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Background Cyclin-Dependent Kinase (CDK) 4/6 inhibitors have significantly improved progression-free survival of Hormone Receptor positive (HR+), Human Epidermal Growth Factor Receptor type 2 negative (HER2-) luminal breast cancers (LBC). Several studies demonstrated that the addition of CDK4/6 inhibitors to endocrine therapy results in a significant prolongation of progression-free survival in patients with endocrine-sensitive or endocrine-resistant LBCs. However, the percentage of patients unresponsive or refractory to these therapies is as high as 40%, and no reliable and reproducible biomarkers able to select a priori responder or resistant patients have been validated till now. The main cause of resistance is the selection of mutant clones in the target oncoprotein. Other mechanisms, like oncogene amplification/overexpression or mutations in other pathways, have been described in several models. Here, we focused on palbociclib, a selective inhibitor of CDK4/6. Methods: We generated and characterized human luminal breast cancer MCF-7 and T47D derived cell lines, able to survive and proliferate at different palbociclib concentrations, which also shows cross-resistance to abemaciclib. The resistant MCF7 cell line was characterized by RNA sequencing. Results: To confirm resistance, we performed cell viability assays in MCF-7 and T47D palbociclib sensitive cells (MCF-7pS and T47pS) versus MCF-7 and T47D palbociclib resistant cells (MCF-7pR5), showing a 10-fold increase of IC50 in MCF-7pR5 compared to parental MCF-7pS cells (16.7 vs 1.8 µM) and a 3-fold increase of IC50 in T47DpR5 vs parental T47DpS. We also confirmed a significant cross resistance using abemaciclib in MCF-7pR5 with an IC50 equal to 6.8 vs 0.35 µM and in T47DpR with an IC50 of 10.72 vs 0.5 µM. RNA sequencing, qRT-qPCR and Western blot results demonstrated a dramatic downregulation of the CDK4 inhibitor CDKN2B in both cell lines and we found upregulation of an miR-31, a putative regulator of CDKN2B. This finding was further validated in a biopsy from a patient progressing on CDK4/6 inhibitor therapy. Conclusions: This study provides new relevant information regarding the mechanism of resistance to CDK4/6 inhibitors and suggests potential new markers to follow up patients during the treatment. Citation Format: Nicoletta Cordani, Luca Mologni, Rocco Piazza, Viola Cogliati, Francesca Pepe, Serena Capici, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Matteo Villa, Pietro Tettamanti, Guido Cavaletti, Marialuisa Lavitrano, Marina Elena Cazzaniga. Loss of CDKN2B expression as a potential marker of resistance to CDK4/6 inhibitor in Luminal Breast Cancer cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-21.

We have read with great interest the scientific literature regarding the diagnosis and treatment of skin cancer during COVID-19 pandemic.1-5 The cancellation of routine dermatologic visits could lead to the risk of neglecting cutaneous melanoma (CM), with potential consequences in terms of morbidity and mortality,1,2 even though the specific impact of the pandemic on CM has yet to be estimated.

(1) Background: The aim of the work is to identify some imaging parameters in osteogenesis imperfecta to assist the dentist in the diagnosis, planning, and orthodontic treatment of Osteogenesis Imperfecta (OI) using 3D cone beam Computed Tomography (CBCT) and the Double Energy X-ray Absorptiometry (DEXA) technique. (2) Methods: 14 patients (9 males and 5 females, aged mean &plusmn, SD 15 &plusmn, 1.5) with a clinical-radiological diagnosis of OI were analyzed and divided into mild and moderate to severe forms. The patients&rsquo, samples were compared with a control group of 14 patients (8 males and 6 females, 1.7), free from osteoporotic pathologies. (3) Results: The statistical analysis allowed us to collect four datasets: in the first dataset (C1 sick population vs. C1 healthy population), the t-test showed a p-value &lt, 0.0001, in the second dataset (C2 sick population vs. C2 healthy population), the t-test showed a p-value &lt, in the third dataset (parameter X of the sick population vs. parameter X of the healthy population), the t-test showed a p-value &lt, in the fourth dataset the bone mineralometry (BMD) value detected by the DEXA technique compared to the C2 value of the OI affected population only) the Welch&ndash, Satterthwaite test showed a p-value &lt, 0.0001. (4) Conclusions: The research has produced specific imaging parameters that assist the dentist in making diagnostic decisions in OI patients. This study shows that patients with OI have a characteristic chin-bearing symphysis, thinned, and narrowed towards the center, configuring it with a constant &ldquo, hourglass&rdquo, appearance, not reported so far in the literature by any author.

Traffic accidents have increased in the last decade, pedestrians being the most affected group. At autopsy, it is evident that the most common cause of pedestrian death is central nervous system injury, followed by skull base fractures, internal bleeding, lower limb haemorrhage, skull vault fractures, cervical spinal cord injury and airway compromise. The attribution of accident responsibility can be realised through reconstruction of road accident dynamics, investigation of the scene, survey of the vehicle involved and examination of the victim(s). A case study concerning a car accident where both humans and pets were involved is reported here. Investigation and reconstruction of the crime scene were conducted by a team consisting of forensic pathologists and forensic veterinarians. At the scene investigation, the pedestrian and his dog were recovered on the side of the road. An autopsy and a necropsy were conducted on the man and the dog, respectively. In addition, a complete inspection of the sports utility vehicle (SUV) implicated in the road accident was conducted. The results of the autopsy and necropsy were compared and the information was used to reconstruct the collision. This unusual case was solved through the collaboration between forensic pathology and veterinary forensic medicine, emphasising the importance of this kind of co-operation to solve a crime scene concerning both humans and animals.

Collaboration is still being debated in public management studies. As specific way of creating public value, the collaborative working is mainly encouraged by the austerity, that implies putting resources together, not only the financial ones. Hence, new forms of service integration are asked in order to improve public service delivery in a more efficient and effectiveness way. Even if public administrations have embraced this trend, the focus adopted is mainly oriented to the planning and the programming approach rather than to the evaluation phase. What is the outcome of public service delivered through a collaborative approach? What is the outcome evaluation of the collaborative process? These kinds of outcome are evaluated? This study aims at investigating which kind of outcome is outlined by the Italian Strategic Cities in their collaborative strategic planning for cultural services delivery. As a main finding, the research extends the knowledge on the outcome evaluation of the collaboration in terms of process and in terms of impact of public services delivered.