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Journal articleCelsa C, Pressiani T, Nishida N, et al., 2026, , JHEP Reports, Vol: 8, ISSN: 2589-5559
Background & AimsDurvalumab plus tremelimumab (STRIDE) has emerged as a first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC). This international multicentre study aimed to evaluate the efficacy and tolerability of STRIDE or durvalumab monotherapy in routine clinical practice, comparing outcomes between patients within and outside key eligibility criteria for the HIMALAYA trial.MethodsFrom a database of 1,423 patients with advanced/unresectable HCC treated with immunotherapy across 35 centres, we analysed 233 patients receiving STRIDE or durvalumab monotherapy. Patients were categorized as HIMALAYA-IN or HIMALAYA-OUT based on key trial eligibility criteria (no prior systemic therapy, ECOG-PS 0–1, Child-Pugh class A, no Vp4 thrombosis). Baseline characteristics were assessed for overall survival (OS) and hepatic decompensation using a multivariable Cox model and competing-risk analysis, respectively. Objective response rates and treatment-related adverse events were recorded.ResultsOf the 233 patients, 123 (53%) were HIMALAYA-IN and 110 (47%) were HIMALAYA-OUT. STRIDE was given in 95% of HIMALAYA-IN patients. After median follow-up of 6.0 months, median OS was 20.4 months (95% CI 11.7-NR) in the overall population. HIMALAYA-IN patients achieved significantly longer OS than HIMALAYA-OUT patients (23.0 vs. 12.2 months; hazard ratio 0.61; 95% CI 0.39-0.96; p = 0.03). Macrovascular invasion and hepatic decompensation were independent negative prognostic factors in the whole cohort. Hepatic decompensation occurred in 10.5% of patients within 12 months from treatment start. Objective response rate was 23.7% and 17.8% of HIMALAYA-IN and -OUT patients, respectively. Patients achieving disease control (whole cohort: 59.4%) demonstrated 24-month OS of 58.2% in HIMALAYA-IN and 44.8% in HIMALAYA-OUT groups. Grade 3-4 treatment-related adverse events occurred in 16.3% of patients.ConclusionsSTRIDE shows reproducible effectiveness and an ac
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Journal articleLightstone L, 2026, , J Am Soc Nephrol, Vol: 37, Pages: 1379-1381
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Journal articleBhoori S, Rivoltini L, Pinato DJ, et al., 2026, , J Hepatol, Vol: 85, Pages: 117-129
BACKGROUND & AIMS: Liver transplantation (LT) is a curative treatment option in early and intermediate hepatocellular carcinoma (HCC) following downstaging with locoregional therapies (LRT). Tumor response to immune checkpoint inhibitors may extend LT eligibility to intermediate and advanced stages. METHODS: In this prospective phase II study, patients with intermediate and advanced HCCs beyond extended transplant criteria, not amenable to further LRTs, were downstaged with atezolizumab-bevacizumab (Atezo-Bev) prior to LT. The primary endpoint was recurrence-free survival with safety and efficacy as additional outcomes. Spectral quantitative pathology and immune signatures in tumor tissue and peripheral blood were studied longitudinally. RESULTS: Sixteen patients with HCC beyond expanded transplant criteria (median tumor size 6.5 cm [IQR 3-8], median AFP 283 ng/ml [IQR 6-1,080], portal vein thrombosis 50%) were downstaged to LT after a median of 4.7 months (IQR 2.4-7.6). Prior LRTs were used in 15 (94%) patients. The washout period from the last Atezo-Bev dose to transplant was 57.5 (IQR 29-87) days. Median follow-up was 16 months (95% CI 4-22). Pre-transplant immune-related adverse events occurred in 3 (19%) patients and post-transplant acute rejection in 4 (25%). Post-LT 90-day morbidity and mortality were 62.5% (95% CI 35-85%) and 6.3% (95% CI 0.2-30%) respectively. Explant pathology revealed 10 complete and 6 partial responses. Responding patients harboured a tumor microenvironment with features suggestive of immune activation/extinguishment, correlated with duration of Atezo-Bev treatment and length of pre-LT washout. One (6.2%) HCC post-LT recurrence occurred during follow-up. Recurrence-free and post-transplant overall survival were 90% and 94% after 2 years, respectively. CONCLUSIONS: LT following Atezo-Bev downstaging achieves promising recurrence-free survival in intermediate and advanced HCC beyond conventional transplant criteria. Acute rejection see
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Journal articleMarkiewicz PJ, Thompson G, Wardlaw JM, et al., 2026, , Eur J Nucl Med Mol Imaging, Vol: 53, Pages: 5110-5129
PURPOSE: Positron emission tomography combined with magnetic resonance imaging (PET/MR) has not yet achieved the level of adoption of PET/CT. This study aimed to harmonise PET imaging protocols across a national PET/MR network and to quantitatively assess whether PET/MR can achieve reliability comparable to PET/CT. While previous PET test-retest studies have demonstrated good repeatability, they have typically been limited to small cohorts or restricted site configurations. METHODS: We conducted a multi-site harmonisation and rigorous test-retest study across the network of eight PET/MR scanners. Thirty-seven healthy older participants (65-90 years) underwent harmonised one-hour amyloid PET/MR scans using either [[Formula: see text]F]flutemetamol or [[Formula: see text]F]florbetaben on two occasions. Retest scans were performed under conditions of same-site repeatability or multi-site reproducibility. Harmonised acquisition and reconstruction protocols were applied, and amyloid burden was quantified on the Centiloid (CL) scale. RESULTS: CL values across 74 scans showed excellent test-retest agreement (ICC = 0.968), improving to 0.987 after exclusion of one attenuation correction related outlier. Mean test-retest variability was 2.58%. No statistically significant differences were observed across repeatability versus reproducibility conditions, scanner types, or tracers. CL measurements were highly consistent with three independent blinded visual reads. CONCLUSION: This study demonstrates that harmonised PET/MR achieves high reliability comparable to PET/CT. Although the accuracy of attenuation maps requires checks, this study supports the use of PET/MR for quantitative amyloid imaging in research and therapeutic trials, and provides a valuable open resource of image and raw PET/MR data for further methodological development.
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Journal articleGiotis S, 2026,
Microbiome stability in wild and rehabilitated insectivorous bats revealed by shotgun metagenomics
, Microorganisms, ISSN: 2076-2607Wildlife rehabilitation can alter host-associated microbial communities, yet the effects of temporary managed care on the gut microbiome of insectivorous bats remain poorly understood. We used shotgun metagenomic sequencing to investigate gut microbiome composition in wild and rehabilitated bats from Yorkshire, United Kingdom. A total of 25 faecal metagenomes were analysed from four bat species (Myotis daubentonii, Pipistrellus pipistrellus, Nyctalus noctula, and Nyctalus leisleri), including wild baseline individuals and bats undergoing temporary managed care for 1-49 days. Microbial community structure clustered primarily according to host species and roost location, with no significant separation associated with rehabilitation status. Among bats in managed care, bacterial alpha diversity did not differ significantly with time in care (H = 2.30, p = 0.32). Archaeal communities displayed markedly lower interindividual variation than bacterial communities (coefficient of variation: 12.2% vs. 41.8%), indicating a highly conserved archaeal microbiome across hosts. Rehabilitated bats exhibited modest compositional shifts in bacterial communities, including increased relative abundances of Yersiniaceae and Lactobacillaceae and reduced abundances of environmentally associated taxa such as Pseudomonadaceae and Erwiniaceae. These changes may reflect controlled dietary provision and reduced environmental exposure during care. Overall, no marked rehabilitation- associated differences in gut microbiome diversity or community structure were detected under the current sampling design. These findings are consistent with microbiome stability during temporary managed care, although longitudinal studies are required to confirm microbiome dynamics within individual bats. Nonetheless, this study provides an initial baseline for future microbiome-informed wildlife rehabilitation studies.
