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The Turkish Journal of Pediatrics May 2024Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous...
BACKGROUND
Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey.
METHODS
Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser.
RESULTS
Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years.
CONCLUSIONS
HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.
Topics: Humans; Hyaline Fibromatosis Syndrome; Male; Female; Infant; Child, Preschool; Receptors, Peptide; Turkey; Child
PubMed: 38814306
DOI: 10.24953/turkjpediatr.2024.4511 -
Aging May 2024Hypertension is a complex disease with unknown causes. Therefore, it's crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene...
Hypertension is a complex disease with unknown causes. Therefore, it's crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene Expression Omnibus data base (GEO), and miRNA regulating central hub genes was screened via weighted gene co-expression network (DEGs) and gene set enrichment (GSEA). Cell experiments validated TSR2's role and the PPAR signaling pathway through western blotting. 500 DEGs were identified for hypertension, mainly enriched in actin cross-linking, insulin signaling, PPAR signaling, and protein localization. Eight hub genes (SEC61G, SRP14, Liy AR, NIP7, SDAD1, POLR1D, DYNLL2, TSR2) were identified. Four hub genes (LYAR, SDAD1, POLR1D, TSR2) exhibited high expression levels in the hypertensive tissue samples, while showing low expression levels in the normal tissue samples. This led us to speculate that they may have relevant regulatory effects on hypertension. When TSR2 was knocked down in the hypertension peripheral blood mononuclear cells (PBMC) model, the critical proteins in the PPAR signaling pathway (FABP, PPAR, PLTP, ME1, SCD1, CYP27, FABP1, OLR1, CPT-1, PGAR, CAP, ADIPO, MMP1, UCP1, ILK, PDK1 UBC AQP7) were downregulated. This also occurred in the hypertension peripheral blood mononuclear cells (PBMC) + TSR2_ OV model. TSR2 is highly expressed in individuals with hypertension and may play a significant role in the development of hypertension through the PPAR signaling pathway. TSR2 could serve as a molecular target for the early diagnosis and precise treatment of hypertension, providing a valuable direction for the mechanism research of this condition.
PubMed: 38814181
DOI: 10.18632/aging.205852 -
Computational and Structural... Dec 2024Lung cancer is the main cause of cancer-related deaths worldwide. Due to lack of obvious clinical symptoms in the early stage of the lung cancer, it is hard to...
Lung cancer is the main cause of cancer-related deaths worldwide. Due to lack of obvious clinical symptoms in the early stage of the lung cancer, it is hard to distinguish between malignancy and pulmonary nodules. Understanding the immune responses in the early stage of malignant lung cancer patients may provide new insights for diagnosis. Here, using high-through-put sequencing, we obtained the TCRβ repertoires in the peripheral blood of 100 patients with Stage I lung cancer and 99 patients with benign pulmonary nodules. Our analysis revealed that the usage frequencies of TRBV, TRBJ genes, and V-J pairs and TCR diversities indicated by D50s, Shannon indexes, Simpson indexes, and the frequencies of the largest TCR clone in the malignant samples were significantly different from those in the benign samples. Furthermore, reduced TCR diversities were correlated with the size of pulmonary nodules. Moreover, we built a backpropagation neural network model with no clinical information to identify lung cancer cases from patients with pulmonary nodules using 15 characteristic TCR clones. Based on the model, we have created a web server named "Lung Cancer Prediction" (LCP), which can be accessed at http://i.uestc.edu.cn/LCP/index.html.
PubMed: 38813092
DOI: 10.1016/j.csbj.2024.05.010 -
Turkish Journal of Medical Sciences 2023The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease...
BACKGROUND/AIM
The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19.
MATERIALS AND METHODS
Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction.
RESULTS
This study found that gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase ( and ) and second-phase ( and ) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. gene expression was lower in pediatric COVID-19.
CONCLUSION
The interrelationship between the and genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.
Topics: Humans; COVID-19; Child; Male; Female; Adult; SARS-CoV-2; Child, Preschool; Adolescent; Middle Aged; Age Factors
PubMed: 38813031
DOI: 10.55730/1300-0144.5685 -
Turkish Journal of Medical Sciences 2023Children with coronavirus disease 2019 (COVID-19) present milder symptoms than adults and are at lower risk of hospitalization and life-threatening complications....
BACKGROUND/AIM
Children with coronavirus disease 2019 (COVID-19) present milder symptoms than adults and are at lower risk of hospitalization and life-threatening complications. However, the kinetics of lymphocyte subsets and serum immunoglobulins in the peripheral blood during COVID-19 infection remains unclear. In this study, it was aimed to determine the changes in hematological and immunological parameters, especially in the lymphocyte subsets, in the peripheral blood of children with different COVID-19 disease severity.
