Search Results (303)

This paper analyzes factors affecting school absenteeism due to an injury or illness among the US school student population between 6 and 15 years of age. The number of missed school days displays overdispersion and is modeled using the Finite Mixture Roy (FMR) model for count variables. The married/single parent family status (treatment) is potentially endogenous to the dependent variable (missed days). The Roy structure controls observed heterogeneity due to the mother’s marital status. Finite mixtures are intended to control unobserved heterogeneity due to healthy and unhealthy children in the sample. This approach facilitates identification of latent subpopulations in which treatment and marginal effects are relatively homogeneous. The model also incorporates two application-driven extensions. First, probabilities of the latent components are modeled as functions of regressors. Secondly, the mother’s income affects treatment nonparametrically. The FMR model is estimated with two latent components in each state, corresponding to healthy and unhealthy students. The results indicate that maternal marital status decreases annual missed school days by approximately 13 percent for a randomly drawn child; however, this increases absenteeism by about 14 percent among families that self-select into two-parent households, which is evidence of adverse selection. Full article

This paper reports a magnetically tunable U-band metallic waveguide isolator based on the ferromagnetic resonance (FMR) absorption effect. The device features a BaFe₁₂O₁₉ (BaM) single-crystal array integrated into a rectangular waveguide. By leveraging the high intrinsic magnetocrystalline anisotropy and narrow FMR linewidth of the single-crystal material, the isolator achieves high-frequency operation with a significantly reduced external bias field. Experimental results demonstrate a broad continuous tuning range from 50 GHz to 66 GHz. The device exhibits exceptional efficiency, with a typical insertion loss of less than 0.5 dB (minimum 0.24 dB) and an isolation exceeding 15 dB across the operating band. The cascaded array configuration ensures uniform magnetization and stable performance. This combination of ultra-low insertion loss and frequency agility makes the proposed isolator an ideal candidate for next-generation adaptive millimeter-wave communication and radar systems. Full article

Background: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder characterised by intellectual disability, developmental delays, anxiety, and social and behavioural challenges. Currently, no effective treatments exist to address the root cause of FXS. Mouse models are the most widely used for studying molecular pathogenesis and conducting preclinical treatment testing. However, therapeutic interventions that show promise in rodent models have yet to succeed in clinical trials. After evaluating the current models, we have developed an ovine model to address this clinical translation gap. We expect this model to more accurately reflect the human condition in brain size, structure, and neurodevelopmental trajectory. We aim to establish this model as a valuable preclinical platform for testing therapies for FXS. Methods: To generate the sheep model, we used CRISPR-Cas9 dual-guide editing to knock out the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene in ovine embryos. Results: Two founder animals were created, one ram (male) and one ewe (female), both of which carried FMR1 gene knockouts. The ewe carries inactivating mutations on both alleles, with the edits in both animals resulting in no detectable Fragile X Messenger Ribonucleoprotein (FMRP) as expected. Both founders have undergone molecular characterisation and basic health checks, with the female founder showing increased joint flexibility, a characteristic of FXS. The ram has been used for breeding, with the successful transmission of the edited allele to his offspring. Importantly, specific lamb cohorts for postnatal treatment testing can be produced efficiently utilising accelerated breeding methods and preimplantation selection. Full article

Background: TCF20-associated neurodevelopmental disorder (TCF20-NDD) is a heterogeneous clinical condition resulting from defects in gene-encoding Transcription Factor 20, which plays a key role in neuronal development and synaptic function. Here, we present a novel case involving an 11-year-old boy who was referred to us for a neuro-developmental disorder characterized by attention deficit hyperactivity disorder (ADHD), tremor in the upper limbs, tilted head posture, motor delay, impaired executive functioning, and oculomotor dyspraxia. Methods: Genetic tests were performed, including CGH array, molecular analysis of the FMR1 gene, molecular analysis using a next-generation sequencing gene panel targeted for spinocerebellar diseases, and finally, WES including mitochondrial genome analysis. A neuroimaging study of brain and spine was performed using MRI. Results: Trio Whole Exome Sequencing revealed a de novo pathogenic frameshift variant NM_001378418.1:c.5009dup, p.(Thr1671Aspfs*5) in the TCF20 gene. The MRI scan of the brain, cervical, dorsal, and lumbosacral spine revealed Chiari type I malformation. Regarding the pathogenic mechanism underlying Chiari I malformation, it could be found in the homology between TCF20 and the RAI1 gene, the latter being associated with alterations in the posterior cranial fossa. Conclusions: We emphasize the use of exome sequencing in patients with unclear clinical presentations, with awareness of TCF20-associated neurodevelopmental disorder; paying attention to brain MRI findings would be useful to further expand the phenotype of TCF20-NDD. Full article

