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Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.

The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (> 10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.

The study of nuclear fragmentation plays a central role in many important applications: from the study of Particle Therapy (PT) up to radiation protection for space (RPS) missions and the design of shielding for nuclear reactors. The FragmentatiOn Of Target (FOOT) collaboration aims to study the nuclear reactions that describe the interactions with matter of different light ions (like H1, He4, C12, O16) of interest for such applications, performing double differential fragmentation cross section measurements in the energy range of interest for PT and RPS. In this manuscript, we present the analysis of the data collected in the interactions of an oxygen ion beam of 400 MeV/u with a graphite target using a partial FOOT setup, at the GSI Helmholtz Center for Heavy Ion Research facility in Darmstadt. During the data taking the magnets, the silicon trackers and the calorimeter foreseen in the final FOOT setup were not yet available, and hence precise measurements of the fragments kinetic energy, momentum and mass were not possible. However, using the FOOT scintillator detectors for the time of flight (TOF) and energy loss (ΔE) measurements together with a drift chamber, used as beam monitor, it was possible to measure the elemental fragmentation cross sections. The reduced detector set-up and the limited available statistics allowed anyway to obtain relevant results, providing statistically significant measurements of cross sections eagerly needed for PT and RPS applications. Whenever possible the obtained results have been compared with existing measurements helping in discriminating between conflicting results in the literature and demonstrating at the same time the proper functioning of the FOOT ΔE-TOF system. Finally, the obtained fragmentation cross sections are compared to the Monte Carlo predictions obtained with the FLUKA software.

Extension agents serve important roles in communities but often begin their careers lacking skills crucial for success. We aimed to understand the professional development needs of Florida early-career Extension agents beyond the first year as perceived by eight county Extension directors (CEDs). Through semistructured interviews, CEDs indicated that building community relationships, managing volunteers, communicating effectively, and other Extension-related skills are areas for which early-career Extension agents need professional development. These results suggest a need for additional development opportunities beyond the first year, with a professional development model that is continually adapted as an Extension professional's skill set changes. Our findings have implications for those involved in Extension practice and research beyond Florida.

Breast carcinoma with tubulopapillary features is a newly described entity associated with poor prognosis with only 14 tumors reported in the literature. We report 2 additional tumors and identify novel immunohistochemical and molecular features of the tumor. The first tumor was from a 72-year-old woman with nonmetastatic breast carcinoma and the second was from a 32-year-old woman with metastatic breast carcinoma who received neoadjuvant therapy. Both tumors had high-grade nuclear features with a distinctive morphology characterized by infiltrating open glands with intratubular papillary and micropapillary projections in >90% of the invasive carcinoma. In addition to the usual predictors of aggressive behavior, both tumors showed a high expression of p16 and SOX10, which has not been previously described. Targeted tumor sequencing revealed pathogenic variants of TP53 in both tumors, in agreement with previous reports. Prior studies have shown a correlation between p16 and SOX10 expression with high-grade features and worse prognosis; typically seen in triple-negative carcinomas as demonstrated in both of our tumors. However, not all reported tumors of breast carcinoma with tubulopapillary features have demonstrated a triple-negative profile as there are a few reports of tumors with estrogen receptor and/or human epidermal growth factor 2 expression. Due to their distinct morphologic and molecular characteristics, breast carcinoma with tubulopapillary features may represent a new breast cancer histologic subtype. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by irreversible scarring of lung tissue, leading to death. Despite recent advancements in understanding its pathophysiology, IPF remains elusive, and therapeutic options are limited and non-curative. This review aims to synthesize the latest research developments, focusing on the molecular mechanisms driving the disease and on the related emerging treatments. Unfortunately, several phase 2 studies showing promising preliminary results did not meet the primary endpoints in the subsequent phase 3, underlying the complexity of the disease and the need for new integrated endpoints. IPF remains a challenging condition with a complex interplay of genetic, epigenetic, and pathophysiological factors. Ongoing research into the molecular keystones of IPF is critical for the development of targeted therapies that could potentially stop the progression of the disease. Future directions include personalized medicine approaches, artificial intelligence integration, growth in genetic insights, and novel drug targets. [ABSTRACT FROM AUTHOR]

Understanding the molecular basis of leukaemia predisposition is essential for intervention. The authors here investigate germline genetic leukaemia predisposition by studying Shwachman-Diamond syndrome and report compensatory inactivating mutations in EIF6 and transforming biallelic TP53 alterations.

