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PubMed2026

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day ≤ 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans↗

PubMed2026

Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation.

BACKGROUND: Metformin is a popular first-line glucose-lowering medication for type 2 diabetes mellitus (T2DM). Although metformin reduces the risks of various complications of diabetes, its potential to cause polyneuropathy by depleting vitamin B12 levels is concerning. This study investigated whether the adherence or discontinuation of metformin after adding-on a second-line antiglycemic agent increases the risk of polyneuropathy in patients with T2DM. METHODS: Data from TriNetX were obtained, and patients with T2DM who were receiving second-line antiglycemic agents were divided into metformin-adherent and metformin-nonadherent groups based on prescription claims data. Neuropathy incidence was evaluated using diagnostic claims and nerve conduction examinations. For independent confirmation and external validation of the primary findings, we used data from the National Health Insurance Research Database (NHIRD) of Taiwan. RESULTS: After matching, 58,027 patients were included in each group. Compared with metformin adherent patients, metformin nonadherent patients had a higher risk of polyneuropathy (adjusted hazard ratios [aHR] 1.26; 95% confidence interval [CI] 1.23-1.29; P < 0.001). Risks of diabetic foot ulcer, amputation, neuropathy-related medication use, and bone fracture were also higher among nonadherent patients. Sensitivity analyses confirmed the robustness of findings. In the validation NHIRD cohort (31,384 matched pairs), metformin nonadherence remained associated with increased polyneuropathy risk (aHR 1.25; 95% CI 1.10-1.42; P < 0.001). CONCLUSIONS: Metformin adherence in patients with T2DM who require second-line treatment may reduce the risk of polyneuropathy; vitamin B supplementation may enhance this benefit.

Humans↗

PubMed2026

Biliary Cirrhosis in Myhre Syndrome: The First Case Report of Liver Transplantation and a Review of Reported Hepatic Findings.

Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function pathogenic variants in SMAD4 and is now recognized as a progressive multisystem fibrotic disease. Although transforming growth factor-β (TGF-β) signaling plays a central role in hepatic fibrogenesis, hepatobiliary involvement in Myhre syndrome has not been systematically evaluated. We report the first case of Myhre syndrome complicated by rapidly progressive biliary cirrhosis requiring liver transplantation in a 15-year-old male with a confirmed SMAD4 p.Ile500Val variant. Following an infectious episode, the patient developed severe cholestasis with imaging and histopathologic findings consistent with fibro-obliterative cholangiopathy, ultimately necessitating living donor liver transplantation. A systematic review of 55 published reports comprising 217 patients with Myhre syndrome revealed that hepatic evaluation was rarely performed and that previously reported liver abnormalities were mild and secondary, most commonly related to right heart dysfunction or metabolic disease, with no prior cases of progressive biliary fibrosis. This case suggests that dysregulated SMAD4-TGF-β signaling may predispose selected organs to fibro-obliterative injury and that infection-driven inflammation may act as a critical trigger for hepatic fibrosis in Myhre syndrome, expanding the recognized spectrum of organ involvement in this disorder.

Humans↗

PubMed2026

Decoding the spatiotemporal patterns of food spoilage microbial communities: Integrating multi-omics and artificial intelligence to enable precision preservation.