Background/Objectives: Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor, gait ataxia, and cerebellar white matter degeneration, along with possible cognitive and cerebral changes. Although diagnostic criteria were originally developed in males, emerging evidence suggests that FXTAS may present differently in females. The present study examined sensorimotor and memory features of aging in female premutation carriers with (FXTAS+) and without FXTAS (FXTAS−). Methods: We studied 51 female premutation carriers (FXTAS+ = 16, FXTAS− = 35) and 24 age-matched female controls. Participants ranged in age from 47–80 years. All participants completed genetic testing, clinical evaluations, T2-weighted MRIs, and quantitative assessments of sensorimotor (precision grip force task) and memory (reading span; visual paired associates task) functions. Results: During precision grip testing, FXTAS+ carriers showed higher sustained force regularity than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.004, d = 1.1) at low gain levels only. FXTAS+ participants were slower than controls on motor reaction time (p = 0.009, d = 0.82). Initial force output was higher in FXTAS+ than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.03, d = 1.0) but at low gain only. FXTAS+ carriers exhibited poorer working memory than FXTAS− carriers (p = 0.03, d = 0.91) and controls (p = 0.02, d = 1.0). During a long-term memory task, FXTAS+ participants were less accurate than FXTAS− carriers (p = 0.04, d = 0.86) and controls (p = 0.004, d = 1.1) and showed increased reaction times relative to FXTAS− carriers (p = 0.03, d = −0.82) and controls (p = 0.01, d = −1.2). Conclusions: Together, these findings indicate that FXTAS+ females exhibit distinct motor and cognitive impairments, underscoring the value of quantitative behavioral measures for detecting and tracking neurodegenerative progression in female premutation carriers. Full article

Fragile X syndrome (FXS, OMIM#300624) is the most common inherited cause of X-linked intellectual disability and behavior difficulties. In 99% of cases, it is caused by the pathological expansion (>200 repeats, full mutation -FM) of the CGG trinucleotide located at the 5′ UTR of the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene, leading to the lack of production of the FMRP. Clinical manifestations are well known in boys but are sometimes overlooked in girls, who may remain underdiagnosed. Premutation (PM) populations (55–200 repeats) may present other medical issues, such as FXPOI or FXTAS. Mosaic conditions, such as a combination of PM and FM lines in the same patient, may lead to milder phenotypes. With the improvement of genetic testing, information regarding the exact number of CGG triplet repeats and methylation status could help explain milder phenotypes in patients who may produce some FMRP. Chromosome X preferential inactivation (XCI) in FXS women can also play a role in clinical severity. We present four non-related families who were followed up in our FXS clinic. Some of their members showed FM on Southern blot, but had milder symptoms than expected. To rule out size mosaicism, a RT-PCR was performed, giving a different and more consistent molecular diagnosis. When mosaicism was not present, methylation status was performed, excluding full methylation. For females, XCI showed preferential inactivation in one case. Revisiting old molecular diagnoses should be considered in clinical practice, especially for patients with a milder phenotype than expected from their molecular reports. This personalized follow up may change their former diagnosis, prognosis, and expectations. Full article

Background: Fragile X Syndrome (FXS) is the most common monogenic cause of autism spectrum disorders, and is characterized by the excessive immature excitatory synapses in cortical neurons, leading to excitatory/inhibitory imbalance and core autistic behaviors. This synaptic pathology has been attributed to dysregulated levels of synaptic proteins, including CYFIP2: a key regulator of synaptic structure and plasticity. However, the mechanism underlying the increased CYFIP2 protein level in FXS neurons remains unclear. Neurons abundantly secrete extracellular vesicles (EVs) enriched with bioactive cargos (proteins and miRNAs). Objectives: the goal of this research is to identify whether EV-dependent secretion plays important roles in regulating the intracellular CYFIP2 protein level in WT and FXS neurons. Methods and Results: our proteomic analysis reveals that CYFIP2 protein is packaged in EVs released by mouse cortical neurons. Pharmacological and genetic blockades of neuronal EV release significantly elevated intracellular CYFIP2 levels by 78 ± 14% and 168 ± 39%, respectively. Glutamate-evoked EV release significantly reduced the CYFIP2 level by 24 ± 2%. Neurons from Fmr1 KO mice, an FXS model, secreted significantly less EVs (46 ± 5%) than the wild type, and showed significantly elevated CYFIP2 (by 155 ± 31%). Evoking EV release in FXS neurons significantly lowered the intracellular CYFIP2 (by 53 ± 6%). Conclusions: these findings identify an EV-secretion-dependent mechanism that controls neuronal CYFIP2 level, implicating EV-mediated export in the regulation of synaptic protein homeostasis, synaptic remodeling, and FXS-associated synaptic deficits. Full article

Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are neurodevelopmental disorders marked by deficits in communication and social interaction, often accompanied by anxiety, seizures, and intellectual disability. FXS, the most common monogenic cause of ASD, results from silencing of the FMR1 gene and consequent loss of FMRP, a regulator of synaptic protein synthesis. Disruptions in cyclic nucleotide (cAMP and cGMP) signaling underlie both ASD and FXS contributing to impaired neurodevelopment, synaptic plasticity, learning, and memory. Notably, reduced cAMP levels have been observed in platelets, lymphoblastoid cell lines and neural cells from FXS patients as well as Fmr1 KO and dfmr1 Drosophila models, linking FMRP deficiency to impaired cAMP regulation. Phosphodiesterase (PDE) inhibitors, which prevent the breakdown of cAMP and cGMP, have emerged as promising therapeutic candidates due to their ability to modulate neuronal signaling. Several PDE isoforms—including PDE2A, PDE4D, and PDE10A—have been implicated in ASD, and FXS, as they regulate pathways involved in synaptic plasticity, cognition, and social behavior. Preclinical and clinical studies show that PDE inhibition modulates neuroplasticity, neurogenesis, and neuroinflammation, thereby ameliorating autism-related behaviors. BPN14770 (a PDE4 inhibitor) has shown promising efficacy in FXS patients while cilostazol, pentoxifylline, resveratrol, and luteolin have showed improvements in children with ASD. However, challenges such as isoform-specific targeting, optimal therapeutic window, and timing of intervention remain. Collectively, these findings highlight PDE inhibition as a novel therapeutic avenue with the potential to restore cognitive and socio-behavioral functions in ASD and FXS, for which effective targeted treatments remain unavailable. Full article

