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AbstractLocally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient’s quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Abstract Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms.

Abstract Background Circulating cell-free DNA (cfDNA, liquid biopsy) is a powerful tool to detect molecular alterations. However, depending on tumor characteristics, biology and anatomic localization, cfDNA detection and analysis may be challenging. Gliomas are enclosed into an anatomic sanctuary, which obstacles the release of cfDNA into the peripheral blood. Therefore, the advantages of using liquid biopsy for brain tumors is still to be confirmed. The present study evaluates the ability of liquid biopsy to detect IDH1 mutations and its correlation with survival and clinical characteristics of glioma patients. Methods Blood samples obtained from glioma patients were collected after surgery prior to the adjuvant therapy. cfDNA was extracted from plasma and IDH1 p.R132H mutation analysis was performed on a digital droplet PCR. χ2-test and Cohen k were used to assess the correlation between plasma and tissue IDH1 status, while Kaplan Meier curve and Cox regression analysis were applied to survival analysis. Statistical calculations were performed by MedCalc and GraphPad Prism software. Results A total of 67 samples were collected. A concordance between IDH1 status in tissue and in plasma was found (p = 0.0024), and the presence of the IDH1 mutation both in tissue (138.8 months vs 24.4, p

Abstract Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk. Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change. Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site. Conclusion: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or ‘bone builders’ in patients with very high or imminent risk of fracture.

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

Wood distillate (WD) has recently emerged as a promising bio-stimulant for sustainable legume crop production, owing to its ability to enhance seed yield and quality. However, no studies exist on the effects of WD on chickpea plants at pre-harvesting stages, hindering the farmers’ ability to acquire valuable knowledge on the early action of WD on the plants’ status and preventing the establishment of proactive measures to optimize WD use in agriculture. In this study, two multispectral, thermographic and spectroradiometric surveys, along with in-situ measurements of specific plant biometric traits, were conducted across the reproductive stage of field-grown chickpea in order to evaluate the early involvement of WD on plant health. The acquired multispectral images were used to calculate the Normalized Difference Vegetation Index (NDVI), revealing a notable ~35% increase in NDVI scores of WD-treated plants at the onset of physiological maturity, and indicating an improved plant status compared to the control (water-treated) plants. Moreover, control and WD-treated plants exhibited distinct spectral signatures across the visible, near-infrared (NIR) and short-wave infrared (SWIR) spectra, suggesting potential changes in their photosynthetic capacity, structural properties and water content both at the leaf and at the pod level. Furthermore, WD-treated plants showed a 25% increase in pod production, particularly at the beginning of seed maturity, suggesting that enhancements in plant status were also reflected in higher pod yields. These results point to a beneficial effect of WD on plant health during the preliminary stages of seed formation and indicate that a combination of both multispectral and spectroradiometric analyses can provide critical insights on the status of chickpea crops at pre-harvesting stages. In addition, these findings emphasize the importance of analyzing pre-harvesting stages to gain insights into the early involvement of WD in promoting plant health and, ultimately, in predicting final crop yields.

Abstract Hydrogen (H) plays a key role in the near-to-room temperature superconductivity of hydrides at megabar pressures. This suggests that H doping could have similar effects on the electronic and phononic spectra of materials at ambient pressure as well. Here, we demonstrate the non-volatile control of the electronic ground state of titanium diselenide (1T-TiSe2) via ionic liquid gating-driven H intercalation. This protonation induces a superconducting phase, observed together with a charge-density wave through most of the phase diagram, with nearly doping-independent transition temperatures. The H-induced superconducting phase is possibly gapless-like and multi-band in nature, in contrast with those induced in TiSe2 via copper, lithium, and electrostatic doping. This unique behavior is supported by ab initio calculations showing that high concentrations of H dopants induce a full reconstruction of the bandstructure, although with little coupling between electrons and high-frequency H phonons. Our findings provide a promising approach for engineering the ground state of transition metal dichalcogenides and other layered materials via gate-controlled protonation.

