Cervical Cancer Detection Techniques: A Chronological Review.

Cervical cancer is known as a major health problem globally, with high mortality as well as incidence rates. Over the years, there have been significant advancements in cervical cancer detection techniques, leading to improved accuracy, sensitivity, and specificity. This article provides a chronological review of cervical cancer detection techniques, from the traditional Pap smear test to the latest computer-aided detection (CAD) systems. The traditional method for cervical cancer screening is the Pap smear test. It consists of examining cervical cells under a microscope for abnormalities. However, this method is subjective and may miss precancerous lesions, leading to false negatives and a delayed diagnosis. Therefore, a growing interest has been in shown developing CAD methods to enhance cervical cancer screening. However, the effectiveness and reliability of CAD systems are still being evaluated. A systematic review of the literature was performed using the Scopus database to identify relevant studies on cervical cancer detection techniques published between 1996 and 2022. The search terms used included "(cervix OR cervical) AND (cancer OR tumor) AND (detect* OR diagnosis)". Studies were included if they reported on the development or evaluation of cervical cancer detection techniques, including traditional methods and CAD systems. The results of the review showed that CAD technology for cervical cancer detection has come a long way since it was introduced in the 1990s. Early CAD systems utilized image processing and pattern recognition techniques to analyze digital images of cervical cells, with limited success due to low sensitivity and specificity. In the early 2000s, machine learning (ML) algorithms were introduced to the CAD field for cervical cancer detection, allowing for more accurate and automated analysis of digital images of cervical cells. ML-based CAD systems have shown promise in several studies, with improved sensitivity and specificity reported compared to traditional screening methods. In summary, this chronological review of cervical cancer detection techniques highlights the significant advancements made in this field over the past few decades. ML-based CAD systems have shown promise for improving the accuracy and sensitivity of cervical cancer detection. The Hybrid Intelligent System for Cervical Cancer Diagnosis (HISCCD) and the Automated Cervical Screening System (ACSS) are two of the most promising CAD systems. Still, deeper validation and research are required before being broadly accepted. Continued innovation and collaboration in this field may help enhance cervical cancer detection as well as ultimately reduce the disease's burden on women worldwide.

Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease.

Neonatal AAV9-gene therapy of the lysosomal enzyme galactosylceramidase (GALC) significantly ameliorates central and peripheral neuropathology, prolongs survival, and largely normalizes motor deficits in Twitcher mice. Despite these therapeutic milestones, new observations identified the presence of multiple small focal demyelinating areas in the brain after 6-8 months. These lesions are in stark contrast to the diffuse, global demyelination that affects the brain of naive Twitcher mice. Late-onset lesions exhibited lysosomal alterations with reduced expression of GALC and increased psychosine levels. Furthermore, we found that lesions were closely associated with the extravasation of plasma fibrinogen and activation of the fibrinogen-BMP-SMAD-GFAP gliotic response. Extravasation of fibrinogen correlated with tight junction disruptions of the vasculature within the lesioned areas. The lesions were surrounded by normal appearing white matter. Our study shows that the dysregulation of therapeutic GALC was likely driven by the exhaustion of therapeutic AAV episomal DNA within the lesions, paralleling the presence of proliferating oligodendrocyte progenitors and glia. We believe that this is the first demonstration of diminishing expression in vivo from an AAV gene therapy vector with detrimental effects in the brain of a lysosomal storage disease animal model. The development of this phenotype linking localized loss of GALC activity with relapsing neuropathology in the adult brain of neonatally AAV-gene therapy-treated Twitcher mice identifies and alerts to possible late-onset reductions of AAV efficacy, with implications to other genetic leukodystrophies.

Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.

We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic.