An Optimized NGS Workflow Defines Genetically Based Prognostic Categories for Patients with Uveal Melanoma.

Background: Despite advances in uveal melanoma (UM) diagnosis and treatment, about 50% of patients develop distant metastases, thereby displaying poor overall survival. Molecular profiling has identified several genetic alterations that can stratify patients with UM into different risk categories. However, these genetic alterations are currently dispersed over multiple studies and several methodologies, emphasizing the need for a defined workflow that will allow standardized and reproducible molecular analyses.

A Digital Workflow for Automated Assessment of Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma Using QuPath and a StarDist-Based Model.

The search for reliable prognostic markers in oral squamous cell carcinoma (OSCC) remains a critical need. Tumor-infiltrating lymphocytes (TILs), particularly T lymphocytes, play a pivotal role in the immune response against tumors and are strongly correlated with favorable prognoses. Computational pathology has proven highly effective for histopathological image analysis, automating tasks such as cell detection, classification, and segmentation.

A machine learning approach to predict HPV positivity of oropharyngeal squamous cell carcinoma.

HPV status is an important prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), with HPV-positive tumors associated with better overall survival. To determine HPV status, we rely on the immunohistochemical investigation for expression of the P16 protein, which must be associated with molecular investigation for the presence of viral DNA. We aim to define a criterion based on image analysis and machine learning to predict HPV status from hematoxylin/eosin stain.

Interventional cytopathologist perspective on the Milan System Classification: a study on 929 consecutive salivary gland fine-needle aspirations with a focus on challenging diagnostic categories.

Background: Although the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has improved the diagnosis and management of salivary gland lesions, determining the risk of malignancy (ROM) for AUS and SUMP categories remains challenging. We investigated the role of interventional cytopathologists in refining the differential diagnosis of these categories.

Methods: We searched for salivary gland fine-needle aspirations (FNAs) performed at our Institution since the publication of the first edition of MSRSGC.

Leveraging deep learning for identification and segmentation of "CAF-1/p60-positive" nuclei in oral squamous cell carcinoma tissue samples.

In the current study, we introduced a unique method for identifying and segmenting oral squamous cell carcinoma (OSCC) nuclei, concentrating on those predicted to have significant CAF-1/p60 protein expression. Our suggested model uses the StarDist architecture, a deep-learning framework designed for biomedical image segmentation tasks. The training dataset comprises painstakingly annotated masks created from tissue sections previously stained with hematoxylin and eosin (H&E) and then restained with immunohistochemistry (IHC) for p60 protein.

SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity.

Time to Recurrence of Intracranial Meningiomas from a Monoinstitutional Surgical Series.

Background: Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to recurrence. Our purpose was to identify main factors affecting the time to recurrence to assist preoperative treatment decision-making strategy and to define a tailored clinical and neuroradiological follow-up.

A deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma.

Anatomical pathology is undergoing its third revolution, transitioning from analogical to digital pathology and incorporating new artificial intelligence technologies into clinical practice. Aside from classification, detection, and segmentation models, predictive models are gaining traction since they can impact diagnostic processes and laboratory activity, lowering consumable usage and turnaround time. Our research aimed to create a deep-learning model to generate synthetic Ki-67 immunohistochemistry from Haematoxylin and Eosin (H&E) stained images.

Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification.

Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, βFSH, βLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases.

DSM 17938 reverses gut metabolic dysfunction induced by Western diet in adult rats.

Introduction: Microencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance.

Methods: Male Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated DSM 17938 (WRM).

Immunohistochemical expression of PRAME is a marker of poor prognosis in uveal melanoma: A clinico-pathologic and immunohistochemical study on a series of 85 cases.

PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, first isolated in tumor-reactive T-cell clones from a metastatic melanoma patient. It has been widely studied in skin pathology as an immunohistochemical marker capable of distinguishing between benign nevi and malignant melanomas. PRAME has been found to be also expressed in non-melanocytic tumors, including lung, breast, kidney and ovarian cancer.

Outcomes of Thoracoscopic Lobectomy after Recent COVID-19 Infection.

Background: The COVID-19 outbreak had a massive impact on lung cancer patients with the rise in the incidence and mortality of lung cancer.

Methods: We evaluated whether a recent COVID-19 infection affected the outcome of patients undergoing thoracoscopic lobectomy for lung cancer using a retrospective observational mono-centric study conducted between January 2020 and August 2022. Postoperative complications and 90-day mortality were reported.

Age-Dependent Skeletal Muscle Mitochondrial Response to Short-Term Increased Dietary Fructose.

The harmful effect of a long-term high-fructose diet is well established, but the age-dependent physiological responses that can be triggered by a short-term high-fructose diet in skeletal muscles have not been deeply explored. Therefore, the aim of this work was to compare the alterations in mitochondrial energetic and insulin responsiveness in the skeletal muscle induced by a short-term (2 weeks) fructose feeding in rats of different ages. For this purpose, fructose and uric acid levels, insulin sensitivity, mitochondrial bioenergetics and oxidative status were evaluated in the skeletal muscles from young (30 days old) and adult (90 days old) rats.

SARS-CoV-2 Spike Protein Activates Human Lung Macrophages.

COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells.

Skeletal muscle insulin resistance and adipose tissue hypertrophy persist beyond the reshaping of gut microbiota in young rats fed a fructose-rich diet.

To investigate whether short term fructose-rich diet induces changes in the gut microbiota as well as in skeletal muscle and adipose tissue physiology and verify whether they persist even after fructose withdrawal, young rats of 30 d of age were fed for 3 weeks a fructose-rich or control diet. At the end of the 3-weeks period, half of the rats from each group were maintained for further 3 weeks on a control diet. Metagenomic analysis of gut microbiota and short chain fatty acids levels (faeces and plasma) were investigated.

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

Background: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies.

Methods: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA.

The methyltransferase domain of DNMT1 is an essential domain in acute myeloid leukemia independent of DNMT3A mutation.

Aberrant DNA methylation patterns are a prominent feature of cancer. Methylation of DNA is mediated by the DNA methyltransferase (DNMT) protein family, which regulates de novo (DNMT3A and DNMT3B) and maintenance (DNMT1) methylation. Mutations in DNMT3A are observed in approximately 22% of acute myeloid leukemia (AML).

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art.

Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes.

Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosome‒positive leukemias.

The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph+ patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment.

Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation.