Search Results (157)

Background/Objectives: Patients with early-stage non-small cell lung cancer (NSCLC) or limited lung metastases and compromised lung function, such as those with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD), or other factors rendering them high-risk for surgery or medically inoperable, face increased risks of treatment-related toxicity from stereotactic ablative radiation therapy (SABR). This study evaluated a novel treatment approach to mitigate these risks. Methods: We investigated Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR), delivered as pulsed radiation every three weeks, in patients with <5 cm lung tumors and ILD, COPD, or prior therapy. Treatment occurred between 2022 and 2024. Online adaptive radiotherapy (o-ART) was employed in 20 patients (80%) to modify treatment plans when anatomical changes warranted replanning. Primary outcomes included volumetric tumor response, changes in dose to organs at risk (OARs) and acute events, while secondary outcomes included local and tumor control, and overall survival. Results: Twenty-three patients received PULSAR treatment at doses between 40 Gy and 60 Gy in 5 fractions and one patient received 54 Gy in 3 fractions, with a median follow-up time of 16.2 months. Approximately half of treated patients demonstrated volumetric tumor response, with median residual volume of 70% (range 36–100%) at maximal response. Among the 20 patients (80%) who underwent online adaptive replanning, significant reductions in OAR dosimetry were observed for all organs assessed including the Dmax for heart (p = 0.0053), bronchus (p = 0.0003), esophagus (p = 0.0005), spinal cord (p = 0.025), and the lung V20 Gy and V12.5 Gy (p < 0.0001). Treatment-related toxicity included two grade 1–2 adverse events and six grade 3 events consisting of pneumonitis, dyspnea or lung infection, with no grade 4 or 5 events. Median progression-free survival was 21.1 months, with 1-year overall survival of 74% and 1-year local control of 100%. Conclusions: PULSAR shows promise as a feasible treatment option for high-risk patients with NSCLC or lung metastases, demonstrating no grade 5 events and complete tumor control. Additional research is needed to fully evaluate the safety profile of PULSAR in the high-risk subgroups and whether PULSAR’s treatment intervals and adaptive planning advantages lead to improved long-term outcomes compared to conventional, uninterrupted SABR regimens. Full article

This study investigates the flow and heat transfer mechanisms of high-temperature air flowing across staggered lined fine tubes in a SABRE-type precooler. Large-Eddy Simulation (LES) was employed to model three-dimensional unsteady flow under constant-property and variable-property air models at inlet temperatures of 400–800 K. The results show that increasing temperature substantially enhances vorticity, turbulent kinetic energy, heat flux, and Nusselt number, while flow separation and pressure drop are intensified. However, when temperature-dependent air properties are incorporated, the wake width increases and the separated shear layers become thicker, while the turbulence/unsteadiness intensity decreases. Consequently, the near-wall shear is reduced and the heat transfer coefficients are lower. Compared with variable-property predictions, constant-property models overestimate the average Nusselt number by 20–40% and the local pressure drop by 40–65%, and they underestimate the air-side temperature drop along the tube rows. These findings demonstrate that real-gas effects significantly alter both aerodynamic resistance and thermal performance. Overall, accurate representation of temperature-dependent air properties is essential for the reliable design, evaluation, and optimization of micro-tube precoolers. Full article

We present hybrid quantum–classical algorithms to compute time-dependent Møller wavepacket correlation functions via digital quantum simulation. Reactant and product channel wavepackets are encoded as qubit states, evolved under a discretized molecular Hamiltonian, and their correlation is reconstructed using both a modified Hadamard test and a multi-fidelity estimation (MFE) protocol. The method is applied to the collinear H + H₂ exchange reaction on a London–Eyring–Polanyi–Sato potential energy surface. Quantum-estimated correlation functions show quantitative agreement with high-resolution classical wavepacket simulations across the full time domain, reproducing both short-time scattering peaks and long-time oscillatory dynamics. The ancilla-free MFE protocol achieves matching results with reduced circuit depth. These results provide a proof of principle that digital quantum circuits can be used to accurately calculate the wavepacket correlation functions for a benchmark chemical reaction system. Full article

The mechanism by which odorants are recognized by olfactory receptors remains primarily unresolved. While charge transport is believed to play a significant role, its precise nature is still unclear. Here, we present a novel perspective by exploring the interplay between the intrinsic energy scales of odorant molecules and the gap states that facilitate intermolecular charge transport. We find that odorants act as weak tunneling conductors mainly because of the limited magnitude of electronic coupling between frontier molecular levels. This behavior is further connected to electron–phonon interaction and reorganization energy, suggesting that physically meaningful values for the latter parameter emerge only in the deep off-resonant tunneling regime. These findings complement the swipe card model of olfaction, in which an odorant needs both the right shape to bind to a receptor and the correct vibrational frequency to trigger signal transduction. Moreover, they reveal that the underlying mechanisms are much more complex than previously assumed. Full article

Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease. Full article

Quantum energy teleportation (QET) has been proposed to overcome the restrictions of strong local passivity (SLP) and to facilitate energy transfer in quantum systems. Traditionally, QET has only been considered under strict constraints, including the requirements that the initial state be the ground state of an interacting Hamiltonian, that Alice’s measurement commute with the interaction terms, and that entanglement be present. These constraints have significantly limited the broader applicability of QET protocols. In this work, we demonstrate that SLP can arise beyond these conventional constraints, establishing the necessity of QET in a wider range of scenarios for local energy extraction. This leads to a more flexible and generalized framework for QET. Furthermore, we introduce the concept of a “local effective Hamiltonian,” which eliminates the need for optimization techniques in determining Bob’s optimal energy extraction in QET protocols. As an additional advantage, the amount of energy that can be extracted using our new protocol is amplified to be 7.2 times higher than that of the original protocol. These advancements enhance our understanding of QET and extend its broader applications to quantum technologies. To support our findings, we implement the protocol on quantum hardware, confirming its theoretical validity and experimental feasibility. Full article

Parahydrogen-induced hyperpolarization (PHIP), introduced nearly four decades ago, provides an elegant solution to one of the fundamental limitations of nuclear magnetic resonance (NMR)—its notoriously low sensitivity. By converting the spin order of parahydrogen into nuclear spin polarization, NMR signals can be boosted by several orders of magnitude. Here we present a portable, compact, and cost-effective setup that brings PHIP and Signal Amplification by Reversible Exchange (SABRE) experiments within easy reach, operating seamlessly across ultra-low-field (0–10 μT) and high-field (>1 T) conditions at 50% parahydrogen enrichment. The system provides precise control over bubbling pressure, temperature, and gas flow, enabling systematic studies of how these parameters shape hyperpolarization performance. Using the benchmark Chloro(1,5-cyclooctadiene)[1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene]iridium(I) (Ir–IMes) catalyst, we explore the catalyst activation time and response to parahydrogen flow and pressure. Polarization transfer experiments from hydrides to [1-¹³C]pyruvate leading to the estimation of heteronuclear J-couplings are also presented. We further demonstrate the use of Chloro(1,5-cyclooctadiene)[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene]iridium(I) (Ir–SIPr), a recently introduced catalyst that can also be used for pyruvate hyperpolarization. The proposed design is robust, reproducible, and easy to implement in any laboratory, widening the route to explore and expand the capabilities of parahydrogen-based hyperpolarization. Full article

Stereotactic ablative radiotherapy (SABR) has revolutionized the management of patients with oligometastatic and selected primary cancers due to its ability to deliver highly conformal, high-dose radiation in few fractions with minimal toxicity. However, the biological heterogeneity among patients treated with SABR results in variable outcomes, emphasizing the need for predictive and prognostic biomarkers to guide patient selection and post-treatment management. This narrative review discusses the current landscape of biomarker development in the context of SABR across tumor types. Key classes include circulating tumor DNA (ctDNA), extracellular vesicles (EVs), radiomic features, and immunological markers. We highlight the role of each biomarker category in refining therapeutic approaches, their integration into ongoing clinical trials, and future directions for personalized SABR paradigms. Translating these promising biomarker strategies into clinical SABR workflows will require further standardisation, validation, and regulatory alignment. Full article

Colorectal cancer (CRC) is a major cause of cancer mortality worldwide, with metastatic disease remaining the main driver of poor prognosis. In recent years, the concept of oligometastatic disease, where patients present with a limited number of metastases, has created an opportunity to use local therapies with curative intent. Stereotactic ablative radiotherapy (SABR) has become increasingly important in this setting, as it allows the delivery of high, ablative doses with excellent local control and generally low toxicity. Notably, randomised data such as SABR-COMET, alongside large prospective series including SABR-5, have demonstrated improvements in survival outcomes in the context of oligometastatic disease across mixed primary tumour types, with CRC patients making up a relatively small proportion in these trials. This has presented SABR as a practical treatment option for patients with oligometastatic CRC, although more CRC-specific phase III trials are needed. Other challenges include the radioresistance of CRC metastases, and treatment outcomes that vary depending on the anatomical site, tumour biology, and prior therapies. Technical issues such as motion management and organ-at-risk constraints also continue to limit dose escalation. Emerging strategies—including MR-guided radiotherapy, proton-based SABR, integration with systemic agents such as immunotherapy, and the use of biomarkers and artificial intelligence to refine patient selection—are beginning to address these limitations. This review summarises the current evidence and emerging advancements to highlight how SABR may evolve as part of an integrated approach to oligometastatic CRC. Full article

Background: Primary cicatricial alopecias (PCA) are inflammatory disorders that cause permanent hair loss through follicular destruction and fibrosis. Hair transplantation (HT) may restore coverage in stable or end-stage PCA cases. This review assesses the efficacy of HT in PCA including optimal timing, graft survival rates, and the risk of disease reactivation. Material & Methods: A PubMed literature search identified 33 studies of HT in lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), discoid lupus erythematosus, central centrifugal cicatricial alopecia, pseudopelade of Brocq, morphea en coup de sabre, and folliculitis decalvans from the 1960s to present. Reviews were excluded. Results: Among 147 PCA patients, 87.8% had positive HT outcomes. LPP showed high graft survival (70–90%). In contrast, eyebrow FFA (75%), folliculitis decalvans (25%), and scalp FFA (8.6%) had the highest failure rates. Follicular unit extraction was used slightly more than follicular unit transplantation. Notably, 46 patients developed PCA post-HT for presumed androgenetic alopecia. Discussion: HT in PCA can succeed with careful patient selection and stable disease (ideally ≥12–24 months). Graft survival varies by subtype. LPP has consistently reported successful outcomes post-transplantation, whereas folliculitis decalvans and FFA had the poorest outcomes. Adjuncts like immunosuppressants, PRP, and minoxidil may enhance results. Conclusions: Hair transplantation is viable in quiescent PCA, but outcomes are subtype-dependent. Many surgeons already perform these surgeries, but the published literature is lacking, and more research is needed to establish standardized timing, improve long-term graft survival, and clarify the risk of post-HT PCA onset. Full article

The Signal Amplification By Reversible Exchange (SABRE) technique provides enhancement of Nuclear Magnetic Resonance (NMR) signals up to several orders of magnitude using chemical exchange of a substrate and parahydrogen on an iridium complex. Therefore, the availability of such a catalytic complex to a broader community is an absolutely vital step for dissemination of the groundbreaking SABRE methodology. The most common SABRE catalyst, which is activated in situ, is based on Ir-IMes system (IMes = 1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). Earlier approaches for the synthesis of this catalyst often relied on specialized equipment and were limited to a comparatively small scale. This, in turn, increased the barrier of entry for new scientists to the area of SABRE hyperpolarization. Here, we present a robust, inexpensive, and easy to reproduce synthetic procedure for the preparation of this SABRE catalyst, which does not require specialized inert atmosphere equipment like a glove box or Schlenk line. The synthesis was validated on the scale of several grams vs. tens of milligrams scale in the reported approaches. The resulting SABRE catalyst, [Ir(IMes)(COD)Cl], was activated in situ and further evaluated in hyperpolarization experiments resulting in signal enhancements comparable to (or higher than) those for the catalyst prepared using Schlenk line equipment. Full article

Hyperpolarization (HP) techniques, such as Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and dissolution Dynamic Nuclear Polarization (d-DNP), significantly enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy for chemical analysis and metabolic imaging. However, the high cost of equipment, ranging from tens of thousands to millions of dollars, limits accessibility of hyperpolarization for the broad scientific community. In this work, we aim to mitigate some of the challenges by developing a cost-effective solution for parahydrogen (pH₂)-based PHIP and SABRE HP methods. A custom coil-winding machine was designed to fabricate solenoid magnet coils, which were then evaluated for their magnetic field profiles, demonstrating a high degree of magnetic field homogeneity. A model ¹H SABRE experiment successfully implemented the constructed solenoid, achieving efficient hyperpolarization. Additionally, the solenoid magnet can be utilized for in situ detection of hyperpolarization when integrated with a low-field NMR spectrometer, reducing the total setup cost to a few thousand dollars. These findings suggest that our approach makes HP technology more affordable and accessible, potentially broadening its applications in chemical and biomedical research, as well as educational settings involving undergraduate student researchers. This work provides a practical pathway to lower the financial barriers associated with pH₂ HP setups. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) is a therapeutic option for hepatocellular carcinoma (HCC). This study reviewed outcomes and toxicities of SBRT for HCC using a gimbal-mounted linear accelerator and real-time monitoring system. Methods: A single-institution, retrospective review of SBRT for HCC using DTT between January 2018 and December 2020 was undertaken. Endpoints included local control (LC) and overall survival (OS). Results: A total of 74 patients with 82 tumors treated were identified. Median follow-up was 40.8 months. LC at 1, 3, and 5 years was 89.6%, 71.0%, and 59.9%, respectively. Median time to local failure was not reached. Median OS was 41.3 months (95% CI 30.7–51.8 months). OS at 1, 3, and 5 years was 89.2%, 60.6%, and 33.9%, respectively. On UVA, GTV ≥ 30 cm³ (p = 0.038), and PTV ≥ 150 cm³ (p = 0.010) were associated with an absolute drop in platelet count by ≥50,000/mm³ within six weeks of SBRT, while prior focal liver treatment (p = 0.097) showed a trend toward significance. Underlying viral cirrhosis (p = 0.033), A6 or higher pre-SBRT Child–Pugh score (p = 0.010), and pre-SBRT platelet count <100,000/mm³ (p = 0.017) were significant for a rise in Child–Pugh score of 2 points or more, and the volume of liver-GTV <1000 cm³ (p = 0.093) approached significance. Conclusions: SBRT using DTT is an effective therapeutic option for selected patients with HCC, providing acceptable local control and toxicity. Full article

Purpose: This systematic review aims to analyze the literature on the application of AI in predicting patient outcomes and treatment-related toxicity in those undergoing SBRT or SRS across heterogeneous tumor sites. Materials and methods: Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, EMBASE and Scopus were systematically searched for English-language human studies evaluating AI for outcome and toxicity prediction in patients undergoing SBRT or SRS for solid tumors. Search terms included (“Stereotactic Body Radiotherapy” OR “SBRT” OR “Stereotactic Radiosurgery” OR “SRS” OR “Stereotactic Ablative Radiotherapy” OR “SABR”) AND (“Artificial Intelligence” OR “AI” OR “Machine Learning” OR “Deep Learning” OR “Radiomics”) AND (“Response Prediction” OR “Response to Treatment” OR “Outcome Prediction”) AND (“Toxicity” OR “Side Effects” OR “Treatment Toxicities” OR “Adverse Events”). Results: The search yielded 29 eligible retrospective studies, published between 2020 and 2025. Eight studies addressed early-stage primary lung cancer, highlighting the potential of AI-based models in predicting radiation-induced pneumonitis, fibrosis and local control. Five studies investigated AI models for predicting hepatobiliary toxicity following SBRT for liver tumors. Sixteen studies involved SRS-treated patients with brain metastases or benign intracranial neoplasms (e.g., arteriovenous malformations, vestibular schwannomas, meningiomas), exploring AI algorithms for predicting treatment response and radiation-induced changes. In the results, AI might have been exploited to both reaffirm already known clinical predictors and to identify novel imaging, dosimetric or biological biomarkers. Examples include predicting radiation pneumonitis in lung cancer, residual liver function in hepatic tumors and local recurrence in brain metastases, thus supporting tailored treatment decisions. Conclusions: Combining AI with SBRT could greatly enhance personalized cancer care by predicting patient-specific outcomes and toxicity. AI models analyze complex datasets, including imaging and clinical data, to identify patterns that traditional methods may miss, thus enabling more accurate risk stratification and reducing variability in treatment planning. With further research and clinical validation, this integration could make radiotherapy safer, more effective and contribute to advancement in precision oncology. Full article

Purpose or Objective: To evaluate the feasibility and clinical utility of integrating sequential PSMA-PET imaging into an offline–online adaptive workflow for response-based dominant intraprostatic lesion (DIL)-boosting high-risk prostate cancer treated with stereotactic ablative radiotherapy (SABR). Materials and Methods: As part of a prospective trial, patients were treated on MR- or CBCT-guided adaptive radiotherapy (ART) systems with prostate/pelvic node 5-fraction SABR (36.25 Gy/25 Gy) with DIL boost (50 Gy). Whereas traditional DIL boost volumes delineate full pre-therapy imaging-defined disease (GTVinitial), this study serially refined DIL boost volumes based on treatment response defined by PSMA-PET scans after neoadjuvant androgen deprivation therapy (nADT, GTVmb1) and fraction 3 SABR (GTVmb2). DIL delineation employed PET-PSMA fusion to CT/MR simulation and was guided by a rule-based %SUVmax threshold approach. Comparisons of GTV volumes and OAR dosimetry were performed between plans using GTVinitial versus GTVmb1/GTVmb2 for DIL boost, for each of the initial cohorts of five patients from the initially treated cohorts. Results: Five patients treated on MR-Linac (n = 3) or CBCT-based ART (n = 2) were analyzed. Three patients exhibited complete imaging response after nADT, omitting GTVmb boosts. Offline GTVmb refinements based on PSMA-PET were seamlessly integrated into ART workflows without introducing additional treatment time. DIL GTV volumes significantly decreased (p = 0.03) from an initial mean of 11.4 cc (GTVinitial) to 4.1 cc (GTVmb1) and 3.0 cc (GTVmb2). Dosimetric analysis showed meaningful reductions in OAR doses: rectal wall D0.035 cc decreased by up to 12 Gy, while bladder wall D0.035 cc and V18.3 Gy reduced from 52.3 Gy and 52.3 cc (Plan_initial) to 42.9 Gy and 24.9 cc (Plan_mb2), respectively. Urethra doses remained stable, with minor reductions. Sigmoid and femoral head doses remained within acceptable limits. Online adaptation efficiently addressed daily anatomical variations, enabling simulation-free plan re-optimization. Conclusion: PSMA-PET-guided adaptive microboosting for HRPCa SABR is feasible and effective. Standard MR-Linac and CBCT systems offer practical alternatives to BgRT platforms, enabling biology-driven dose personalization and potentially reducing toxicity. Full article