👤 Justin J Taylor

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by triglyceride accumulation and insulin resistance. Currently, weight loss remains the primary strategy for reducing liver fat. High-protein diets (HPDs) may improve metabolism, lower body weight, and reduce hepatic fat; however, the effects of specific protein sources are largely unknown. This study examines the effects of HPDs from animal and plant protein sources, separately and in combination, on hepatic steatosis and MASLD-related metabolic pathways. Obese fa/fa Zucker male rats received HPDs (35% kcal from protein) containing egg white, plant (soy+pea protein, 1:1), mixed (egg white+soy+pea protein, 2:1:1), or casein (HPcasein) as the protein sources, or a normal protein diet (15% kcal from protein) containing casein, for 8 weeks. HPplant and HPmixed diets increased body weight by 1.2-fold versus HPcasein. HPDs containing egg white, plant or mixed protein sources reduced the liver-body weight ratio by ∼30% and liver triglycerides by ∼50% compared to the casein diets. These changes were linked to smaller lipid droplets, less fibrosis, and decreased lipid peroxidation in liver. HPDs containing egg white, plant or mixed protein increased markers of VLDL synthesis (ApoB-100, MTP) via ChREBP. These diets also lowered HOMA-IR, and reduced HMGCS2 (ketogenesis marker). In conclusion, HPDs containing egg white or plant proteins reduced hepatic steatosis and indices of insulin resistance, unconnected to body weight. Determining the effects of specific protein sources in HPDs is an important consideration for further research on MASLD management. Show less

Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and executive functioning. In a prospective sample ( Show less

Lecanemab is an anti-amyloid monoclonal antibody, recently approved in the UK as a treatment for mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD) in adults who are apolipoprotein E ε4 gene ( Show less

Tau neurofibrillary tangles are a hallmark of several neurodegenerative diseases called tauopathies, including frontotemporal dementia and Alzheimer's Disease. Ongoing clinical trials for tauopathies seek to reduce Tau in the brain through immunotherapy, antisense oligonucleotides, and siRNA. Show less

Supercritical fluid chromatography is traditionally employed for nonpolar and moderately polar analytes, while the analysis of ionic compounds remains a recognized limitation of the technique. Moreover, some polar lipids may contain a chromatographically challenging ionic group, which can interact with the metal surfaces of the instrument and column, resulting in poor peak shape and loss of sensitivity. Here, we introduce a novel ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC/MS) method using a bioinert column, enabling the separation of lipids with a broad polarity range from nonpolar to ionic species. The UHPSFC/MS method was optimized using 79 lipid species across 41 lipid subclasses, achieving a total run time of 7.5 min, including the column equilibration. The comparison of the separation with conventional and bioinert columns revealed a substantial improvement in peak shapes for ionic lipid classes, such as PS, LPS, PA, LPA, CerP, and SPBP. Additionally, we introduce a combination of the modified chloroform-free extraction followed by a hexane elimination step. The optimized methodology was applied for the untargeted analysis of human plasma and erythrocyte-rich fraction to achieve highly confident identification of 657 lipid species across 37 lipid subclasses in human blood. The method follows the recommendations for validation of (bio)analytical methods, and its accuracy was confirmed by quantitative analysis of the reference material NIST SRM 1950, with the determined concentrations in agreement with the consensus values from ring trials. The current methodology represents a novel high-throughput and comprehensive quantitative lipidomic method for biological samples. The modified MTBE extraction enhances workflow efficiency by reducing concentrations of nonpolar lipids, which enables injection of more concentrated lipid extracts while minimizes ion source contamination. Moreover, the findings highlight the potential for the development of bioinert components specifically designed for SFC platforms, enabling broader applicability of the technique. Show less

Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare reproductive disorders with known genetic heterogeneity. Using exome sequencing, our group previously reported the prevalence of pathogenic and likely pathogenic (P/LP) variants in genes causing IHH/KS as the primary endpoint of our study. Here, we investigate the frequency of secondary findings (SF) to determine whether individuals with IHH/KS harbor an increased burden of P/LP variants in medically actionable genes (MAGs) defined by the American College of Medical Genetics and Genomics (ACMG). We analyzed exome sequencing data from 156 individuals with clinically confirmed IHH/KS. Variants were filtered for P/LP classification using ACMG guidelines across all 84 MAGs in ACMG SF v3.3. Sanger sequencing was used for orthogonal confirmation. The prevalence of MAG variants was compared to external control datasets from the U.K. Biobank (UKB, ~ 50,000 genomes) and the NIH eMERGE Network (~ 21,000 genomes), both based on the ACMG SF v2.0 59-gene list. Among 370,000 variants, 2 individuals (1.3%) carried validated P/LP variants in two distinct MAGs: SCN5A and MYBPC3. Genes 60-84, the additional 25 genes on the ACMG SF v3.3 list, yielded no additional variants. The prevalence of MAG variants in IHH/KS (1.3%) was not significantly different from UKB (2.0%) or eMERGE (2.5%) (OR vs. UKB: OR 0.64; 95% CI, 0.16-2.61; P = 0.57). The frequency of P/LP variants in MAGs among IHH/KS patients is comparable to the general population, suggesting that MAG variants are not common in IHH/KS in contrast to some other types of infertility. Show less

Driving integrates multiple cognitive, sensory, and motor systems and may serve as a real-world indicator of functional decline in aging. Older adults with mild cognitive impairment (MCI) often experience subtle driving changes before formal dementia diagnosis, but longitudinal, real-world evidence is limited. This study examined whether naturalistic driving data can differentiate older adults with MCI from those with normal cognition (NC) over time and evaluated the discriminative ability of driving features compared with conventional risk factors. We conducted a prospective, observational cohort study of community-dwelling older drivers enrolled in the Driving Real-World In-Vehicle Evaluation System Project at Washington University. Participants underwent annual Clinical Dementia Rating assessment, neuropsychological testing, and apolipoprotein ε4 (APOE ε4) genotyping. Driving behaviors were captured daily for up to 40 months using global positioning system-enabled in-vehicle dataloggers, recording trip frequency, duration, distance, time of day, speeding, hard braking, and spatial mobility (entropy, maximum distance, radius of gyration). Longitudinal changes were analyzed using linear mixed-effect models, adjusting for age, sex, race, education, and APOE ε4. Logistic regression with reciever operator curve analysis evaluated discrimination between older adults with MCI and those with NC, compared with conventional sociodemographic and genetic markers. Among 298 participants (MCI, n = 56; NC, n = 242; mean age 75.1 years; 45.6% female), the groups were similar in age, sex, race, and APOE ε4 status at baseline, as well as in most driving behaviors. Over time, drivers with MCI showed greater reductions in monthly trip count (MCI: -0.501, standard error [SE]: 0.21, 95% CI [-0.923 to -0.083] vs NC: -0.523, SE: 0.09, 95% CI [-0.709 to -0.337]; MCI was associated with progressive declines in driving frequency, complexity, and spatial range, supporting naturalistic driving data as a potential unobtrusive digital biomarker for early cognitive decline. Limitations of the study include a predominantly White, highly educated sample and a lack of external validation, warranting cautious interpretation. Continuous monitoring could augment clinical assessments, inform driving safety decisions, and guide interventions to preserve mobility in aging. Show less

ObjectiveTo describe characteristic CLEFT-Q response profiles and patterns in patients with cleft palate and/or lip (CP ± L).DesignRetrospective analysis using latent profile analysis (LPA) to categorize patient-reported outcome responses into distinct profiles.SettingTertiary care pediatric hospital with multidisciplinary cleft team.Patients, ParticipantsPatients aged 8-29 years with CP ± L completing CLEFT-Q questionnaires from September 2021 to June 2025 ( Show less

