Publications by authors named "Jacobs F"

Modern healthcare is experiencing a significant transformation, utilizing technology to improve patient outcomes and make processes more efficient. Breast cancer, being the most commonly diagnosed cancer in women globally, requires innovative approaches for effective management. Digital Therapeutics (DTx) and Clinical Decision Support Systems (CDSSs) have emerged as pivotal technologies, offering personalized, patient-centered care and optimizing clinical decision-making.

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Background: As a result of recent advances in the development of small microelectromechanical system mirrors, a novel forward-looking optical coherence tomography (OCT) probe with a uniquely large field of view is being commercially developed. The aim of this study is to prospectively assess the feasibility of this advanced OCT probe in interpreting ex vivo images of colorectal polyp tissue and to identify necessary steps for further development.

Methods: A total of 13 colorectal lesions from 9 patients, removed during endoscopic resection, were imaged ex vivo with the OCT device and compared with histopathological images that served as the gold standard for diagnostics.

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The retention of the covalent binding of an organometalllic rhenium complex as a model for a technetium-99m imaging agent, to a protein at physiological body temperature 37 °C is described. Detailed structure comparisons are made to the related 100 K crystal structure. The generality of the need for this sort of analytical procedure for guiding ligand lead compound discovery is emphasised.

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Chronic pain is a common consequence of breast cancer (BC) and its treatments. Pain neuroscience education (PNE) is a non-pharmacological intervention that adopts a biopsychosocial approach and has already been proven to be effective for different chronic pain syndromes. The present review aims to critically assess clinical trials comparing the efficacy of PNE to traditional biomedical education (BME) in reducing BC-related pain and improving quality of life.

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X-linked dystonia-parkinsonism (XDP) is a severe neurodegenerative disorder resulting from an inherited intronic SINE-Alu-VNTR (SVA) retrotransposon in the gene that causes dysregulation of transcription. The specific mechanism underlying this dysregulation remains unclear, but it is hypothesized to involve the formation of G-quadruplexes (G4) structures within the XDP-SVA that impede transcription. In this study, we show that ZNF91, a critical repressor of SVA retrotransposons, specifically binds to G4-forming DNA sequences.

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The treatment of early triple-negative breast cancer (eTNBC) has improved patients' prognosis but often leads to adverse events and sequelae affecting quality of life (QoL). Pain Neuroscience Education (PNE) is a promising non-pharmacological intervention in this field. Preliminary data have shown the beneficial effect of PNE in BC survivors.

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Article Synopsis
  • - Tobacco use is linked to various cancers and causes about 25% of cancer-related deaths, primarily due to harmful substances in tobacco smoke, including tobacco-specific nitrosamines like NNN and NNK that create damaging DNA adducts.
  • - The study identified new mutational patterns induced by these DNA adducts, particularly in certain cancer cell lines and rat tumors, indicating specific mutations that occur in the DNA from exposure to these harmful compounds.
  • - Analyzing 2,780 cancer genomes revealed that these mutational patterns were present in around 180 tumors from types of cancer not typically associated with smoking, suggesting that the damage caused by the POB pathway could play a unique role in various cancers, including hematological
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In this study, we investigated recurrent copy number variations (CNVs) in the 19p12 locus, which are associated with neurodevelopmental disorders. The two genes in this locus, ZNF675 and ZNF681, arose via gene duplication in primates, and their presence in several pathological CNVs in the human population suggests that either or both of these genes are required for normal human brain development. ZNF675 and ZNF681 are members of the Krüppel-associated box zinc finger (KZNF) protein family, a class of transcriptional repressors important for epigenetic silencing of specific genomic regions.

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The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3.

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Article Synopsis
  • The SOLAR-1 and CAPItello-29 studies show that the PI3Ki alpelisib and AKTi capivasertib are beneficial for patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have specific genetic alterations.
  • Despite their effectiveness, these drugs can cause significant toxicities that may limit their use, especially in frail patients, highlighting the need for careful patient selection.
  • The review emphasizes the importance of identifying predictive biomarkers, particularly PIK3CA mutations and AKT pathway alterations, while noting that current diagnostic methods are not yet optimal, and suggests that ongoing monitoring of mutations in metastatic tissue and blood is crucial for effective treatment.
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Background: Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it.

Materials And Methods: We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer.

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Metal-based complexes with their unique chemical properties, including multiple oxidation states, radio-nuclear capabilities and various coordination geometries yield value as potential pharmaceuticals. Understanding the interactions between metals and biological systems will prove key for site-specific coordination of new metal-based lead compounds. This study merges the concepts of target coordination with fragment-based drug methodologies, supported by varying the anomalous scattering of rhenium along with infrared spectroscopy, and has identified rhenium metal sites bound covalently with two amino acid types within the model protein.

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Article Synopsis
  • - SARS-CoV-2 infection can cause both immediate and long-lasting neurological issues, complicating the understanding of the virus's impact on the brain after COVID-19.
  • - Research using brain models and samples shows that while SARS-CoV-2 can infect neural cells, the extent is low, but it can lead to abnormal changes in synapses and electrical activity in the brain.
  • - The study found that treating brain organoids with a specific compound could help restore normal brain activity and reduce the negative effects caused by the virus at synapses, highlighting potential avenues for understanding and treating COVID-19-related brain complications.
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Based on the unprecedented results observed in recent clinical trials, antibody-drug conjugates (ADCs) have revolutionized the treatment algorithm of metastatic breast cancer (mBC). The strategy of sequencing different ADCs in other lines of therapy is highly attractive, but the proportion of patients who have undergone such a strategy in the context of published clinical trials is still limited, especially for modern ADCs. HER2-positive disease is primarily managed with a sequence of different ADCs.

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Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.

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Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen.

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Aberrant cyclin-dependent kinase 2 (CDK2) activation has been identified as a main resistance mechanism to CDK4/6 inhibition in hormone-receptor positive (HR+) breast cancer. Additionally, consistent preclinical evidence states its crucial role in MYC and CCNE1 overexpressed cancer survival, such as triple-negative breast cancers (TNBC), thus representing an appealing and relatively unexplored target treatment opportunity. Despite emerging initial results of novel CDK2 inhibitors (CDK2i) activity, a comprehensive outcomes collection is currently absent from the scientific literature.

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Article Synopsis
  • Linezolid is a special antibiotic used when other antibiotics don't work, but it can cause side effects like low platelet counts (thrombocytopenia).
  • Researchers studied patients taking Linezolid to find out how often these side effects happen and what might increase the risk, especially with longer treatments and higher drug levels in the blood.
  • They found that patients on Linezolid for more than 10 days or with high blood levels were more likely to have problems, and they suggested ways to monitor and adjust treatment to keep patients safe.
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Backgrounds: The majority of breast cancer (BC) patients treated with neo-adjuvant chemotherapy (NAC) achieves a pathologic partial response with different patterns of residual disease. No clear correlation between these patterns and oncological results was described. Our aims were to define the predictive factors for different patterns of residual disease and compare the outcomes between the scattered versus the circumscribed pattern.

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