Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer.

Uveal melanoma (UM) is the most common intraocular cancer in adults, with metastatic disease (mUM) occurring in approximately half of the patients. Tebentafusp, an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC), is a therapeutic shown to improve overall survival (OS) in HLA-A*02:01 adult patients with mUM. Here we investigate the impact of tumor-associated macrophages (TAM) on ImmTAC activity.

Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells.

Sarcomas are rare, mesenchymal tumors, representing about 10-15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use of iCasp9.

Freezing of movements and its correspondence with MLG1 neuron response to looming stimuli in the crab Neohelice.

Upon visually detecting a moving predator, animals often freeze, i.e. stop moving, to minimize being uncovered and to gather detailed information of the object's movements and properties.

From data to practice: brain meningioma treatment in elderly patients - a survey of the Italian Society of Neurosurgery (SINch®) and systematic review and meta-analysis.

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature.

Asymptomatic Empty Sella Syndrome: A "New" Hypothalamic Pathology or Paraphysiological Variant.

Introduction: The term empty sella refers to a shrunken or displaced (by a subarachnoid diverticulum) pituitary gland. It can be primary (genetically determined) or secondary (due to trauma/surgery/radiation). It has been reported that 50% of patients are asymptomatic, and others experience symptoms, such as headache, hypertension, or visual field defects.

Aging and putative frailty biomarkers are altered by spaceflight.

Human space exploration poses inherent risks to astronauts' health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth.

Ethical considerations for the age of non-governmental space exploration.

Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.

Diabulimia and Type 1 Diabetes: An Unknown and Emerging Problem.

Background: T1DM patients have a higher prevalence of eating disorders than the general population, and up to 30-40% of young T1DM patients suffer from an eating disorder, including diabulimia. Eating disorders worsen glycemic control and make insulin therapy management more difficult. Closed loop systems (HCLS) allow major therapeutic flexibility; however, proper carbohydrate (CHO) counting remains a fundamental feature for insulin dose adjustments.

Pathophysiological basis of the cardiological benefits of SGLT-2 inhibitors: a narrative review.

In recent years, GLP-1 receptor agonists (GLP-1RA), and SGLT-2 inhibitors (SGLT-2i) have become available, which have become valuable additions to therapy for type 2 diabetes as they are associated with low risk for hypoglycemia and cardiovascular benefits. Indeed, SGLT-2i have emerged as a promising class of agents to treat heart failure (HF). By inhibiting SGLT-2, these agents lead to excretion of glucose in urine with subsequent lowering of plasma glucose, although it is becoming clear that the observed benefits in HF cannot be explained by glucose-lowering alone.

Adaptive Staged-Dose Gamma Knife Radiosurgery for the Treatment of Large Brain Metastases: Report of 40 Consecutive Cases and Analysis of Literature.

Background: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic radiosurgery is efficacious and safe in the treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity.

Matched function of the neuropil processing optic flow in flies and crabs: the lobula plate mediates optomotor responses in .

When an animal rotates (whether it is an arthropod, a fish, a bird or a human) a drift of the visual panorama occurs over its retina, termed optic flow. The image is stabilized by compensatory behaviours (driven by the movement of the eyes, head or the whole body depending on the animal) collectively termed optomotor responses. The dipteran lobula plate has been consistently linked with optic flow processing and the control of optomotor responses.

Stereotactic Radiosurgery with Gamma Knife in Recurrent Rathke's Cleft Cyst: Case Report and Literature Analysis.

Background: Rathke's cleft cyst is a benign expansive lesion of the sella turcica. If related to clinical disorders, the patient needs surgical treatment.

Objective: To demonstrate the efficacy of radiosurgery in the treatment of relapse of Rathke's cleft cyst as an alternative to surgery.

Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review.

Outer space is an extremely hostile environment for human life, with ionizing radiation from galactic cosmic rays and microgravity posing the most significant hazards to the health of astronauts. Spaceflight has also been shown to have an impact on established cancer hallmarks, possibly increasing carcinogenic risk. Terrestrially, women have a higher incidence of radiation-induced cancers, largely driven by lung, thyroid, breast, and ovarian cancers, and therefore, historically, they have been permitted to spend significantly less time in space than men.

Antibody Response to COVID-19 mRNA Vaccines in Oncologic and Hematologic Patients Undergoing Chemotherapy.

Background: Information on immune responses in cancer patients following mRNA COVID-19 vaccines is still insufficient, but generally, patients had impaired serological responses, especially those with hematological malignancies. We evaluated serological response to COVID-19 mRNA vaccine in cancer patients receiving chemotherapy compared with healthy controls.

Methods: In total, 195 cancer patients and 400 randomly selected controls who had been administered a Pfizer-BioNTech or Moderna COVID-19 vaccines in two doses were compared.

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study.

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m during induction or maintenance.

Targeting cancer stem cells in medulloblastoma by inhibiting AMBRA1 dual function in autophagy and STAT3 signalling.

Medulloblastoma (MB) is a childhood malignant brain tumour comprising four main subgroups characterized by different genetic alterations and rate of mortality. Among MB subgroups, patients with enhanced levels of the c-MYC oncogene (MB) have the poorest prognosis. Here we identify a previously unrecognized role of the pro-autophagy factor AMBRA1 in regulating MB.

Innovative and Promising Strategies to Enhance Effectiveness of Immunotherapy for CNS Tumors: Where Are We?

Although there are several immunotherapy approaches for the treatment of Central Nervous System (CNS) tumors under evaluation, currently none of these approaches have received approval from the regulatory agencies. CNS tumors, especially glioblastomas, are tumors characterized by highly immunosuppressive tumor microenvironment, limiting the possibility of effectively eliciting an immune response. Moreover, the peculiar anatomic location of these tumors poses relevant challenges in terms of safety, since uncontrolled hyper inflammation could lead to cerebral edema and cranial hypertension.

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts.

Unlabelled: Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk of CD19-/CAR+ leukemic relapse due to inadvertent transduction of leukemia cells.

Background: METHODS: We evaluated the impact of a high percentage of leukemia blast contamination in patient-derived starting material (SM) on CAR T-cell drug product (DP) manufacturing.

An Emerging Innovative UV Disinfection Technology (Part II): Virucide Activity on SARS-CoV-2.

The coronavirus SARS-CoV-2 pandemic has become a global health burden. Surface sanitation is one of the key points to reduce the risk of transmission both in healthcare and other public spaces. UVC light is already used in hospital and laboratory infection control, and some recent studies have shown its effectiveness on SARS-CoV-2.

GD2 redirected CAR T and activated NK-cell-mediated secretion of IFNγ overcomes MYCN-dependent IDO1 inhibition, contributing to neuroblastoma cell immune escape.

Immune escape mechanisms employed by neuroblastoma (NB) cells include secretion of immunosuppressive factors disrupting effective antitumor immunity. The use of cellular therapy to treat solid tumors needs to be implemented. Killing activity of anti-GD2 Chimeric Antigen Receptor (CAR) T or natural killer (NK) cells against target NB cells was assessed through coculture experiments and quantified by FACS analysis.

Multielectrode Recordings From Identified Neurons Involved in Visually Elicited Escape Behavior.

A major challenge in current neuroscience is to understand the concerted functioning of distinct neurons involved in a particular behavior. This goal first requires achieving an adequate characterization of the behavior as well as an identification of the key neuronal elements associated with that action. Such conditions have been considerably attained for the escape response to visual stimuli in the crab .

Restoring global offset and lower limb length with a 3 offset option double-tapered stem.

Background: A proper restoration of hip biomechanics is fundamental to achieve satisfactory outcomes after total hip arthroplasty (THA). A global hip offset (GO) postoperatively reduction of more than 5 mm was known to impair hip functionality after THA. This study aimed to verify the restoration of the GO radiographic parameter after primary THA by the use of a cementless femoral stem available in three different offset options without length changing.