Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia.

Background: Myeloid neoplasms, including acute myeloid leukemia, have been traditionally among the less investigated cancer types concerning germline predisposition. Indeed, myeloid neoplasms with germline predisposition are challenging to identify because often display similar clinical and morphological characteristics of sporadic cases and have similar age at diagnosis. However, a misidentifications of familiarity in myeloid neoplasms have a critical impact on clinical management both for the carriers and their relatives.

Pharmacogenetics in Italy: current landscape and future prospects.

Pharmacogenetics investigates sequence of genes that affect drug response, enabling personalized medication. This approach reduces drug-induced adverse reactions and improves clinical effectiveness, making it a crucial consideration for personalized medical care. Numerous guidelines, drawn by global consortia and scientific organizations, codify genotype-driven administration for over 120 active substances.

Predelivery sonographic predictors of obstetric anal sphincter injury among nulliparous women.

Objective: Data available at admission to delivery of nulliparous has rarely been investigated for prediction of obstetric anal sphincter injury (OASI). The aim of the present study was to study risk factors for OASI in nulliparous based on information available at admission.

Methods: A retrospective study of all nulliparous women undergoing labor, during March 2011 to January 2021 was performed.

High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors.

Unlabelled: Risk and outcome of acute promyelocytic leukemia (APL) are particularly worsened in obese-overweight individuals, but the underlying molecular mechanism is unknown. In established mouse APL models (Ctsg-PML::RARA), we confirmed that obesity induced by high-fat diet (HFD) enhances leukemogenesis by increasing penetrance and shortening latency, providing an ideal model to investigate obesity-induced molecular events in the preleukemic phase. Surprisingly, despite increasing DNA damage in hematopoietic stem cells (HSC), HFD only minimally increased mutational load, with no relevant impact on known cancer-driving genes.

Acknowledging and citing core facilities: Key contributions to data lifecycle should be recognised in the scientific literature: Key contributions to data lifecycle should be recognised in the scientific literature.

Core facilities play a central role in the life sciences by generating data and ensuring quality standards. Their contributions to research should be appropriately acknowledged or cited in research papers.

HDAC6 inhibition decreases leukemic stem cell expansion driven by Hedgehog hyperactivation by restoring primary ciliogenesis.

Aberrant activation of the Hh pathway promotes cell proliferation and multi-drug resistance (MDR) in several cancers, including Acute Myeloid Leukemia (AML). Notably, only one Hh inhibitor, glasdegib, has been approved for AML treatment, and most patients eventually relapse, highlighting the urgent need to discover new therapeutic targets. Hh signal is transduced through the membrane of the primary cilium, a structure expressed by non-proliferating mammalian cells, whose stabilization depends on the activity of HDAC6.

Hematological disorders after salvage PARPi treatment for ovarian cancer: Cytogenetic and molecular defects and clinical outcomes.

Inhibitors of poly(ADP-ribose) polymerase (PARPi) are increasingly employed as salvage therapy in epithelial ovarian cancer (EOC), but cytotoxic drug exposure along with PARP inhibition may favor development of hematological disorders. In our study, of 182 women with EOC treated with PARPi, 16 (8.7%) developed therapy-related myeloid neoplasms (t-MNs), with 12 cases of myelodysplasia and 4 of acute myeloid leukemia.

Cohesin Mutations Induce Chromatin Conformation Perturbation of the / Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines.

Traditionally, Cornelia de Lange Syndrome (CdLS) is considered a cohesinopathy caused by constitutive mutations in cohesin complex genes. Cohesin is a major regulator of chromatin architecture, including the formation of chromatin loops at the imprinted / domain. We used 3C analysis on lymphoblastoid cells from CdLS patients carrying mutations in and genes to explore 3D chromatin structure of the /  and evaluate the influence of cohesin alterations in chromatin architecture.

Biomedical omics: first insights of a new MSc degree of the University of Milan.

