Mario Negri Institute for Pharmacological Research

Causality-integrated graph learning for multi-endpoint toxicity prediction

Toxicity prediction remains a longstanding challenge in the safety assessment of numerous artificial chemicals. While conventional single-endpoint models are effective for predicting many molecular properties, they fail to capture the complex mechanisms underlying toxicity, which...

Off-label prescribing in pediatrics: between regulatory gaps and clinical evidence

Despite important regulatory progress, evidence supporting the use of medicines in children remains limited, and off-label prescribing continues to be common in pediatric practice. Regulatory initiatives such as the United States Pediatric Research Equity Act (PREA) and the Europ...

Evaluating the Role of Anti-PEG Antibodies in Hypersensitivity to PEG-Asparaginase Through Clinically Relevant Cut-Points Defined by ELISA and Surface Plasmon Resonance

Background/Objectives: Conjugation of polyethylene glycol (PEG) to L-asparaginase (ASP) reduces immunogenicity and prolongs the half-life of this biological drug used to treat acute lymphoblastic leukemia (ALL). However, some patients develop anti-drug antibodies (anti-ASP and an...

Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial

Oxaliplatin–fluoropyrimidine combinations are standard adjuvant therapy after radical resection of high-risk stage II and stage III colon cancer but expose many patients to toxicity while failing to prevent relapse in others. PEGASUS was a multicenter, single-arm, phase 2 trial e...

Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC

Abstract Despite a decade in, immunotherapy (IO) treatment selection in non-small cell lung cancer (NSCLC) remains largely guided by subgroup analyses and imperfect programmed death ligand 1 (PD-L1) and clinical scores. To our knowledge, I 3 LUNG ( NCT05537922 ) is currently the...

Exploring Hippuric Acid’s Putative Protective Role in Aging through In Silico and In Vitro Screening

Abstract Hippuric acid (HA) is a diet- and microbiome-derived metabolite consistently associated with healthy aging, yet whether it is a passive biomarker or an active effector remains unresolved. To investigate mechanisms underlying its protective role, in silico screening of la...

Bioactive Nanocoatings Encode Bacterial Settlement Cues for Coral Restoration

Abstract Increasing larval settlement can substantially accelerate coral reef restoration by overcoming a key bottleneck in coral population recovery. Successful settlement depends on biological and chemical cues associated with microbial biofilms and crustose coralline algae tha...

Assistive technologies (lumbar supports and other devices) for treating chronic low back pain

RATIONALE: Low back pain (LBP) is a major global health problem. It is the most common cause of activity limitation amongst individuals younger than 45 years, and one of the most frequent reasons for visits to a doctor. The 2019 Global Burden of Disease study named LBP as the lea...

HPV DNA negativity following AHCC or nonavalent vaccination or their combination in women with persistent HPV infection without HSIL

Persistent infection with high-risk human papillomavirus (HR-HPV) is a common clinical condition for which no validated systemic antiviral therapy is currently available, and in the absence of high-grade cervical lesions management is generally limited to surveillance. Active Hex...

Bone marrow–derived thrombospondin-1 programs tumor cell dormancy via CD47–integrin αvβ3 axis

Dormant disseminated tumor cells are responsible for late metastatic relapses, a current clinical challenge. This study investigates the microenvironmental signals that maintain breast cancer cell quiescence in the bone marrow. 4T1.2-CVp27 cells, engineered to enable quiescence d...

Cholesterol nose-to-brain delivery as a possible therapeutic strategy in Huntington’s disease

Abstract Background Huntington’s disease (HD) is a genetically dominant neurodegenerative disorder characterized by several pathological mechanisms, including the disruption of brain cholesterol homeostasis. In several HD animal models, brain cholesterol biosynthesis and levels a...