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Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

Introduction Microwave imaging presents several potential advantages including its non-ionising and harmless nature. This open, multicentric, interventional, prospective, non-randomised trial aims to validate MammoWave’s artificial intelligence (AI)-based classification algorithm, leveraging microwave imaging, to achieve a sensitivity exceeding 75% and a specificity exceeding 90% in breast screening.Methods and analysis 10 000 volunteers undergoing regular mammographic breast cancer screening will be recruited across 9 European centres and invited to participate in the clinical study, involving MammoWave testing on both breasts. MammoWave results will be checked against the reference standard, to be intended as the output of conventional breast examination path (with histological confirmation of cancer cases) with 2 years follow-up. Anonymised clinical and MammoWave’s results, including microwave images, associated features and a label provided by the AI-based classification algorithm, will be collected and stored in a dedicated electronic case report form. The prospective study will involve a comparative analysis between the output of the conventional breast examination path (control intervention) and the labels provided by MammoWave’s AI system (experimental intervention). These labels will categorise breasts into two groups: breast With Suspicious Finding, indicating the presence of a suspicious lesion or No Suspicious Finding, indicating the absence of a lesion or the presence of a low-suspicion lesion. This trial aims to provide evidence regarding the novel MammoWave’s AI system for detecting breast cancer in asymptomatic populations during screening.Ethics and dissemination This study was approved by the Research Ethics Committee of the Liguria Region (CET), Italy (CET-Liguria: 524/2023—DB id 13399), the Research Ethics Committee of Complejo Hospitalario de Toledo (CEIC), Spain (CEIC-1094), the National Ethics Committee for Clinical Research (CEIC), Portugal (CEIC-2311KC814), the Bioethical Committee of Pomeranian Medical University in Szczecin, Poland (KB-006/23/2024) and the Zurich Cantonal Ethics Commission, Switzerland (BASEC 2023-D0101). The findings of this study will be disseminated through academic and scientific conferences as well as peer-reviewed journals.Trial registration number NCT06291896.

This study describes a series of interventions that enhanced preservice teachers' experiences with online discussion boards. Data were analyzed using an experimental posttest design, and findings indicate that the interventions not only improved the quality and substance of students' responses, but also promoted an equitable distribution of course-based social capital.

This paper takes into account, starting from the provisions of the Twelve Tables, the personal execution on the body of the debtor insolvent, up to the definitive abolition of the debt imprisonment in the italian legal order.

Abstract COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge.

Este trabajo se propone contribuir a la historia de las Fuerzas Armadas (FF. AA.), a partir del caso de la Marina, en lo referido a la represión en clave antisubversiva durante la década del sesenta. Se propone explorar el impacto de la contrainsurgencia, es decir, la teoría y la práctica para la “guerra interna” en el pensamiento militar, especialmente en lo que concierne a la definión de un “enemigo interno”. Gracias al uso de fuentes primarias relativas a las FF. AA. y artículos de revistas militares, junto a otros materiales, primero, se analiza la recepción de las ideas contrainsurgentes francesas y estadounidenses, y su irradiación en las FF. AA. y los gobiernos civiles y militares. Luego, se estudia la forma en que algunos miembros de la Marina incorporan una preocupación en sentido anticomunista. Por último, se indaga sobre el “enemigo interno” desde el concepto de “guerra revolucionaria”.

Background: Severe cases of Coronavirus Disease 2019 (COVID-19) that require admission to the Intensive Care Unit (ICU) and mechanical ventilation assistance show a high mortality rate with currently few therapeutic options available. Severe COVID-19 is characterized by a systemic inflammatory condition, also called “cytokine storm”, which can lead to various multi-organ complications and ultimately death. Lidocaine, a safe local anesthetic that given intravenously is used to treat arrhythmias, has long been reported to have an anti-inflammatory and pro-homeostatic activity. Methods: We studied the capacity of lidocaine to modulate cytokine secretion of mouse and human myeloid cell lines activated by different cytokines or Toll Like Receptor (TLR) ligands (flagellin (FliC), Lipopolysaccharide (LPS), Polyinosinic:polycytidylic acid (Poly I:C) and N-Palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine x 3HCl (Pam3Cys-SKKKK)) or by Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection to epithelial cells. Reporter cell lines were used to study modulation of lidocaine of specific signaling pathways. Results: Lidocaine used in combination with dexamethasone, had an additive effect in the modulation of cellular inflammatory response triggered by Tumoral Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1β) as well as different TLR ligands. We also found that lidocaine in combination with dexamethasone modulates the Nuclear factor kappa B (NF-κB) pathway, inflammasome activation as well as interferon gamma receptor (IFNγR) signaling without affecting the type I interferons (Type I IFNs) pathway. Furthermore, we showed that lidocaine and dexamethasone treatment of epithelial cells infected with SARS-CoV-2 modulated the expression of chemokines that contribute to pro-inflammatory effects in severe COVID. Conclusions: We reported for the first time in vitro anti-inflammatory capacity of lidocaine on SARS-CoV-2 triggered immune pathways. These results indicated the potential of lidocaine to treat COVID-19 patients and add tools to the therapeutic options available for these concerning cases.