MATERIALS AND METHODS
The study was planned as a prospective cohort and included 68 children aged 0-18 years who were admitted to Ege University Faculty of Medicine Department of Pediatrics and diagnosed with COVID-19 infection between May 2020 and December 2021. In addition to demographic characteristics, clinical findings, and severity criteria, hematological, biochemical, and immunological laboratory (T/B lymphocyte subgroups, serum immunoglobulins) results were noted and examined if there were some correlations between disease severity and the laboratory values.
RESULTS
In the study group, while 60.6% (n = 40) of the patients received treatment in the hospital, 10.6% (n = 7) needed intensive care treatment. Lymphopenia (35.3%) was more common than neutropenia (14.7%) in the COVID-19-infected children. CD19+ B cells were low in a very high percentage of patients (26.5%), and 16.2% had low levels of NK cells. Significant correlation between disease severity and CD19+lymphocytes, CD19+CD38+IgM lymphocytes, CD19+CD38+CD27IgM lymphocytes, CD19+CD81+ lymphocytes (p = 0.001, p = 0.008, p = 0.014, p = 0.025, and r = 0.394, r = 0.326, r = 0.303, r = 0.280, respectively), significant inverse correlation between disease severity and absolute lymphocytes counts and CD3-CD16+CD56+ lymphocytes (p = 0.004, 0.014, and r = -0.353, r = -0.304, respectively) were observed. The percentage of hospitalized patients with low CD3 levels (15%) was significantly higher than that of the outpatients with low CD3 levels.
CONCLUSION
As the severity of the disease increased, the CD19, CD19CD38IgM, CD19CD38CD27IgM, and CD19CD81 lymphocytes percentages increased, while the lymphocyte count and NK cell percentage decreased. Therefore, detecting these prognostic immunobiomarkers related to the severity of the disease may contribute considerably to management of the illness.
Topics: Humans; COVID-19; Child; Killer Cells, Natural; Male; Female; Child, Preschool; Severity of Illness Index; Infant; Adolescent; Prospective Studies; B-Lymphocytes; SARS-CoV-2; Lymphopenia; Infant, Newborn; Lymphocyte Count; Lymphocyte Subsets
PubMed: 38813014
DOI: 10.55730/1300-0144.5686 -
Digital Health 2024Acute leukemia (AL) is a life-threatening malignant disease that occurs in the bone marrow and blood, and is classified as either acute myeloid leukemia (AML) or acute...
OBJECTIVE
Acute leukemia (AL) is a life-threatening malignant disease that occurs in the bone marrow and blood, and is classified as either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Diagnosing AL warrants testing methods, such as flow cytometry, which require trained professionals, time, and money. We aimed to develop a model that can classify peripheral blood images of 12 cell types, including pathological cells associated with AL, using artificial intelligence.
METHODS
We acquired 42,386 single-cell images of peripheral blood slides from 282 patients (82 with AML, 40 with ALL, and 160 with immature granulocytes).
RESULTS
The performance of EfficientNet-V2 (B2) using the original image size exhibited the greatest accuracy (accuracy, 0.8779; precision, 0.7221; recall, 0.7225; and F1 score, 0.7210). The next-best accuracy was achieved by EfficientNet-V1 (B1), with a 256 × 256 pixels image. F1 score was the greatest for EfficientNet-V1 (B1) with the original image size. EfficientNet-V1 (B1) and EfficientNet-V2 (B2) were used to develop an ensemble model, and the accuracy (0.8858) and F1 score (0.7361) were improved. The classification performance of the developed ensemble model for the 12 cell types was good, with an area under the receiver operating characteristic curve above 0.9, and F1 scores for myeloblasts and lymphoblasts of 0.8873 and 0.8006, respectively.
CONCLUSIONS
The performance of the developed ensemble model for the 12 cell classifications was satisfactory, particularly for myeloblasts and lymphoblasts. We believe that the application of our model will benefit healthcare settings where the rapid and accurate diagnosis of AL is difficult.
