Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial.

Background: Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations.

Autoimmune-Like Mechanism in Heart Failure Enables Preventive Vaccine Therapy.

Background: Heart failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO-HF might fulfill the often-used criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF; it should also be possible to identify self-antigens driving the autoimmune response.

C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer.

NK cells are endowed with tumor killing ability, nevertheless most cancers impair NK cell functionality, and cell-based therapies have limited efficacy in solid tumors. How cancers render NK cell dysfunctional is unclear, and overcoming resistance is an important immune-therapeutic aim. Here, we identify autophagy as a central regulator of NK cell anti-tumor function.

Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites.

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.

From Adolescence to Adulthood: Understanding Care Trajectories in an Early Detection and Intervention Centre in France.

Background: Psychiatric disorders often emerge during adolescence or young adulthood, leading to significant disability among youth. The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) is critical for individuals experiencing emerging psychopathology, with delayed access to care negatively impacting long-term outcomes. Accessing mental health services for adolescents and young adults is often complex and delayed due to challenges in service visibility, accessibility and appropriateness.

Integrated approach to generate artificial samples with low tumor fraction for somatic variant calling benchmarking.

Background: High-throughput sequencing (HTS) has become the gold standard approach for variant analysis in cancer research. However, somatic variants may occur at low fractions due to contamination from normal cells or tumor heterogeneity; this poses a significant challenge for standard HTS analysis pipelines. The problem is exacerbated in scenarios with minimal tumor DNA, such as circulating tumor DNA in plasma.

Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report.

Background: We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks' recurrence.

Case Report: A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly).

In-Silico Identification of Novel Pharmacological Synergisms: The Trabectedin Case.

The in-silico strategy of identifying novel uses for already existing drugs, known as drug repositioning, has enhanced drug discovery. Previous studies have shown a positive correlation between expression changes induced by the anticancer agent trabectedin and those caused by irinotecan, a topoisomerase I inhibitor. Leveraging the availability of transcriptional datasets, we developed a general in-silico drug-repositioning approach that we applied to investigate novel trabectedin synergisms.

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.

Erythropoietic protoporphyria: case reports for clinical and therapeutic hints.

Background: Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity.

A pan-cancer landscape of pathogenic somatic copy number variations.

Objective: Copy number variations (CNVs) play crucial roles in physiological and pathological processes, including cancer. However, the functional implications of somatic CNVs in tumor progression and evolution remain unclear. This study focuses on identifying CNV alterations with high pathogenic potential that drive and sustain tumorigenesis, distinguishing them from passenger alterations that accumulate during tumor growth.

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.

ICARUS at the Fermilab Short-Baseline Neutrino program: initial operation.

The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation.

Emotional status of children aged 7 to 17 of health workers and in the general population during the COVID-19 pandemic: A cross-sectional comparative study in Belgium.

Background: We assessed the mental health of children and adolescents aged 7 to 17 and their parents immediately after the first wave of the COVID-19 pandemic.

Method: A survey online was conducted in Belgium between May 29th and August 31st 2020.

Results: (1) Anxious and depressive symptoms were self-reported by one out of four children and hetero-reported by parents for one out of five children; (2) Anxiety scores were higher in children compared to adolescents; (3) Social introversion scores were significantly higher in adolescents compared to children; (4) No significant differences for anxio-depressive symptoms were found between healthcare worker parents and the other parents.

Machine Learning Application Identifies Germline Markers of Hypertension in Patients With Ovarian Cancer Treated With Carboplatin, Taxane, and Bevacizumab.

Pharmacogenomics studies how genes influence a person's response to treatment. When complex phenotypes are influenced by multiple genetic variations with little effect, a single piece of genetic information is often insufficient to explain this variability. The application of machine learning (ML) in pharmacogenomics holds great potential - namely, it can be used to unravel complicated genetic relationships that could explain response to therapy.

Coping with the mental health impact of COVID-19: A study protocol for a multinational longitudinal study on coping and resilience during the COVID-19 pandemic.

Background: Mental health is challenged due to serious life events such as the COVID-19 pandemic and can differ by the level of resilience. National studies on mental health and resilience of individuals and communities during the pandemic provide heterogeneous results and more data on mental health outcomes and resilience trajectories are needed to better understand the impact of the pandemic on mental health in Europe.

Methods: COPERS (Coping with COVID-19 with Resilience Study) is an observational multinational longitudinal study conducted in eight European countries (Albania, Belgium, Germany, Italy, Lithuania, Romania, Serbia, and Slovenia).

Dimensional model on how familial vulnerability and environmental factors impact transitional age youth psychopathology: The study.

Background: Understanding psychopathology in transitional age youth (TAY) requires a complex model, incorporating familial vulnerability and environmental factors. A trans-diagnostic and dimensional approach seems the most appropriate. study aims to assess factors playing a role in TAY psychopathology and to define predictors.

High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis.

Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance.

A comprehensive investigation of histotype-specific microRNA and their variants in Stage I epithelial ovarian cancers.

isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In our study, we explored for the first time the expression of isomiRs across different Stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multicentric retrospective cohort of tumor biopsies (n = 215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs.

A wicked environmental challenge: collaboration network for free-ranging dog management in an urban environment.

Invasive species possess wide-ranging social and ecological impacts globally. Although the ecological impacts are well studied, social aspects especially in developing countries are often poorly understood. Free-ranging dogs (FRDs) (Canis familiaris) are the most abundant carnivore on earth with a high level of invasion.

Case report: From anxiety disorders to psychosis, a continuum in transitional age youth?

Introduction: To date, among individuals meeting ultra-high risk criteria for psychosis, the relationship between the presence of anxiety disorders and the risk of psychotic transition raises several unanswered questions.

Case Description: This case report describes the clinical progression of a 17-year-old male initially presenting anxious symptoms meeting the DSM-V criteria for panic disorder. The patient also reported social withdraw, mild depressive symptoms, insomnia and fatigue.

Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial.

Background: The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms.