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Prognostic factors in first-line atezolizumab-bevacizumab treatment of intermediate or advanced hepatocellular carcinoma

Purpose To analyze the prognostic factors influencing outcomes in hepatocellular carcinoma (HCC) patients initially treated with atezolizumab-bevacizumab (Ate-Bev). Methods We conducted a retrospective study on 47 treatment-naïve HCC patients (40 men; median age, 56 years) who were treated with Ate-Bev between September 2020 and July 2022 and underwent at least one response assessment based on the Response Evaluation Criteria in Solid Tumors 1.1. We evaluated the clinical variables and imaging features of pre-treatment magnetic resonance imaging (MRI). Using multivariable Cox hazard regression analysis, we analyzed prognostic factors for progression-free survival (PFS). Results During the follow-up period (range, 1.5–24.9 months), 33 patients (70.2%) experienced tumor progression. The median PFS was 4.3 months (95% confidence interval [CI], 2.8–8.5 months). Nine patients received concomitant radiotherapy. Multivariable analysis indicated that younger age (hazard ratio [HR], 0.95; 95% CI, 0.92–0.99; P  = 0.013), absence of concomitant radiation therapy (HR, 0.22; 95% CI, 0.07–0.69; P  = 0.009), tumor extent ≥10 cm (HR, 2.54; 95% CI, 1.17–5.55; P  = 0.019), and peritumoral arterial-phase hyperenhancement on the MRI (HR, 2.15; 95% CI, 1.00–4.63; P  = 0.049) were factors associated with poor PFS. Conclusions Age, concomitant radiation therapy, tumor extent, and peritumoral arterial-phase hyperenhancement on MRI were associated with PFS in patients with HCC who were initially treated with Ate-Bev.

ZNF263–NuRD-mediated repression of STAT1 curtails MHC-I antigen presentation and IFN-γ efficacy in prostate cancer

Loss of major histocompatibility complex (MHC)-I is a hallmark of prostate cancer (PCa) immune evasion and immunotherapy failure. Here, we identify ZNF263 as a transcriptional repressor that silences MHC-I by recruiting nucleosome-remodeling and deacetylase (NuRD) to the STAT1 promoter, reducing STAT1 and MHC-I expression. Hypoxia enhances this repression through two ZNF263 modifications: phosphorylation-driven phase separation that strengthens NuRD interaction and O-GlcNAcylation at S662 that aids STAT1 promoter binding. O-GlcNAcylation also promotes interaction with protein kinase, DNA‑activated catalytic subunit (PRKDC), amplifying phosphorylation. Interferon‑gamma (IFN‑γ)‑induced MHC-I induction is augmented upon ZNF263 loss. In silico docking identified Viroptic as a Krüppel‑associated box (KRAB) pocket binder disrupting ZNF263–NuRD, derepressing STAT1, and potentiating IFN-γ antitumor immunity in vivo. High ZNF263 correlates with low MHC-I, scarce CD8+ T cells, and poor survival, providing rationale for targeting ZNF263 in PCa immunotherapy.

New insights into the Trans-Saharan gold trade in the Islamic Middle Ages revealed by multi-isotopic (Pb–Fe–Cu) and elemental characterization of Fatimid gold coins

The use of West African gold in medieval times is thought to have enabled the first globalized trade in history: the Trans-Saharan Trade, through the minting of Islamic dinars, which were considered as the equivalent of today’s dollar or euro currencies. Yet, the precise origin of this gold remains debated, as archaeological evidence for such trade is scarce. While textual sources are numerous, they provide only indirect accounts, and the large corpus of surviving dinars has so far yielded limited insight as elemental analyses are not discriminating enough to establish geological provenance. To address this, we combined multi-elemental analysis by LA-ICP-MS with multi-isotope (Pb, Cu, and Fe) data measured by MC-ICP-MS after wet purification chemistry on 11 dinars. This revealed two distinct metal stocks, differentiated by PGE concentrations and Cu isotopes. The Cu and Fe isotope signatures are consistent with supergene and oxidized ores, typical of West African gold mineralization. In contrast, the lead isotopes and calculated model ages of the gold coins do not match the signatures expected for West African mineralization, suggesting that a different, exogenous source is involved in the gold chaîne opératoire . These new data then raise two key historical questions: the location of gold processing, whether it occurred North or South of the Sahara, and the hypothetical reuse of older metal stocks.