W-type hexaferrites with compositions Ba_0.5Sr_0.5Zn_2-xMe_xFe₁₆O₂₇ (Me = Fe, Ni, Co, Cu, Mn; x = 1) and Ba_0.5Sr_0.5Zn_2−xMn_xFe₁₆O₂₇ (x = 0–2.0) were synthesized via solid-state reaction and optimized using a two-step calcination process to obtain single-phase or nearly single-phase structures. Their electromagnetic (EM) wave absorption properties were investigated by fabricating composites with 10 wt% epoxy and measuring the complex permittivity and permeability across two frequency bands: 0.1–18 GHz and 26.5–40 GHz. Reflection loss (RL) was calculated and visualized as two-dimensional (2D) maps with respect to frequency and sample thickness. In the 0.1–18 GHz range, only the Co-substituted sample exhibited strong ferromagnetic resonance (FMR) and broadband absorption, achieving a minimum RL of −41.5 dB at 4.84 GHz and a −10 dB bandwidth of 11.8 GHz. In contrast, the other Ba_0.5Sr_0.5Zn_2-xMe_xFe₁₆O₂₇ samples (Me = Fe, Mn, Ni, Cu) showed no significant absorption in this range due to the absence of FMR. However, all these samples clearly exhibited FMR characteristics and distinct absorption peaks in the 26.5–40 GHz range, particularly the Mn-substituted series, which demonstrated RL values below −10 dB over the 32.0–40 GHz range with absorber thicknesses below 1 mm. The FMR frequency varied depending on the substitution type and amount. In the Mn-substituted series, the FMR frequency was lowest at x = 1.0 and increased as x deviated from this composition. This study confirms the potential of Co-free W-type hexaferrites as efficient, cost-effective, and broadband EM wave absorbers in the 26.5–40 GHz range. Full article

In this study, we investigate the dominant electromagnetic wave absorption mechanism–ferromagnetic resonance (FMR) loss versus quarter-wave cancellation in a novel PVDF-based polymer composite embedded with carbonaceous nanostructures incorporating FeCoCr ternary alloy. The majority of the nanoparticles are embedded at the terminal ends of the carbon nanotubes, while a small fraction exists as isolated core–shell, carbon-coated spherical particles. Overall, the synthesized material predominantly exhibits a nanotubular carbon morphology. High-resolution transmission electron microscopy (HRTEM) confirms that the encapsulated nanoparticles are quasi-spherical in shape, with an average size ranging from approximately 25 to 40 nm. The polymeric composite was synthesized via solution casting, ensuring homogenous dispersion of filler constituent. Electromagnetic interference (EMI) shielding performance and reflection loss characteristics were evaluated in the X-band frequency range. Experimental results reveal a significant reflection loss exceeding −20 dB at a matching thickness of 2.5 mm, with peak absorption shifting across frequencies with thickness variation. The comparative analysis, supported by quarter-wave theory and FMR resonance conditions, indicates that the absorption mechanism transitions between magnetic resonance and interference-based cancellation depending on the material configuration and thickness. This work provides experimental validation of loss mechanism dominance in magnetic alloy/polymer composites and proposes design principles for tailoring broadband microwave absorbers. Full article

Functional mitral regurgitation (FMR) is a common condition with significant prognostic implications, primarily driven by left atrial or ventricular remodeling secondary to ischemic or non-ischemic cardiomyopathies. While guideline-directed medical therapy (GDMT) remains the cornerstone of management, reducing mitral regurgitation severity in up to 40–45% of cases, additional interventions are often necessary. In patients where atrial fibrillation (AF) or ventricular dyssynchrony due to abnormal electrical conduction contributes to disease progression, guideline-directed AF management or cardiac resynchronization therapy plays a pivotal role. For those with persistent moderate to severe MR and unresolved symptoms despite optimal GDMT, percutaneous intervention may be warranted, provided specific clinical and echocardiographic criteria are met. This review highlights a precision-medicine approach to patient selection for transcatheter treatment of functional mitral regurgitation (FMR), emphasizing the integration of clinical characteristics with advanced multimodal imaging, including echocardiography, cardiac magnetic resonance, and computed tomography. In anatomically or clinically complex cases, complementary use of these imaging modalities is essential to ensure accurate phenotyping and procedural planning. Once a suitable candidate for percutaneous intervention has been identified, we provide a detailed overview of current transcatheter strategies, with a focus on device selection tailored to anatomical and pathophysiological features. Finally, we discuss emerging technologies and evolving therapeutic paradigms that are shaping the future of individualized FMR management. Full article