In the global food supply chain, food wastage caused by spoilage has resulted in significant economic losses, food shortages, and environmental pressure. This process is fundamentally driven by the spatiotemporal dynamics of microbial communities. However, traditional research methods struggle to elucidate the complex mechanisms of spatial heterogeneity, interspecies interactions, and functional succession. This limits the development of effective preservation strategies. This review systematically reviews the cutting-edge progress of integrating multi-omics technologies and artificial intelligence (AI) to study food spoilage microbial communities, breaking through this bottleneck. We propose an intelligent theoretical framework that could potentially analyze microbial metabolic activities and predict dynamic shelf life if implemented. The conceptual framework integrates multidimensional data, including spatial metabolomics, temporal metatranscriptomics, single-cell transcriptomics, and longitudinal metagenomics. It can also be combined with AI models, such as graph neural networks. The article elaborates on the principles and applications of spatio-temporal monitoring technologies, such as nano secondary ion mass spectrometry, hyperspectral imaging, and the Internet of Things sensing. Through illustrative cases of typical perishable foods, it also explores how such a multi-omics - AI system might be applied to spoilage warning and precise intervention. Additionally, the article addresses the current challenges in data coverage, model generalization, and federated learning implementation. Then the research further explores emerging areas such as engineered probiotics, edge AI, and microfluidic sensing. These areas are targeted at transforming food preservation from an empirical control approach to a data-driven, precise regulatory framework. This transformation provides theoretical support and technical approaches for developing a smart, sustainable food preservation system.

Multiomics↗

PubMed2026

GSTT1 promotes stemness and FGFR inhibitor sensitivity in pancreatic cancer through regulation of CD133 (PROM1).

Pancreatic ductal adenocarcinoma (PDA) is among the deadliest malignancies, driven by metastatic progression and profound cellular heterogeneity. We previously identified glutathione S-transferase theta 1 (GSTT1) as a regulator of a slow-cycling, highly metastatic tumor cell population, suggesting that GSTT1High cells may possess stem-like properties. Here, we define the functional and molecular features of this subpopulation in metastatic PDA. Using a mCherry-tagged Gstt1 reporter system in metastatic murine PDAC cells, we enriched for Gstt1High cells and observed increased tumor sphere formation, accompanied by upregulation of stemness-associated genes including PROM1 (CD133) and activation of Wnt and FGF signaling pathways. In human PDA models, CD133HighGSTT1High cells exhibited enhanced tumor sphere initiation and expansion compared to other populations, defining a maximal stem-like state. Notably, sensitivity to FGFR inhibitors was observed only under tumor sphere conditions, highlighting a context-dependent therapeutic vulnerability. Mechanistically, FGFR3 expression correlated with GSTT1 and CD133 levels, and FGF signaling was required to sustain this state. GSTT1 knockdown reduced CD133 protein levels, impaired tumor sphere formation, and altered sensitivity to FGFR inhibition. These findings were largely recapitulated in patient-derived PDA organoids, where GSTT1 and PROM1 co-expression predicted increased tumor sphere formation and enhanced response to the multi-kinase inhibitor Nintedanib. Together, these results identify a GSTT1HighCD133High stem-like subpopulation in metastatic PDA and identify an FGFR-dependent signaling axis that sustains this state, representing a potential therapeutic vulnerability.

AC133 Antigen↗

PubMed2026

The combined and independent influence of food texture and a 'mindful eating' instruction on eating rate and food intake among Dutch primary schoolchildren.

Eating rate (ER), the amount of food consumed per unit of time, is a key determinant of food intake, with faster ER associated with larger meal size. Research in adults has shown that both sensory properties like texture, and instructions can influence ER and intake. However, their independent and combined effect on ER and intake in children remain poorly understood. This study examined the effects of food texture and a 'mindful eating' instruction on ER and food intake in children. Children (N = 73), 38 boys, aged 4-12 years, participated in a 4-week cluster-randomized incomplete cross-over study conducted during regular school lunches. Using a 2×3 factorial design, children were exposed to two levels of food texture (softer vs. harder whole-grain buns) and three types of instructions (none, control, 'mindful'). Linear mixed models with repeated measures were used, adjusting for sex and group. As the interaction between food-texture and type of instructions was non-significant, it was excluded from the final models. Results revealed a strong main effect of food texture on ER and food intake (all p < 0.001), where compared with softer buns, harder buns were associated with a slower eating rate (Δ = -6.67 g/min, SE = 0.59) and reduced food intake (Δ = -70 g, SE = 8). In contrast, type of instruction had no significant effect on ER or intake (p = 0.85). Our findings demonstrate that food texture exerts a dominant influence on children's eating rate and food intake, highlighting texture modification as a potential leverage point for influencing ER and intake in children.