A minimal wake–vortex model explains formation flight of flapping birds

Collective patterns of motion emerge across biological taxa: insects swarm, fish school, and birds flock. In particular, many large migratory bird species form distinctly ordered V-shaped formations, which experiments and direct numerical simulations have demonstrated provide substantial energetic benefits during long-distance flight. However, the precise aerodynamic and morphological mechanisms which underlie these benefits remain unclear. In this work, we develop a reduced-order model of the wake–vortex interactions between two flapping birds flying in tandem. The model retains essential unsteady flapping dynamics while remaining computationally tractable. By optimizing over a six-dimensional state space, which comprises the follower’s three-dimensional relative position as well as three independent flapping parameters, we identify the energetically optimal leader–follower configuration of northern bald ibises ( Geronticus eremita ). The predicted optimum agrees quantitatively with live-bird measurements. Because of its simplicity, the model allows for direct interrogation of the physical mechanisms responsible for this optimum. In particular, it isolates precisely how the follower’s wing kinematics interact with the leader’s wake to enhance aerodynamic efficiency. The model predicts an 11% reduction in total mechanical power for a follower in formation flight—consistent with experimental estimates—and shows that this saving arises from reductions in both induced and profile power, dominated by decreased profile power enabled primarily through reduced flapping amplitude and, secondarily, reduced upstroke flexion. These results provide a mechanistic explanation for the structure of V-formations and offer insight into the aerodynamic principles governing collective flight.

Early-warning signals for infectious diseases with a social-media compartment

Early-warning signals (EWSs) are crucial tools for anticipating disease emergence and guiding public-health responses, but uncertainties in transmission and incomplete data can limit their reliability. Additionally, the performance of EWSs is rarely evaluated when disease emergence is delayed, and their use in the context of interactions between disease transmission and communication through social-media platforms has largely not been considered. We evaluate the relative performance of EWSs in predicting disease emergence under varying noise conditions and explore the use of EWSs with social-media dynamics to predict disease emergence. We develop a mechanistic model coupling infectious disease and social-media dynamics, introduce stochasticity and generate simulated time series. We detect changepoints, quantify delays relative to the bifurcation point and assess the performance of EWSs across different segments of the time series. The “reporting” infected compartment proves most reliable, and variance outperforms autocorrelation in high-noise scenarios. However, in the social-media compartment, variance and autocorrelation have weak predictive power. Our work provides a framework to advance understanding of how EWSs can be applied to forecasting disease emergence, contributing to improved disease preparedness and response.

Light- and temperature-sensitive seizures are regulated by spatially distinct cortex glial populations in the central nervous system

Epilepsy is characterized by recurrent seizures due to abnormal neuronal activity originating from a population of neurons. Seizures are often associated with abnormal glial cell function at the seizure focus. Studies have shown that each glial type, such as astrocytes, displays a significant degree of heterogeneity in their development, molecular signatures, and function depending on the brain region in which they are located. It is unknown, however, if such heterogeneity differentially influences or causes seizures. Previous studies in Drosophila have shown that aberrant Cortex glia (CG) function led to light-inducible (LI) seizures in Ceramide phosphoethanolamine synthase ( cpes ) and temperature-sensitive (TS) seizures in zydeco ( zyd 1 ) mutants. Here, we have optimized Gal4/Split-Gal4/Gal80/LexA drivers to specifically express a gene of interest throughout development in CG subpopulations in different parts of the brain including optic lobe (OL), central brain (CB), and ventral nerve cord (VNC). Using these tools, we performed brain region–specific CG rescue experiments in cpes and zyd 1 mutants. We found that OL- and CB-specific, but not VNC-specific CG expression of CPES significantly suppressed LI seizures in cpes mutants. In contrast, VNC- but not OL- or CB-specific CG expression of ZYD suppressed TS seizures. In a third model, expression and activation of transient receptor potential, dTRPA1, exclusively in the VNC-specific CG was sufficient to induce TS seizures in wild-type flies. Our findings suggest that regionally specialized CG subtypes differentially regulate seizure susceptibility in seizure models.

Extent of therapeutic support in Positive Psychotherapy: A randomized comparative efficacy study for the treatment of anxiety disorders in an online group setting

Objective Positive Psychotherapy (PPT) is increasingly being studied as a potential treatment option for psychological diseases. In recent years the internet has been incorporated into traditional face-to-face therapy which, if successful in its treatment outcome, could lead to a more economic and affordable therapy since a certain proportion of therapy could be done without real-time therapist contact. The aim of this study is to investigate whether significant differences in outcome are found when comparing the effectiveness of PPT with complete therapeutic support (cPPT) in treating anxiety disorders compared to PPT with minimal therapeutic supervision (mPPT) in an online group setting. Participants in the cPPT group took part in ten weekly 120-minute online sessions with a therapist, while the mPPT group only had three 60-minute online sessions. For the remaining seven sessions, participants received videos. This paper presents the outcomes of both groups. Methods This randomized controlled trial involved 106 participants allocated into either a group with complete therapeutic support (cPPT; n  = 53) or a group with minimal supervision (mPPT; n  = 53) for ten weeks. Data collection occurred through online questionnaires, evaluating anxiety levels, subjective happiness, quality of life, and psychological distress. These assessments were conducted at three time points: baseline (T0), post-intervention (T1), and three-month follow-up (T2). Results Significant improvements over time were observed in both the cPPT and mPPT groups across several outcomes. Anxiety symptoms decreased substantially from pre-treatment to post-treatment and remained stable at the three-month follow-up. Significant time effects were found for fear and anxiety-related outcomes, including FQ ( η 2 = 0.10 , η w 2 = 0.32 ), BAI ( η 2 = 0.17 , η w 2 = 0.42 ), PAS ( η 2 = 0.14 , η w 2 = 0.39 ), GAD-7 ( η 2 = 0.16 , η w 2 = 0.36 ), with gains maintained at the three-month follow-up. Positive psychological outcomes also improved significantly over time. Significant effects were observed for subjective well-being and flourishing, including PPTI ( η 2 = 0.04 , η w 2 = 0.15 ), FS ( η 2 = 0.02 , η w 2 = 0.07 ), and SWLS ( η 2 = 0.04 , η w 2 = 0.14 ). Psychological distress likewise decreased significantly across treatment. Significant time effects were found for ISR ( η 2 = 0.11 , η w 2 = 0.29 ), PHQ-9 ( η 2 = 0.06 , η w 2 = 0.17 ), with improvements remaining stable at follow-up. In all cases, there were no significant group × time interactions, indicating that the mPPT and cPPT groups showed comparable changes over time. Conclusion Our study did not find significant differences between Positive Psychotherapy with minimal therapeutic supervision and PPT with complete therapeutic supervision. These findings challenge the traditional notion regarding the significance of face-to-face contact and therapist-patient interaction and suggest an economic and efficient alternative to the regular individual face-to-face therapy. As the participants were predominately female, further research should focus on a more gender-equal sample to generalize these findings.

Correction for Kuyyamudi et al., Heterotypic intercellular adhesion tunes efficiency of cell-on-cell migration

A mask-based peak-to-average power ratio reduction scheme for affine frequency division multiplexing systems using Volterra Series-Driven PolyNet

Affine frequency division multiplexing (AFDM) demonstrates exceptional resilience to Doppler effects in doubly dispersive channels, making it a promising waveform for 6G high-mobility communications, but its high peak-to-average power ratio (PAPR) problem severely limits system energy efficiency. When migrated to AFDM, existing mask-based deep learning PAPR reduction schemes face the challenges of contextual loss caused by local sampling and the lack of physical interpretability in black-box models. Therefore, this paper proposes a physics-aware mask-based PAPR reduction scheme tailored for AFDM. First, a full-frame input strategy is introduced to exploit the global time-domain correlation of AFDM signals for precisely recovering the impaired symbols. Second, to address the nonlinear distortion induced by masking, a PolyNet-Volterra network is proposed by integrating Volterra series theory. Departing from the traditional design of blindly stacking layers, this model explicitly constructs first-order linear and third-order power feature layers, which substantially enhances the nonlinear reconstruction accuracy while avoiding overfitting. Simulation results demonstrate that, under a threshold of 0.9, the proposed scheme achieves a significant PAPR reduction of approximately 5.9 dB. Furthermore, requiring only about 165,000 parameters, the PolyNet-Volterra model comprehensively outperforms baseline models such as DNN and ResNet in terms of both bit error rate (BER) and mean squared error (MSE). Compared with the conventional PolyNet, the proposed model reduces the parameter and computational overhead, suggesting its potential as a low-complexity receiver-side reconstruction module for resource-constrained future wireless systems. Further hardware-oriented and over-the-air validation is still needed before drawing deployment-level conclusions.

Integrated thermal and phytoremediation of agricultural soils impacted by PFAS

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic compounds that have contaminated millions of hectares of agricultural land through decades of biosolids application. Conventional remediation approaches, such as thermal destruction or excavation, are prohibitively expensive, carbon intensive, and leave affected farmland unfit for agriculture. Here, we present a potential scalable remediation strategy that combines phytoremediation, biochar production, and enhanced weathering to simultaneously remove PFAS from soil, immobilize residual contamination, and achieve durable carbon dioxide removal (CDR). Using stochastic modeling constrained by experimental data, we show that soil pH management through alkaline rock amendment can accelerate PFOS removal, shortening remediation timelines by more than a decade under typical contamination levels. Pyrolysis of harvested biomass effectively destroys PFAS and produces biochar, which, when reapplied to soil, substantially reduces leaching to groundwater and the surrounding environment. National-scale simulations across the estimated one million hectares of PFAS-impacted cropland indicate a combined CDR potential of approximately 11 Mt CO 2 y –1 , equivalent to 4 to 6% of the US 2050 carbon removal target. We estimate a median remediation cost of $1,460 USD ha –1 y –1 —more than an order of magnitude lower than current technologies, with costs substantially reduced through carbon removal revenues valued near the social cost of carbon. This integrated thermal and phytoremediation framework provides a viable pathway to restore contaminated farmland, mitigate PFAS exposure risks, and contribute meaningfully to national climate mitigation goals.

GridCL for fine-grained load profiling in smart grids under limited labels

Fine-grained load profiling is important for demand response and energy management in smart grids, yet supervised approaches remain constrained by the scarcity of high-quality labeled datasets. To address this limitation, we propose GridCL, a self-supervised contrastive learning framework for low-label load profiling in smart grids. GridCL forms paired daily-load views using conservative input perturbations—small temporal rolling, multiplicative perturbation, and energy renormalization—and combines them with a temporal convolutional encoder to learn discriminative representations from unlabeled data. Experiments on three anonymized city datasets and one pooled benchmark show that GridCL achieves strong clustering quality on the pooled AllCities benchmark, reaching 0.648 ± 0.115 ARI, 0.719 ± 0.064 NMI, and 0.620 ± 0.046 silhouette, while also attaining a best city-level ARI of 0.804 ± 0.084 . Under sparse-label evaluation, GridCL reaches 0.845 ± 0.042 accuracy on the pooled benchmark with only 10% labeled users, and remains stable at 20% and 30% labeled users with accuracies of 0.851 ± 0.033 and 0.849 ± 0.034 , respectively. These results indicate that GridCL provides an effective low-label solution for fine-grained load profiling in practical smart-grid settings.

Conservation of a lateralized visuomotor axis in hawkmoth proboscis probing

Lateralization of behavior, including motor control and sensory processing, is widespread across bilaterians. In visually guided tasks it often manifests as an axis aligning eye, appendage, and a target within a shared reference frame, such as eye-hand coordination in humans or eye-beak coordination in birds. While studied intensively in a few vertebrate systems, whether similar control principles apply to invertebrates, and more generally, how sensory and motor lateralization are linked mechanistically, remains unclear. Using the proboscis inspection behavior of hummingbird hawkmoth Macroglossum stellatarum as a model for visual appendage guidance, our study provides evidence for lateralized visuo-motor control in an invertebrate. Combining high-speed videography and markerless pose estimation, we establish the underlying control axis between the hawkmoths’ unpaired appendage and its eye. We demonstrate that individuals displayed stable, idiosyncratic proboscis lateralization, which was tightly linked to their instantaneous viewing angle of visual targets, thus forming a persistent eye–proboscis–target axis. This axis also had functional consequences for feature-targeting. Assessing the sensory–motor plasticity using monocular occlusion, we found that moths preserved their lateralized visuo-motor geometry by adjusting body posture during flower inspection. Our findings suggest convergent control principles with vertebrate models of lateralized visual appendage guidance, while highlighting stark differences in sensory–motor plasticity, thus adding to our general understanding of how lateralization shapes control strategies across nervous systems.

