PubMed Health⌕ Search

SEARCH · PubMed Health

Search PubMed Health

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2026

Genomic and Transcriptomic Correlates of Deep PSA Response in Patients with Metastatic Androgen Pathway Modulation-Sensitive Prostate Cancer.

BACKGROUND: Despite advances in metastatic androgen pathway modulation-sensitive prostate cancer (mAPMS) treatment, outcomes remain heterogeneous. Achieving a post-treatment undetectable prostate specific antigen (PSA) is a strong prognostic marker. We aimed to identify genomic and transcriptomic determinants of PSA response in a real-world clinical-genomic cohort. PATIENTS AND METHODS: Patients with mAPMS who underwent DNA (Tempus xT) and, in a subset, RNA (Tempus xR) sequencing were identified from the Tempus Lens database. Inclusion required stage IV disease within 90 days of sample collection and samples obtained within 12 months before or 3 months after treatment initiation. Patients with PSA at 6 months (n&#x2009;=&#x2009;525) were classified as PSA-low (<0.1&#x2009;ng/mL, n&#x2009;=&#x2009;240) or PSA-high (&#x2265;0.1&#x2009;ng/mL, n&#x2009;=&#x2009;285). Overall survival (OS) was assessed by 6-month landmark analysis with delayed-entry adjustment. Logistic and Cox models were adjusted for clinical variables. Sensitivity analyses used a relative definition of&#x2009;>&#x2009;95% PSA decline from baseline. RESULTS: Baseline PSA was lower in PSA-low versus PSA-high patients (24 vs 36&#x2009;ng/mL, p&#x2009;=&#x2009;0.01). SPOP (17% vs 11%) and ZFHX3 (2.5% vs 6%) alterations differed between groups, but neither persisted after adjustment. Using the relative definition, ZMYM3 and JAK1 alterations were independently associated with failure to achieve a deep PSA response. Expression of PSMA, TROP2, B7-H3, and STEAP1 did not differ between groups. PSA-low status was independently associated with improved OS, as was deep relative response. CONCLUSION: Deep PSA response at 6 months correlates with improved OS in mAPMS. Integrating molecular markers with PSA response may inform treatment intensification or de-escalation strategies.

Biomarkers↗
PubMed2026

E2F7 promotes lung adenocarcinoma progression by affecting phosphorylation and stabilization of &#x3b2;-catenin.

BACKGROUND: E2F transcription factor 7 (E2F7) has been implicated in the tumorigenesis and progression of multiple cancer types; however, the molecular mechanisms through which E2F7 regulates malignant phenotypes in cancer cells remain largely undefined. In this study, we investigated the biological functions and underlying mechanisms of E2F7 in lung adenocarcinoma (LUAD). METHODS: E2F7 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) datasets and further validated in clinical specimens via quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. The effects of E2F7 on cancer cell self&#x2011;renewal and epithelial-mesenchymal transition (EMT) were assessed using sphere formation and Transwell assays, respectively. In vivo tumorigenicity and metastasis were evaluated using xenograft models combined with extreme limiting dilution analysis to assess tumor-initiating capacity. Wnt/&#x3b2;&#x2011;catenin pathway activity was measured using T-cell factor optimal promoter luciferase reporter plasmid/far-from optimal promoter luciferase reporter plasmid (TOP/FOP) flash reporter assays. &#x3b2;&#x2011;Catenin expression, stability, and ubiquitination were examined via western blotting, cycloheximide chase assays, and ubiquitination assays. Protein-protein interactions among E2F7, &#x3b2;&#x2011;catenin, and glycogen synthase kinase 3 beta (GSK3&#x3b2;) were verified through co&#x2011;immunoprecipitation (Co&#x2011;IP), glutathione S&#x2011;transferase (GST) pull&#x2011;down, and immunofluorescence assays. Truncated mutants were generated to map the functional binding domains of E2F7. In vitro immunoprecipitation and kinase assays were further performed to confirm that E2F7 regulates GSK3&#x3b2; autophosphorylation and &#x3b2;&#x2011;catenin phosphorylation. RESULTS: Bioinformatic analyses revealed that E2F7 was significantly upregulated in LUAD tissues, and elevated E2F7 expression correlated with poor patient prognosis. Functional assays demonstrated that E2F7 promoted LUAD cell self&#x2011;renewal and EMT. Mechanistically, cytoplasmic E2F7 directly associated with &#x3b2;&#x2011;catenin through its DNA&#x2011;binding domain (DBD) and PHA03247 domain. E2F7 modulated &#x3b2;&#x2011;catenin phosphorylation at Ser675 and Ser33/37/T41, thereby inhibiting ubiquitin&#x2011;mediated degradation and enhancing &#x3b2;&#x2011;catenin protein stability. Furthermore, E2F7 interacted with GSK3&#x3b2; and suppressed its autophosphorylation at Tyr216, concomitant with reduced &#x3b2;-catenin phosphorylation at Ser33/37/T41 and its accumulation. CONCLUSION: Collectively, these findings indicate that E2F7 drives LUAD malignant progression through regulation of the GSK3&#x3b2;/&#x3b2;&#x2011;catenin signaling axis and stabilization of &#x3b2;&#x2011;catenin. This study unveils a novel oncogenic mechanism of E2F7 in LUAD and identifies E2F7 as a promising therapeutic target for clinical intervention in LUAD.

