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Vaccination is a crucial tool for the primary prevention of infectious diseases. Thanks to the widespread of vaccinations it has been possible to eradicate very serious diseases. Unfortunately, vaccination coverage in Italy has been decreasing starting from 2015, getting worse during COVID-19. Nowadays, very few Italian regions have achieved the goal of 95% coverage. In this study we present a vaccination recovery model proposed by Local Health Department "Napoli 3 Sud" in Campania. An evaluation of the vaccination coverage from January 2019 to December 2021 of the 13 Districts of the Local Health Department "Napoli 3 Sud" in Campania was carried out, by extraction from the regional computerized platform "GE.VA" Regional Vaccine Registry and from Sinfonia Vaccini Soresa platform. Vaccination coverage of the Local Health Department "Napoli 3 Sud" for the cohorts of newborns in the year 2019–2021 improved to an average of 96.29% for Pneumococco, of 84.78% for Meningococcal, of 94.3% for Measles, Mumps and Rubella, 91.4% for chickenpox. This study highlights how the collaboration between family pediatricians and the Local Health Department, with the help of a regional computerized platform GE.VA, is effective in improving vaccination coverage. [ABSTRACT FROM AUTHOR]

The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non‐invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour‐related analytes. The advent of multiomics – enabled by deep learning algorithms – offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi‐marker, multi‐analyte and multi‐source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of Platelet Concentrates (PCs) in the contest of Hemorrhagic, Actinic, and Radiation Cystitis, plus Urethral Obstruction or Stenosis. Eligibility criteria: Open article in English or Italian regarding in situ applications of PCs for the selected pathologies. Information sources: MEDLINE, Cochrane Library, and ELSEVIER. Risk of bias: High (and discussed). Methods for synthesis of results: Selection of relevant contents, resumed by digital tools, checked by authors and used throughout the manuscript. Included studies: 13 screened articles + 7 personal sources + 37 "extra" articles. Synthesis of results: Pre-clinical and clinical studies demonstrated substantial symptom relief, mucosal restoration, and improved growth factor levels, reducing recurrence rates and complications. However, preparation protocols and results varied among studies. Limitations of evidence: Frequent low-quality studies with mall sample size, plus heterogeneous experimental setups and nomenclature/preparations. Interpretation: PCs demonstrate promise due to their bioactive components, enhancing tissue repair and reducing inflammation with no significant adverse events. Despite positive outcomes in pre-clinical and clinical studies, variability in preparation protocols and small sample sizes, together with inconsistent results, highlight the need for high-quality research to validate PCs' clinical efficacy and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: Lung Cancer (LC) continues to be a leading cause of cancer-related mortality globally, largely due to the asymptomatic nature of its early stages and the limitations of current diagnostic methods such as Low-Dose Computed Tomography (LDCT), whose often result in late diagnosis, highlighting an urgent need for innovative, minimally invasive diagnostic techniques that can improve early detection rates. Areas covered: This review delves into the potential of genomic characterization and mutational profiling to enhance early LC diagnosis, exploring the current state and limitations of traditional diagnostic approaches and the revolutionary role of Liquid Biopsies (LB), including cell-free DNA (cfDNA) analysis through fragmentomics and methylomics. New genomic technologies that allow for earlier detection of LC are scrutinized, alongside a detailed discussion on the literature that shaped our understanding in this field. Expert opinion: Despite the promising advancements in genomic characterization techniques, several challenges remain, such as the heterogeneity of LC mutations, the high cost, and limited accessibility of Next-Generation Sequencing (NGS) technologies. Additionally, there is a critical need of standardized protocols for interpreting mutational data. Future research should focus on overcoming these barriers to integrate these novel diagnostic methods into standard clinical practice, potentially revolutionizing the management of LC patients. [ABSTRACT FROM AUTHOR]

Background The aim of this meta-analysis was to synthesize the available evidence from the literature on the efficacy and safety of integrase inhibitor-based two drug regimens compared to triple drug regimens in virosuppressed people living with HIV (PLWH) in a long-term follow-up (at 96 weeks). Materials and Methods A systematic review and meta-analysis were conducted to evaluate the efficacy, safety, and adverse drug reactions leading to discontinuation of two drug regimens compared to triple drug regimens in virosuppressed PLWH patients at 96 weeks of follow-up. We searched MEDLINE, Google Scholar, and the Cochrane Library up to March 15, 2024, and studies were selected for eligibility based on predefined criteria. Data were extracted independently by two reviewers, and risk ratios (RRs) were calculated as the measure of association between therapy and incidence of events. Results Six studies were included in the analysis, both clinical trials and observational studies. The two drug regimens included cabotegravir/rilpivirine, dolutegravir/lamivudine, and dolutegravir/rilpivirine. No significant differences were observed in treatment failure (RR, 0.77; 95% confidence interval [CI], 0.53–1.13; P=0.182), virological failure (RR, 0.79; 95% CI, 0.48–1.29; P=0.341), adverse drug reactions leading to discontinuation (RR, 1.74; 95% CI, 0.73–4.17; P=0.215), or appearance of mutation (RR, 2.48; 95% CI, 0.33–18.68; P=0.379) between two drug regimen and triple drug regimen groups at 96 weeks of follow up. Conclusion The meta-analysis provide an overview of the available evidence and supports the use of two drug regimens as an option for simplifying treatment and improving clinical outcomes in virosuppressed PLWH. [ABSTRACT FROM AUTHOR]

Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical–radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development. This review paper aims to provide a comprehensive framework for a better understanding of the present and future potential applications of neuroimaging techniques for evaluating nonsyndromic CRS, highlighting strategies for optimizing their use in clinical practice and offering an overview of the most relevant technological advancements in terms of diagnostic performance, radiation exposure, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: The need for a standardized core curriculum in regional anesthesia has become essential, particularly with the integration of ultrasound revolutionizing and exponentially increasing clinical practice and possibilities. In fact, numerous novel techniques, often overlapping, can confuse practitioners. This study aims to establish a core curriculum for upper limb, lower limb, paraspinal and fascial plane blocks for residency training, addressing potential educational gaps caused by the multitude of techniques, through a Delphi consensus process involving recognized Italian regional anesthesia experts. Methods: A steering committee was formed in order to select a panel of experts in regional anesthesia. A three-round Delphi consensus was planned: two rounds of electronic voting and a final round of mixed electronic voting and round table discussion. The consensus was defined as ≥ 75% agreement for inclusion and lower than ≤ 25% agreement for exclusion from the core curriculum list. Techniques reaching the 50% threshold were included with low consensus. Results: Twenty-nine techniques were selected to be included in the ultrasound-guided regional anesthesia core curriculum. Twenty-two were included with strong consensus: Upper limb: interscalene brachial plexus block, supraclavicular brachial plexus block, infraclavicular brachial plexus block, axillary brachial plexus block, intermediate cervical plexus block Lower limb: femoral nerve block, pericapsular nerve group block, adductor canal block, sciatic nerve block (transgluteal approach, infragluteal approach, and at the popliteal fossa), ankle block Paraspinal/fascial plane blocks: erector spinae plane block, deep serratus anterior plane block, superficial pectointercostal plane block, interpectoral plane block, pectoserratus plane block, rectus sheath block, ilioinguinal iliohypogastric nerves block, transversus abdominis plane block (with subcostal and midaxillary approaches) The remaining seven techniques were included with low consensus: superficial cervical plexus block, lumbar plexus block, fascia iliaca block (suprainguinal approach), anterior quadratus lumborum block, lateral quadratus lumborum block, paravertebral block, and serratus anterior plane block. Conclusions: This curriculum aims to standardize training and ensure that residents acquire the essential skills required for effective and safe practice regardless of the residents' subsequent specialization. By incorporating these techniques, educational programs can provide a structured and consistent approach to regional anesthesia, enhancing the quality of patient care and improving outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations. Patients and methods: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the "Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults" of the University-Hospital Policlinico "P. Giaccone" of Palermo (Italy). Results: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing. Discussion: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care. [ABSTRACT FROM AUTHOR]

Despite advancements in therapeutic strategies, the development of drug resistance and metastasis remains a serious concern for the efficacy of chemotherapy against colorectal cancer (CRC). We have previously demonstrated that low expression of ribosomal protein uL3 positively correlates with chemoresistance in CRC patients. Here, we demonstrated that the loss of uL3 increased the metastatic capacity of CRC cells in chick embryos. Metabolomic analysis revealed large perturbations in amino acid and glutathione metabolism in resistant uL3-silenced CRC cells, indicating that uL3 silencing dramatically triggered redox metabolic reprogramming. RNA-Seq data revealed a notable dysregulation of 108 genes related to ferroptosis in CRC patients. Solute Carrier Family 7 Member 11 (SLC7A11) is one of the most dysregulated genes; its mRNA stability is negatively regulated by uL3, and its expression is inversely correlated with uL3 levels. Inhibition of SLC7A11 with erastin impaired resistant uL3-silenced CRC cell survival by inducing ferroptosis. Of interest, the combined treatment erastin plus uL3 enhanced the chemotherapeutic sensitivity of uL3-silenced CRC cells to erastin. The antimetastatic potential of the combined strategy was evaluated in chick embryos. Overall, our study sheds light on uL3-mediated chemoresistance and provides evidence of a novel therapeutic approach, erastin plus uL3, to induce ferroptosis, establishing individualized therapy by examining p53, uL3 and SLC7A11 profiles in tumors. [ABSTRACT FROM AUTHOR]

This study retrospectively evaluated the influence of prosthetic features on marginal bone level changes around bone-level implants with an external hex connection. A total of 100 patients with 166 implants and cemented crowns were included. Demographic and clinical data were collected. Prosthetic features were radiographically evaluated, including emergence angle (EA), emergence profile (EP), crown-implant ratio (CIR), and abutment height. Marginal bone levels were measured on intraoral radiographs taken at baseline and after at least 1 year. The correlation between prosthetic features and marginal bone loss (MBL) was then investigated. The mean follow-up time was 43.94 months. Implant length varied between 5 and 13 mm. The mean height of the abutments used was 1.55 mm. EA measured an average 30.62 degrees (± 13.20) mesially and 29.45 degrees (± 13.07) distally. The CIR was 0.99 (± 0.26). The mean MBL was 0.19 mm on the mesial side and 0.20 mm on distal side of the implants. Significant positive associations emerged between MBL and implant length (P < .005) and with EA (P < .05). A convex profile of the crown was shown to be associated with a higher distal MBL (P = .025) compared to concave and str aight profiles. [ABSTRACT FROM AUTHOR]

A20X is an advanced and high-strength additive manufacturing aluminum alloy with promising applications in several fields, including aerospace and aeronautics. However, its assembling through fusion welding technologies poses challenges due to the detrimental effects of melting and solidification. Friction stir welding offers a promising solution for joining A20X, producing components with superior mechanical properties while preserving the engineered microstructures. This study investigates the influence of friction stir welding on the quality of butt joints made of 4 mm thick additively manufactured A20X plates produced by laser powder bed fusion. Different rotational (900 and 1500 rpm) and welding speeds (100 and 500 mm/min) were tested to evaluate the influence of the joining process on weld quality (mechanical strength, microstructures, welding defects, and surface roughness). Friction stir welding maintains a very fine microstructure in the welds, with only a slight reduction of the mechanical strength compared to the base material (335 MPa vs. 385 MPa on average). The hardness of the welded joints increases, attributed to local aging caused by the heat input during the joining process. Lower tool rotation and welding speed result in tunnel defects, notably reducing joint strength. 3D X-ray computed tomography reveals that the metal stirring occurring during the joining process notably reduces the intrinsic porosity of A20X. It also breaks up Ti borides and promotes the growth of Al-Cu precipitates within the stir zone. The fractographic analysis highlights the ductile behavior of A20X after welding, emphasizing the critical role of welding parameters in joint integrity. [ABSTRACT FROM AUTHOR]