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10 Show less

Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm We used the Ibidi perfusion system to determine whether HSS applied to human PA endothelial cells (ECs) induces EndMT when compared with physiological laminar shear stress (15 dyn/cm EndMT, a feature of PAH not previously attributed to HSS, was observed. HSS did not alter the induction of transcription factors KLF (Krüppel-like factor) 2/4, but an ERG (ETS-family transcription factor) was reduced, as were histone H3 lysine 27 acetylation enhancer-promoter peaks containing ERG motifs. Consequently, there was reduced interaction between ERG and KLF2/4, a feature important in tethering KLF and the chromatin remodeling complex to DNA. In PA ECs under laminar shear stress, reducing ERG by siRNA caused EndMT associated with decreased BMPR2 (bone morphogenetic protein receptor 2), CDH5 (cadherin 5), and PECAM1 (platelet and EC adhesion molecule 1) and increased SNAI1/2 (Snail/Slug) and ACTA2 (smooth muscle α2 actin). In PA ECs under HSS, transfection of ERG prevented EndMT. HSS was then induced in mice by an aortocaval shunt, causing progressive PAH over 8 weeks. An adeno-associated viral vector (AAV2-ESGHGYF) was used to replenish ERG selectively in PA ECs. Elevated PA pressure, EndMT, and vascular remodeling (muscularization of peripheral arteries) in the aortocaval shunt mice were markedly reduced by ERG delivery. Pathological HSS reduced lung EC ERG, resulting in EndMT and PAH. Agents that upregulate ERG could reverse HSS-mediated PAH and occlusive vascular remodeling resulting from high flow or narrowed PAs. Show less

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m Show less

Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 Show less

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P Show less

Oncogenic activation of fibroblast growth factor receptor 2 (FGFR2) drives multiple cancers and represents a broad therapeutic opportunity, yet selective targeting of FGFR2 has not been achieved. Although the clinical efficacy of pan-FGFR inhibitors (pan-FGFRi) validates FGFR2 driver status in FGFR2 fusion-positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- and FGFR4-mediated toxicities (hyperphosphatemia and diarrhea, respectively) and the emergence of FGFR2 resistance mutations. RLY-4008 is a highly selective, irreversible FGFR2 inhibitor designed to overcome these limitations. In vitro, RLY-4008 demonstrates >250- and >5,000-fold selectivity over FGFR1 and FGFR4, respectively, and targets primary alterations and resistance mutations. In vivo, RLY-4008 induces regression in multiple xenograft models-including models with FGFR2 resistance mutations that drive clinical progression on current pan-FGFRi-while sparing FGFR1 and FGFR4. In early clinical testing, RLY-4008 induced responses without clinically significant off-isoform FGFR toxicities, confirming the broad therapeutic potential of selective FGFR2 targeting. Patients with FGFR2-driven cancers derive limited benefit from pan-FGFRi due to multiple FGFR1-4-mediated toxicities and acquired FGFR2 resistance mutations. RLY-4008 is a highly selective FGFR2 inhibitor that targets primary alterations and resistance mutations and induces tumor regression while sparing other FGFRs, suggesting it may have broad therapeutic potential. See related commentary by Tripathi et al., p. 1964. This article is featured in Selected Articles from This Issue, p. 1949. Show less

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JAM2 to be responsive to RELA at the messenger RNA and protein levels. IL-27Rα and JAM2 were expressed on primary MM cells at higher levels than on healthy long-lived plasma cells (PCs) in the bone marrow. IL-27 activated STAT1, and to a lesser extent STAT3, in MM cell lines and in PCs generated from memory B cells in an IL-21-dependent in vitro PC differentiation assay. Concomitant activity of IL-21 and IL-27 enhanced differentiation into PCs and increased the cell-surface expression of the known STAT target gene CD38. In accordance, a subset of MM cell lines and primary MM cells cultured with IL-27 upregulated CD38 cell-surface expression, a finding with potential implications for enhancing the efficacy of CD38-directed monoclonal antibody therapies by increasing CD38 expression on tumor cells. The elevated expression of IL-27Rα and JAM2 on MM cells compared with that on healthy PCs may be exploited for the development of targeted therapeutic strategies that modulate the interaction of MM cells with the TME. Show less