PubMed: 38812848
DOI: 10.1177/20552076241258079 -
Frontiers in Endocrinology 2024In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population... (Review)
Review
In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population had prediabetes. A large American study conducted in 2021 and supported by many other studies, concluded that about 47% of diabetes patients have peripheral neuropathy and that diabetic neuropathy was present in 7.5% of patients at the time of diabetes diagnosis. In subjects deemed to be pre-diabetes and impaired glucose tolerance there was a wide range of prevalence estimates (interquartile range (IQR): 6%-34%), but most studies (72%) reported a prevalence of peripheral neuropathy ≥10%. There is no recognized treatment for diabetic peripheral neuropathy (DPN) other than good blood glucose control. Good glycemic control slows progression of DPN in patients with type 1 diabetes but for patients with type 2 diabetes it is less effective. With obesity and type 2 diabetes at epidemic levels the need of a treatment for DPN could not be more important. In this article I will first present background information on the "primary" mechanisms shown from pre-clinical studies to contribute to DPN and then discuss mono- and combination therapies that have demonstrated efficacy in animal studies and may have success when translated to human subjects. I like to compare the challenge of finding an effective treatment for DPN to the ongoing work being done to treat hypertension. Combination therapy is the recognized approach used to normalize blood pressure often requiring two, three or more drugs in addition to lifestyle modification to achieve the desired outcome. Hypertension, like DPN, is a progressive disease caused by multiple mechanisms. Therefore, it seems likely as well as logical that combination therapy combined with lifestyle adjustments will be required to successfully treat DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Combined Modality Therapy; Animals; Drug Therapy, Combination
PubMed: 38812811
DOI: 10.3389/fendo.2024.1357859 -
Frontiers in Cardiovascular Medicine 2024Vascular endothelial cells play an important role in regulating peripheral circulation by modulating arterial tone in the microvasculature. Elevated intracellular Ca... (Review)
Review
Vascular endothelial cells play an important role in regulating peripheral circulation by modulating arterial tone in the microvasculature. Elevated intracellular Ca levels are required in endothelial cells to induce smooth muscle relaxation via endothelium-dependent mechanisms such as nitric oxide production, prostacyclin, and endothelial cell hyperpolarization. It is well established that exogenous administration of acetylcholine can increase intracellular Ca concentrations, followed by endothelium-dependent vasodilation. Although endogenous acetylcholine's regulation of vascular tone remains debatable, recent studies have reported that endogenously derived acetylcholine, but not neuronal cell-derived acetylcholine, is a key modulator of endothelial cell function. In this minireview, we summarize the current knowledge of the non-neuronal cholinergic system (NNCS) in vascular function, particularly vascular endothelial cell function, which contributes to blood pressure regulation. We also discuss the possible pathophysiological impact of endothelial NNCS, which may induce the development of vascular diseases due to endothelial dysfunction, and the potential of endothelial NNCS as a novel therapeutic target for endothelial dysfunction in the early stages of metabolic syndrome, diabetes, and hypertension.
PubMed: 38812748
DOI: 10.3389/fcvm.2024.1388528 -
Diabetes, Metabolic Syndrome and... 2024The clinical background and prognostic impact of diabetes mellitus (DM) on vasospastic angina (VSA) are unclear; thus, in this retrospective study, we investigated...
PURPOSE
The clinical background and prognostic impact of diabetes mellitus (DM) on vasospastic angina (VSA) are unclear; thus, in this retrospective study, we investigated whether they differ based on the presence or absence of DM in patients with VSA.
PATIENTS AND METHODS
We included 272 Japanese patients with VSA diagnosed by coronary angiography (CAG) and the spasm provocation test (SPT). The diagnosis of DM was determined by measuring fasting blood glucose and hemoglobin A1C and by the patient's current oral medications. On CAG, the presence of atherosclerotic lesions (20%-50%) was checked. On SPT, the coronary spasm was defined as transient coronary vasoconstriction >90% on CAG, accompanied by chest symptoms and/or ST-T changes. Focal spasm was defined as coronary spasm occurring within one segment of the American Heart Association classification on CAG. Blood and urine tests and vascular endothelial function were also evaluated when possible. A major adverse cardiovascular event (MACE), which is defined as cardiac mortality and rehospitalization due to cardiovascular illness, was the basis for determining the prognosis.
RESULTS
There were 49 patients (18%) in the DM group and 223 (82%) in the non-DM group. No significant differences in urinary albumin levels and peripheral vascular function were between groups. On CAG, atherosclerotic lesions were observed significantly more frequently in the DM group (63% vs 46%; P = 0.028). Results of SPT showed a trend toward fewer focal spasms in the DM group (24% vs 39%; P = 0.072). No significant differences in MACE were noted between groups in the primary analysis of DM, whereas sub-analyses of focal spasms showed lower MACE-free survival in the DM group (P = 0.042).
CONCLUSION
The study results support the hypothesis that DM associated with VSA should be treated appropriately, especially in cases of focal spasm, which may require more attention in treatment.
PubMed: 38812745
DOI: 10.2147/DMSO.S462234 -
Central-European Journal of Immunology 2024Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can... (Review)
Review
Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA. In recent years, great progress has been made in the field of pathogenesis and molecularly targeted therapy of neoplastic eosinophilia. The diagnostic procedure should include, among other things, morphologic analysis of blood and bone marrow samples, cytogenetics and fluorescence in situ-hybridization tests to detect evidence of an acute or chronic myeloid or lymphoid disorder. Secondary eosinophilia follows a cell-extrinsic mechanism as a response to exogenous cytokines. In most clinical cases, peripheral blood eosinophilia is reactive and typically associated with non-hematological disorders such as infections, allergic conditions, connective tissue disorders, vasculitis, malignancy, or endocrinopathies. Nonetheless, the cause of most cases of hypereosinophilic syndrome remains unknown. In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.
PubMed: 38812609
DOI: 10.5114/ceji.2024.136512