E2F7↗
PubMed2026

Hepatocellular Carcinoma With JAK1 Mutations Harbors Distinct Histologic Features and Specific Mutational Hotspots in an Asian Cohort.

The pathogenesis and clinicopathological features of hepatocellular carcinoma (HCC) harboring JAK1 mutation have not been reported. Sixty inflammatory hepatocellular adenoma-like HCCs (IHA-like HCCs) and 16 IHAs were analyzed using targeted next-generation sequencing. Nearly all IHA-like HCCs (n=59, 98%) showed positive SAA/CRP expression. Genetic alterations of the JAK/STAT pathway were detected in 35 (58%) IHA-like HCCs, encompassing mutations in JAK1 (n=22), STAT3 (n=8), and IL6ST (n=5). Nine (56%) IHAs harbored mutations in STAT3 (n=3), IL6ST (n=4), GNAS (n=1), and FRK (n=1). All the mutations occurred in a mutually exclusive manner. JAK1 mutations were frequent (22/60, 37%) in IHA-like HCCs. JAK1-mutated IHA-like HCCs displayed distinctive cytologic characteristics, including abundant eosinophilic cytoplasm, vesicular chromatin, and prominent central nucleoli. Recurrent hotspot JAK1 mutations were identified at S703, S729, and L910. Surveillance for JAK1 mutations in the HCC genomics of other cohorts also revealed recurrent mutations at S703, S729, and L910. In particular, the S703 and S729 mutations were strongly associated with the features of Asian ethnicity, presence of chronic viral hepatitis, and hepatic fibrosis/cirrhosis. In conclusion, JAK1 mutations were frequent in HCC with IHA-like morphology in an Asian cohort. JAK1 mutation exhibited recurrent and specific hotspot mutations at S703, S729, and L910 in HCC. Patients diagnosed with JAK1-mutated HCC may be eligible for JAK-targeted molecular therapy.

JAK therapeutics↗
PubMed2026

CircExor enables interpretable prediction of circRNA localization into extracellular vesicles.

Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with k-mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.

Journal Article↗
PubMed2026

Post-Hoc Long-Read Sequencing Links Leukemic Mutation Status to Single-Cell Transcriptomes.

Single-cell RNA-sequencing-based characterization of cells that belong to the neoplastic clone is a major challenge in hematologic neoplasms, where malignant and normal cells coexist. Confident molecular profiling requires simultaneous analysis of gene expression and genetic mutations in individual cells, an ability that is not supported by the standard 10X Genomics workflow. Here, we systematically evaluated the potential and limitations of repurposing amplified cDNA generated during the 10X Genomics 3' workflow for post hoc genotyping of individual cells. We first established a mixed leukemic cell line system comprising one cell line with KIT point mutations and another with the BCR::ABL1 fusion gene. Targeted long-read PacBio sequencing enabled post hoc assignment of mutation data to transcriptionally profiled cells, but recovery differed between targets. Consistent with ambient RNA in microfluidics-based single-cell workflows, mutation-associated transcripts were detected in cells not expected to carry the corresponding mutations, illustrating how transcript recovery complicates cell-level genotype assignment. Target-specific thresholds mitigated this source of misclassification. In primary chronic myeloid leukemia samples, the post hoc approach detected BCR::ABL1-positive cells at diagnosis, but not during imatinib treatment. Together, we present a framework for adding mutation status to cells already profiled using the 10X Genomics workflow and highlight broader considerations for transcript-based single-cell genotyping.

BCR::ABL1↗
PubMed2026

Ancient DNA unveils distinctive ancestries in the Bronze and Iron Ages of East Tianshan.