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Journal articleBose A, Bopanna Y, Shetty P, et al., 2026, , Am J Physiol Gastrointest Liver Physiol
Hyperactivating mutations in guanylyl cyclase C (GC-C) are monogenic causes of early-onset inflammatory bowel disease, familial diarrheal syndrome and congenital secretory diarrhea. The mechanisms linking elevated cGMP levels to immune imbalance remain poorly defined. Here, using a preclinical model of a disease-associated GC-C mutation, we observe pleiotropic alterations in the small intestinal epithelium. Transcriptomic and functional analyses revealed impaired Paneth and goblet cell differentiation, compromised barrier integrity, heightened epithelial permeability, and increased proinflammatory cytokine levels. Intestinal organoids from mutant mice exhibited amplified cGMP responses to GC-C ligands and defects in secretory lineage specification, confirming cell-autonomous mechanisms. Strikingly, oral zinc administration suppressed aberrant GC-C activity, normalized cGMP levels and restored barrier function. These findings highlight the central role of epithelial cGMP signaling in coordinating barrier integrity and immune-epithelial interactions, and identify zinc as a tractable therapeutic strategy for GC-C-mediated intestinal disorders.
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Journal articleBranchett WJ, Kim J-W, Shields J, et al., 2026, , Nature Immunology, ISSN: 1529-2908
<jats:title>Abstract</jats:title> <jats:p> The local immune factors dictating whether individuals who have been infected with <jats:italic>Mycobacterium tuberculosis</jats:italic> remain healthy or progress to active tuberculosis (TB) have not been defined. Here we interrogated the airway immune response at single-cell resolution in bronchoalveolar lavage from positron emission and computed tomography-characterized recent TB household contacts, who either controlled the infection or progressed to TB disease, as well as of patients with active TB at diagnosis. Single-cell RNA sequencing revealed type I IFN-dependent and IFN-independent neutrophil signatures in bronchoalveolar lavage from patients with active TB and TB progressors. We report an inverse relationship between airway neutrophils and T cells, with T cells showing signatures of exhaustion, cytotoxicity and cell death in progressors and patients with active TB with a neutrophil-dominated airway profile. Conversely, we identified T cell signatures of protection in nonprogressor contacts dominated by genes related to regulation, quiescence and a stem-like profile. Our findings from early human airway responses in TB contacts reveal genes, pathways and cell states that may dictate infection outcome and inform strategies for developing effective host-directed therapies and vaccines. </jats:p>
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Journal articleAnand PK, Aljadeed NM, 2026, , Communications Biology, Vol: 9, ISSN: 2399-3642
The NLRP3 inflammasome has been shown to assemble on multiple organelles, including the mitochondria, endoplasmic reticulum, trans-Golgi network, and endosomes. Yet, the precise site of assembly remains unresolved. Emerging evidence suggests that membrane lipid composition may play a critical role with phosphoinositides, cholesterol, and cardiolipin, alongside membrane biophysical properties and cellular metabolic state, collectively shaping membranes where inflammasome assembles. Here, we review how lipid-dependent mechanisms regulate NLRP3 assembly across membranes and consider whether a defined membrane lipid signature governs inflammasome assembly. This understanding may have broader implications for therapeutic targeting in inflammatory and metabolic diseases.
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Journal articleLeishman S, Aljadeed NM, Anand PK, 2026, , STAR Protocols, Vol: 7
(STAR Protocols 5, 103054; June 21, 2024) During manuscript preparation, two concentration volumes were inadvertently misreported in the “materials and equipment” and “step-by-step method details” sections of this protocol.•Under “materials and equipment,” (1) the stock concentration for hydroxylamine reads “32 mM” while it should read “32 M,” and (2) the final concentration for biotin-HPDP reads “1.0 M” while it should read “1.0 mM.”•In step 32 of “step-by-step method details,” the “20 mM Biotin-HPDP” that is mentioned should instead read “Biotin-HPDP to 1 mM final concentration” due to the above changes. Under “materials and equipment,” (1) the stock concentration for hydroxylamine reads “32 mM” while it should read “32 M,” and (2) the final concentration for biotin-HPDP reads “1.0 M” while it should read “1.0 mM.” In step 32 of “step-by-step method details,” the “20 mM Biotin-HPDP” that is mentioned should instead read “Biotin-HPDP to 1 mM final concentration” due to the above changes. The authors apologize for the errors and regret any confusion caused.
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Journal articleTsamouri L, Aljadeed N, Olona A, et al., 2026,
Distinct lipid transport proteins are regulated by innate immune stimuli
, Discovery Immunology, ISSN: 2754-2483
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