De Ritis (AST/ALT) ratio as a predictor of early adverse outcomes following transcatheter aortic valve replacement

Background Simple biochemical markers that capture systemic stress could refine short-term risk stratification after TAVR. We evaluated whether an elevated AST/ALT ratio predicts early adverse outcomes following transfemoral TAVR. Methods We retrospectively analyzed 733 consecutive patients undergoing transfemoral TAVR. The exposure was the preprocedural AST/ALT ratio categorized as low (<1.4; n = 478) or high (≥1.4; n = 255). Baseline characteristics were compared using t/Wilcoxon tests and χ²/Fisher’s exact tests. Thirty-day endpoints included all-cause mortality, acute kidney injury (AKI), stroke, and new-onset atrial fibrillation (NOAF). Kaplan–Meier failure curves were compared by the log-rank test. Cox models estimated hazard ratios (HRs) with 95% CIs; candidate covariates were prespecified and further refined with LASSO (10-fold cross-validation). Model assumptions were checked with Schoenfeld residuals. Results High AST/ALT was associated with greater 30-day risk of AKI (adjusted HR 3.18, 95% CI 1.80–5.63), stroke (adjusted HR 2.73, 95% CI 1.31–5.69), and NOAF (adjusted HR 2.35, 95% CI 1.57–3.51). For mortality, the crude association was not statistically significant (HR 2.07, 95% CI 0.91–4.68; p = 0.082) and remained non-significant after adjustment (HR 1.74, 95% CI 0.75–4.04; p = 0.197). Additional adjusted associations included higher AKI risk with high-intensity statins (HR 3.51, 95% CI 1.75–7.06) and baseline complete right bundle-branch block (HR 3.77, 95% CI 1.49–9.57). Conclusions An elevated preprocedural AST/ALT ratio independently identifies TAVR recipients at increased 30-day risk of AKI, stroke, and NOAF, but not mortality. Incorporating this inexpensive marker into routine assessment may help tailor periprocedural strategies and early surveillance after TAVR.

HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis

Mitochondrial biogenesis is a fundamental process that ensures energy supply and supports steroidogenesis in ovarian cells. Lactate has recently been identified as a signaling metabolite that promotes mitochondrial biogenesis; however, the underlying regulatory mechanisms remain poorly defined. Here, we identify Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90α) lactylation as a key mediator that links glycolytic metabolism to mitochondrial function. Specifically, lactylation of HSP90α at K58 recruits ULK1, thereby enhancing phosphorylation at S39; lactylation at K616 prevents CDK5-mediated phosphorylation at S596. This dual regulation facilitates the nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and its isoform LRPGC1, which activate NRF1/2-dependent transcription of mitochondrial biogenesis genes, such as Tfb1m , Tfb2m , and Tfam . Functionally, mitochondrial mass expansion both enhances cellular energy metabolism and promotes cholesterol import into mitochondria, thereby driving estrogen biosynthesis. Together, these findings reveal a lactate–HSP90α–PGC1α/LRPGC1 axis that metabolically couples glycolysis to mitochondrial biogenesis and reproductive hormone production, providing insights into the epigenetic regulation of follicular development.

From participation to systematization: A scoping review of theoretical frameworks guiding process evaluations in community mental health interventions

Background Process evaluations are essential for understanding how community mental health interventions are implemented and why they succeed or fail. While numerous theoretical frameworks exist to guide such evaluations, the landscape of framework use in mental health contexts remains uncharted, limiting methodological guidance for researchers and practitioners. Methods Scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Systematic searches of three databases (PubMed, Web of Science, EBSCOhost) identified 1,143 records, from which process evaluations of community mental health interventions published between 2006 and 2025 were selected. Data extraction captured framework characteristics, study context, and methodological features. Frameworks were inductively categorized into a hierarchical typology based on theoretical orientation and stated function. Results Eighty-three studies met inclusion criteria, employing 54 distinct primary frameworks organized into 14 categories. Implementation science frameworks dominated (39.8%), followed by process evaluation-specific frameworks (8.4%), behavior change theories (8.4%), and participatory approaches (6.0%). A marked temporal shift was observed: participatory and community-based frameworks characterized early publications (23.8% in 2006–2015) but were absent as primary frameworks after 2015, while implementation science frameworks rose from 14.3% to over 50% of studies. Geographic concentration in North America (54.2%) and high-income countries (83.1%) was pronounced. Conclusions The field has undergone a paradigm shift from community-engaged to systematized evaluation approaches. While framework consolidation offers methodological consistency, the decline of participatory approaches raises questions about the role of community voice in evaluation design. We propose a typology to guide framework selection and identify priorities for methodological development in community mental health process evaluation.

Radial gradient of superionic hydrogen in the Earth’s inner core

Hydrogen is considered a key light element in Earth’s core, yet the thermodynamics of its superionic phase and its distribution in the inner core remain unclear. Here, we compute ab initio Gibbs free energies for liquid and superionic hcp and bcc Fe–H phases and construct the superionic–liquid phase diagram over pressure–temperature conditions relevant to the Earth’s inner core. We find that phase diagrams at different inner-core pressures collapse when temperatures are scaled by the melting temperature of pure iron, indicating that solid–liquid partitioning is controlled primarily by a reduced temperature relative to iron melting and is weakly sensitive to pressure. This scaling relation further reconciles previously reported discrepancies in partition coefficients among theoretical studies and yields good agreement with available experimental data at low pressures. By applying thermochemical constraints, our free-energy results reveal a radial hydrogen gradient within the inner core. These results demonstrate that compositional gradients of superionic hydrogen in the inner core emerge naturally from equilibrium thermodynamics and suggest a general mechanism governing the depth-dependent distribution of light elements within Earth’s inner core.

Development and validation of a photogrammetry-based preoperative method (BREAST-E) for quantitative breast morphometric analysis and volume estimation of breast in reconstructive surgery

Background The demand for reproducible, reliable, and cost-effective tools regarding preoperative breast surgery planning is significant in low- and middle-income countries (LMICs) due to limited advanced imaging access, insufficient standardisation, and high cost. This study developed the BREAST-E technique for accurate and standardised breast volume analysis. Methodology A photogrammetry method assessed four ptosis levels: (i) no-ptosis, (ii) mild, [Watterson PA, et al. Plastic and Reconstructive Surgery. 1995;95:1185–94] moderate, and (iv) severe. Key parameters included marker counts (20, 40, and 60), photo angles (10°, 20°, and 30°), and offset adjustments (−0.01, 0, and +0.01). Two-dimensional (2D) images were converted into 3D models via Photomodeler for volume estimation. Clinical validation involved 12 patients (13 breasts) undergoing mastectomy, comparing estimated breast volumes to mastectomy specimens. The primary endpoint was accuracy of volume estimation compared with mastectomy specimen volume, while secondary endpoints included reliability, agreement, and workflow feasibility. Results The BREAST-E technique yielded promising accuracy [Pearson correlation coefficient ( R ) = 0.899 and mean absolute error (MAE) = 98.12 mL] and encouraging reliability (ICC = 0.995–0.996) across ptosis levels. Bland-Altman analysis indicated negligible bias, while Cronbach’s alpha (reaching 0.994) demonstrated robust internal consistency. Clinical validation also implied strong performance ( R  = 0.789, MAE = 104.69 mL, and mean error = −27.00 mL). Consequently, no-ptosis presented the highest reliability (ICC = 0.81 and Cronbach’s alpha = 0.92) with minimal bias, whereas moderate and severe ptosis levels demonstrated greater variability. Conclusion This study successfully indicated that a reproducible, accessible, and cost-effective method for analysing breast volume was accomplished through the proposed BREAST-E technique for LMICs.

FGFR2 is an oncogenic driver critical for successful human gammaherpesvirus latent infection and oncogenesis

Epstein–Barr virus (EBV) and Kaposi’s sarcoma–associated herpesvirus (KSHV) drive multiple aggressive lymphomas, yet effective targeted therapies for these virus-associated malignancies remain limited. Using an unbiased kinome-wide screen combined with analysis of virus-positive patient tumors, we identified fibroblast growth factor receptor 2 (FGFR2) as a selectively activated host kinase in EBV- and KSHV-associated lymphomas. Importantly, FGFR2 is required for efficient establishment of EBV latent infection, and its knockdown markedly impairs the formation of viral latency programs. Viral latency proteins EBV nuclear antigen 2 (EBNA2) and latency-associated nuclear antigen (LANA) recruit STAT3 and RBP-Jκ to the FGFR2 promoter to drive its transcription, enabling efficient establishment of EBV latency and activation of downstream STAT3/AKT signaling. This feed-forward signaling circuit suppresses apoptosis, promotes S-phase progression, and sustains proliferation of infected lymphoma cells. Targeting FGFR2 genetically or pharmacologically using clinically relevant inhibitors markedly suppresses tumor growth in vitro and in vivo. This study identifies FGFR2 as a critical oncogenic driver in EBV and KSHV infections, highlighting its potential as a therapeutic target to inhibit tumor growth and treat associated viral malignancies.