The East Tianshan Mountains occupy a key corridor between Central and East Asia, but their population history remains poorly understood. Here we report genome-wide data from 135 ancient individuals from 11 archaeological sites. We identify a previously unrecognized Bronze Age admixture between populations related to Yellow River millet farmers and steppe pastoralists associated with the Chemurchek culture. In contrast, we find little genetic contribution from contemporaneous middle-to-late Bronze Age steppe pastoralists, despite their eastward expansion across the Eurasian Steppe. By the Iron Age, regional populations had become more heterogeneous, incorporating additional eastern and steppe-related sources while retaining variable contributions from Early Bronze Age groups. These results reveal sustained demographic interactions in eastern Central Asia nearly 1800 years preceding the establishment of the historic Silk Road.

DNA, Ancient↗
PubMed2026

Protecting tropical forests is more cost-effective for biodiversity and climate than restoration.

Halting deforestation and promoting restoration are at the core of strategies to confront the biodiversity and climate crises in tropical forests. Avoiding forest disturbances is also critically important but has received far less attention, and there is a lack of clarity about the relative cost-effectiveness of these three interventions. We compare the biodiversity and carbon benefits and costs associated with each intervention, comparing observed and counterfactual outcomes based on in-depth field assessments and high-resolution remote sensing in the Brazilian Amazon deforestation frontier. Avoidance interventions delivered the greatest benefits and were more cost-effective than restoration, with results being robust to a range of benefit and cost assumptions. However, combined interventions delivered the greatest gains and were essential to reverse biodiversity and carbon losses.

Biodiversity↗
PubMed2026

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas.

CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors and VIPR RNAs (vrRNAs) comprising alternating GGY/NN motifs. Unlike canonical guide RNAs that pair with target nucleic acids through contiguous complementarity, vrRNAs recognize double-stranded DNA through a noncontiguous code in which the variable NN dinucleotides collectively specify a gapped target sequence. Natural vrRNA targets suggest that VIPR systems act against competing phages, and we demonstrate programmable phage defense by redirecting the complex for transcriptional repression. These results suggest that adaptive immunity originated from ancient warfare between viruses, revealing a previously unidentified logic for encoding information in sequence.

CRISPR-Cas Systems↗
PubMed2026

VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation.

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo-electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.

DNA↗
PubMed2026

Performance of seven carbapenemase detection assays in Pseudomonas aeruginosa across different epidemiological settings: a multicenter cross-sectional study.

The detection of carbapenemases in Pseudomonas aeruginosa remains challenging due to a great variety of other resistance mechanisms, and most laboratories, therefore, do not test for them. This study aimed to comparatively evaluate seven phenotypic carbapenemase detection assays across three epidemiological settings. A total of 320 P. aeruginosa isolates from three German centers with varying carbapenemase prevalences (5.8%-51.4%), including 113 carbapenemase-producing isolates carrying VIM-2 (n = 58), NDM-1 (n = 19), and GIM-1 (n = 16), underwent whole-genome sequencing as reference to assess seven phenotypic carbapenemase-detection tests: modified- and modified-zinc-supplemented carbapenem inactivation method (mCIM and mzCIM), simplified carbapenem inactivation method (sCIM), Carba NP, imipenem-cloxacillin test (IC-4000), and two imipenem-EDTA disk assays. Of all confirmation assays, mzCIM and sCIM showed the best overall performance for carbapenemase detection (sensitivity/specificity: 100%/94.2% and 99.1%/92.8%), followed by mCIM (93.8%/96.1%). Carba NP achieved the highest specificity (99.0%), but the lowest sensitivity (85.8%). EDTA-based assays and IC-4000 were highly sensitive (96.5%-100%) but less specific (79.7%-87.0%). Negative predictive values were consistently high (&#x2265;98%-100%) across all assays and prevalence settings, whereas positive predictive values varied (72.5%-98.0%). Both mzCIM and sCIM exhibited robust performance for carbapenemase detection in P. aeruginosa, representing the most suitable approach across diverse epidemiological settings. Their high negative predictive values indicate that these assays are particularly effective for ruling out carbapenemase production. Furthermore, both assays are cost-effective, simple to perform, and can be readily implemented in any routine microbiology laboratory.IMPORTANCEThis study provides comparative diagnostic accuracy data for seven phenotypic carbapenemase detection assays in Pseudomonas aeruginosa (PA) across different prevalence settings. Modified-zinc-supplemented carbapenem inactivation method (mzCIM) and simplified carbapenem inactivation method (sCIM) are the most robust screening tools and show that local carbapenemase-producing P. aeruginosa (CP-PA) prevalence substantially influences the utility of all evaluated assays.

CIM↗
PubMed2026

Regulation and function of the HPV16 CircE7 RNA.

High-risk human papillomaviruses (HPV), including HPV16, produce circular RNA that encompasses the E7 oncogene (circE7). CircE7 can be detected in HPV16-positive cells and tumors, is preferentially localized to the cytoplasm, is N6-methyladenosine (m6A)-modified, and can be translated into the E7 oncoprotein. Here, we explored the regulation and function of circE7. Mutation of m6A motifs flanking the backsplice junction revealed a single m6A motif to be essential for circE7 formation. Mutation of this m6A motif promoted linear splicing of the E6*I splice site (226^409), suggesting that linear and circular E7 splicing are inversely regulated. Additionally, mutation of an IRES-like motif in circE7 significantly decreased E7 protein expression, without having significant effects on circE7 RNA levels. Knockdown of YTHDC1, but not other m6A-binding proteins, decreased both circE7 RNA and protein expression. BaseScope ISH was used to confirm the expression of circE7 in head and neck squamous cell carcinoma cell lines and tumors. Using both qRT-PCR and BaseScope ISH, we found that serum and amino acid starvation significantly increased circE7. Finally, we generated an HPV16 genome with mutations in the circE7 m6A motif (Mut2). Stable transduction of primary keratinocytes with Mut2 confirmed the loss of circE7 and increased expression of E6*I. The Mut2 HPV16 genome exhibited significantly decreased viral replication but an increased ability to transform primary keratinocytes. Our studies reveal that the precise regulation of circE7 and E6*I by m6A is critical for the ability of HPV16 to infect and transform keratinocytes.IMPORTANCEHigh-risk human papillomaviruses (HPVs), such as HPV16, must carefully control how much E6 and E7 proteins they make. This study shows that HPV16 toggles a single chemical tag on the viral RNA (an m&#x2076;A mark) to control the production of early region RNAs, including a circular RNA called circE7. The same site coordinately regulates splicing of the E6*I isoform. CircE7 uses m&#x2076;A-binding proteins to control its production and a specific sequence to promote its translation. It is present in HPV-positive cancers and can respond to nutrient starvation. Regulation of circE7 through this m6A site also impacted viral replication and transformation capacity, indicating that this regulatory mechanism is critical for HPV biology.

RNA splicing↗
PubMed2026

Complete genome sequence of Rhodococcus qingshengii strain A3-8.

A chemostat culture was constructed with phenol and forest soil as an inoculum. We report the complete genome sequence of Rhodococcus qingshengii strain A3-8, which was isolated from the culture. The genome consists of a chromosome (6,436,695 bp) and a linear plasmid pA38 (257,365 bp).

Rhodococcus↗
PubMed2026

Complete genome sequence of a multidrug-resistant Proteus mirabilis clinical isolate harboring 22 antimicrobial resistance genes including blaCTX-M-15.

Proteus mirabilis causes urinary tract infections and wound infections and frequently exhibits multidrug resistance, complicating patient treatment. Here, we describe the complete genome sequence of a multidrug-resistant P. mirabilis wound isolate from 2025, providing insight into the repertoire of antimicrobial resistance genes in a recent P. mirabilis clinical isolate.

Proteus mirabilis↗
PubMed2026

Whole-genome sequence of the type strain and two field strains of Arsenicicoccus dermatophilus causing pododermatitis in greater flamingos (Phoenicopterus roseus).

The complete genome sequence of the type strain KM894/11T and two field strains of Arsenicicoccus dermatophilus (KM18/12; KM9/12) isolated from foot skin lesions of captive greater flamingos was determined using Oxford Nanopore and Illumina sequencing technologies. The genomes differ structurally by a large ~650 kb inverted chromosomal fragment and plasmid content.

dermatitis↗
PubMed2026

Draft genome sequences of non-endemic Mycobacterium tuberculosis Indo-Oceanic and West African lineages recovered in Panama.

We report the draft genome sequences of three Mycobacterium tuberculosis isolates recovered from Panamanian residents belonging to the Indo-Oceanic (Lineage 1) and West African (Lineage 5) lineages. These isolates exhibit various drug-resistance profiles, including rifampicin-resistant and multidrug-resistant phenotypes. This highlights the changing molecular epidemiology of tuberculosis in Central America.

DNA sequencing↗