Systemic lupus erythematosus (SLE) is a relatively common autoimmune disease characterized by the presence of autoantibodies against nucleic acids and proteins that associate with them, such as the ORF1p protein encoded by the long interspersed element-1 (LINE-1 or L1). Because well-known lupus autoantigens like RO60 associate with ORF1p in macromolecular assemblies, together with many other RNA-binding proteins, we tested whether these other proteins are also recognized by IgG autoantibodies in SLE patients. By ELISAs and immunoblots, we detected autoantibodies in the serum of SLE patients recognizing proteins encoded by Show less

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals ( Show less

The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two endometrioid and two serous; n = 4) or normal atrophic endometrium (n = 4), providing 888 differentially expressed proteins with 246 of these previously documented elsewhere as expressed in EC and 372 proteins not previously demonstrated to be expressed in EC but associated with other types of cancer. Additionally, 33 proteins not recorded previously in PubMed as being expressed in any forms of cancer were also identified, with only 26 of these proteins having a publication associated with their expression patterns or putative functions. The putative functions of the 26 proteins (GRN, APP, HEXA, CST3, CAD, QARS, SIAE, WARS, MYH8, CLTB, GOLIM4, SCARB2, BOD1L1, C14orf142, C9orf142, CCDC13, CNPY4, FAM169A, HN1L, PIGT, PLCL1, PMFBP1, SARS2, SCPEP1, SLC25A24 and ZC3H4) in other tissues point towards and provide a basis for further investigation of these previously unrecognised novel EC proteins. The developmental biology, disease, extracellular matrix, homeostatic, immune, metabolic (both RNA and protein), programmed cell death, signal transduction, molecular transport, transcriptional networks and as yet uncharacterised pathways indicate that these proteins are potentially involved in endometrial carcinogenesis and thus may be important in EC diagnosis, prognostication and treatment and thus are worthy of further investigation. Show less

The melanocortins are derived from proopiomelanocortin (POMC) and include three forms of melanocyte-stimulating hormone (α-, β-, γ-, MSH) and adrenocorticotropic hormone. α-MSH, a potent POMC-derived neuropeptide, binds to melanocortin 4 receptor (MC4R) in the brain to reduce food intake (via appetite suppression) and increase energy expenditure (via sympathetic nervous system) after integration of central neuronal signal (e.g. serotonin, glutamate) and peripheral signals such as anorexigenic hormones (e.g. leptin, insulin) and nutrient (e.g. glucose). Mutations in POMC or MC4R can cause increase in food intake and body weight. Weight gain and obesity in turn result in a phenotypic switch of white adipose tissue, which then secretes proinflammatory cytokines that play a role in the development of insulin resistance and type 2 diabetes. Besides α-MSH's effects in decreasing food intake and body weight, α-MSH also carries protective anti-inflammatory properties in both immune cells and non-immune cells (e.g. adipocyte) that express melanocortin receptors. Since type 2 diabetic patients who have overweight or obese are recommended to lose body weight while current available anti-obesity drugs have various side effects, α-MSH-based therapeutics might be hopeful for the management of both obesity and type 2 diabetes. Show less