Successful CRISPR/Cas9-based gene editing in skeletal muscle is dependent on efficient propagation of Cas9 to all myonuclei in the myofiber. However, nuclear-targeted gene therapy cargos are strongly restricted to their myonuclear domain of origin. By screening nuclear localization signals and nuclear export signals, we identify "Myospreader," a combination of short peptide sequences that promotes myonuclear propagation. Appending Myospreader to Cas9 enhances protein stability and myonuclear propagation in myoblasts and myofibers. AAV-delivered Myospreader dCas9 better inhibits transcription of toxic RNA in a myotonic dystrophy mouse model. Furthermore, Myospreader Cas9 achieves higher rates of gene editing in CRISPR reporter and Duchenne muscular dystrophy mouse models. Myospreader reveals design principles relevant to all nuclear-targeted gene therapies and highlights the importance of the spatial dimension in therapeutic development. [ABSTRACT FROM AUTHOR]

The main aim of this work is to optimize a Quantum Drift Diffusion model (QDD) (V. Romano, M. Torrisi, and R. Tracinà, "Approximate solutions to the quantum drift-diffusion model of semiconductors," J. Math. Phys., vol. 48, p. 023501, 2007; A. El Ayyadi and A. Jüngel, "Semiconductor simulations using a coupled quantum drift-diffusion schrödinger-Poisson model," SIAM J. Appl. Math., vol. 66, no. 2, pp. 554–572, 2005; L. Barletti and C. Cintolesi, "Derivation of isothermal quantum fluid equations with Fermi-Dirac and bose-einstein statistics," J. Stat. Phys., vol. 148, pp. 353–386, 2012) by comparing it with the Boltzmann-Wigner Transport Equation (BWTE) (O. Muscato, "Wigner ensemble Monte Carlo simulation without splitting error of a GaAs resonant tunneling diode," J. Comput. Electron., vol. 20, pp. 2062–2069, 2021) solved using a signed Monte Carlo method (M. Nedjalkov, H. Kosina, S. Selberherr, C. Ringhofer, and D. K. Ferry, "Unified particle approach to Wigner-Boltzmann transport in small semiconductor devices," Phys. Rev. B, vol. 70, pp. 115–319, 2004). A situation of high non equilibrium regime is investigated: electron transport in a Resonant Tunneling Diode (RTD) made of GaAs with two potential barriers in GaAlAs. The range of the suitable voltage bias applied to the RTD is analyzed. We find an acceptable agreement between QDD model and BWTE when the applied bias is low or moderate with a threshold of about 0.225 V over a length of 150 nm; it is found out that the use of a field dependent mobility is crucial for getting a good description of the negative differential conductivity in such a range. At higher bias voltages, we expect that QDD model loses accuracy. [ABSTRACT FROM AUTHOR]

Objective(s): This randomized controlled study evaluated the effectiveness of a Telehealth Aural Rehabilitation (TeleAR) training protocol to improve outcomes for adult cochlear implant (CI) users. Methods: This was a multisite clinical study with participants randomized to either an AR treatment or active control group. The AR protocol consisted of auditory training (words, sentences, and speech tracking), informational counseling, and communication strategies. The control group participants engaged in cognitive stimulation activities (crosswords, sudoku, etc.). Each group completed 6 weekly 90‐min individual treatment sessions delivered remotely. Twenty postlingually deafened adult CI users participated. Assessments were completed pretreatment and 1 week and 2 months posttreatment. Results: Repeated‐measures ANOVA and planned contrasts were used to compare group performance on AzBio Sentences, Hearing Handicap Inventory (HHI), Client Oriented Scale of Improvement (COSI), and Glasgow Benefit Inventory (GBI). The two groups were statistically equivalent on all outcome measures at pre‐assessment. There was a statistically significant main effect of time for all measures. Improvement over time was observed for participants in both groups, with greater improvement seen for the AR than the CT group on all outcome measures. The AR group showed medium to large effect sizes on all measures over time, suggesting clinically significant outcomes. Conclusion: This randomized controlled study provides evidence of improved speech recognition and psychosocial outcomes following 6 weeks of TeleAR intervention. For adult post‐lingually deafened CI users, including those >3 months post‐activation, AR treatment can leverage neuroplasticity to maximize outcomes. Level of Evidence: 2 Laryngoscope, 134:1861–1867, 2024 [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; tothis aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model. Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data. Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained. Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths. [ABSTRACT FROM AUTHOR]

