Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. The genetic abnormalities in BPDCN are heterogeneous; ...therefore, its molecular pathogenesis and the prognostic importance of genomic alterations associated with the disease are not well defined. Here we report a case of BPDCN with a novel AFF4::IRF1 fusion predicted to lead to a loss-of-function of the IRF1 tumor suppressor, somatic mutations of ASXL1, TET2, and MYD88, as well as multiple intrachromosomal deletions. The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.
This paper presents an improved vibration control method that controls the amplitudes of residual vibrations of a flexible non-uniform shaped manipulator with higher suppression ratio. The proposed ...new method suppresses the residual vibrations that occur after motion by shaping the velocity input. By considering the parameters of the experimental system, an analytical model is established according to the natural frequency of the system which is effective in the vibrations that occur in the direction of motion. To demonstrate the accuracy of the established model, transient analysis is performed by the Fast Fourier Transform (FFT) method and the resulting dynamic response is compared with the response of the experimental system. The motivation of this study is to add the shaped exponential-harmonic velocity input to the end of the trapezoidal or triangular velocity input to suppress the velocity response that is in the region of the residual vibrations. The effects of changes in the amplitude, frequency, exponential decay factor, phase angle and application time parameters of the exponential-harmonic input on the control of the residual vibration amplitudes are examined. The obtained results are compared with the experimental results and it is observed that the proposed vibration control method has succeeded in suppressing the residual vibrations by up to 99%. Thanks to the proposed method, the time needed for the manipulator to reach the steady-state time at the end of the motion was reduced from 18 s to the motion time.
Developmental and epileptic encephalopathies (DEEs) are heterogeneous severe neurodevelopmental disorders characterized by recurrent clinical seizures that begin in the neonatal period and early ...childhood and regression or delay in cognitive, sensory and motor skills in the context of accompanying epileptiform abnormalities. Adaptor-related protein complex 3 beta-2 subunit (AP3B2) gene variants are thought to cause disruption of neuron-specific neurotransmitter release.
In this case report, whole exome sequencing (WES) was performed on two of the four pediatric patients who came from two unrelated families and were affected by DEE. As a result of WES, previously unreported variants, that is, p.Ala149Serfs* 34 and p.Pro993Argfs* 5, were detected in the AP3B2 gene. These variants were studied using Sanger sequencing in the siblings affected by DEE of the said pediatric patients and in their healthy parents.
Autosomal recessive variants of the AP3B2 are associated with the development of DEE. To date, only 14 cases of AP3B2 mutations have been reported in the literature. Consequentially, DEE phenotype involving severe global developmental delay emerged, which is characterized by early-onset infantile epileptic encephalopathy, severe hypotonia, postnatal microcephaly, poor eye contact, speech retardation, abnormal involuntary movements, stereotypical hand movements, progressive intellectual disability, and behavioral and neuropsychiatric findings.
Given the limited number of patients reported in the literature, detailed studies of the specific clinical and molecular features of AP3B2 gene variants, will shed light on the genotype-phenotype correlation.
•Homozygous AP3B2 pathogenic variant is very rare.•p.Ala149Serfs* 34 and p.Pro993Argfs* 5 variants as homozygous have never been reported before.•Frameshift AP3B2 gene variants are thought to cause disruption of neuron-specific neurotransmitter release.•The variants of the AP3B2 genotype are considered to be related to clinical severity.•Four individuals with developmental and epileptic encephalopathy related homozygous AP3B2 gene mutations in the present article reveal intrafamilial and interfamilial phenotypic variation.
This study investigated surface spreading and underground dam recharge methods to replenish groundwater in Turkey’s Egri Creek Sub-basin of the Kucuk Menderes River Basin. A three-dimensional ...numerical model was employed for this purpose. Field and lab data are provided to the model for realistic simulations. Pumping test results were used to determine the aquifer parameters. The laboratory works involved sieve analysis, permeability tests, and porosity and water content prediction. The numerical model’s boundary conditions were determined from the geological and hydrogeological characteristics of the study area. Initial conditions were expressed regarding water content and pressure head in the vadose zone. The numerical model was satisfactorily validated by simulating water levels in three different pumping wells in the study area. Seven different scenarios, each having a different pool size, were investigated for the surface spreading recharge method. The results showed that a pool size of 30 × 30 m with a 6-m depth basin was the most optimal choice, raising the groundwater level to about 29.3 m. On the other hand, it was found that an underground dam could raise the levels by an average of 9.5 m, which might not be significant to warrant the construction.
Abstract Hereditary congenital facial paresis (HCFP) is characterized by isolated dysfunction of the facial nerve (CN VII) due to congenital cranial dysinnervation disorders. HCFP has genetic ...heterogeneity and HOXB1 is the first identified gene. We report the clinical, radiologic and molecular investigations of three patients admitted for HCFP in a large consanguineous Turkish family. High-throughput sequencing and Sanger sequencing of all patients revealed a novel homozygous mutation p.Arg230Trp (c.688C>T) within the HOXB1 gene. The report of the mutation brings the total number of HOXB1 mutations identified in HCFP to four. The results of this study emphasize that in individuals with congenital facial palsy accompanied by hearing loss and dysmorphic facial features, HOXB1 mutation causing HCFP should be kept in mind.
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related gene ...fusions. Despite the significant degree of heterogeneity in its pathogenesis, many gene fusions and point mutations are recurrent in AML and have been employed in risk stratification over the last several decades. Gene fusions have long been recognized for understanding tumorigenesis and their proven roles in clinical diagnosis and targeted therapies. Advances in DNA sequencing technologies and computational biology have contributed significantly to the detection of known fusion genes as well as for the discovery of novel ones. Several recurring gene fusions in AML have been linked to prognosis, treatment response, and disease progression. In this report, we present a case with a long history of essential thrombocythemia and hallmark CALR mutation transforming to AML characterized by a previously unreported AKAP9::PDGFRA fusion gene. We propose mechanisms by which this fusion may contribute to the pathogenesis of AML and its potential as a molecular target for tyrosine kinase inhibitors.
PDF