A study was carried out to determine the concentration of heavy metals and trace elements in milk and dairy products collected from local farms, supermarkets, or food retailers in the region of Lazio (Central Italy). Persistent exposure to metal contamination is of particular concern for human health, as it can cause different serious disorders. The monitoring of the matrices studied is therefore important, given their high consumption in the daily diet. The elements determined by ICP-MS (Inductively Coupled Plasma – Mass Spectrometry) were lead (Pb), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), nickel (Ni), molybdenum (Mo) and thallium (Tl), for a total of 151 measurements in 98 samples. The results showed that 11.3% of the measurements were quantifiable but below the legal maximum limits (MLs) set by EU regulations. The data obtained may be useful for dietary exposure information, inter-regional comparisons and for planning regional surveillance strategies. [ABSTRACT FROM AUTHOR]

Syphilis is a systemic infection caused by the spirochete Treponema pallidum. It is transmitted during pregnancy or through sexual contact. Signs and symptoms vary depending on the clinical stage of the disease. Syphilis has been well-studied, and the introduction of penicillin has resulted in a decline in the number of new cases and deaths. Recently, however, there has been a surge in new cases in young people, especially those with human immunodeficiency virus (HIV). This epidemiological shift has been attributed to increased sexual activity, risky sexual behaviors, and immunodeficiency. There is a paucity of data on gastrointestinal (GI) manifestations of syphilis owing to its rarity and lack of physician awareness. T. pallidum can seed to any part of the GI tract, resulting in esophagitis, gastritis, hepatitis, pancreatitis, or proctocolitis. Depending on the affected part of the GI tract, syphilis can present with nausea, vomiting, painless esophageal ulcers, dysphagia, abdominal pain, weight loss due to early satiety, diarrhea, melena, hematochezia, dyschezia, or anorectal ulcers. Given its indolent clinical course and vague presentation, GI syphilis can mimic other GI disorders, which can delay diagnosis and treatment. A detailed medical history, physical examination, serological tests, and endoscopy can provide a definitive diagnosis. Syphilis and its GI complications are usually treated with long-acting intramuscular penicillin benzathine, and rarely with a 14-day course of intravenous penicillin. Herein, we describe the clinical features, etiopathogenesis, diagnosis, and treatment of GI syphilis. This primer should aid clinicians in timely diagnosis and treatment of various presentations of GI syphilis. [ABSTRACT FROM AUTHOR]

Nematodes are a common soybean threat, and the search for new solutions for controlling them has been the focus of many studies worldwide. Crotalaria spp. are known sources of pyrrolizidine alkaloids with nematicidal activities. In this study, the nematicidal and nematostatic effects of C. spectabilis extracts were evaluated in vitro over two different nematode species (Heterodera glycines and Meloidogyne javanica). A full factorial experimental design was employed to understand the effects and interactions of input factors (plant organ, extraction solvent, and nematode species) on the output response (nematode mortality). Ethanolic and alkaline extracts of leaves and seeds were tested at concentrations of 5, 10 and 20 mg L-1 in bioassays with 48 hours of incubation. The C. spectabilis seed's alkaline extract assessed for H. glycines resulted in higher mortality rates (close to 96%) compared to the other experiments. Therefore, this combination was also evaluated in vivo in a soybean plantation, resulting in a decrease of about 90% in the nematode multiplication factor compared to the control group. Ultra-High Performance Liquid Chromatography coupled to a tandem High-Resolution Mass Spectrometer (UHPLC-HRMS/MS) analyses revealed pyrrolizidine alkaloids in the extract, such as senecionine N-oxide, besides monocrotaline and its derivatives. The results obtained in this study allow new possibilities to handle nematode infections. The direct application of C. spectabilis extracts or their isolated bioactive compounds on soil can be a promising approach. [ABSTRACT FROM AUTHOR]

Introduction: The transverse cerebral fissure of Bichat is a complex anatomic space formed by a median portion (the velum interpositum) and two oblique lateral branches terminating anteriorly at the medial temporal lobes. Its complexity derives from both its embryological development and from its own nature of "virtual anatomic space". Previous imaging studies have addressed the issue of its anatomical description by using pneumoencephalography or transcranial ultrasound and magnetic resonance imaging especially in those cases with expansile lesions into its anatomical borders. Methods: We describe the transverse cerebral fissure anatomy in two 20th gestational week fetuses studied with three-tesla MR fetal autopsy with an eye to its embryological development. Results: We were able to define its anatomical borders thanks to the presence of hemosiderin components that spontaneously layered inside its slit-like boundaries as result of postmortem phenomena and that were depica as T2 hypointensity on MR images. Conclusions: This Pictorial essay aims to give a concise and novel description of the transverse cerebral fissure: a deep understanding of the Bichat's fissure embryology and anatomy can help to identify and correctly locate abnormalities arising from this virtual anatomic space in the everyday clinical practice. [ABSTRACT FROM AUTHOR]