Myasthenia gravis: Diagnostic journey and therapeutic outcomes in patients followed at a Brazilian public tertiary center — A retrospective cohort study

Background Myasthenia gravis (MG) is a heterogeneous autoimmune disorder of the neuromuscular junction. Diagnosis and management remain challenging in real-world settings, particularly in public health systems. Data from resource-constrained countries are limited. This study aimed to characterize the epidemiological, clinical, and therapeutic profile of MG patients followed in a Brazilian public tertiary center, emphasizing diagnostic delay and treatment outcomes. Methods We conducted a retrospective single-center cohort study of 150 adult MG patients evaluated from 2024 to 2025. Clinical, immunological, therapeutic, and diagnostic-journey data were extracted from institutional electronic and paper medical records, and structured patient questionnaires, when available. Patients were classified as drug-responsive, corticosteroid-dependent, or drug-refractory using predefined operational criteria informed by international consensus guidance. Between-group comparisons used parametric or nonparametric tests, and categorical variables were analyzed with chi-square, Fisher’s exact, or Monte Carlo permutation chi-square tests, as appropriate. Results The cohort had female predominance (65.3%), with a median age at onset 35.5 years (IQR 25–48). Among those tested, most were AChR antibody–positive (67.6%) and presented generalized MG (93.3%). Median diagnostic delay was 11 months, and 47.3% had delays ≥1 year. Refractory MG occurred in 14% and corticosteroid dependence in 10.6%. Documented myasthenic crisis and impending crisis occurred in 25.2% (35/139) and 27.3% (38/139), respectively; documented myasthenic crisis was more frequent in refractory than in drug-responsive patients (45.0% vs 21.0%). Treatment-related adverse events were documented in 47.5% (67/141); among affected patients, the most common were hyperglycemia (37.3%), osteoporosis/osteopenia (17.9%), and weight gain (16.4%). Conclusions MG patients followed at this Brazilian public tertiary center showed clinical profiles broadly comparable to those reported in international cohorts, but diagnostic delays were frequent. The frequencies of refractory disease and corticosteroid dependence highlight the need for earlier recognition, specialized management, optimized steroid-sparing strategies, and improved access to comprehensive MG care.

Excitonic energy transfer in red algal Photosystem I reveals an evolutionary bridge between cyanobacteria and plants

Photosystem I (PSI) converts light into chemical energy with near-unity quantum efficiency, yet its energy-transfer and charge-separation mechanisms remain debated. Evolution has diversified PSI architectures: Cyanobacterial PSI trimers confine red-shifted pigments to the core, whereas plant PSI-Light Harvesting Complex Isupercomplexes incorporate extensive peripheral red and charge-transfer states that reshape trapping. The unicellular red alga Cyanidioschyzon merolae exemplifies functional diversification across distinct evolutionary branches, combining a photosystem II and plant-like monomeric PSI core associated with a varying number of light harvesting antenna subunits, Light Harvesting Complexes from Red Lineage (LHCR). This hybrid organization functionally bridges mechanistic models across different lineages. We applied two-dimensional electronic spectroscopy at ultralow temperatures (8 and 80 K) to disentangle overlapping excitation pathways in C. merolae PSI. Cryogenic measurements suppressed thermal broadening, resolving five dynamical components: subpicosecond equilibration (0.3 to 0.8 ps) across the core–LHCR interface, subsequent population transfer (2.6 to 4 ps) into progressively lower-energy manifolds, and slower feeding (18 to 53 ps) into red pools distributed across both core and antenna. On the longest timescales (hundreds of ps), a persistent ground-state bleach signifies excitons stabilized in terminal sinks. Notably, comparison of 8 K and 80 K spectra reveals that excitations are heterogeneously partitioned among multiple sinks at low disorder, whereas modest thermal activation (kT ∼ 55 cm −1 ) promotes selective convergence into core-associated red chlorophylls. Atomistic excitonic modeling with time-nonlocal master equations supports these observations, revealing temperature-dependent energy redistribution. Overall, C. merolae PSI expands the kinetic funnel by distributing trapping sites, enhancing spectral coverage while maintaining high efficiency, which is an important functional diversification during evolution.