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The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA). The trajectory of scRNA data of the MuSCs under four different conditions undergoing differentiation is analyzed as well as the active molecular pathways and transcription factors driving those differentiation fates. Data revealed the presence of a branching point within the trajectory leading to the emergence of an age-related fibroblastic population characterized by activation of the TNF-related apoptosis-inducing ligand (TRAIL) pathway, which is significantly activated in aged cells cultured on stiff substrates. Next, using the collagen cross-linking inhibitor β-aminopropionitrile (BAPN) in vivo, the study elucidates stiffness changes on TRAIL downstream apoptotic targets (caspase 8 and caspase 3) using immunostaining. TRAIL activity is significantly inhibited by BAPN in aged animals, indicating a complex mechanism of age-related declines in muscle function through inflammatory and apoptotic mediators., (© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.)

The oxidation free energies of DNA nucleobases in aqueous solution are still matter of extensive discussion because of the contrasting results reported so far. With the aim of settling a longstanding debate about the oxidation potentials of DNA constituents, herein we report the results of state-of-the-art DFT-based molecular dynamics simulations, in which the whole solvent environment is modeled at the atomistic level, by using DFT supercell calculations, with periodic boundary conditions. Calculated vertical ionization energies are very close to those observed by photoelectron spectroscopy both in the gas phase and in solution. One-electron oxidation free energies in aqueous solution agree well with the results of differential pulse voltammetry measurements and with those inferred by photoelectron spectroscopy with the aid of theoretical computations to estimate vibrational relaxation.

Objectives: Can the type of implant rehabilitation influence peri-implant bone loss in case of full-arch mandibular prosthesis? The purpose of the study was to assess, using orthopantomograms (OPGs), the bone loss around implants in different types of implant-supported prosthetic rehabilitations and identify potential risk factors, associated with the number and location of implants, that may have an association with bone defects., Methods: A radiographic study was conducted on 22,317 OPGs from 2010 to 2024. All OPGs with implant-supported prosthetic mandibular rehabilitations were included in the study., Results: A total of 155 OPGs were evaluated, with peri-implant bone loss identified in 64 (41.3%). Distal implants (furthest from the center) across various positioning patterns were most susceptible to bone loss, with positions 3.6 and 4.6 demonstrating the most frequent occurrence (25 and 26 cases, respectively). The χ 2 test revealed significant associations between both the implant positioning pattern ( p < 0.001) and number of implants ( p < 0.001) with peri-implant bone loss. Also, by updating the sample of OPGs, increased susceptibility to bone resorption was found for implants placed distal to the mental foramen compared to mesial ones in full-arch-implant-supported fixed prostheses., Conclusions: Prospective clinical studies will therefore be useful in investigating this finding further.

Background and Aims: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction-associated steatotic liver disease (MASLD). B-cell activity can be assessed by serum-free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non-invasive biomarkers for the stratification of MASLD., Methods: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay., Results: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m 2 . A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction-associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction-associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p < .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p < .01). At multivariable analysis, sFLCs were associated with cACLD (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p < .05) independently from γ-globulins and other known dysmetabolic risk factors., Conclusion: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle., Methods: We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Na v ) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Na v activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Na v in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo., Results: We demonstrated that Na v is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Na v made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Na v substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Na v positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Na v ., Conclusions: This insight positions Na v as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment., (© 2024. The Author(s).)