In this study, it was found that myositis-specific and myositis-associated antibodies (MSAs and MAAs) improved the recognition of idiopathic inflammatory myopathies (IIMs) in interstitial lung disease (ILD) patients. The objective of this study is to propose a clinical method to evaluate myalgia in respiratory settings as a possible tool for the recognition of MSA/MAA positivity in ILD patients. We prospectively enrolled 167 ILD patients with suspected myositis, of which 63 had myalgia evoked at specific points (M+ILD+). We also enrolled in a 174 patients with only myalgia (M+ILD-) in a rheumatological setting. The patients were assessed jointly by rheumatologists and pulmonologists and were tested for autoantibodies. M+ILD+ patients were positive for at least one MAA/MSA in 68.3% of cases, as were M-ILD+ patients in 48.1% of cases and M+ILD- patients in 17.2% of cases (p = 0.01 and p = 0.02). Myalgia was significantly associated with positivity for MSA/MAAs in ILD patients (p = 0.01, X2: 6.47). In conclusion, myalgia in ILD patients with suspected myositis is associated with MSA/MAA positivity, and could support a diagnosis of IIM. A significant proportion of M+ILD- patients also had MSA/MAA positivity, a phenomenon warranting further study to evaluate its clinical meaning.

Abstract Silicon nanowires (SiNWs) are quasi-one-dimensional structures in which electrons are spatially confined in two directions and they are free to move in the orthogonal direction. The subband decomposition and the electrostatic force field are obtained by solving the Schrödinger–Poisson coupled system. The electron transport along the free direction can be tackled using a hydrodynamic model, formulated by taking the moments of the multisubband Boltzmann equation. We shall introduce an extended hydrodynamic model where closure relations for the fluxes and production terms have been obtained by means of the Maximum Entropy Principle of Extended Thermodynamics, and in which the main scattering mechanisms such as those with phonons and surface roughness have been considered. By using this model, the low-field mobility of a Gate-All-Around SiNW transistor has been evaluated.

Charge transport phenomena can been tackled in silicon quantum wires using a subband hydrodynamic model. This has been formulated by closing the moment system derived from the Schrodinger-Poisson-Boltzmann equations on the basis of the Maximum Entropy Principle. The model can be used to deal with thermoelectric effects in Local equilibrium and off-equilibrium regimes.

Endocrine-disrupting chemicals (EDC) are widespread in the built and natural environments. Heightened public awareness of their potential danger has led to concern about whether EDC and their metabolites have significant negative biological effects. Studies have shown that EDC like DDT and other organochlorine pesticides, such as methoxychlor (MXC), have adverse effects on immune cells, but no studies have addressed the impact of HPTE, the primary metabolite of MXC. To elucidate the presence and significance of HPTE adverse effects, this study explored the impact of HPTE on a critical window and component of immune system development, embryonic T-cell development. Lesions at this phase of development can lead to lifelong immune dysfunction and increased incidence of immune disease, such as autoimmunity. Embry-onic thymocytes (GD 16-18) from C57BL/6 mice were subjected to an in vitro differentiation culture that mimicked early steps in thymocyte development in the presence of 0.005, 0.05, 0.5, 5, or 50 μM HPTE, or a model endocrine disruptor, DES. The results indicated that compared to the vehicle control, HPTE- and DES-induced death of thymocytes. Annexin-V staining and Caspase 8, markers of programed cell death, revealed that the loss of cells was due at least in part to induction of apoptosis. Moreover, HPTE-induced cell death not only resulted in selective loss of double positive thymocytes, but also loss of developing CD4 intermediate cells (post-double positive partially differentiated thymocyte population). Phenotypic analysis of thymocyte maturation (T-cell receptor, TCR) and TCR ligation (CD5) surface markers revealed that surviving embryonic thymocytes expressed low levels of both. Taken together these data demonstrate that immature embryonic thymocytes are sensitive to HPTE exposure and that HPTE exposure targets thymocyte populations undergoing critical differentiation steps. These findings suggest HPTE may play a pivotal role in MXC exposure-induced immune dysfunction.