The advent of technologies allowing the global analysis of biological phenomena, referred to as "omics" (genomics, epigenomics, proteomics, metabolomics, microbiomics, radiomics, and radiogenomics), has revolutionized the study of human diseases and traced the path for quantitative personalized medicine. The newly inaugurated Master of Science Program in Biomedical Omics of the University of Milan, Italy, aims at addressing the unmet need to create professionals with a broad understanding of omics disciplines. The course is structured over 2 years and admits students with a bachelor's degree in biotechnology, biology, chemistry, or pharmaceutical sciences.

Dual targeting of the DNA damage response pathway and BCL-2 in diffuse large B-cell lymphoma.

Standard chemotherapies for diffuse large B-cell lymphoma (DLBCL), based on the induction of exogenous DNA damage and oxidative stress, are often less effective in the presence of increased MYC and BCL-2 levels, especially in the case of double hit (DH) lymphomas harboring rearrangements of the MYC and BCL-2 oncogenes, which enrich for a patient's population characterized by refractoriness to anthracycline-based chemotherapy. Here we hypothesized that adaptive mechanisms to MYC-induced replicative and oxidative stress, consisting in DNA damage response (DDR) activation and BCL-2 overexpression, could represent the biologic basis of the poor prognosis and chemoresistance observed in MYC/BCL-2-positive lymphoma. We first integrated targeted gene expression profiling (T-GEP), fluorescence in situ hybridization (FISH) analysis, and characterization of replicative and oxidative stress biomarkers in two independent DLBCL cohorts.

A dynamic prediction score for obstetric anal sphincter injury among nulliparous women delivering vaginally.

Objective: To develop a risk score for obstetric anal sphincter injury (OASI) occurrence among nulliparous women delivering vaginally, based on data available at admission for delivery and as labor progresses.

Methods: A retrospective study of all nulliparous women who delivered vaginally between March 2011 and January 2021. Characteristics were compared between OASI and no-OASI groups.

Risk factors for obstetric anal sphincter injury among women undergoing a trial of labor after cesarean.

Objective: Data regarding the risks of obstetrical anal sphincter injury (OASI) among women who never delivered vaginally undergoing a trial of labor after cesarean (TOLAC) are scarce. We aimed to evaluate the risk factors and the rate of OASI among women undergoing TOLAC who never delivered vaginally.

Study Design: A retrospective cohort study of all women undergoing a TOLAC and never delivered vaginally between 3/2011 and 6/2020.

HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia.

Histone deacetylase 8 (HDAC8), a class I HDAC that modifies non-histone proteins such as p53, is highly expressed in different hematological neoplasms including a subtype of acute myeloid leukemia (AML) bearing inversion of chromosome 16 [inv(16)]. To investigate HDAC8 contribution to hematopoietic stem cell maintenance and myeloid leukemic transformation, we generated a zebrafish model with Hdac8 overexpression and observed an increase in hematopoietic stem/progenitor cells, a phenotype that could be reverted using a specific HDAC8 inhibitor, PCI-34051 (PCI). In addition, we demonstrated that AML cell lines respond differently to PCI treatment: HDAC8 inhibition elicits cytotoxic effect with cell cycle arrest followed by apoptosis in THP-1 cells, and cytostatic effect in HL60 cells that lack p53.

The association between vacuum-assisted vaginal delivery and anal sphincter injury.

Introduction: Vacuum-assisted vaginal delivery (VAVD) is considered a major risk factor for obstetric anal sphincter injuries (OASIS). However, it is difficult to estimate its true contribution to the occurrence of OASIS, as its performance may be confounded by other determinants. Therefore, we aimed to evaluate the association of VAVD with OASIS among primiparous women compared to SVD.

Fractional-Pixel CO Laser Treatment in Patients With Urodynamic Stress Urinary Incontinence: 1-Year Follow-Up.

Background And Objectives: Vaginal pixelated low power and long pulses (LPLP) CO laser has been suggested as an optional treatment for stress urinary incontinence (SUI) with many studies reporting short-term improvements. The objective of this study was to assess the 1-year subjective and objective efficacy of vaginal CO laser in women with urodynamic SUI.

Study Design/materials And Methods: This was a prospective multicenter study.

Risk of anal sphincter injury in trial of labor post cesarean section.

Introduction: We wanted to evaluate whether secundiparas who achieved vaginal birth after cesarean (VBAC) were at an increased risk for obstetric anal sphincter injury (OASI) compared to primiparas who delivered vaginally, with a stratification by the mode of delivery-spontaneous or operative vaginal delivery.

Material And Methods: We conducted a retrospective cohort study of primiparous women who delivered by vacuum-assisted delivery between March 2011 and June 2019. Primiparas delivering vaginally and secundiparas undergoing VBAC were compared.

Magnetic imaging defecography results are comparable to high-resolution manometry and conventional X-ray defecography in the assessment of functional pelvic floor disorders.

Background: X-ray defecography or magnetic resonance defecography (MRD) and high-resolution anorectal manometry (HR-ARM) are essential for the diagnosis of pelvic floor disorders (PFD). However, there is only scarce information available about the accuracy of MRD in the functional assessment of the pelvic floor. The aim of this study was to examine the accuracy of MRD in the diagnosis of pelvic floor disorders by examining the intra-test agreement with x-ray defecography and HR-ARM in patients with PFD.

Validation of the Wexner scale in a Hebrew-speaking population.

Introduction: The Cleveland Clinic Incontinence Score, known as the Wexner Score (WS), is a simple, disease-specific questionnaire for anal incontinence (AI) assessment. We aimed to translate and validate a Hebrew version of the WS.

Methods: Between November 2018 and December 2019, the WS was back translated and reviewed by a multidisciplinary pelvic floor team.

The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

Aim: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs).

Method: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences.

Has Drug Repurposing Fulfilled its Promise in Acute Myeloid Leukaemia?

Drug repurposing is a method of drug discovery that consists of finding a new therapeutic context for an old drug. Compound identification arises from screening of large libraries of active compounds, through interrogating databases of cell line gene expression response upon treatment or by merging several types of information concerning disease-drug relationships. Although, there is a general consensus on the potential and advantages of this drug discovery modality, at the practical level to-date no non-anti-cancer repurposed compounds have been introduced into standard acute myeloid leukaemia (AML) management, albeit that preclinical validation yielded several candidates.

The role of fetal head circumference in the formation of obstetric anal sphincter injuries following vacuum deliveries among primiparous women.

Purpose: To evaluate the association of sonographic fetal head circumference (HC) with obstetric anal sphincter injury (OASIS) occurrence among primiparous women who underwent vacuum-assisted delivery (VAD).

Methods: A retrospective study of all primiparous women who delivered at term by VAD between 2011 and 2019 and underwent ultrasound with fetal biometry within 1 week prior to delivery. Women who suffered OASIS were compared to women without OASIS.

Sonographic fetal head circumference and the risk of obstetric anal sphincter injury following vaginal delivery.

Introduction: High birth weight is strongly associated with OASIS; nevertheless, it has not been determined which biometric characteristics most affect OASIS occurrence. We aimed to evaluate the association of estimated fetal head circumference with OASIS occurrence among primiparous women delivering by unassisted vaginal delivery.

Methods: A retrospective study included all primiparous women who delivered at term by spontaneous vaginal delivery from 2011-2019.

Wnt Signalling in Acute Myeloid Leukaemia.

Acute myeloid leukaemia (AML) is a group of malignant diseases of the haematopoietic system. AML occurs as the result of mutations in haematopoietic stem/progenitor cells, which upregulate Wnt signalling through a variety of mechanisms. Other mechanisms of Wnt activation in AML have been described such as Wnt antagonist inactivation through promoter methylation.