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Treelines mark a functional limit of upright tree growth rather than a strict survival boundary. At these cold margins, photosynthesis and nonstructural carbohydrate reserves often remain sufficient, whereas apical and cambial growth decline, arguing against carbon limitation as the primary cause of growth cessation. We propose that chronic low temperature may contribute importantly to this pattern through hormonal regulation, notably reduced gibberellin availability and persistence of DELLA-like repressors, together with altered auxin and brassinosteroid signaling. This could maintain meristems in a growth-repressive state despite continued metabolic activity. We do not present this as the sole explanation for treeline formation, but as a plausible and testable regulatory mechanism that may operate alongside generally reduced metabolic rates and hydraulic or energetic constraints.
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Polyvinylsiloxane (PVS) is a molding compound originally developed for dental applications that, over the past 50 years, has also been widely used in archaeology to produce negative surface replicas of artifacts, owing to its excellent detail reproduction and dimensional stability. However, most studies assessing its replication accuracy have focused on bones, teeth, and flint tools, leaving ground stone tools (GSTs) largely unexplored. This study fills this gap by assessing the accuracy of PVS molding on GSTs, whose uneven surfaces and heterogeneous textures present particular challenges for both qualitative and quantitative analyses. We tested the accuracy and precision of PVS copies on a reference collection of GST replicas based on archaeological artifacts from Upper Paleolithic sites, representing four diverse lithologies. Confocal profilometry was used to acquire microtopographic maps of selected areas, enabling in-depth statistical comparisons between original surfaces and corresponding molds, with emphasis on key roughness descriptors. The results show that PVS molds effectively capture fine surface details, making them suitable for rough and irregular surfaces, though minor deviations and parameters overestimation must be considered in quantitative traceological analyses. By evaluating replication accuracy, this study contributes to the refinement of analytical methodologies for GSTs and improves the reliability of functional investigations.
To describe the incidence, management, and outcomes of segmental and subsegmental pulmonary embolism (PE) in intensive care unit (ICU) patients and to explore associations between therapeutic-dose anticoagulation and clinical outcomes. Single-center retrospective cohort study. Tertiary academic hospital ICU between January 2019 and June 2025. Critically ill adults (≥18 years) who underwent computed tomography pulmonary angiography (CTPA) during ICU admission and had radiologically confirmed segmental or subsegmental PE. None. Radiology reports of all CTPA examinations performed in ICU-admitted patients were screened to identify the most proximal level of thrombus. Clinical records were reviewed for demographics, illness severity, radiologic characteristics, anticoagulation practice, bleeding, venous thromboembolism (VTE) recurrence, and mortality. Among 896 CTPA examinations performed in 804 patients, 164 examinations (18.3%) identified PE. Of these, 115 scans (12.8% of all CTPAs) demonstrated distal PE only, corresponding to 104 patients (12.9%) (61 segmental, 43 subsegmental). Overall, 96% of patients with distal PE received anticoagulation and 86% of anticoagulated patients received therapeutic-dose regimens. Bleeding occurred in 15% (major bleeding 12%), 90-day VTE recurrence in 7.8%, and 90-day mortality in 24%. No statistically significant association was found between the use of therapeutic-dose anticoagulation and 90-day mortality (adjusted odds ratio [OR], 0.70; 95% CI, 0.21-2.45), bleeding episodes (adjusted OR, 2.34; 95% CI, 0.47-19.2), or VTE recurrence (adjusted OR, 0.69; 95% CI, 0.11-6.22). In critically ill adults, segmental and subsegmental PE are commonly detected on CTPA and are usually treated with therapeutic-dose anticoagulation. Although VTE recurrence was less frequent than bleeding episodes and mortality, our study did not find a significant association between therapeutic-dose anticoagulation and bleeding episodes, recurrent VTE, or mortality. Larger prospective studies are needed to define optimal anticoagulation strategies for ICU patients with distal PE.
Chronic kidney disease (CKD) is a multifactorial clinical condition consisting of a complex set of manifestations that, in addition to renal involvement, involve multiple organ systems. Endocrine disorders are particularly common in patients with CKD and require proper management given their multisystemic effects. The main endocrine disorder found in patients with kidney disease is alterations in the calcium-phosphorus (PTH) axis, which is why nephrologists often focus exclusively on managing this condition, neglecting any other endocrine alterations observed in this patient group. Thyroid involvement appears worthy of attention both in terms of its numerical frequency and therapeutic implications. The aim of this review is to enable a proper assessment of thyroid disease in patients with kidney disease and to provide the tools for appropriate assessment and treatment.
