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International Journal of Molecular... Jun 2024The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hemoglobin A (Hb A), which is not elevated. The...
The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hemoglobin A (Hb A), which is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. Red Blood Cells (RBC) indices were analyzed using mathematical formulas, and the sensitivity and negative predictive value (NPV) were calculated. Among 1334 blood counts suspected of α-thal analyzed, only the Shine and Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33%, and NPV was 98.93 and 99.93%, respectively. Molecular defects were found in 291, and 81 had normal α genes. Molecular analysis was not performed in 962 of the samples. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results, increase the awareness of the primary physicians about the carrier risk, and send an alert with a recommendation for further testing.
Topics: Humans; Support Vector Machine; alpha-Thalassemia; Heterozygote; Female; Male; Erythrocyte Indices; beta-Thalassemia; Genetic Carrier Screening
PubMed: 38928152
DOI: 10.3390/ijms25126446 -
International Journal of Molecular... Jun 2024Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic...
Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic β-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). -MODY 2 was the most frequently detected variant, but rare forms of -MODY 13, specifically, -MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype-phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context.
Topics: Humans; Diabetes Mellitus, Type 2; Genetic Testing; Male; Female; Genetic Counseling; Adult; Precision Medicine; High-Throughput Nucleotide Sequencing; Adolescent; Potassium Channels, Inwardly Rectifying; Young Adult; Child; Hepatocyte Nuclear Factor 4; Exome Sequencing; Genetic Predisposition to Disease; Mutation
PubMed: 38928025
DOI: 10.3390/ijms25126318 -
Cancers Jun 2024Chondroblastoma metastasis, though rare, represents a clinically significant and notably important aspect of bone tumors. Understanding its epidemiological... (Review)
Review
Chondroblastoma metastasis, though rare, represents a clinically significant and notably important aspect of bone tumors. Understanding its epidemiological characteristics, pathological features, and treatment modalities, despite its infrequency, is imperative for comprehensive patient management. This review aims to elucidate the epidemiology, molecular mechanisms, diagnostic challenges, and therapeutic strategies associated with chondroblastoma metastasis. The patterns, prognostic factors, and treatment outcomes were explored through an analysis of case studies and clinical reports. Notably, we highlighted emerging therapeutic perspectives aimed at improving patient outcomes. To the best of our knowledge, there has been no previous review addressing these matters cumulatively, highlighting a significant gap in the existing scholarly literature. By shedding light on the nuances of chondroblastoma metastasis, this review contributes to the advancement of knowledge in this field and informs clinical decision-making for improved patient care.
PubMed: 38927987
DOI: 10.3390/cancers16122283 -
Cancers Jun 2024The purpose of this study was to investigate the utility of reconstructed CT images perpendicular to the artery for assessing arterial involvement from pancreatic cancer...
The purpose of this study was to investigate the utility of reconstructed CT images perpendicular to the artery for assessing arterial involvement from pancreatic cancer and compare the interobserver variability between it and the current diagnostic imaging method. This retrospective study included patients with pancreatic cancer in the pancreatic body or tail who underwent preoperative pancreatic protocol CT and distal pancreatectomy. Five radiologists used axial and coronal CT images (current method) and perpendicular reconstructed CT images (proposed method) to determine if the degree of solid soft-tissue contact with the splenic artery was ≤180° or >180°. The generalized estimating equations were used to compare the diagnostic performance of solid soft-tissue contact >180° between the current and proposed methods. Fleiss' statistics were used to assess interobserver variability. The sensitivity and negative predictive value for diagnosing solid soft-tissue contact >180° were higher ( < 0.001 for each) and the specificity ( = 0.003) and positive predictive value ( = 0.003) were lower in the proposed method than the current method. Interobserver variability was improved in the proposed method compared with the current method ( = 0.87 vs. 0.67). Reconstructed CT images perpendicular to the artery showed higher sensitivity and negative predictive value for diagnosing solid soft-tissue contact >180° than the current method and demonstrated improved interobserver variability.
PubMed: 38927975
DOI: 10.3390/cancers16122271 -
Cancers Jun 2024Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence,... (Review)
Review
Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.
PubMed: 38927967
DOI: 10.3390/cancers16122262 -
Cancers Jun 2024Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside analogs...
Recommendations for the Management of Patients with Hairy-Cell Leukemia and Hairy-Cell Leukemia-like Disorders: A Work by French-Speaking Experts and French Innovative Leukemia Organization (FILO) Group.
INTRODUCTION
Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside analogs (PNAs), such as cladribine (CDA) or pentostatin (P). However, some patients eventually relapse and over time HCL becomes resistant to chemotherapy. Many discoveries have been made in the pathophysiology of HCL during the last decade, especially in genomics, with the identification of the BRAF mutation and cellular biology, including the importance of signaling pathways as well as tumor microenvironment. All of these new developments led to targeted treatments, especially BRAF inhibitors (BRAFis), MEK inhibitors (MEKis), Bruton's tyrosine kinase (BTK) inhibitors (BTKis) and recombinant anti-CD22 immunoconjugates.
RESULTS
The following major changes or additions were introduced in these updated guidelines: the clinical relevance of the changes in the classification of splenic B-cell lymphomas and leukemias; the increasingly important diagnostic role of BRAF mutation; and the prognostic role of the immunoglobulin (IG) variable (V) heavy chain (H) () mutational status and repertory. We also wish to insist on the specific involvement of bones, skin, brain and/or cerebrospinal fluid (CSF) of the disease at diagnosis or during the follow-up, the novel targeted drugs (BRAFi and MEKi) used for HCL treatment, and the increasing role of minimal residual disease (MRD) assessment.
CONCLUSION
Here we present recommendations for the diagnosis of HCL, treatment in first line and in relapsed/refractory patients as well as for HCL-like disorders including HCL variant (HCL-V)/splenic B-cell lymphomas/leukemias with prominent nucleoli (SBLPN) and splenic diffuse red pulp lymphoma (SDRPL).
PubMed: 38927891
DOI: 10.3390/cancers16122185 -
Bioengineering (Basel, Switzerland) Jun 2024This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great...
This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of "network structure" and "loss function", and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of "nnUNet" network structure and "Cross-Entropy + Iou + Boundary" hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.
PubMed: 38927831
DOI: 10.3390/bioengineering11060595 -
Genes Jun 2024This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID),...
This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID), while also exploring the utility of Reverse Phenotyping (RP) in refining diagnoses. A cohort of 100 pediatric patients underwent WES, yielding a diagnosis in 66% of cases. Notably, RP played a significant role in cases with negative prior genetic testing, underscoring its significance in complex diagnostic scenarios. The study revealed a spectrum of genetic conditions contributing to DD/ID, illustrating the heterogeneity of etiological factors. Despite challenges, WES demonstrated effectiveness, particularly in cases with metabolic abnormalities. Reverse phenotyping was indicated in half of the patients with positive WES findings. Neural network models exhibited moderate-to-exceptional predictive abilities for aiding in patient selection for WES and RP. These findings emphasize the importance of employing comprehensive genetic approaches and RP in unraveling the genetic underpinnings of DD/ID, thereby facilitating personalized management and genetic counseling for affected individuals and families. This research contributes insights into the genetic landscape of DD/ID, enhancing our understanding and guiding clinical practice in this particular field of clinical genetics.
Topics: Humans; Exome Sequencing; Developmental Disabilities; Child; Male; Intellectual Disability; Female; Child, Preschool; Phenotype; Infant; Adolescent; Genetic Testing
PubMed: 38927725
DOI: 10.3390/genes15060789 -
Integrating Genetic Services in the Philippine Public Health Delivery System: The Value of Networks.Genes Jun 2024The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines,... (Review)
Review
The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling.
Topics: Humans; Philippines; Genetic Services; Neonatal Screening; Infant, Newborn; Public Health; Delivery of Health Care; Genetic Counseling; Health Services Accessibility
PubMed: 38927716
DOI: 10.3390/genes15060780 -
Genes May 2024Genetic counseling and treatment options for rare developmental disabilities (DDs) have been revolutionized by the opportunities made possible by using massively...
Genetic counseling and treatment options for rare developmental disabilities (DDs) have been revolutionized by the opportunities made possible by using massively parallel sequencing for diagnostic purposes [...].
Topics: Humans; Rare Diseases; Genetic Counseling; Phenotype; High-Throughput Nucleotide Sequencing; Genetic Testing; Developmental Disabilities
PubMed: 38927651
DOI: 10.3390/genes15060715