Introduction: One of the leading causes of morbidity and mortality worldwide is out-of-hospital cardiac arrest. Early defibrillation and high-quality cardiopulmonary resuscitation (CPR) have improved survival. The main goal of CPR is to achieve return of spontaneous circulation (ROSC), which is assessed by looking for a pulse, analyzing the heart rhythm, and assessing carbon dioxide levels. The use of cartography during CPR to confirm the correct position of the endotracheal tube during intubation or to assess the effectiveness of chest compressions has increased significantly in the last years. The aim of this review was to identify correlations between end-tidal carbon dioxide levels and the likelihood of ROSC in patients with out-of-hospital cardiac arrest., Methods: A literature search was performed in MEDLINE (via Pubmed), Scopus, Web of Science, and Google Scholar databases from September to November 2022. Keywords combined with the Boolean operators (AND/OR) were used in both free text and Medical Subject Headings. Studies on adult patients published between 01/01/2016 and 28/09/2022 were searched, with no geographical restrictions., Results: At the end of the selection process, 14 studies were included that investigated capnography in out-of-hospital CPR and reported at least 1 outcome between end-tidal carbon dioxide and ROSC or survival., Discussion: Capnography is an advantageous tool due to its noninvasive characteristics, ease of use, and immediacy of data. In out-of-hospital cardiac arrest, the use of the end-tidal carbon dioxide appears to be an appropriate complementary tool to support clinical decisions, such as correct positioning of the endotracheal tube, optimizing ventilation in CPR, and as a predictor of ROSC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Intraarticular knee injuries and subsequent posttraumatic arthritis (PTOA) are common in athletes. Unfortunately, PTOA may significantly affect performance and overall function, but this condition remains difficult to characterize. In this review, we provide an overview of imaging modalities used to evaluate PTOA among athletes and physically active individuals following knee injury, with the goal to discuss the strengths and limitations of their application in this population. A literature search was performed to identify clinical studies focusing of knee injuries in athletes and athletic persons, specifically using imaging for diagnosis or monitoring disease progression. A total of 81 articles were identified, and 23 were included for review. Studies on plain radiographs (n = 8) and magnetic resonance imaging (MRI) assessed arthritic burden (n = 13), with MRI able to depict the earliest cartilage changes. Few studies (n = 2) leveraged ultrasound. Challenges persist, particularly regarding standardization and reliability across different radiographic grading systems. Additionally, further research is needed to establish the clinical significance of techniques to assess cartilage composition on MRI, including ultrashort echo-time enhanced T2*, T1rho and T2 imaging. Addressing these challenges through standardized protocols and intensified research efforts will enhance the diagnostic utility of imaging modalities in musculoskeletal medicine and enable high-quality prospective studies., (© 2024 The Author(s). PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Skeletal muscle wasting is the hallmark pathophysiological adaptation to unloading or disuse that demonstrates the dependency on frequent mechanical stimulation (e.g. muscle activation and subsequent loading) for homeostasis of normally load-bearing muscles. In the absence of mitigation strategies, no mammalian organism is resistant to muscle atrophy driven by unloading. Given the profound impact of unloading-induced muscle wasting on physical capacity, metabolic health and immune function; mitigation strategies during unloading and/or augmentation approaches during recovery have broad healthcare implications in settings of bed-bound hospitalization, cast immobilization and spaceflight. This topical review aims to: (1) provide a succinct, state-of-the-field summary of seminal and recent findings regarding the mechanisms of unloading-induced skeletal muscle wasting; (2) discuss unsuccessful vs. promising mitigation and recovery augmentation strategies; and (3) identify knowledge gaps ripe for future research. We focus on the rapid muscle atrophy driven by relatively short-term mechanical unloading/disuse, which is in many ways mechanistically distinct from both hypermetabolic muscle wasting and denervation-induced muscle atrophy. By restricting this discussion to mechanical unloading during which all components of the nervous system remain intact (e.g. without denervation models), mechanical loading requiring motor and sensory neural circuits in muscle remain viable targets for both mitigation and recovery augmentation. We emphasize findings in humans with comparative discussions of studies in rodents which enable elaboration of key mechanisms. We also discuss what is currently known about the effects of age and sex as biological factors, and both are highlighted as knowledge gaps and novel future directions due to limited research., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

The novel 2D quasi-hexagonal phase of covalently bonded fullerene molecules (qHP C 60 ), the so-called graphullerene, has displayed far superior electron mobilities, if compared to the parent van der Waals three-dimensional crystal (vdW C 60 ). Herein, we present a comparative study of the electronic properties of vdW and qHP C 60 using state-of-the-art electronic-structure calculations and a full quantum-mechanical treatment of electron transfer. We show that both materials entail polaronic localization of electrons with similar binding energies (≈0.1 eV) and, therefore, they share the same charge transport via polaron hopping. In fact, we quantitatively reproduce the sizable increment of the electron mobility measured for qHP C 60 and identify its origin in the increased electronic coupling between C 60 units.

The COVID-19 pandemic has put a lot of pressure on all the world's health systems and public health leaders who have often found themselves unprepared to handle an emergency of this magnitude. This study aims to bring together published evidence on the qualities required to leaders to deal with a public health issue like the COVID-19 pandemic. This scoping literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A search of relevant articles was performed in the PubMed, Scopus and Web of Science databases. A total of 2499 records were screened, and 45 articles were included, from which 93 characteristics of effective leadership were extrapolated and grouped into 6 clusters. The qualities most frequently reported in the articles were human traits and emotional intelligence (46.7%) and communication skills such as transparency and reliability (48.9%). Responsiveness and preparedness (40%), management skills (33.3%) and team working (35.6%) are considered by a significant percentage of the articles as necessary for the construction of rapid and effective measures in response to the emergency. A considerable proportion of articles also highlighted the need for leaders capable of making evidence-based decisions and driving innovation (31.1%). Although identifying leaders who possess all the skills described in this study appears complex, determining the key characteristics of effective public health leadership in a crisis, such as the COVID-19 pandemic, is useful not only in selecting future leaders but also in implementing training and education programmes for the public health workforce., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Toward an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EV). EVs support physiological adaptations to exercise by transporting their cargo (e.g., microRNA (miRNA)) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways., Methods: Ten participants (5 men; age, 26.9 ± 5.5 yr; height, 173.4 ± 10.5 cm; body mass, 74.0 ± 11.1 kg; body fat, 25.7% ± 11.6%) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways., Results: Overall, 34 miRNAs were altered by AHRET ( P < 0.05), targeting 4895 mRNAs, with enrichment of 175 canonical pathways ( P < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/β-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and 8 to inflammation signaling (TGF-β, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10)., Conclusions: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training., (Copyright © 2024 by the American College of Sports Medicine.)

Understanding the microbiological profiles of peri-implant conditions is crucial for developing effective preventive and therapeutic strategies. This narrative review analyzes the microbial profiles associated with healthy peri-implant sites, peri-implant mucositis, and peri-implantitis, along with related microbiological sampling and analyses. Healthy peri-implant sites are predominantly colonized by Streptococcus , Rothia , Neisseria , and Corynebacterium species, in addition to Gram-positive cocci and facultatively anaerobic rods, forming a stable community that prevents pathogenic colonization and maintains microbial balance. In contrast, peri-implant mucositis shows increased microbial diversity, including both health-associated and pathogenic bacteria such as red and orange complex bacteria, contributing to early tissue inflammation. Peri-implantitis is characterized by even greater microbial diversity and a complex pathogenic biofilm. Predominant pathogens include Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , Fusobacterium nucleatum , and unique species like Filifactor alocis and Fretibacterium fastidiosum . Additionally, less common species such as Staphylococcus and Enterobacteriaceae , contributing to disease progression through biofilm formation and increased inflammatory response, along with EBV and human cytomegalovirus with a still not defined role, and Candida albicans contribute to disease progression through biofilm formation, immune modulation, and synergistic inter-kingdom interactions. Future research should standardize diagnostic criteria, employ advanced molecular techniques, integrate microbial data with clinical factors, and highlight inter-kingdom interactions.

Concurrent resistance and endurance exercise training (CET) has well-studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET. 18 young healthy participants underwent 12-weeks of CET. Prior to and following CET, subjects performed an acute bout of heavy resistance exercise (AHRET) consisting of 6 × 10 back squats at 75% 1RM. At rest and following AHRET, EVs were isolated from plasma and characteristics and miRNA contents were analyzed. AHRET elevated EV abundance in trained men only (+51%) and AHRET-induced changes were observed for muscle-derived EVs and microvesicles. There were considerable sex-specific effects of CET on EV miRNAs, highlighted by larger variation following the 12-week program in men compared to women at rest. Pathway analysis based on differentially expressed EV miRNAs predicted that AHRET and 12 weeks of CET in men positively regulates hypertrophy and growth pathways more so than in women. This report highlights sex-based differences in the EV response to resistance and concurrent exercise training and suggests that EVs may be important adaptive signaling factors altered by exercise training., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Falls are a major worldwide health problem in older people. Several physical rehabilitation programs with home-based technologies, such as the online DigiRehab platform, have been successfully delivered. The PRECISE project combines personalized training delivered through the application with an artificial intelligence-based predictive model (AI-DSS platform) for fall risk assessment. This new system, called DigiRehab, will enable early identification of significant risk factors for falling and propose an individualized physical training plan to attend to these critical areas., Methods: The study will test the usability of the DigiRehab platform in generating personalized physical rehabilitation programs at home. Fifty older adults participants will be involved, 20 of them testing the beta version prototype, and 30 participants testing the updated version afterwards. The inclusion criteria will be age ≥65, independent ambulation, fall risk (Tinetti test), Mini Mental State Examination ≥24, home residents, familiarity with web applications, ability and willingness to sign informed consent. Exclusion criteria will be unstable clinical condition, severe visual and/or hearing impairment, severe impairment in Activities of Daily Living and absence of primary caregiver., Discussion: The first part of the screening consists in a structured questionnaire of 10 questions regarding the user's limitations, including the risk of falling, while the second consists in 10 physical tests to assess the functional status. Based on the results, the program will help define the user's individual profile upon which the DSS platform will rate the risk of falling and design the personalized exercise program to be carried out at home. All measures from the initial screening will be repeated and the results will be used to optimize the predictive algorithms in order to prepare the tool in its final version. For the usability assessment, the System Usability Scale will be administered. The follow-up will take place after the 12-week intervention at home. A semi-structured satisfaction questionnaire will also be administered to verify whether the project will meet the needs of older adults and their family caregiver., Conclusion: We expect that personalized training prescribed by DigiRehab platform could help to reduce the need for care in older adults subjects and the care burden. Clinical trial registration : [https://clinicaltrials.gov/], identifier [NCT05846776]., Competing Interests: MH and NH were employed by DigiRehab A/S. AR is employed by DigiRehab Benelux, B.V. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 D’Ambrosio, Harbo, Contiero, Bonfigli, Cicconi, Heuer, Roos, Fischer Pedersen, Fabbietti and Gagliardi.)

We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase ( pol ) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02&#95;AG (2.5 per cent) and CRF02&#95;AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02&#95;AG/B (24.3 per cent), B/CRF02&#95;AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02&#95;AG-like and CRF02&#95;AG/B, an eighteen-member CRF02&#95;AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02&#95;AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02&#95;AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02&#95;AG, and CRF02&#95;AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02&#95;AG; B and CRF02&#95;AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread., Competing Interests: None declared., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine-mediated pathological communication between the synovium and cartilage. Cartilage-specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network-based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M (OSM), as a driver of the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of OSM recapitulated an "inflammatory" phenotype of knee osteoarthritis and highlighted high-value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation-driven osteoarthritis phenotype., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented., Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy., Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027)., Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Longo, Della Corte, Russo, Spinnato, Ambrosio, Ronga, Marchese, Del Giudice, Sergi, Casaluce, Gilli, Montrone, Gristina, Sforza, Reale, Di Liello, Servetto, Lipari, Longhitano, Vizzini, Manzo, Cristofano, Paolelli, Nardone, De Summa, Perrone, Bisceglia, Derosa, Nardone, Viscardi, Galetta and Vitiello.)