With the aid of structured catalysts and reactors, such as monoliths, solid foams, and 3D printed structures, the limitations of conventional slurry and packed‐bed reactors can be surmounted. Multiphase mathematical models were presented for solid foam structures and the models were verified for the hydrogenation of arabinose, galactose, and xylose to the corresponding sugar alcohols. High product selectivities were obtained in batch and continuous experiments. Three kinetic models were considered: a competitive adsorption model, a semi‐competitive adsorption model as well as a non‐competitive adsorption model for sugar monomers and hydrogen. The models gave a good reproduction of the data, but the semi‐competitive adsorption model was the most plausible one because of the size difference between adsorbed sugar and hydrogen molecules. [ABSTRACT FROM AUTHOR]

Chronic low back pain (LBP) represents a leading cause of absenteeism from work. An accurate knowledge of complex interactions is essential in understanding the difficulties of return to work (RTW) experienced by workers affected by chronic LBP. This study aims to identify factors related to chronic LBP, the worker, and the psycho-social environment that could predict and influence the duration of an episode of sick leave due to chronic LBP.Studies reporting the relation between prognostic factors and absenteeism from work in patients with LBP were included. The selected studies were grouped by prognostic factors. The results were measured in absolute terms, relative terms, survival curve, or duration of sick leave. The level of evidence was defined by examining the quality and the appropriateness of findings across studies in terms of significance and direction of relationship for each prognostic factor.A total of 20 studies were included. Prognostic factors were classified in clinical, psycho-social, and social workplace, reaching a total of 31 constructs. Global conditions with less favorable repercussions on worker's lives resulted in a delay in time to RTW. Older age, female, higher pain or disability, depression, higher physical work demands, and abuse of smoke and alcohol have shown strong level of evidence for negative outcomes.High global health well-being, great socioeconomic status, and good mental health conditions are decisive in RTW outcomes. Interventions that aim at RTW of employee's sick-listed with LBP should focus on psycho-social aspects, health behaviors, and workplace characteristics. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is a lethal brain tumor that rapidly adapts to the dynamic changes of the tumor microenvironment (TME). Mesenchymal stem/stromal cells (MSCs) are one of the stromal components of the TME playing multiple roles in tumor progression. GB progression is prompted by the immunosuppressive microenvironment characterized by high concentrations of the nucleoside adenosine (ADO). ADO acts as a signaling molecule through adenosine receptors (ARs) but also as a genetic and metabolic regulator. Herein, the effects of high extracellular ADO concentrations were investigated in a human glioblastoma cellular model (U343MG) and MSCs. The modulation of the purinome machinery, i.e., the ADO production (CD39, CD73, and adenosine kinase [ADK]), transport (equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2)), and degradation (adenosine deaminase [ADA]) were investigated in both cell lines to evaluate if ADO could affect its cell management in a positive or negative feed‐back loop. Results evidenced a different behavior of GB and MSC cells upon exposure to high extracellular ADO levels: U343MG were less sensitive to the ADO concentration and only a slight increase in ADK and ENT1 was evidenced. Conversely, in MSCs, the high extracellular ADO levels reduced the ADK, ENT1, and ENT2 expression, which further sustained the increase of extracellular ADO. Of note, MSCs primed with the GB‐conditioned medium or co‐cultured with U343MG cells were not affected by the increase of extracellular ADO. These results evidenced how long exposure to ADO could produce different effects on cancer cells with respect to MSCs, revealing a negative feedback loop that can support the GB immunosuppressive microenvironment. These results improve the knowledge of the ADO role in the maintenance of TME, which should be considered in the development of therapeutic strategies targeting adenosine pathways as well as cell‐based strategies using MSCs. [ABSTRACT FROM AUTHOR]

The article discusses informal coercion in psychiatric contexts, particularly focusing on the lack of consideration for the perspectives of individuals subjected to involuntary psychiatric treatment. It critiques existing models and approaches that overlook the lived experiences of psychiatric patients, calling for greater epistemic responsibility and the inclusion of first-person accounts in debates about coercion.

Background: The perivascular spaces of the brain are also known as Virchow-Robin spaces (VRSs). Dilated Virchow-Robin spaces in the brainstem are rare and mainly cause symptoms due to obstructive hydrocephalus, less frequently because of their size, mass effect, and impact on eloquent structures. Case illustration: We present a patient with giant tumefactive VRS with hydrocephalus and neurological symptoms who was treated with endoscopic third ventriculostomy (ETV) followed by microscopic cyst fenestration. On the basis of this observation, we performed a thorough review of the literature to evaluate different treatment options. Results: An 11-year-old girl presented with a headache for 3 months. The patient had a giant tumefactive mesencephalothalamic VRS with triventricular hydrocephalus. She was initially treated with endoscopic third ventriculostomy and multiple cyst fenestration. Symptomatic cyst regrowth required multiple cyst fenestrations via transcallosal transchoroidal (N = 2) and subtemporal approaches (N = 1) at the 2- and 4-year follow-ups. A literature review of these conditions allowed the detection of 12 cases (including our index case), and only 25% (3/12) of the patients underwent cyst fenestration 16.7% (2/12) required endoscopic fenestration and 8.3% (1/12) required microscopic fenestration. Conclusion: Giant mesencephalothalamic dVRSs are rare in the pediatric population. These patients are usually symptomatic due to obstructive hydrocephalus. Surgical options are endoscopic third ventriculostomy, ventricular shunt procedures, or direct cyst fenestration (microscopic or endoscopic). Close follow-up is mandatory owing to the risk of progression of the disease. Cyst fenestration resolves symptoms immediately, as it addresses both hydrocephalus and mass effects due to the cystic lesion in the same setting. [ABSTRACT FROM AUTHOR]