The melanocortin system plays an essential role in the regulation of immune activity. The anti-inflammatory microenvironment of the eye is dependent on the expression of the melanocortin-neuropeptide alpha-melanocyte stimulating hormone (α-MSH). In addition, the melanocortin system may have a role in retinal development and retinal cell survival under conditions of retinal degeneration. We have found that treating experimental autoimmune uveitis (EAU) with α-MSH suppresses retinal inflammation. Also, this augmentation of the melanocortin system promotes immune tolerance and protection of the retinal structure. The benefit of α-MSH-therapy appears to be dependent on different melanocortin receptors. Therefore, we treated EAU mice with α-MSH-analogs with different melanocortin-receptor targets. This approach demonstrated which melanocortin-receptors suppress inflammation, preserve retinal structure, and induce immune tolerance in uveitis. At the chronic stage of EAU the mice were injected twice 1 day apart with 50 μg of α-MSH or an α-MSH-analog. The α-MSH-analogs were a pan-agonist PL8331, PL8177 (potent MC1r-only agonist), PL5000 (a pan-agonist with no MC5r functional activity), MT-II (same as PL5000) and PG901 (MC5r agonist, but also an antagonist to MC3r, and MC4r). Clinical EAU scores were measured until resolution in the α-MSH-treated mice, when the eyes were collected for histology, and spleen cells collected for retinal-antigen-stimulated cytokine production. Significant suppression of EAU was seen with α-MSH or PL8331 treatment. This was accompanied with significant preservation of retinal structure. A similar effect was seen in EAU-mice that were treated with PL8177, except the suppression of EAU was temporary. In EAU mice treated with PL5000, MTII, or PG901, there was no suppression of EAU with a significant loss in whole retina and outer-nuclear layer thickness. There was significant suppression of IL-17 with induction of IL-10 by retinal-antigen stimulated spleen T cells from EAU mice treated with α-MSH, PL8331, PL8177, or PL5000, but not from EAU mice treated with MT-II, or PG901. Our previous studies show the melanocortin system's importance in maintaining ocular immune privilege and that α-MSH-treatment accelerates recovery and induces retinal-antigen-specific regulatory immunity in EAU. Our current results show that this activity is centered around MC1r and MC5r. In addition, the results suggest that a therapeutic potential to target MC1r and MC5r together to suppress uveitis induces regulatory immunity with potentially maintaining a normal retinal structure. Show less

The β-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is an extensively studied therapeutic target for Alzheimer's disease (AD), owing to its role in the production of neurotoxic amyloid beta (Aβ) peptides. However, despite numerous BACE1 inhibitors entering clinical trials, none have successfully improved AD pathogenesis, despite effectively lowering Aβ concentrations. This can, in part, be attributed to an incomplete understanding of BACE1, including its physiological functions and substrate specificity. We propose that BACE1 has additional important physiological functions, mediated through substrates still to be identified. Thus, to address this, we computationally analysed a list of 533 BACE1 dependent proteins, identified from the literature, for potential BACE1 substrates, and compared them against proteins differentially expressed in AD. We identified 15 novel BACE1 substrates that were specifically altered in AD. To confirm our analysis, we validated Protein tyrosine phosphatase receptor type D (PTPRD) and Netrin receptor DCC (DCC) using Western blotting. These findings shed light on the BACE1 inhibitor failings and could enable the design of substrate-specific inhibitors to target alternative BACE1 substrates. Furthermore, it gives us a greater understanding of the roles of BACE1 and its dysfunction in AD. Show less

Rare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such variants in adults without clinical cardiovascular disease (CVD) in whom cardiac MRI (CMR)-derived measures of myocardial fibrosis were obtained in the Multi-Ethnic Study of Atherosclerosis (MESA). To identify CM-associated pathogenic variants and assess their relative prevalence in participants with extensive myocardial fibrosis by CMR. MESA whole-genome sequencing data was evaluated to capture variants in CM-associated genes ( A total of 1,135 MESA participants had available genetic data and phenotypic measures and were free of clinical CVD at the time of CMR. We identified 6,349 rare variants in CM-associated genes in the overall MESA population, of which six pathogenic/likely pathogenic (P/LP) variants were present in the phenotyped subpopulation. The genes harboring P/LP variants in the case group were We observed a higher prevalence of rare potentially pathogenic CM associated genetic variants in participants with significant myocardial fibrosis quantified in CMR as compared to controls without significant fibrosis. No cardiac structural or functional differences were found between participants with or without P/LP variants. Show less

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18-43 to p.20-43) in 16/24 trypsin-digested amyloid deposits but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20-43, and to a far lesser extent the N-terminal peptide, p.21-43, were fibrillogenic in vitro at physiological pH, generating Congo red-positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV-associated pathologies. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. Show less