Abstract Background By 2020, the World Health Organization predicts that two-thirds of all diseases worldwide will be the result of lifestyle choices. Physicians often do not counsel patients about healthy behaviors, and lack of training has been identified as one of the barriers. Between 2010 and 2014, Hebrew University developed and implemented a 58-h Lifestyle Medicine curriculum spanning five of the 6 years of medical school. Content includes nutrition, exercise, smoking cessation, and behavior change, as well as health coaching practice with friends/relatives (preclinical years) and patients (clinical years). This report describes this development and diffusion process, and it also presents findings related to the level of acceptance of this student-initiated Lifestyle Medicine (LM) curriculum. Methods Students completed an online semi-structured questionnaire after the first coaching session (coaching questionnaire) and the last coaching session (follow-up questionnaire). Results Nine hundred and twenty-three students completed the coaching questionnaire (296 practices were with patients, 627 with friends /relatives); and 784 students completed the follow-up questionnaire (208 practices were with patients, 576 with friends /relatives). They reported overall that health coaching domains included smoking cessation (263 students), nutrition (79), and exercise (117); 464 students reported on combined topics. Students consistently described a high acceptance of the curriculum and their active role in coaching. Further, most students reported that they were eager to address their own health behaviors. Conclusions We described the development and acceptance of a student-initiated comprehensive LM curriculum. Students perceived LM as an important component of physicians’ professional role and were ready to explore it both as coaches and in their personal lives. Thus, medical school deans might consider developing similar initiatives in order to position medical schools as key players within a preventive strategy in healthcare policy.

We present a theoretical study of the low-field electron mobility in rectangular gated silicon nanowire transistors at 300 K based on a hydrodynamic model and the self-consistent solution of the Schrödinger and Poisson equations. The hydrodynamic model has been formulated by taking the moments of the multisubband Boltzmann equation, and closed on the basis of the Maximum Entropy Principle. It includes scattering of electrons with acoustic and non-polar optical phonons and surface roughness scattering.

The Internet of Things paradigm envisions the interoperation among objects, people, and their surrounding environment. In the last decade, the spread of IoT-based solutions has been supported in various domains and scenarios by academia, industry, and standards-setting organizations. The wide variety of applications and the need for a higher level of autonomy and interaction with the environment have recently led to the rise of the Internet of Robotic Things (IoRT), where smart objects become autonomous robotic systems. As mentioned in the recent literature, many of the proposed solutions in the IoT field have to tackle similar challenges regarding the management of resources, interoperation among objects, and interaction with users and the environment. Given that, the concept of the IoT pattern has recently been introduced. In software engineering, a pattern is defined as a general solution that can be applied to a class of common problems. It is a template suggesting a solution for the same problem occurring in different contexts. Similarly, an IoT pattern provides a guide to design an IoT solution with the difference that the software is not the only element involved. Starting from this idea, we propose the novel concept of the IoRT pattern. To the authors’ knowledge, this is the first attempt at pattern authoring in the Internet of Robotic Things context. We focus on pattern identification by abstracting examples also in the Ambient Assisted Living (AAL) scenario. A case study providing an implementation of the proposed patterns in the AAL context is also presented and discussed.

The problem of autonomous navigation of a ground vehicle in unstructured environments is both challenging and crucial for the deployment of this type of vehicle in real-world applications. Several well-established communities in robotics research deal with these scenarios such as search and rescue robotics, planetary exploration, and agricultural robotics. Perception plays a crucial role in this context, since it provides the necessary information to make the vehicle aware of its own status and its surrounding environment. We present a review on the recent contributions in the robotics literature adopting learning-based methods to solve the problem of environment perception and interpretation with the final aim of the autonomous context-aware navigation of ground vehicles in unstructured environments. To the best of our knowledge, this is the first work providing such a review in this context.