Yttrium iron garnet (YIG), as a core material in microwave devices, remains a key focus in materials science for performance optimization. In this study, Y₃Fe_4.8Cu_0.1Sn_0.1O₁₂ samples were prepared via the solid-phase method with the co-doping of low-magnetic-anisotropy Cu²⁺ and Sn⁴⁺, combined with hot-press sintering under different conditions. Systematic analyses revealed that hot-press sintering optimized the microstructure, reduced porosity, and improved the compactness to 5.60 g/cm³. The sample hot-pressed sintered at 1200 °C achieved a maximum ε′ of 34, the lowest dielectric loss and a minimal FMR linewidth of 21 Oe, thus holding great potential for applications in high-frequency microwave devices requiring low loss and high integration. This work provides a viable approach to regulating the microstructure, dielectric properties, and magnetic properties of YIG ferrites. Full article

Two products fermented with lactic acid bacteria (LAB) were obtained using malted rice (FR) and mashed malted rice (FMR). Peptide, phenolic acids, and γ-aminobutyric acid (GABA) contents and neuroprotective activities were evaluated before and after simulated gastrointestinal digestion. GABA contents of fermented products were 45 and 51 mg 100 g⁻¹, with a bioaccessibility of 51 and 45% for FR and FMR, respectively. Both fermented malted rice products exhibited inhibitory effects against tyrosinase, acetylcholinesterase, and prolyl oligopeptidase, with FR demonstrating the highest inhibitory activity. The neuroprotective properties were increased after digestion and could potentially be attributed to bioactive peptides generated by germination, fermentation, and digestion, as well as free phenolic acids. These findings suggest that fermented malted rice possesses promising biofunctional properties and may serve as suitable dietary options for individuals with gluten and lactose intolerance, offering additional neuroprotective benefits. Full article

Fragile X syndrome (FXS) is the most common form of X-linked intellectual disability (ID). This study aimed to share 30 years of experience in diagnosing FXS and determine its frequency in Thailand. We retrospectively reviewed 1480 unrelated patients (1390 males and 90 females) with ID, developmental delay, or autism spectrum disorder, or individuals referred for FXS DNA testing at Songklanagarind Hospital, Thailand, over a 30-year period. The samples were analyzed using cytogenetic methods, PCR-based techniques, and/or Southern blot analysis. Full mutations (>200 CGG repeats) were identified in 100 males (7.2%) and three females (3.3%). An intermediate allele was detected in one male, while no premutation was found in the index cases. Two males were suspected to have FMR1 gene deletions. Twelve families underwent prenatal testing during this study. Most families undergoing prenatal FXS diagnosis involved mothers who were premutation carriers and had given birth to children affected by FXS. This study represents the largest series of molecular genetic FXS testing cases reported in Thailand. The frequency of FXS identified in different cohorts of Thai patients across various periods was approximately 7%. This study enhances public awareness of at-risk populations and highlights the importance of prenatal testing and genetic counseling for vulnerable families. Full article

Background/Objectives: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with early onset of clinical manifestations. ASD etiology is highly heterogeneous, with genetic factors being strong determinants of the behavioral problems and neurodevelopmental deficits. Fragile X syndrome (FXS) (OMIM #300624), caused by the transcriptional silencing of the FMR1 gene, represents the most common monogenic cause of autism. Our study included 226 boys with a diagnosis of ASD, for a systematic screening of genetic and epigenetic defects in the FMR1 gene promoter in a Romanian pediatric cohort. Methods: The methods, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and triplet-primed PCR (TP-PCR)/melt curve analysis (MCA), were chosen for their ability to detect the methylation anomalies (the former) as well as repeat expansions in the FMR1 promoter (the latter). Results: Both methods used in our screening generated concordant results, detecting FMR1 full mutation in 4 out of 226 patients (~1.8%). This yield is similar to data obtained in larger studies. Three out of four boys presented the typical clinical features, in correlation with genetic findings. Conclusions: The combined use of MS-MLPA and TP-PCR/MCA-based assay was, in our experience, useful to fully describe the genetic defects responsible for FXS. A significant variability of clinical presentations was observed in our small group of children with FXS, from mild to severe intellectual disability and from atypical to characteristic dysmorphic features, as well as various behavioral problems. Full article