iScience

PurposeSepsis-associated immunothrombosis significantly contributes to high mortality, yet the role of N-glycosylation in this process remains poorly understood. This study aimed to comprehensively profile the plasma N-glycosylation landscape in sepsis and elucidate how its specific reprogramming in the complement and coagulation cascades influences immunothrombotic balance and patient outcomes. MethodsWe performed in-depth 4D-DIA proteomic and N-glycomic analyses on plasma from 43 sepsis patie...

An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...

BackgroundDengue virus (DENV) appears to manipulate several cellular metabolic pathways to permit its replication and immune evasion in the host. Here, we employed high-resolution mass spectrometry (HR-MS) to investigate the serum metabolomic landscape of clinical DENV infection. MethodsSerum specimens from primary dengue (n=11), secondary dengue (n=9) samples, and healthy controls (n=10) were used for untargeted and targeted metabolomic quantification on a Waters Xevo G2-XS QTof Mass Spectrome...

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregula...

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive head and neck cancer of the sinonasal cavity which has not benefitted from therapeutic advances over decades1. Though historically attributed to inhaled carcinogens such as hardwood dust and tobacco smoking2, SNSCC is incidentally associated with human papillomavirus (HPV)3,4. Importantly, HPV is the primary oncogenic driver of >80% of anatomically adjacent oropharyngeal cancers5. While viral status drives clinical staging and treatment ...

Cancer heterogeneity is traditionally attributed to multiple parallel signaling pathways. This belief is challenged here by proposing the ER/PR axis as the dominant pathway underlying the full spectrum of breast cancer. Absolutely quantitated ER, PR, Her2 and Ki67 protein levels were accumulated over 8 years from 1652 specimens collected non-selectively and measured with Quantitative Dot Blot (QDB) method over time. Cox analysis showed ER and Ki67 as independent adverse prognostic factors while ...

Meningiomas are the most common primary brain tumors and, despite their benign reputation, often behave aggressively. Meningiomas are morphologically heterogeneous, yet the full significance of their histologic diversity is unclear. This is in large part because many features are not readily quantifiable by traditional observer-based light microscopy. Molecular testing improves prognostic stratification, but is not universally accessible. We therefore sought to determine whether an artificial in...

STUDY QUESTIONAre pathogenic variants in Homeodomain-interacting protein kinase (HIPK4) associated with sperm head abnormalities causing male infertility? SUMMARY ANSWERHIPK4 is a novel candidate gene associated with sperm head defects and human male infertility. WHAT IS KNOWN ALREADYNumerous genes causing male infertility due to Multiple Morphological Abnormalities of the sperm flagella (MMAF) have been described but the genetic basis of sperm head defects is less well understood. STUDY DESI...

Background Short-chain fatty acids (SCFAs) are widely used as functional readouts of gut microbial activity in vivo. The growing adoption of decentralised study designs and self-collection protocols has amplified the need for reliable room-temperature storage and shipment strategies. However, SCFAs volatility and the persistence of post-collection microbial metabolism raise concerns regarding pre-analytical stability and the interpretability of measured concentrations. Methods We assessed the te...

Background & AimsThe increasing global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) including metabolic dysfunction-associated steatohepatitis (MASH) creates an urgent need for objective methods of histopathological assessment. Conventional histological approaches are time-consuming and rely on interpreters experience. Therefore, the results obtained may suffer from high variability and only offer coarse categorisation. In this study, we propose a fully automate...

BK polyomavirus (BKPyV) is a major complication in kidney transplant recipients (KTR), for whom no specific antiviral therapy is available. Modulation of immunosuppressive therapy results in virus clearance in most KTR with BKPyV DNAemia (controllers), but a significant minority fail to clear the virus (non-controllers). Here, we adapt LIBRA-seq, which links antibody sequence data to antigen specificity, to intact viral capsids of the four BKPyV genotypes to study and compare BKPyV-specific B-ce...

BackgroundSickle Cell Anaemia (SCA), a genetic blood disorder caused by a single mutation in the beta globin gene, displays a highly variable clinical course. Hydroxyurea (HU), an effective treatment, has an unclear mechanism of action. Plasma proteins can act as biomarkers for understanding disease states and response to HU treatment in SCA patients. MethodsPlasma proteome profiling of 31 healthy individuals and 76 SCA patients, including those with and without HU treatment, was performed usin...

Syphilis remains a major public health concern. However, current serologic assays are limited in their ability to distinguish active from previously treated disease. We applied tandem mass tag-based quantitative proteomics to plasma from 10 adults with active syphilis and 10 age- and gender-matched non-diseased controls. We identified 54 differentially regulated proteins (36 upregulated, 18 downregulated). Those proteins map to immune and inflammatory responses, acute-phase signaling, coagulatio...

Why do some individuals develop mild COVID-19 while others progress to severe disease remains a central challenge in SARS-CoV-2 immunology. In this study, we leveraged the BACO Cohort - a unique historical cohort of immunologically naive, hospitalized COVID-19 patients from the first pandemic wave - to investigate early immune determinants of clinical disease trajectories. Integrating bulk RNA-seq, Olink proteomics, and systems serology, we identified two fundamentally distinct immune trajectori...

Clear cell renal cell carcinoma (ccRCC) is the leading cause of kidney cancer-related death, but how the tumor microenvironment shapes patient survival is not completely understood. Here, we describe the characterization of ccRCC tumor ecosystems from 498 patients using imaging mass cytometry with a focus on tumor, myeloid, and T cell landscapes. Data from more than 3 million single cells is analyzed using machine-learning to identify key ecosystem features that outperform basic clinical data fo...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by profound molecular heterogeneity and inconsistent responses to gemcitabine-based therapy. Although KRAS mutations are nearly ubiquitous, the broader RTK-RAS and MAPK signaling networks, and their association with therapeutic response, remain insufficiently characterized. We performed an integrative clinical-genomic study of 184 PDAC tumors, stratified by age at diagnosis and gemcitabine exposure, systematically...

Immunotherapy with immune checkpoint inhibitors and immunotherapy combined with chemotherapy have represented promising treatments for NSCLC patients leading to prolonged survival. However, the majority of patients with advanced NSCLC have a poor prognosis. The identification and development of biomarkers for stratifying responders and non responders to immune checkpoint inhibitors contribute to unravel the mechanism of immune checkpoint pathway and the immune tumor interaction underlying the re...

BackgroundThe role of the gut microbiome and specific enteric bacteria in influencing the development of colorectal cancer (CRC) remains incompletely understood. Recently, it was shown that human CRC-derived strains of Clostridioides difficile were capable of inducing colonic tumorigenesis in a susceptible mouse model. We hypothesized that C. difficile contributes to the pathogenesis of human CRC and would be enriched in CRC tumors compared to paired normal tissues from the same individual. Met...

Allogeneic hematopoietic cell transplantation is the only curative option for many patients with acute myeloid leukemia (AML). In the current study, we designed and implemented a personalized assay, called v96, incorporating up to 96 mutations in 30 AML patients undergoing transplantation. The assay was performed on DNA derived in cells from the bone marrow as well as in cell-free plasma. All 30 (100%) of patients harbored molecular evidence of residual leukemia during remission that was detecta...

BackgroundIn lung transplantation, de novo immunodominant donor-specific anti-HLA antibodies recognizing HLA-DQ antigens (dn-iDSA-DQ) are predominant and can induce chronic lung allograft dysfunction (CLAD). We previously developed a method to measure the active concentration of dn-iDSA-DQ. We aimed to determine whether this new quantitative biomarker is associated with transplantation outcomes. MethodsThis retrospective multicentre cohort study included 90 lung transplant recipients (LTRs) dev...