HIV-1 transcription start sites usage and its impact on unspliced RNA functions in people living with HIV.

HIV-1 unspliced RNA serves two distinct functions during viral replication: it is packaged into particles as the viral genome, and it is translated to generate Gag/Gag-Pol polyproteins required for virus assembly. Recent studies have demonstrated that in cultured cells, HIV-1 uses multiple transcription start sites to generate several unspliced RNA species, including two major transcripts with three and one 5' guanosine, referred to as 3G and 1G RNA, respectively. Although nearly identical, 1G RNA is selected over 3G RNA to be packaged as the virion genome, indicating that these RNA species are functionally distinct.

Impact of dyslipidemia and lipid-lowering therapy with statins in patients with neuroendocrine tumors.

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included.

Rhino-orbital-cerebral mucormycosis in acute myeloid leukemia patients: a case series from Sri Lanka.

Background: Mucormycosis, is a rare yet potentially life-threatening fungal infection common in immunocompromised patients. Despite optimal care, mucormycosis in haemato-oncological patients often results in poor outcomes. This case series details the presentations and unique challenges faced during the management of patients with acute myeloid leukemia who developed rhino-cerebral mucormycosis.

Vodobatinib overcomes cancer multidrug resistance by attenuating the drug efflux function of ABCB1 and ABCG2.

Multidrug resistance (MDR) remains a significant obstacle in cancer treatment, primarily attributable to the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2 within cancer cells. These transporters actively diminish the effectiveness of cytotoxic drugs by facilitating ATP hydrolysis-dependent drug efflux, thereby reducing intracellular drug accumulation. Given the absence of approved treatments for multidrug-resistant cancers and the established benefits of combining tyrosine kinase inhibitors (TKIs) with conventional anticancer drugs, we investigate the potential of vodobatinib, a potent c-Abl TKI presently in clinical trials, to restore sensitivity to chemotherapeutic agents in multidrug-resistant cancer cells overexpressing ABCB1 and ABCG2.

A COMPARATIVE STUDY OF CARDIOVASCULAR TOXICITY OF EPIRUBICIN AND DOXORUBICIN IN PATIENTS WITH BREAST CANCER.

Unlabelled: Patients with breast cancer (BC) are at high risk of cardiotoxicity (CT) due to combination of anticancer treatment.Cardio-vascular (СV) complications lead to the delay or discontinuation of anticancer therapy, which significantlyworsens the prognosis. Anthracyclines (AC) are the main drugs included in most anticancer treatment regimens.

METHODOLOGY OF RECONSTRUCTION OF INTERNAL DOSES FROM 137Cs AND 134Cs OF RESIDENTS OF RADIOACTIVELY CONTAMINATED SETTLEMENTS IN UKRAINE NOT COVERED BY WBC MONITORING.

Objective: Scientific justification of the methodology for calculating radiation internal doses from 137Cs and 134Cs intake for residents of Ukrainian settlements radioactively contaminated as a result of the Chornobyl (Chernobyl) accident in which measurements of incorporated radiocesium isotopes in humans using whole-body counters (WBC) were not carried out.

Materials And Methods: The paper presents a new methodology for reconstructing doses due to internal irradiation from Chornobyl fallout for both surface (in 1986) and root (in 1987-2023) contamination of vegetation with 137Cs and 134Cs and their transfer into the human body. The methodology for calculating the dose due to surface contamination of vegetation was based on the theoretical model of the transfer of radiocesium isotopes through the food chain with further adjustment of this model to the results of WBC measurements carried out between 15 July and 31 December 1986.

RADIOPHARMACEUTICALS BASED ON ANTAGONISTS OF CHEMOCINE RECEPTOR CXCR4 IN DIAGNOSTICS AND TREATMENT OF ONCOLOGICAL DISEASES.

The review is devoted to the use of a new class of radiopharmaceuticals (RPs) - chemokine receptor ligands - in oncological practice. The chemokine receptor CXCR4 is of particular interest as a molecular target in the diagnosis and treatment of malignant tumors, as it plays an important role in carcinogenesis. By interacting with the chemokine CCXL12, it activates cell signaling pathways that affect tumor cell proliferation, angiogenesis, metastasis growth, and apoptosis inhibition.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats.

Species-specific interferon responses are shaped by the virus-host arms race. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviral IFITM genes that arose by gene duplication. These genes restrict virus entry and are key players in antiviral interferon responses.

RcsF-independent mechanisms of signaling within the Rcs phosphorelay.

The Rcs (regulator of capsule synthesis) phosphorelay is a conserved cell envelope stress response mechanism in enterobacteria. It responds to perturbations at the cell surface and the peptidoglycan layer from a variety of sources, including antimicrobial peptides, beta-lactams, and changes in osmolarity. RcsF, an outer membrane lipoprotein, is the sensor for this pathway and activates the phosphorelay by interacting with an inner membrane protein IgaA.

Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients.

Background: The immune response against tumors relies on distinguishing between self and non-self, the basis of cancer immunotherapy. Neoantigens from somatic mutations are central to many immunotherapeutic strategies and understanding their landscape in breast cancer is crucial for targeted interventions. We aimed to profile neoantigens in Kenyan breast cancer patients using genomic DNA and total RNA from paired tumor and adjacent non-cancerous tissue samples of 23 patients.

Brain tumor-related epilepsy: an overview on neuropsychological, behavioral, and quality of life issues and assessment methodology.

Brain tumor-related epilepsy (BTRE) is a rare disease in which brain tumor (BT) and epilepsy overlap simultaneously and can have a negative impact on a patient's neuropsychological, behavioral, and quality of life (QoL) spheres. In this review we (a) addressed the main neuropsychological, behavioral, and QoL issues that may occur in BTRE patients, (b) described how BT, BTRE, and their respective treatments can impact these domains, and (c) identified tools and standardized evaluation methodologies specific for BTRE patients. Neuropsychological disorders and behavioral issues can be direct consequences of BTRE and all related treatments, such as surgery, anti-cancer and anti-seizure medication, corticosteroids, etc.

A systematic review and meta-analysis of randomized trials comparing carbetocin to oxytocin in prevention of postpartum hemorrhage after cesarean delivery in low-risk women.

Objectives: To evaluate the efficacy and safety of Carbetocin compared to oxytocin in prevention of postpartum hemorrhage (PPH) after low-risk cesarean delivery (CD).

Search Strategy: Screening of Medline, Web Of Science, Scopus, Google scholar, and clinical trials registry till January 2024 using the key words related to carbetocin, blood loss, PPH, Cesarean section and their MeSH terms was done.

Selection Criteria: This study included all RCTs conducted on women with low risk for developing PPH after CD and compared the administration of carbetocin to oxytocin without any language limitation.

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV.

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses).

Prioritizing cases from a multi-institutional cohort for a dataset of pathologist annotations.

Objective: With the increasing energy surrounding the development of artificial intelligence and machine learning (AI/ML) models, the use of the same external validation dataset by various developers allows for a direct comparison of model performance. Through our High Throughput Truthing project, we are creating a validation dataset for AI/ML models trained in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC).

Materials And Methods: We obtained clinical metadata for hematoxylin and eosin-stained glass slides and corresponding scanned whole slide images (WSIs) of TNBC core biopsies from two US academic medical centers.

Non-V600E BRAF mutations and treatment for Hairy Cell Leukemia.

We found 18 patients with immunophenotype consistent with classic hairy cell leukemia (HCL) and BRAF mutations other than just V600E. Twelve had 1 non-V600E BRAF mutation and 6 had V600E with 1 (n=5) or 2 (n=1) non-V600E BRAF co-mutations.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.

CDK4/6 inhibitors (CDK4/6i) have significantly impacted on the treatment of HR + HER2 negative (HER2-) metastatic breast cancer (BC) when combined with endocrine therapy. Nonetheless, despite significant research efforts, the mechanisms of de novo and acquired resistance to CDK4/6i have not yet been fully elucidated, highlighting the need for a deeper understanding of these process. Additionally, the importance of dissecting CDK4/6i resistance from endocrine resistance for personalized treatment is increasingly recognized.

Multiple Instance Learning for WSI: A comparative analysis of attention-based approaches.

Whole slide images (WSI), obtained by high-resolution digital scanning of microscope slides at multiple scales, are the cornerstone of modern Digital Pathology. However, they represent a particular challenge to artificial intelligence (AI)-based/AI-mediated analysis because pathology labeling is typically done at slide-level, instead of tile-level. It is not just that medical diagnostics is recorded at the specimen level, the detection of oncogene mutation is also experimentally obtained, and recorded by initiatives like The Cancer Genome Atlas (TCGA), at the slide level.

Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma.

Low intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogeneous tumors are variably aggressive, and the immunological factors impacting aggressiveness remain understudied. Here, we analyzed the mechanisms underlying immune escape in murine tumors with low ITH.

Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report.

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

The Submental Artery Island Flap for Reconstruction of Acquired Maxillary and Palatal Defects After Tumor Ablation: Reversed Flow Versus the Extended Antegrade Design.

Background: The submental artery island flap (SIF) is a valid option for palatal reconstruction. However, the main limitation for its application for palatal defects is the arc of rotation. A novel modification for tunneling of the antegrade design of SIF that allows a compliant easy reach to the defect is described.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers.

While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs.

Innovative utilization of cell membrane-coated nanoparticles in precision cancer therapy.

Cell membrane-coated nanoparticles (CMNPs) have recently emerged as a promising platform for cancer therapy. By encapsulating therapeutic agents within a cell membrane-derived coating, these nanoparticles combine the advantages of synthetic nanoparticles and natural cell membranes. This review provides a comprehensive overview of the recent advancements in utilizing CMNPs as effective drug delivery vehicles for cancer therapy.