Objective: To investigate the reliability of parental recall of birth weight, birth length and gestational age several years after birth. Methods: Parentally recalled birth parameters were obtained from the European multicentric cohort study IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) and compared to the corresponding data externally recorded in the child's medical check-up booklet. The agreement between the two sources was examined using Bland–Altman plots, intraclass correlation coefficients and Cohen's kappa for clinically relevant categories. Additionally, logistic regression models were used to identify factors related to parental recall accuracy. Results: A total of 4930 children aged 2 to 11 years were included. Accuracy of birth weight within 100 g was 88%, 94% of the recalled birth length was within 2 cm, and 99% of the parents could recall with 2 weeks accuracy how many weeks their child was delivered preterm. Discrepancies of more than two weeks or more than 100 g were more likely in parents of low or medium socioeconomic status. Non-biological parents were 3.4 times more likely to have a discrepancy of more than 100 g compared to biological mothers (95% CI 1.7–6.7). Moreover, parents were less likely to accurately recall their child's birth parameters with increasing number of children within a family. Conclusions for Practice.: In general, parents' information matched well with the medical check-up booklet. However, accuracy varied among different groups which should be taken into consideration when using birth data recalled by parents in studies of child health. Significance: What Is Already Known?: Parentally recalled birth data have been shown to be generally reliable but there is evidence that the accuracy depends on various sociodemographic factors. What This Study Adds?: Most studies analyzing the reliability of parentally recalled birth data include only limited age ranges of the children and are relatively small. This study comprises a large sample, covers a wide age range of the children and identifies several factors (e.g. interviewed parent, socioeconomic status, number of siblings) that may influence the accuracy of reported information. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether the duration of disease may influence the surgical success of Endonasal Endoscopic DCR (EE-DCR) in patients affected by nasolacrimal duct obstruction (NLDO). Methods: Single-center observational retrospective analysis on EE-DCR via posterior trans-ethmoidal approach. Consecutive patients were enrolled in 2021–2024 and evaluated with proper questionnaires; resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Also, patients were asked to complete the Hospital Anxiety and Depression Scale (HADS) at each timepoint. The sample was divided based on the duration of disease (group A: ≤ 24 months, group B: > 24 months). Results: Ninety-one patients were included. At baseline no differences were observed between the two groups. At both timepoints, Munk score was significantly lower in Group A compared to Group B, while a difference in dacryocystitis rate was observed only at T2. Anxiety scores differed significantly at T2, although no differences were observed for depression. At paired analysis, all groups improved significantly at T1 compared to baseline, whereas no further improvement was observed between T2 and T1. A significantly higher improvement was observed in group A for the Munk and HADS-A scores over timepoints, whereas there was no significance for dacryocystitis rate and HADS-D. Also, group A showed a higher complete success rate compared to group B (p = 0.041). Finally, linear regression confirmed a positive relationship between Munk and anxiety scores and the duration of disease at T2. Conclusions: Our findings showed that long-lasting NLDO symptoms may be associated with worse EE-DCR surgical outcomes. [ABSTRACT FROM AUTHOR]

In 2019, members of the Global Indigenous Data Alliance (GIDA) published the CARE Principles (Collective Benefit, Authority to Control, Responsibility, and Ethics) for Indigenous Data Governance (IDGov). CARE has since been referenced, leveraged, and adopted in various ways across disciplines and sectors worldwide. In this article, GIDA members from Aotearoa New Zealand, Australia, Canada, and the United States share examples of IDGov models that predate and emerged after the development of CARE. Together, we reflect upon the affordances and limitations of the broad uptake of CARE. We argue that renewed attention is needed to the original intent of CARE: to direct data actors to local communities' protocols and frameworks for IDGov, and to transform institutional policies and practices to fortify Indigenous Peoples' authority to control their data. [ABSTRACT FROM AUTHOR]

This study investigated the involvement of Italian preschool and primary school teachers in outdoor education and scouting activities and their association with student cooperation and personal care. While outdoor education has various psychophysiological, psychosocial, social, and pedagogical benefits, some teachers express concerns about their readiness to implement such activities. We hypothesized that preschool teachers are more willing to participate in outdoor education and scouting than primary school teachers. We also hypothesized that outdoor education teachers would score higher in all survey items compared to regular teachers (see Table 2). The results indicated no significant difference between preschool and primary school teachers. However, there were differences in the survey items between outdoor education and regular teachers, except for item 11. The study suggests that providing appropriate instruction and teaching tools to teachers, their students' schooling experiences and skills are likely to improve. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, but dopamine also plays a role in the pathophysiology of migraine. Objective: The aim of this study is to assess lifetime and previous year prevalence rates of headache in PD patients compared with controls. Patients and methods: We enrolled 101 patients (57 M and 44 W) and 101 controls (62 M and 39 W), comparable for age and gender, who underwent a semi-structured questionnaire to assess the occurrence and the features of headache, and Beck Depression Inventory (BDI). Results: We did not find any significant differences in the overall prevalence of lifetime and last 12-month headache between the two groups, as well as lifetime and last year tension-type headache (TTH) and migraine. Patients, especially those suffering from migraine and treated with dopamine agonists (DA), more frequently showed headache remission after the onset of motor symptoms compared to the age-related remission observed in controls (p = 0.001). Patients affected by headache were less frequently treated with DA in comparison with those without (p = 0.051). Depression of mood was more severe among PD patients with migraine than with TTH (p = 0.021). PD patients with headache exhibiting the akinetic-rigid subtype more frequently reported motor fluctuations than those presenting with tremor-dominant disease (p = 0.040). Conclusions: The prevalence of headache in PD follows that described in the general population, but dopaminergic pathway degeneration, loss of dopamine activation on the trigeminal-vascular system, and DA treatment might favor migraine improvement and remission in PD patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6‐month effectiveness and tolerability of anti‐CGRP mAbs in combination with other mAbs for different diseases. Methods: Patients included in the Italian Headache Registry and treated concomitantly with an anti‐CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test‐6 (HIT‐6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. Results: Thirty‐eight patients were included. In 27 patients (71.1%), the anti‐CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti‐CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti‐CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow‐up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT‐6 scores at 3 and 6 months (p < 0.001). For anti‐CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). Conclusions: In this real‐world study, anti‐CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs. [ABSTRACT FROM AUTHOR]

PURPOSE: The clinical and research FPG500 program (ClinicalTrials.gov identifier: NCT06020625) is currently ongoing at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS to tailor matched targeted therapies (MTTs) according to biomarkers predictive of response identified by comprehensive genome profiling (CGP). MATERIALS AND METHODS: The non–small cell lung cancer (NSCLC) cohort results from the FPG500 program are outlined. CGP was performed by TruSight Oncology 500 High Throughput (TSO500HT) assay or Oncomine Focus Assay plus Archer's FusionPlex Lung Panel according to tumor cell content and DNA/RNA quantity. Relevant issues for Molecular Tumor Board (MTB) evaluation included uncommon genomic findings, evaluation for off-label therapies, uncertain result confirmation, and variants of suspect germline origin requiring genetic counseling. Progression-free survival (PFS) and overall survival (OS) for the enrolled patients were assessed using Kaplan-Meier analysis. RESULTS: In 2022, 283 patients with NSCLC were considered for sequencing, with 93% meeting eligibility criteria. TSO500HT sequencing was conducted in 76% of patients. Follow-up data were obtained for 187 patients, among whom 81% received treatment. Potential driver alterations were identified in 59% of patients, with 41% receiving MTT: 25% were prescribed approved MTTs, whereas 16% gained access to experimental drugs post-MTB evaluation; of note, 18% did not receive any MTT because the regimen was not yet reimbursed in our country. Median PFS and OS varied among treatment groups, with standard chemotherapy/immunotherapy at 7.7 and 10.7 months, approved tyrosine kinase inhibitors at 18.8 and 23.9 months, and MTT post-MTB discussion at 14 and 23.4 months, respectively. CONCLUSION: The early data of the FPG program (NSCLC cohort) support the implementation of CGP and MTB in clinical practice to grant access to patients harboring actionable molecular alterations to the most effective and individualized available treatment options, thus improving their survival outcomes. [ABSTRACT FROM AUTHOR]

PURPOSE: We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations. METHODS: Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data. RESULTS: A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients. CONCLUSION: The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations. [ABSTRACT FROM AUTHOR]

PURPOSE: Studies have investigated the early use of liquid biopsy (LBx) during the diagnostic workup of patients presenting with clinical evidence of advanced lung cancer, but real-world adoption and impact has not been characterized. The aim of this study was to determine whether the use of LBx before diagnosis (Dx; LBx-Dx) enables timely comprehensive genomic profiling (CGP) and shortens time until treatment initiation for advanced non–small-cell lung cancer (aNSCLC). MATERIALS AND METHODS: This study used the Flatiron Health-Foundation Medicine electronic health record-derived deidentified clinicogenomic database of patients with aNSCLC from approximately 280 US cancer clinics. RESULTS: Of 1,076 patients with LBx CGP ordered within 30 days prediagnosis/postdiagnosis, we focused on 56 (5.2%) patients who ordered LBx before diagnosis date (median 8 days between order and diagnosis, range, 1-28). Compared with 1,020 patients who ordered LBx after diagnosis (Dx-LBx), LBx-Dx patients had similar stage and ctDNA tumor fraction (TF). LBx-Dx patients received CGP results a median of 1 day after Dx versus 25 days for Dx-LBx patients. Forty-three percent of LBx-Dx were positive for an National Comprehensive Cancer Network driver, and 32% had ctDNA TF >1% but were driver negative (presumed true negatives). In 748 patients with previously untreated aNSCLC, median time from Dx to therapy was shorter in the LBx-Dx versus Dx-LBx group (21 v 35 days; P <.001). CONCLUSION: Early LBx in anticipation of pathologic diagnosis of aNSCLC was uncommon in this real-world cohort, yet this emerging paradigm was associated with an abbreviated time to CGP results and faster therapy initiation. Forthcoming prospective studies will clarify the utility of LBx in parallel with biopsy for diagnostic confirmation for patients presenting with suspected advanced lung cancer. Early liquid biopsy in aNSCLC in parallel with path dx is associated with shorter time to treatment. [ABSTRACT FROM AUTHOR]

Video slot machines (VSM) are considered a particularly harmful gambling format; however, scant data is available on their use among underage Italian individuals. Two surveys were conducted in 2018 and 2022 involving 7,959 underage high school students (57.8% female) in Pavia, Northern Italy. We estimated adjusted odds ratios (aOR) and corresponding 95% confidence intervals (CI) for lifetime experience and current regular (at least monthly) use of VSM, according to family, educational and behavioral factors. Overall, participants reporting lifetime VSM experience were 13.2% (95% CI: 12.5 − 13.9), 15.2% (95% CI: 14.0–16.4%) in 2018, and 12.0% (95% CI: 11.1–13.0%) in 2022. Current regular VSM users were 1.4% (95% CI: 1.1–1.7) in total, 1.2% (95% CI: 0.8–1.6%) in 2018 and 1.5% (95% CI: 1.1–1.8%) in 2022. VSM lifetime experience and current regular use were significantly more frequent in males (aORs: 1.55 and 4.81, respectively), students who failed a year (aORs: 2.07 and 3.44), or with daily gambling parents/siblings (aORs: 2.83 and 4.86). Lifetime use of alcohol, tobacco, or illicit substances was significantly directly associated with lifetime VSM use (aORs between 2.64 and 4.75); monthly alcohol, tobacco, or illicit substances use was significantly directly associated with current regular VSM use (aORs between 4.47 and 18.21). Sexting and voluntary self-injury were significantly more frequent among VSM lifetime/current regular users. VSM use, which is directly associated with other risky behaviors, may be pervasive among Italian minors. Such public health concern calls for legislative enforcements and integrated multidisciplinary health promotion and prevention strategies. [ABSTRACT FROM AUTHOR]

Purpose: Hashimoto's thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFβ1) in HT patients with different patterns of thyroid function. Methods: A total of 29 HT patients, with a median age of 52 years (21–68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFβ1 assayed by ELISA. Results: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = −0.60, P < 0.01). Serum TGFβ1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFβ1 (r = −0.75, P < 0.01). Conclusions: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFβ1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFβ1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT. [ABSTRACT FROM AUTHOR]

Marine biodiversity monitoring in the Mediterranean's increasingly threatened ecosystems is crucial for effective ecosystem conservation and management. Here, we leveraged the Mediterranean International Trawl Survey program (MEDITS) to implement eDNA sampling through the recently tested 'metaprobe' procedure and characterize fish assemblages in three separate areas off the Italian coasts: Northern Adriatic Sea (NoAS), Ligurian and Northern Tyrrhenian Sea (LNTS), and Sardinian Sea (SaS). By combining the information from two homologous mitochondrial 12S metabarcodes––i.e., Elas02 and Tele02 targeting elasmobranchs and teleosts, respectively––we identified 108 species, over 60% of which overlapped with those caught by the trawl net. We produced an accurate reconstruction of fish community composition of the examined sites, reflecting differences in species assemblages linked with both geographic area and depth range. Metaprobe eDNA data consistently returned a biodiversity 'bonus' mostly consisting of pelagic taxa not captured through bottom trawl surveys, including rare and endangered taxa (e.g., elasmobranchs). Overall, the spatial characterisation of the assemblages across the surveyed areas was better delineated and more robust using eDNA metabarcoding than trawl data. Our results support the operationalisation of the metaprobe as a simple, inexpensive, versatile sampling tool, in association with pre-existing ship surveys, to overcome many of the limitations of marine data collection and strengthen marine management. [ABSTRACT FROM AUTHOR]

Anxiety is very pertinent to systemic family therapy (SFT), however, there is little research that seeks to understand people's experiences with anxiety symptoms and how they impact people's lives and relationships. The aim of this study was to examine the trending hashtag #ThisIsWhatAnxietyFeelsLike—a commonly used hashtag related to anxiety—to look more closely at how users talk about their anxiety symptoms on Twitter and how these symptoms influence people's interactions and relationships with others. We used a qualitative thematic analysis to analyze 1318 relational tweets posted with this hashtag that occurred between February 2017 and February 2018 and uncover themes related to experiences with anxiety. The analysis revealed six core themes: (a) deflated self in relation to others and their perceptions; (b) fear, worry and avoidance behaviors that influence relationships; (c) negative emotional responses leading to feeling misunderstood, lonely, and like a failure; (d) social triggers; (e) anxiety management strategies; and (f) things for others to avoid. [ABSTRACT FROM AUTHOR]

Background and Purpose: To date, there are limited options for severe Coronavirus disease 2019 (COVID‐19), caused by SARS‐CoV‐2 virus. As ADP‐ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID‐19. Experimental Approach: The effects of PARP inhibitors on virus uptake were assessed in cell‐based experiments using multiple variants of SARS‐CoV‐2. The binding of rucaparib to spike protein was tested by molecular modelling and microcalorimetry. The anti‐inflammatory properties of rucaparib were demonstrated in cell‐based models upon challenging with recombinant spike protein or SARS‐CoV‐2 RNA vaccine. Key Results: We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID‐19 patients, both of which negatively correlated with lymphocytopaenia. Interestingly, rucaparib, unlike other tested PARP inhibitors, reduced the SARS‐CoV‐2 infection rate through binding to the conserved 493–498 amino acid region located in the spike‐ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein and viral RNA‐induced overexpression of cytokines was down‐regulated by the inhibition of PARP1 by rucaparib at pharmacologically relevant concentrations. Conclusion and Implications: These results point towards repurposing rucaparib for treating inflammatory responses in COVID‐19. [ABSTRACT FROM AUTHOR]

Purpose: To investigate longitudinal associations between the vitamin D status and inflammatory markers in children and adolescents. Methods: Children from eight European countries from the IDEFICS/I.Family cohort with repeated measurements were included in this study. A linear mixed-effect model was used to model the association of serum 25(OH)D as independent variable and z-scores of inflammatory markers [CRP, cytokines, adipokines, combined inflammation score] as dependent variables, where one level accounts for differences between individuals and the other for changes over age within individuals. Results: A total of 1,582 children were included in the study. In the adjusted model, 25(OH)D levels were positively associated with adiponectin (β = 0.11 [95% CI 0.07; 0.16]) and negatively with the inflammation score (β = − 0.24 [95% CI − 0.40; − 0.08]) indicating that the adiponectin z-score increased by 0.11 units and the inflammation score decreased by 0.24 units per 12.5 nmol/l increase in 25(OH)D. In children with overweight or obesity, only a positive association between 25(OH)D and IP-10 was observed while in children with normal weight adiponectin was positively and the inflammation score was negatively associated. Associations of vitamin D with adiponectin and the inflammation score were stronger in girls than in boys and a positive association with TNF-α was observed only in girls. Conclusion: Our results suggest that an increase in vitamin D concentrations may help to regulate inflammatory biomarkers. However, it seems to be no benefit of a better vitamin D status in children with overweight/obesity unless their weight is managed to achieve an improved inflammatory marker status. [ABSTRACT FROM AUTHOR]