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Transportation can be a significant stressor to laboratory animals. This study evaluated the efficacy of a five-week kennel conditioning protocol in mitigating stress induced by transportation in adult minipigs. Thirteen animals were randomly assigned to the conditioned (CND) or control (CTR) group. Only the CND group underwent conditioning in the kennel that would be used for transport. After the conditioning period, both groups were subjected to simulated transport. Stress responses were assessed through salivary cortisol levels at baseline, during kennel permanence, and during simulated transport, while heart rate variability (HRV) was continuously monitored. There were no significant differences observed in salivary cortisol levels between groups. Overall, neither group showed clear physiological evidence of transport-related stress. At baseline, CTR minipigs displayed higher Sample Entropy (SampEn), a nonlinear parameter of autonomic complexity, than CND minipigs. This suggests positive emotional arousal due to training. During transport, CND minipigs exhibited a significant intragroup increase in SampEn compared to baseline, indicating differences in autonomic regulation. These results suggest that repeated handling and exposure to non-aversive experimental procedures may contribute to stress resilience, potentially reducing the detectable impact of specific transport-conditioning protocols. Our results underscore the complexity of interpreting physiological stress indicators and support the use of multimodal approaches combining complementary welfare measures. Further studies are necessary to determine the relative contributions of targeted conditioning and general husbandry practices in shaping transport responses in biomedical minipigs.
to evaluate predictive dosimetric factors for fat necrosis (FN) after post-operative single-fraction stereotactic partial breast irradiation (S-PBI) in early-stage breast cancer. This prospective, single-institution phase II trial enrolled 148 patients who received breast-conserving surgery followed by S-PBI. Treatment consisted of a single 17.5 Gy fraction prescribed to 95% of the planning target volume (PTV)using GammaPod™. The nominal dose was 18.4 Gy. FN was evaluated clinically at each follow-up. FN was classified into two categories: FN detected only by imaging (mammography or contrast-enhanced mammography, CEM) and FN detected by imaging and associated with clinical symptoms. To describe the cumulative incidence of FN over time after S-PBI we used the Kaplan Meier method. Univariate and stepwise logistic regression analyses were conducted to predictive factorsassociated with FN. Between January 2022 and May 2024, 148 patients    were enrolled. Median age at diagnosis was 68 years (IQR 58-74). Median follow-up was 29.9 months (IQR 23.5-38.8). Median whole breast volume was 1242.63cc (IQR722.69-1394.42). Median PTV volume was 43.6cc (IQR 32.6-58.5). MedianV19.3(105%) was 0.55cc. Eighteen patients (12.1 %) developed FN and 6 patients (4.1%) symptomatic FN. The incidence rate FN at 6-12-18-24 months were 1.4%, 6.8%, 9.5% and 11.3% respectively. The incidence rate symptomatic FN at 6-12-18-24 months were0.7%, 2.7%, 3.4% and 4.6% respectively. Age ≥60 years and dosimetric parameter V19.3 were independently associated with an increased risk of fat necrosis. Specifically, V19.3 ≥5 cc was a strong predictor for overall FN, while V19.3% (continuous) was the only significant predictor for symptomatic FN. PTV showed only a borderline association, CONCLUSION: The use of S-PBI with GammaPod™ is confirmed as a well-tolerated strategy, with a relatively low incidence of FN. Advanced age and volume of mammary gland exposed to higher doses represent the main risk predictors.
KDIGO and IPNA guidelines indicate a target of proteinuria < 0.2 g/day/1.73m2 in children with Immunoglobulin A nephropathy (IgAN). However, the value of proteinuria remission to this threshold was limited to small monoethnic cohorts, with unknown long-term kidney outcomes. In a previously described multiethnic cohort of 1 298 children with IgAN, we selected those with proteinuria at kidney biopsy ≥ 0.2 g/day/1.73m² and analyzed the occurrence of complete and sustained proteinuria remission lasting > 90 days (CSR). Aim of the study was to investigate clinical and histological factors associated with CSR and the value on long-term eGFR decline. The study enrolled 709 children with different ethnicities (White, Chinese and Japanese). The median age at biopsy was 12.9 years, eGFR 95.7 ml/min/1.73m2 and proteinuria 1.2 g/day/1.73m2. MEST-C scoring detected M1 in 57% of the cases, E1 in 41.3%, S1 in 53.3%, T1-2 in 13.6% and C1-2 in 46.7%. CSR occurred in 395 children (55.7%) after time-averaged observation of 0.7 years (0.4-1.3 years) and was maintained throughout follow-up in 47.3% of the cases. In a sensitivity analysis, children who achieved CSR had significant protection from eGFR decline at 4 and 5-years (p = 0.026 and p = 0.004 respectively). During follow-up, 74.4% were treated with renin-angiotensin system blockers (RASB) and 67.4% with immunosuppressors (IS). In a Cox proportional multivariate model including time-dependent RASB and IS treatment, a significant association with CSR was detected for younger age (p = 0.009), higher eGFR (p = 0.002), absence of segmental sclerosis (p < 0.001) and RASB treatment (p < 0.001). The model including ethnicity showed a strong effect of Japanese and Chinese ethnicity (both p < 0.001) and a significant association of CSR with age, absence of S1 (p < 0.001) and T1-2 (p = 0.016) and RASB and IS treatment (both p < 0.01). The observational study showed that the achievement of CSR in children with IgAN was associated with better eGFR outcome.
We present a unified many-body perturbation theory for open quantum systems that treats dissipation, correlations, and external driving on equal footing. Using a Keldysh-Lindblad formalism, we introduce a diagrammatic treatment of dissipative interaction lines representing quasiparticle flows and fluctuations. Two new Feynman rules render the evaluation of dissipative diagrams compact and systematically improvable, while preserving the Keldysh and anti-Hermitian symmetries of the closed-system theory. Consequently, the structure of the Kadanoff-Baym equations remains unchanged, enabling existing numerical methods to be directly applied. To illustrate this, we derive dissipative versions of the second Born and GW approximations and identify the physical content of the self-energy components. Moreover, we demonstrate that time-linear approximations to the full Kadanoff-Baym equations retain their closed-form structure and can be efficiently used to simulate relaxation and decoherence dynamics. The impact of dissipation-induced correlations is illustrated in the driven Haldane model, where quasiparticles exhibit nontrivial stabilization and acquire lifetimes that far exceed those of the bare system. This framework establishes a general route toward first-principles modeling of correlated, driven, and dissipative quantum materials.
Patients with Cystic fibrosis (CF) require frequent monitoring in evaluating lung infections, but current diagnostic approaches are invasive and resource-intensive. Ethyl acetate (EA) and pH changes in exhaled breath have emerged as promising non-invasive biomarkers. In this context, we report a smart face mask that integrates a dual-function paper-based analytical device (PAD) for sampling exhaled breath and detecting pH and EA after the mask is worn. The system combines molecularly imprinted polymers for selective EA adsorption, Candida antarctica lipase for enzymatic hydrolysis of EA into acetic acid, and an iridium oxide-modified electrode for sensitive pH monitoring. The (bio)sensing platform demonstrated high sensitivity and reproducibility across solution and aerosol, with linear ranges of pH 5.3-9 and EA concentrations from 0.01 to 2.5 mM, and a detection limit of 1.5 μM under breath-like conditions. Tests in human saliva aerosol confirmed high accuracy (89.7-106.8%recovery) and precision (<4.3% RSD), while selectivity studies showed no interference from common breath metabolites. By enabling rapid pH and EA quantification in a portable, low-cost format, this platform provides a robust and non-invasive tool for point-of-care CF diagnostics.
The Johnson-Corey-Chaykovsky reaction stands as an elegant approach for the synthesis of cyclopropanes and epoxides. However, most procedures still rely on the original NaH/DMSO conditions, which pose notable safety and handling issues especially in view of industrial applications. Herein, we combine Bayesian Optimization and mechanochemistry to develop a rapid, solvent-free protocol for the Johnson-Corey-Chaykovsky reaction. By prioritizing efficiency and sustainability, Machine Learning quickly identified a new set of reaction conditions for this transformation, also demonstrating that these transformations can proceed efficiently under air-equilibrated, mild conditions using an inexpensive and safe base (KOH). The method is broadly applicable, scalable, and tolerant to diverse functional groups and enabled the preparation of a wide variety of three-membered homo- and heterocycles. Time-Resolved in situ X-ray Powder Diffraction experiments highlighted the crucial role of active milling in promoting this transformation. Overall, this work establishes a foundation for the integration of Machine Learning and mechanochemistry in designing industrially relevant transformations that prioritize safety and sustainability.
The atmospheric composition of rocky exoplanets offers an important tool for constraining the properties of the interior of this type of planet, beyond what is possible from measurements of their mass and radius alone. However, the interpretation of these observations requires an understanding of the complex interplay of a larger number of coupled planetary and atmospheric processes. This review provides an overview of the current state of knowledge regarding rocky exoplanet atmospheres, beginning with their formation and escape mechanisms. We specifically highlight the importance of long-term interaction between the atmosphere, the surface, and the interior on rocky planets. Furthermore, this review addresses the influence of biological activity and photochemical reactions on the atmospheric compositions. Consequently, establishing how these different processes contribute to shaping the atmospheres of rocky exoplanets during their evolution is fundamental for the characterization of these planets with future space missions and ground-based surveys.
Photon-counting computed tomography (PCCT) enables simultaneous assessment of left ventricular morphology, function, and myocardial tissue characterization. Whether sex influences PCCT findings across hypertrophic phenotypes remains uncertain. We studied consecutive adults with a left ventricular hypertrophic phenotype undergoing PCCT. Patients were classified as hypertrophic cardiomyopathy (HCM), transthyretin amyloid cardiomyopathy (ATTR-CM), or secondary left ventricular hypertrophy (LVH). Sex differences in PCCT-derived left ventricular mass index, volumes, ejection fraction (EF), late iodine enhancement (LIE), and extracellular volume (ECV) were assessed overall and by aetiology. In patients with clinically indicated cardiovascular magnetic resonance (CMR) within ±12 months, sex effects on CT-CMR agreement were also evaluated. Among 182 patients, 50 were women and 132 were men; 83 had paired PCCT-CMR data. In the overall cohort, women had lower left ventricular mass index, smaller left ventricular volumes, higher EF, slightly lower ECV, and lower LIE extent than men. In HCM, women and men showed similar wall thickness, left ventricular mass, LIE burden, and ECV. In secondary LVH, women had smaller volumes and higher EF, without meaningful differences in tissue markers. In ATTR-CM, women appeared less remodelled and less infiltrative, although only four women were included. CT-CMR agreement for wall thickness, left ventricular mass, EF, scar extent, and ECV was similar in women and men. Diagnostic ECV thresholds were also consistent across sexes. Sex influences PCCT hypertrophic phenotypes mainly through remodelling and functional adaptation rather than major differences in tissue characterization. CT-CMR agreement and diagnostic ECV thresholds appear robust across sexes.
The immunosuppressive tumor microenvironment (TME) poses a significant challenge to effective cancer immunotherapy, as it enables tumor escape through redundant checkpoint pathways, metabolic constraints, and direct inhibition of effector cells. To overcome these barriers, we developed a next-generation NK cell platform using a tri-cistronic retroviral vector that enhances NK cell activation, recruitment, survival, and metabolic fitness. Pan-cancer transcriptomic analyses reveal consistent co-expression of PD-L1 and HLA-E across tumors, which correlates with immune infiltration accompanied by strong immunosuppression, highlighting these molecules as key targets for immune evasion. To improve NK cell recruitment, activation, cytolytic function, survival, and metabolic fitness in the TME, we developed a next-generation NK cell platform using a tri-cistronic retroviral vector that encodes an extracellular PD-1 domain (exPD1) fused to the intracellular portion of NKG2D with the costimulatory molecule 4-1BB, and expressing soluble IL15 and NKG2A single-chain variable fragments (scFv). Thus, the exPD1 allows the recognition of cells expressing PD-L1, while the intracellular costimulatory signaling transforms the inhibitory interaction PD-1/PD-L1 into an activating one. This strategy effectively targets PD-L1-positive tumor cells and induces de novo PD-L1 expression in otherwise negative tumors. To further enhance anti-tumor activity, we incorporated a module encoding soluble NKG2A-scFv to mask the NKG2A receptor on NK cells and hinder NKG2A/HLA-E inhibitory interaction. Additionally, we improved NK cell survival and expansion by delivering controlled low doses of IL15, which prevents NK cell exhaustion and extends their presence in vivo. This integrated strategy may provide a novel, ready-to-use allogenic mature NK cell therapy that could overcome checkpoint-mediated inhibition, metabolic suppression, and immune escape, offering a promising model for treating high-risk and treatment-resistant tumors.
Conventional neural interfaces are typically manufactured by photolithographic micromachining using thermoplastic insulators and noble-metal conductors. Although effective, these approaches require costly, time-intensive infrastructure, restrict material selection, and often produce devices with substantial mechanical and interfacial mismatch relative to soft neural tissue, limiting long-term performance. Here, we introduce CASPER (CAsted and Screen-Printed polymeric ElectRodes), a cleanroom-free and low-cost benchtop strategy for the fully manual fabrication of implantable neural interfaces from biocompatible polymeric materials. By combining polymer casting with manual screen printing and reusable molds, CASPER enables rapid electrode fabrication without specialized microfabrication equipment. As a proof of concept, we developed CASPER-cuff, a fully polymeric cuff electrode tailored to the swine cervical vagus nerve, integrating PDMS insulation with metal-free PEDOT:PSS conductive hydrogel active sites. CASPER-cuff exhibited tissue-compliant mechanical properties (E < 1 MPa), together with competitive electrochemical performance (|Z|@1 kHz = 3.58 ± 1.78 kΩ; cCSC = 74.98 ± 20.27 mC cm-2), demonstrating that marked simplification of manufacturing does not compromise device function. In vivo implantation further showed stable nerve coupling and reliable stimulation and recording of evoked compound action potentials, consistent with vagal B-fiber recruitment. CASPER establishes an accessible route toward customizable, fully polymeric soft neural interfaces for bioelectronic medicine.
