaging modalities likely reflects local expertise and availability of the latest imaging technology.

The overlapping genetic architecture of psychiatric disorders and cortical brain structure.

Both psychiatric vulnerability and cortical structure are shaped by the cumulative effect of common genetic variants across the genome. However, the shared genetic underpinnings between psychiatric disorders and brain structural phenotypes, such as thickness and surface area of the cerebral cortex, remains elusive. In this study, we employed pleiotropy-informed conjunctional false discovery rate analysis to investigate shared loci across genome-wide association scans of regional cortical thickness, surface area, and seven psychiatric disorders in approximately 700,000 individuals of European ancestry. Aggregating regional measures, we identified 50 genetic loci shared between psychiatric disorders and surface area, as well as 26 genetic loci shared with cortical thickness. Risk alleles exhibited bidirectional effects on both cortical thickness and surface area, such that some risk alleles for each disorder increased regional brain size while other risk alleles decreased regional brain size. Due to bidirectional effects, in many cases we observed extensive pleiotropy between an imaging phenotype and a psychiatric disorder even in the absence of a significant genetic correlation between them. The impact of genetic risk for psychiatric disorders on regional brain structure did exhibit a consistent pattern across highly comorbid psychiatric disorders, with 80% of the genetic loci shared across multiple disorders displaying consistent directions of effect. Cortical patterning of genetic overlap revealed a hierarchical genetic architecture, with the association cortex and sensorimotor cortex representing two extremes of shared genetic influence on psychiatric disorders and brain structural variation. Integrating multi-scale functional annotations and transcriptomic profiles, we observed that shared genetic loci were enriched in active genomic regions, converged on neurobiological and metabolic pathways, and showed differential expression in postmortem brain tissue from individuals with psychiatric disorders. Cumulatively, these findings provide a significant advance in our understanding of the overlapping polygenic architecture between psychopathology and cortical brain structure.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

OBJECTIVE: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD). METHODS: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission. RESULTS: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024). CONCLUSIONS: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.

Imaging Features of Soft Tissue Tumor Mimickers: A Pictorial Essay.

Soft tissue lesions are commonly encountered and imaging is an important diagnostic step in the diagnosis and management of these lesions. While some of these lesions are true neoplasms, others are not. These soft tissue tumor mimickers can be due to a variety of conditions including traumatic, iatrogenic, inflammatory/reactive, infection, vascular, and variant anatomy. It is important for the radiologist and clinician to be aware of these common soft tissue tumor mimickers and their characteristic imaging features to avoid unnecessary workup and provide the best treatment outcome.

The polarizable and reprogrammable identity of Kupffer cells in Nonalcoholic Steatohepatitis.

Kupffer cells (KCs) are the resident macrophages of the liver with similar origins to myeloid-derived macrophages. Once differentiated, KCs exhibit distinct cellular machinery capable of longevity and self-renewal, making them a crucial player in promoting effective intrahepatic communication. However, this gets compromised in disease states like Nonalcoholic Steatohepatitis (NASH), where the loss of embryo-derived KCs (EmKCs) is observed. Despite this, other KC-like and KC-derived populations start to form and contribute to a variety of roles in NASH pathogenesis, often adopting a NASH-associated molecular signature. Here we offer a brief overview of recent reports describing KC polarization and reprogramming in the liver. We describe the complexities of KC cellular identity, their proposed ability to reprogram to fibroblast-like and endothelial-like cells, and the potential implications in NASH.