A model simulating the initial formation and growth of a phototrophic granular biofilm around wireless light emitter is proposed. The work focuses on the well-posedness and quantitative analysis of the model describing the initiation of the biofilm growth induced by cell attachment in the case of spherical geometry. Biofilm granule generates from the agglomeration of free living cells which lead to the formation of spherical-shaped microbial consortia. Under the hypothesis of radial symmetry, the granular biofilm is modelled as a free boundary domain, where the free boundary is the radius of the granule. The attached species proliferate by consuming dissolved substrates diffusively transported from the bulk liquid within the granule. Granule size evolves over time due to attachment flux, microbial growth and invasion. The evolution of the state variables, that is the concentrations of the microbial cells both in sessile and suspended form and the dissolved substrates, is governed by a nonlinear system of hyperbolic-elliptic differential equations, while the free boundary evolution is governed by an ordinary differential equation. Light intensity provided by the emitter is accounted in the model as a further state variable, as it affects the attachment velocity and metabolic activity of light-dependent microorganisms. By using the method of characteristics, the equations are converted into an equivalent integral system. Existence and uniqueness of solutions are discussed and proved for the attachment regime using fixed point strategies. A numerical study is performed to explore and investigate the role of light-dependent species on the granulation process and how light conditions and concentration of nutrients affect the attachment and granule initiation. [ABSTRACT FROM AUTHOR]

The possibility of inducing value change has attracted interest among scholars and practitioners in developmental and social psychology. This study proposes a new web-based intervention aimed at enhancing the importance adolescents ascribe to social-focused values (i.e., self-transcendence and conservation), which was implemented and evaluated in the context of online schooling during the COVID-19 pandemic. Social-focused values primarily regulate how one relates to others and preserve cooperative relations. These values were found to predict positive outcomes, such as adolescents' well-being, school performance, prosocial behavior, and, most recently, COVID-19 preventive behaviors. The intervention was carried out with a group of 140 high school students (Age: M = 16.53, SD = 0.95) living in Italy during the pandemic. The intervention group (N = 84) completed four tasks, which were based on the value-changing mechanisms of priming, consistency maintenance (raising awareness and knowledge of prosociality), or direct persuasion (trying to convince another person to act prosocially). The intervention significantly increased the importance of conservation values (i.e., tradition, conformity, security) but not of self-transcendence values (i.e., universalism, benevolence) in the intervention group in comparison to the control group (N = 56). This result reflects the reality during the pandemic, where prosociality was more easily expressed through behaviors consistent with conservation values instead of self-transcendence values, which emphasize (physical) proximity to others. The effectiveness of the intervention was further supported by a qualitative analysis of adolescents' writings while completing the tasks. Limitations of the study, future research developments, and practical implications for values education in secondary schools are discussed. [ABSTRACT FROM AUTHOR]

Lung cancer has a significant incidence among the population and, unfortunately, has an unfavourable prognosis in most cases. The World Health Organization (WHO) classifies lung tumours into two subtypes based on their phenotype: the Non-Small Cell Lung Cancer (NSCLC) and the Small Cell Lung Cancer (SCLC). SCLC treatment, despite advances in chemotherapy and radiotherapy, is often unsuccessful for cancer recurrence highlighting the need to develop novel therapeutic strategies. In this review, we describe the genetic landscape and tumour microenvironment that characterize the pathological processes of SCLC and how they are responsible for tumour immune evasion. The immunosuppressive mechanisms engaged in SCLC are critical factors to understand the failure of immunotherapy in SCLC and, conversely, suggest that new signalling pathways, such as cGAS/STING, should be investigated as possible targets to stimulate an innate immune response in this subtype of lung cancer. The full comprehension of the innate immunity of cancer cells is thus crucial to open new challenges for successful immunotherapy in treating SCLC and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The marine drug trabectedin has shown unusual effectiveness in the treatment of myxoid liposarcoma (MLPS), a liposarcoma characterized by the expression of the FUS-DDIT3 chimera. Trabectedin elicits a significant transcriptional response in MLPS resulting in cellular depletion and reactivation of adipogenesis. However, the role of the chimeric protein in the mechanism of action of the drug is not entirely understood. Methods: FUS-DDIT3-specific binding sites were assessed through Chromatin Immunoprecipitation Sequencing (ChIP-Seq). Trabectedin-induced effects were studied on pre-established patient-derived xenograft models of MLPS, one sensitive to (ML017) and one resistant against (ML017ET) trabectedin at different time points (24 and 72 h, 15 days). Data were integrated with RNA-Seq from the same models. Results: Through ChIP-Seq, here we demonstrate that trabectedin inhibits the binding of FUS-DDIT3 to its target genes, restoring adipocyte differentiation in a patient-derived xenograft model of MLPS sensitive to trabectedin. In addition, complementary RNA-Seq data on the same model demonstrates a two-phase effect of trabectedin, characterized by an initial FUS-DDIT3-independent cytotoxicity, followed by a transcriptionally active pro-differentiation phase due to the long-lasting detachment of the chimera from the DNA. Interestingly, in a trabectedin-resistant MLPS model, the effect of trabectedin on FUS-DDIT3 rapidly decreased over time, and prolonged treatment was no longer able to induce any transcription or post-transcriptional modifications. Conclusions: These findings explain the unusual mechanism underlying trabectedin's effectiveness against MLPS by pinpointing the chimera's role in inducing the differentiation block responsible for MLPS pathogenesis. Additionally, the findings hint at a potential mechanism of resistance acquired in vivo. [ABSTRACT FROM AUTHOR]