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Irisin, a muscle-secreted myokine induced by exercise, serves as a molecular bridge between muscle activity and the immune system. This interaction is particularly relevant in aging, where irisin may modulate the transition toward immunosenescence and influence host vulnerability to acute systemic insults, such as sepsis. Irisin regulates immune function and inflammation by suppressing pro-inflammatory cytokines while increasing anti-inflammatory mediators. These effects are primarily driven by the modulation of the AMPK and NF-κB signaling pathways, suggesting irisin may play a role in addressing immunosenescence by orchestrating cellular inflammatory responses. Moreover, recent evidence highlights the possible anti-senescent properties of irisin, specifically through its ability to modulate the senescence-associated secretory phenotype. Dysregulated immune responses and cellular senescence contribute to sepsis pathophysiology, and accordingly, irisin has been shown to improve cognitive impairment as well as respiratory, cardiac, and renal dysfunction in murine models of sepsis. Research indicates that increased expression of FNDC5, the membrane-bound precursor of irisin, enhances these protective effects, while clinical data reveals that low serum irisin correlates with greater sepsis severity. Consequently, decreased circulating irisin may serve as a diagnostic and prognostic biomarker for predicting mortality in septic patients. Irisin represents a promising link between muscle-derived signaling and immune resilience. While clinical application is currently hindered by assay variability and a need for larger human cohorts, its role in modulating both immunosenescence and acute sepsis pathophysiology marks it as a possible prognostic biomarker and a potential therapeutic target in the vulnerable aging population.
Plasmons in low-dimensional materials provide a powerful platform for nanoscale control of light-matter interactions, yet strategies to tailor their coherence and dissipation remain limited. Here, we demonstrate that transition-metal intercalation offers a fundamentally distinct route to engineer plasmonic response in layered materials. By combining high-resolution core-level photoemission spectroscopy with first-principles calculations, we show that Fe and Co intercalation in 2H-TaS2 does not act as conventional electron doping but reshapes the low-energy electronic structure through orbital hybridization and structural reconstruction. This process introduces a dense continuum of low-energy states that ultimately suppresses the plasmon mode. First-principle calculations of the energy-loss function reveal a transition from a well-defined collective excitation to an overdamped response. Our results establish intercalation as a chemically controlled pathway to tune plasmon losses and dielectric response in quantum van der Waals materials, providing a new design principle for plasmonic and optoelectronic functionalities at the nanoscale.
Primary pulmonary B-cell lymphomas are rare, accounting for <1% of non-Hodgkin lymphomas (NHLs) and 3-4% of extranodal NHL. Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT; pulmonary MALT lymphoma), arising from bronchus-associated lymphoid tissue (BALT), represents over 80-90% of cases. These tumors typically develop as a result of chronic antigenic stimulation in the setting of persistent inflammation, due to infection, or autoimmune disease. Two main pathogenetic phases are recognized in their development: an antigen-dependent phase, in which clonal B-cell expansion and survival are driven by ongoing exposure to specific antigens, and an antigen-independent phase, in which B-cell proliferation becomes autonomous due to cytogenetic and molecular alterations. Clinically, pulmonary MALT lymphoma has an indolent course and is often detected incidentally; when symptoms occur, they are non-specific. Radiologic findings include consolidations, nodules, or masses. Diagnosis relies on histopathology, immunophenotyping (CD20+, light-chain restriction, CD5-/CD10-/cyclin D1-), and molecular studies. Most patients present at early Ann Arbor stages, with a 5-year overall survival exceeding 90%. Management should be tailored to the disease stage, symptoms, comorbidities, and patient preferences. A watch-and-wait approach is appropriate for asymptomatic patients without treatment indications. Radiotherapy is highly effective for localized disease, while rituximab alone or with chemotherapy, particularly bendamustine-rituximab, is preferred for advanced symptomatic disease. Bruton's tyrosine kinase inhibitors have shown efficacy in relapsed or refractory cases. This review summarizes the epidemiology, pathogenesis, clinicopathologic features, diagnosis, and evolving treatment strategies of pulmonary MALT lymphoma, highlighting its favorable prognosis and unique immunobiological origin.