Abstract Background Pleural disease (PD), particularly malignant pleural effusion (MPE), is a common cause of hospital admission and its prevalence is rising worldwide. Recent advances in diagnostic and therapeutic options, such as Indwelling Pleural Catheters (IPCs), have simplified PD treatment, allowing an effective outpatients management. Therefore, dedicated pleural services can improve PD care, guaranteeing specialized management and optimizing time and cost. We aimed to provide an overview on MPE management in Italy, mainly focused on distribution and characteristics of pleural services and IPCs use. Methods A nationwide survey, endorsed by the Italian Thoracic Society, was distributed by email to members of selected subgroups in 2021. Results Ninety (23%) members replied, most of whom being pulmonologists (91%). MPE resulted the most common cause of pleural effusion and was managed with heterogenous approaches, including talc pleurodesis via slurry (43%), talc poudrage (31%), repeated thoracentesis (22%) and IPCs insertion (2%). The setting of IPC insertion was inpatient care in 48% of cases, with a predominance of draining frequency every other day. IPC management mainly relied on caregivers (42%). The presence of a pleural service was reported by 37% of respondents. Conclusions The present study provides an extensive overview of MPE management in Italy, showing a highly heterogeneous approach, a scarce prevalence of out-patient pleural services, and a still limited adoption of IPCs, mainly due to lack of dedicated community care systems. This survey emphasizes the need of promoting a higher spreading of pleural services and an innovative healthcare delivery with more favourable cost-benefit ratio.

The new species Silene isabellae is described and illustrated from the Skënderbëut mountain range of central Albania. It grows on the ultramafic mountain slopes around Qafë Shtamë, in the understorey of open Pinus nigra forests and in the rocky grasslands above the forest belt, at 1000–1600 m a.s.l. Silene isabellae is a serpentine endemic likely belonging to section Elisanthe (Fenzl ex Endl.) Ledeb. and shows affinities with the widespread European species S. noctiflora L. It is sharply distinct from the latter species in habit, stem and leaf pubescence, morphology, and biology of the flowers and length of the carpophore. Moreover, the ecology of the two taxa is also contrasting, being S. noctiflora a synanthropic-ruderal, mostly in lowlands. Weaker similarities were also observed with the south European subalpine taxa of the group of S. vallesia L. of section Auriculatae (Boiss.) Schischk., though these are not likely to reflect a real systematic affinity.

Freshwater ecosystems are crucial for biodiversity conservation. They are among the most threatened habitats in the world. However, the wetlands of southern European mountains still lack fine-scale plant community studies. Here we studied submontane and montane palustrine communities of the Tuscan-Romagna Apennines. Data from 123 vegetation plots dominated by palustrine species were analysed by means of cluster analysis. We identified 18 vegetation types that we attributed to five classes (Phragmito-Magnocaricetea, Montio-Cardaminetea, Iso ëto-Nanojuncetea, Molinio-Arrhenatheretea, and Epilobietea angustifolii), and to two Natura 2000 habitats (3130 - Oligotrophic to mesotrophic standing waters with vegetation of the Littorelletea uniflorae and/or of the Iso ëto-Nanojuncetea, and 6430 - Hydrophilous tall herb fringe communities of plains and of the montane to alpine levels). According the 4th edition of the International Code of Phytosociological Nomenclature we corrected the names Phragmition communis Koch 1926 nom. inept. in P. australis Koch 1926 nom. corr., Phragmitetum communis Savič 1926 nom. inept. in P. australis Savič 1926 nom. corr., Glycerietum plicatae Kulczyński 1928 nom. inept. in G. notatae Kulczyński 1928 nom. corr., Beruletum angustifoliae Roll 1938 nom. inept. in Beruletum erectae Roll 1938 nom. corr., and we mutated the name Scirpetum lacustris Chouard 1924 nom. inept. in Schoenoplectetum lacustris Chouard 1924 nom. mut. nov. Our study highlights the diversity of marsh vegetation of montane and submontane areas of Northern Apennines. Most of the palustrine communities, though important from the point of view of conservation, cannot be attributed at present to any habitat type legally protected at the European level.