Introducción: El adecuado tratamiento de los defectos óseos se presenta como un desafío para el cirujano ortopedista, en cuanto a la dificultad en la restitución de un miembro alineado, sin discrepancia ni infección. Se han descrito múltiples técnicas para reconstruir estos defectos, como el injerto óseo autólogo o de banco, la técnica de membrana inducida, la osteogénesis por distracción y los cilindros de titanio trabecular, pero ninguna ha demostrado ser significativamente superior a otra. Materiales y Métodos: Entre 2018 y 2021, 10 pacientes con defectos óseos de la tibia fueron tratados mediante transporte óseo guiado con osteosíntesis endomedular. Se realizó un estudio retrospectivo descriptivo analizando la magnitud de los defectos, el tiempo de transporte, las complicaciones y cirugías adicionales durante el proceso, si hubo consolidación y las deformidades residuales. Al final del proceso, se midió el puntaje de la ASAMI (óseo y funcional). Resultados: La longitud promedio de los defectos tratados fue de 9,75 cm y el índice de fijación externa promedio, de 40,62 días/cm. El 50% tenía un puntaje de la ASAMI óseo bueno; el 10%, excelente y el 40%, pobre al final del proceso reconstructivo. El 20% tenía un puntaje de la ASAMI funcional excelente; el 30%, bueno y el 50%, pobre. Conclusiones: El uso de tutores externos guiados mediante osteosíntesis es un método fiable para tratar defectos óseos, al mismo tiempo que se trata la infección de manera local y sistémica, acortando los tiempos de tutor externo y, por lo tanto, de internación y reintervención.

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention having a diagnosis of “difficult asthma” from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. An HRCT scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients. [ABSTRACT FROM AUTHOR]

Introducción: En pacientes con fracturas de fémur distal con alto grado de conminución metafisaria (AO 33 C2, C3) y fracturas periprotésicas (Vancouver tipo C), el uso de doble osteosíntesis brinda mayor estabilidad a la fractura. Las placas helicoidales se emplean cada vez más con el objetivo de evitar dañar elementos nobles relacionados con el abordaje. Materiales y Métodos: Entre 2017 y 2021, seis pacientes fueron tratados mediante osteosíntesis con doble placa (por vía lateral y helicoidal por vía medial). La serie se compone de cuatro mujeres y dos hombres. El 66% (4 pacientes) tenía fracturas de fémur distal, y el resto (33%), fracturas periprotésicas tipo Vancouver C. Resultados: Se observó la consolidación radiográfica en todos los pacientes, a los 6 meses de la cirugía, con retorno normal a la actividad previa. Ninguno sufrió una lesión vasculonerviosa asociada. Conclusiones: La placa helicoidal es una gran opción para las fracturas de fémur distal con conminución y las fracturas femorales periprotésicas tipo Vancouver C. Esto demuestra que, aplicando los principios básicos de osteosíntesis, con una técnica sencilla, se pueden suplir materiales más sofisticados, y obtener resultados radiográficos similares.

Aims: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). Methods: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). Discussion: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. Trial registration: NCT number: NCT04891471.