Humans↗

PubMed2026

Comprehensive assessment of vasospastic angina using coronary computed tomography angiography: synergistic value of the presence of myocardial bridge, perivascular inflammation, and myocardial extracellular volume fraction.

AIMS: Coronary computed tomography angiography (CCTA) has evolved beyond anatomical assessment to include sophisticated tissue characterization. While an elevated perivascular fat attenuation index around the right coronary artery (FAI-RCA) is known to reflect coronary inflammation in vasospastic angina (VSA), recurrent vasospasms may also induce chronic subclinical myocardial injury and subsequent remodelling, potentially associated with an increased myocardial extracellular volume fraction (ECV). However, the diagnostic integration of ECV and FAI-RCA for identifying VSA in patients with angina with non-obstructive coronary arteries (ANOCA) remains to be elucidated. METHODS AND RESULTS: This study included consecutive ANOCA patients who underwent CCTA with a dedicated ECV protocol, followed by an invasive spasm provocation test. Comprehensive CCTA analysis quantified both FAI-RCA and the transmural ECV gradient (the difference between endocardial and epicardial ECV: ECVEndo - ECVEpi). Of the 100 patients analysed (mean age: 65.3 ± 11.8 years; 55% male), 27 were diagnosed with VSA. Multivariable logistic regression analysis identified transmural ECV gradient [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.01-1.25], presence of myocardial bridging (MB) (OR: 3.49, 95% CI: 1.25-9.74), and high FAI-RCA (> -70.95 Hounsfield units [HU]) (OR: 5.79, 95% CI: 2.06-16.30) as significant independent predictors of VSA (all P < 0.05). Notably, the integration of transmural ECV gradient provided incremental diagnostic value beyond FAI-RCA and MB, as assessed by the Net Reclassification Improvement and Integrated Discrimination Improvement. CONCLUSION: A multi-parametric CCTA approach potentially identifies patients at high risk for VSA. The significant association of the transmural ECV gradient with VSA suggests that myocardial remodelling imaging provides a novel diagnostic window into the cumulative myocardial impact of vasospasm, independent of active adipose tissue inflammation and the presence of MB.

Humans↗

PubMed2026

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals↗

PubMed2026

Genotype II Live-Attenuated ASFV Vaccine Bearing 24 Genes Deletion in 3 Independent Regions Is Able to Provide Complete Protection Against Homologous Lethal Challenge.

African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live-attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV-Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV-Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV-Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF-compatible clinical signs in vaccinated pigs. The ASFV-Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV-Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.

Animals↗

PubMed2026

Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Humans↗

PubMed2026

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKCζ are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans↗

PubMed2026

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 ± 2.3 vs 0.5 ± 1.7 mm; P = .002), as were lesion area (mean, 70 ± 16 vs 58 ± 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans↗

PubMed2025

Impact of stromal maturity and proportion on prognosis and immune landscape in colorectal cancer.

BACKGROUND: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts. METHODS: Two colorectal cancer cohorts (N = 1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity. RESULTS: In the study cohort (N = 1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p < 0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p = 0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p < 0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3+ T cells, B cells, M1-like macrophages, CD66B+ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N = 776) confirmed the association of SMAPS with survival and T cell densities. CONCLUSIONS: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.

Humans↗

PubMed2026

Extent of resection as an independent predictor of survival for patients with glioblastoma as defined by the new WHO 2021 classification.

OBJECTIVE: Extent of resection (EOR) has previously been demonstrated to have an impact on survival in patients with glioblastoma (GBM). However, with the World Health Organization (WHO) 2021 reclassification of GBMs based on IDH-mutation status, patients with "IDH-mutant GBMs," who typically survive long term, were reclassified as WHO grade 4 IDH-mutant astrocytomas and removed from the GBM taxonomy. Therefore, it is unknown whether the previously reported impact of resection on survival was a false-positive result due to the inclusion of the less aggressive IDH-mutant tumors in previous datasets. This study aimed to determine the extent to which EOR remains an independent predictor of survival in patients with WHO 2021 GBM after the reclassification of IDH-mutant grade 4 astrocytomas. METHODS: All cases of GBM tumors (based on the pre-2021 GBM classification) that were newly diagnosed between 2005 and 2021 were identified in our institutional database and subsequently reclassified based on the updated WHO 2021 criteria using IDH status. Multivariable statistical analyses of demographic information, survival time, and EOR based on volumetric MRI were performed to determine the independent predictors of survival for the whole group of patients and for IDH-wildtype GBM patients exclusively. Additional analyses were performed to identify an EOR threshold for improvement in survival. RESULTS: Of the 523 tumors classified as GBM based on the pre-2021 taxonomy, 52 (9.9%) cases were reclassified as WHO grade 4 IDH-mutant astrocytomas, and the median survival of patients in this group was 7.9 years, whereas median survival of the IDH-wildtype GBM patients was 1.4 years. Multivariate analyses of the whole group demonstrated that IDH-mutant astrocytomas were associated with reduced hazard of death. In both the whole group (n = 523) and in IDH-wildtype GBMs (n = 471), higher EOR of the contrast-enhancing (CE) tumor was associated with reduced hazard of death, whereas older age or male sex was associated with increased hazard of death. Because most patients (90%) had high EOR values (> 81%), a statistically meaningful EOR threshold could not be established. CONCLUSIONS: These analyses demonstrated that EOR of the CE tumor is an independent predictor of survival and that greater EOR is associated with improved survival in WHO 2021 IDH-wildtype GBMs even after excluding grade 4 IDH-mutant astrocytomas. However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

Humans↗

PubMed2026

Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.

BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS: We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS: A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION: For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Humans↗

PubMed2026

Normoalbuminuric and albuminuric diabetic kidney disease exhibit divergent renal proteomic characteristics: implications for management.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS: Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR < 30 mg/g, n = 25), microalbuminuric (UACR 30-300 mg/g, n = 26), and macroalbuminuric (UACR > 300 mg/g, n = 244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS: Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION: Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.

Humans↗

PubMed2026

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals↗

PubMed2026

In situ product monitoring in heterogeneous reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3: Effect of environmental factor and particle property.

Gas-particle reactions represent an important atmospheric heterogeneous transformation process for organic amines (OAs). Environmental factors and particle properties may impact the gas-particle reaction products. Although the products from gas-particle reactions can be monitored by various in situ techniques, related data remain scarce. Here, the interfacial and gaseous products from the reaction of trimethylamine on Fe2O3/Fe(NO3)3 particles under light irradiation with mixed NO2, O2, SO2 and H2O were monitored using in-situ diffuse reflectance Fourier transform infrared spectroscopy and proton transfer reaction time-of-flight mass spectrometry. Dark reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3 generated two interfacial products types: N-containing ones (CH3NCH2, CH3NO2, (CH3)2NCHO, and CH3N(OH)CHO) and N-free ones (alcohols, aldehydes and acids), both accumulating with reaction progression. Light irradiation and O2 oxidation enhanced formation of these products, while NO2 promoted the production of CH3NO2 and (CH3)2NCHO. H2O and SO2 occupied the active sites of particles to inhibit the formation of all products. Compared to Fe(NO3)3, Fe2O3 showed absolute dominance in contribution to the formation of products. Considering the smaller particle size of Fe2O3 and excess Fe(NO3)3, the physical mixing of them reduced the generation of interfacial products. Furthermore, gaseous products of CH3OH, HCHO, CH3CHO, HCOOH and CH3COOH detection clarified the N-free interfacial products. The presence of Fe(NO3)3 inhibited the formation of HCOOH and favored the formation of CH3CHO in the gas phase. By combining product information with thermodynamic calculations, the heterogeneous reaction pathways of trimethylamine were tentatively proposed. These findings provide a guiding significance for the migration of OAs in real atmospheric environment.

Methylamines↗