The aim of this study was to evaluate the efficacy of activated irrigants (EDTA e NaOCL) during the cleansing of root walls, of the smear layer, of the debris, and gutta-percha after the preparation of the restorative space. Twenty single and multi-rooted (n = 20) have been collected. All samples were prepared by the same operator, using Nickel-titanium rotating instruments (Mtwo) through the Simultaneous Shaping Technique. The continuous-wave of condensation technique of obturation was used. To all specimens, the restorative space has been made, leaving 5 mm of apical gutta-percha, and postoperative periapical X-rays were performed. The samples were randomly divided into two groups: Group (A): cleansing of the root walls with ultrasonic activation of the irrigants (NEWTRON P5 XS; Satelec Acteon); Group (B): radicular walls wash without ultrasonic activation of endodontic irrigants (NaOCl 5.25% and EDTA 17%). Both dental sample groups were cut longitudinally with a low-speed saw (Isomet); the samples were observed by using a scanning electron microscope (Jeol, Jsm-6060LV) in order to evaluate: (1) the amount of debris/smear layer; (2) the mount of obstruction of dentinal tubules found in the two groups; and (3) evaluation of the presence of gutta-percha. Then, the other five samples each group (with and without ultrasonic activation) were prepared following the same protocol. Then, a universal bonding system (G-Praemio Bond, GC) and a layer of a flowable resin composite (Gaenial Flow, GC) were light-cured and used on top of the prepared root canal walls. The samples were cut in two pieces along the long axis of the root. Then, half sample teeth were kept in an acidic solution (37% HCl) for 48 h in order to completely dissolve dental structures and to have a direct view of resin tags formation under SEM. The other half was prepared to observe the adhesive interface under SEM. The amount of debris was not satisfactory in 9 out of 10 cases in Group B, while in Group A, which has been treated with ultrasounds, the result was either good or great in most of the samples. For the sample group treated with ultrasound, the tubules were evaluated as perfectly clean in 9 out of 10 cases, instead, the results are unsatisfactory for 9 out of 10 cases of group B not treated with ultrasound. Differences between Group A and B were statistically significant. With respect to the presence of debris and tubules obstruction treatment with ultrasonic activation, it offers with no doubt better results. When ultrasonic activation is used in combination with endodontic irrigants, a clean dentin substrate is be obtained for the adhesion of restorative materials, but in order to confirm the findings of this study, further in vivo trials are needed.

Tryptamine and serotonin are indolamines that fulfill diverse biological functions in all kingdoms of life. Plants convert l-tryptophan into tryptamine and then serotonin via consecutive decarboxylation and hydroxylation reactions catalyzed by the enzymes tryptophan decarboxylase (TDC) and tryptamine 5-hydroxylase (T5H). Tryptamine and serotonin accumulate to high levels in the edible fruits and seeds of many plant species, but their biological roles in reproductive organs remain unclear and the metabolic pathways have not been characterized in detail. We identified three TDC genes and a single T5H gene in tomato (Solanum lycopersicum L.) by homology-based screening and confirmed their activity by heterologous expression in Nicotiana benthamiana. The co-analysis of targeted metabolomics and gene expression data revealed complex spatiotemporal gene expression and metabolite accumulation patterns that suggest the involvement of the serotonin pathway in multiple biological processes. Our data support a model in which SlTDC1 allows tryptamine to accumulate in fruits, SlTDC2 causes serotonin to accumulate in aerial vegetative organs, and SlTDC3 works with SlT5H to convert tryptamine into serotonin in the roots and fruits.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Background/Aim: To evaluate the safety and efficacy of lattice radiotherapy (LRT) for large, inoperable breast cancers. Patients and Methods: In this prospective study, patients who underwent LRT for breast tumors that were ulcerating/fungating/extensively eroding the chest wall, and were ineligible/unwilling for surgery, were enrolled from May 2021 to Nov 2023. Baseline Eastern Cooperative Oncology Group (ECOG) status, pre- and post-LRT numerical rating scale (NRS), and post-LRT changes in quality of life (QoL) were recorded. Survival outcomes were reported at 6 months and 1-year. Median rates of survival and dosimetric parameters were calculated. Kaplan–Meier curves for overall survival (OS), cancer-specific survival (CSS), and failure of local control (LC) were constructed. Results: Ten patients (8 females) underwent LRT. The median age was 76 years (range=57-99 years) and the median ECOG performance status was 2.5 (range=1-4). The planned schedule was completed by 9/10 patients, accounting for a 90% compliance rate. Among patients with pain (n=7), NRS rapidly reduced from 7 (range=5-10) to 3 (range=1-6). The median equivalent uniform dose was 0.71 Gy (0.09-1.59 Gy). The actuarial rates of 6-month LC, CSS, and OS were 75%, 89%, and 61%, respectively, with only LC rate changing to 50% at 1 year. Two patients had local relapse at the six-month and 1-year follow-up, respectively, after having achieved a complete response at three months, and two others died of COVID-19 infection and ischemic stroke. Conclusion: LRT was found to be effective and safe in palliating symptoms among patients with large inoperable breast tumors. [ABSTRACT FROM AUTHOR]