Variable Spectrum Research Articles

The Italian political class: two multilevel datasets on the profiles and opinions of elected politicians

Abstract The datasets on the Italian political class provides two sets of information: (a) census data on a broad spectrum of individual-level variables on elected politicians, offering an updated mapping of the characteristics of more than 20,000 Italian representatives at all governmental levels; (b) survey data on politicians' attitudes towards elections, participation, public opinion, several national and international policy issues, and their views of political representation. Between September 2020 and January 2021, 2134 elected politicians at the local (n = 1917), regional (n = 128), national (n = 75) and European (n = 14) levels were interviewed, making this one of the largest surveys of the Italian political elites ever conducted and a valuable resource for researchers interested in the study of democratic representation.

Mutational and clinical spectrum of myofibrillar myopathy in one center from China

Background: Myofibrillar myopathy (MFM) is a heterogeneous group of neuromuscular disorders characterized by degeneration of Z-disk and disintegration of myofibrils. OBJECTIVE: We aimed to analyze the mutational spectrum and phenotypic features of MFM in China. Methods: We used targeted next generation sequencing (NGS) to identify causative mutations in 39 MFM patients with confirmed myopathological diagnosis. Results: The results showed that variants were found in six MFM-associated genes, including DES, FLNC, BAG3, MYOT, TTN and DNAJB6, in 28 (71.7%), 3 (7.7%), 3 (7.7%), 1 (2.6%), 3 (7.7%), and 1 (2.6%), respectively. Of the total 26 variants identified, 19 were reported previously and 7 were novel variants. Missense variant (80.0%) was the most common mutant type of DES. P209L was the hotspot mutation of BAG3 while no obvious hotspot mutation was found of DES. Clinically, distal and proximal weakness were observed in 64.1% and 35.9% patients. Arrythmia and peripheral neuropathy were the most common combined symptoms of desminopathy and BAG3opathy, respectively. Pathologically, rimmed vacuoles (RVs) were present in different genetic type of MFM. Giant axonal nerve fiber was found in BAG3-releated MFM patient. Conlusion: We concluded that MFM showed a highly variable genetic spectrum, with DES as the most frequent causative gene followed by FLNC, BAG3 and TTN. This study expanded the genotypic and phenotypic spectrum of MFM among Chinese cohort.

Do economic uncertainty and political risk steer CDS dynamics? An analysis of the Türkiye CDS

Purpose This study aims to identify critical determinants of sovereign credit risk by examining the influence of oil prices, gold prices, geopolitical risk, market volatility, exchange rates, inflation and non-performing loans on Türkiye’s credit default swap (CDS) spreads. This analysis provides a comprehensive understanding of how economic uncertainty and political risk impact Türkiye’s financial stability, as reflected in its CDS market. This study investigates the importance of ex ante proxies in explaining changes in CDS spread by financial and economic indicators in Türkiye. Design/methodology/approach This research explores the connections between critical financial and economic indicators and the credit risk of Türkiye between 2009 and 2022 by using advanced econometric techniques such as ARDL bound tests, fully modified ordinary least squares (FMOLS), dynamic ordinary least squares (DOLS), Johansen co-integration tests and VECM Granger causality analyses. Findings ARDL bound test results reveal significant negative impacts of BIST and non-performing loans on CDS, and positive associations with inflation, VIX and geopolitical risk on CDSs. The short-term results show that BIST, INFL, NPL, USD, VIX and GPRT have negative coefficients. Johansen co-integration, FMOLS and DOLS results reinforce the ARDL findings. Moreover, BIST is a significant Granger cause of CDS. Originality/value This study is significant, as it jointly considers economic and political risk factors, thereby integrating multiple econometric models to provide more robust, meaningful and comparable results. By examining these factors together, the analysis offers a more comprehensive understanding of risk dynamics, yielding insights relevant to Türkiye. Although the findings are specific to Türkiye, they have broader implications, enriching the understanding of emerging economies. Türkiye’s status as a key representative of emerging markets strengthens the study’s value, as the results can serve as a reference point for other countries with similar economic structures. The importance of this study is also underscored by its potential to inform risk management strategies, guide policy decisions and offer insights to investors and financial analysts. By elucidating the intricate relationships among a broad spectrum of macroeconomic variables, this research contributes to a more comprehensive risk assessment framework. It equips stakeholders with a more informed perspective on the factors influencing credit risk in Türkiye’s economic landscape.

The Impact of Asset & Liability Management on Profitability: Evidence from Selected Private Commercial Banks in Ethiopia

This research meticulously investigates the intricate interplay between Asset and Liability Management (ALM) practices and the profitability dynamics of selected private commercial banks in Ethiopia over the period spanning 2011 to 2023. Employing a comprehensive fixed effect balanced panel regression analysis across a time horizon of 13 years and encompassing data from ten meticulously chosen banks, this study sheds light on critical aspects of financial management in the banking sector. Utilizing a quantitative approach and an explanatory design rooted in secondary data extracted from audited financial statements, the study rigorously examines a spectrum of key variables. These variables include income diversification, liquidity, bank size, GDP, asset quality, capital adequacy, loan and advance, and operational efficiency, all meticulously analyzed using E-view 12 econometrics software. The research findings underscore the pivotal significance of certain factors in enhancing bank profitability. Notably, asset quality, liquidity ratio, GDP, loan and advance, and bank size emerge as positive influencers on bank profitability, exhibiting statistically significant impacts. Conversely, operational efficiency and income diversification were found to exert negative effects on profitability. Surprisingly, capital adequacy was established as statistically insignificant in this context. This study accentuates the critical importance of asset quality, operational efficiency, liquidity management, bank size, GDP, income diversification, and loans as fundamental drivers of banks' return on assets. By accentuating the strategic significance of these variables, bank managers are equipped to navigate the complex financial landscape, leveraging effective ALM strategies to optimize profitability and ensure sustained financial viability.

Thermal runaway behaviour of a cylindrical lithium-ion battery during charge and discharge processes: A comprehensive numerical study

Lithium-ion batteries (LIBs) may experience thermal runaway (TR) accidents during charge and discharge processes. To ensure the safe operation of batteries, it is very important to analyse the TR characteristics during charge and discharge processes. In this work, we have developed a coupled electrochemical thermal (ECT) – TR (ECT-TR) model for a commercial 18,650 type 2.6 Ah NCM523/graphite battery. This model allows for the examination of TR features under different ambient temperatures, effective heat transfer coefficients (h), and C-rates during both charge and discharge processes. We first analysed the temporal evolution of the battery's surface center temperature and the heat generated by chemical reactions under a spectrum of environmental variables. Subsequently, we introduce a battery risk map that delineates distinct zones, including the safe zone, battery chemical reaction zone, battery failure zone, and TR zone, across varying environmental conditions. The results suggest that the battery's TR risk during the charge process exceeds that during the discharge process, with both exhibiting reduced risk compared to that during the cycle process. However, it is noteworthy that the risk of accelerated battery aging due to chemical reactions is more pronounced in the discharge process compared to the charge process.

Prediction of phase stability of UHT reconstituted skim milk after ambient storage using Raman spectroscopy

Milk is a colloidal system, and phase separation within such systems, such as excessive sedimentation and age gelation, is a quality defect in UHT-treated milk that remains challenging to predict. This study aims to investigate the feasibility of using Raman spectroscopy to characterize UHT reconstituted skim milk (RSM) and predict the degree of phase separation in UHT-RSM after storage. UHT-RSM samples after processing (M0) and three-month storage (M3) were vacuum-concentrated and analyzed by Raman spectroscopy. After 7.5 months of storage, the total solids depletion (TSD) of UHT-RSM was used to quantitatively reflect the degree of phase separation. Two independent partial least squares regression models were constructed using TSD7.5-month as the response variable and pre-processed Raman spectra collected from M0 and M3, respectively, as predictor variables. The nuances in UHT-RSM samples captured by Raman spectroscopy are crucial in developing the PLS regression models. Results showed that both M0 and M3 Raman spectra were relatively effective in predicting the phase separation condition (TSD7.5-month) of UHT-RSM at a later stage of storage (R2Pred = 0.74 and 0.85, respectively). This study demonstrated a new approach for forecasting the phase stability of UHT-RSM products based on spectral information. While there is a space for optimization of the presented prediction models, the technical approach shows good potential to be utilized by ingredient manufacturers and UHT milk processors to assist the ingredient screening process. Future research is encouraged to improve prediction accuracy within the framework of this novel approach.

Chronic ischemic gastropathy as an unusual cause of abdominal pain

Abstract Ischaemic gastropathy is a rare condition with a highly variable clinical spectrum. Its presentation varies from chronic abdominal pain to fatal cases of fulminant gastric ischaemia if it develops abruptly. There are several aetiologies of abdominal pain, however, early diagnosis of this pathology will allow a targeted therapeutic approach, which may improve prognosis and avoid fatal consequences.

Improved Synchrosqueezing S-Transform and Its Application in Reinforcement Protection Layer Identification

Abstract Synchrosqueezing is a strategy to enhance the resolution of time-frequency analysis. However, its application in the S-transform leads to complexities due to the variable phase spectrum of the S-transform, resulting in a decrease in resolution and an increase in complexity. This work proposes an Synchrosqueezing Generalized S-Transform (SS-GPST) by introducing phase-shifting and a generalized parameter to simplify the mathematical definition and enhance resolution. Synthetic data trials demonstrate the superiority of SS-GPST over existing synchrosqueezing methods, offering enhanced resolution and minimized inverse transformation errors. In practical ground-penetrating radar applications, we have applied SS-GPST to identify the reinforcement protection layer in tunnel linings. The results show that SS-GPST offers a novel method for thin-layer extraction in ground-penetrating radar applications.

Mutational and Clinical Spectrum of the PAX6 Gene in Bulgarian Patients with Aniridia

The PAX6 gene has highly conservative structure and developmentally essential function and is expressed in structurally different organs and systems. Haploinsufficiency of the PAX6 gene product leads to aniridia and aniridia-like phenotypes. A total of 9 patients and 115 controls were examined with the use of a variety of molecular-genetics methods (SNP array, Sanger sequencing, NGS, WES) and in collaboration with different clinicians. Two pathogenic CNVs, three potentially pathogenic variants and two nonsynonymous SNVs in the PAX6 gene were identified: two out of the three potentially pathogenic variants have not been previously reported. The heterogeneous nature of aniridia and the variable spectrum of the PAX6 mutations were confirmed by our study. Approximately 75% of the registered cases in the Bulgarian population were studied and five disease-related variants were discovered. The small number of polymorphic variants in the controls supports the highly conserved role and nature of the PAX6 and its product.

Simulation of fatigue crack growth in aluminium alloy 7075-T7351 under spike overload and aircraft spectrum loading

The trend towards virtual testing and digital-twin assisted management means that the accurate and reliable simulation of fatigue crack propagation behaviour is more important than ever. Reliable but conservative approaches to support this are in widespread use in the aerospace industry. Nevertheless, the conservatism comes at a significant cost in terms of reduced structural life and an increased ongoing inspection requirement and, as such leads to questions about the economic burden of these approaches. Recent comparisons between blind predictions and test results revealed the extent of the issue for cracking in aluminium alloy 7075-T7351 coupons with configuration and loading representative of military transport aircraft wing skins. The current models were generally conservative by a factor of two or more in terms of crack propagation life. This suggested that there was significant scope to improve the modelling to better reflect all the complex contributing factors. The current work has investigated the issue of changes in the crack front constraint as the crack progresses from a state of high constraint (close to plane strain) to a lower constraint (approaching plane stress). This issue was investigated both experimentally and with the development of an improved analytical model. A test program was conducted on several specimens, loaded under constant-amplitude, constant-amplitude with spike-overloads and a variable amplitude spectrum. Crack-opening stress levels were measured at key points in the tests and the results were used to develop and evaluate improved modelling approaches. The improved model was generally able to predict crack growth within about ± 30 % of that demonstrated along with the correct form of the crack growth, which is a significant advance and will lead to reduced costs and increased safety.

Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome

BackgroundThis report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the AKT3, CCND2, or PIK3R2 genes. We present a patient with a rare CCND2 variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH). MethodsA retrospective chart review and literature search were performed using PubMed. ResultsOur patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal. ConclusionMPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.

What drives the profitability of banking sectors in the European Union? The machine learning approach

Abstract The study aims to establish patterns of relations between the profitability of the European Union (EU) banking sectors between 2007 and 2021 and sets of variables appropriate for clusters of countries into which the 27 countries of the EU are divided. The random forest method is deployed to identify the factors influencing the value of the return on equity. Shapley additive explanations are exploited to add interpretability to the results. The results show that the sets of variables shaping the profitability of banking sectors in the EU grouped by use of sovereign rating criterion are different. However, there are variables common to all banking sectors. These include cost efficiency and default risk. The study’s novelty lies in the reliance on a broad spectrum of explanatory variables assigned to three groups of factors, reference to all EU countries, and decomposition of the sample to identify similarities among the determinants of profitability.

All-fiber spatial and wavelength gain-flattening of few-mode EDFA via mode selective coupler

The mode division multiplexing (MDM) technique together with wavelength division multiplexing (WDM) shows the great prospect to solve the capacity crunch of current standard single mode fiber (SSMF) transmission system. However, the modal and wavelength gain fluctuation fundamentally limit both the capacity and the reach of hybrid MDM-WDM transmission system. Here, we propose an all-fiber few-mode gain-flattening filter (FM-GFF) based on mode selective coupler (MSC), to effectively mitigate the gain fluctuation of few-mode erbium doped fiber amplifier (FM-EDFA) in both spatial and wavelength dimensions. With the help of genetic algorithm (GA), variable mode dependent loss spectra of cascaded MSCs can be efficiently obtained, according to the gain profile of the used FM-EDFA. Consequently, gain-flattening among all guided linearly polarized (LP) mode groups over the C-band can be realized. Simulation results reveal that, as for the spatial and wavelength gain flattening among 4/6-LP mode groups, only 5/7 cascaded MSCs are good enough to mitigate the modal and wavelength gain fluctuation from 9.89 dB and 11.79-dB to less than 0.38 dB and 0.46 dB over the C-band. Finally, we carry out experimental verification based on 2-LP mode groups gain flattening over C-band. When 3 cascaded MSCs are involved, the gain fluctuation of FM-EDFA over the C-band can be flattened from 2.46 dB to less than 0.96 dB.

Adaptive variable sampling T-SSD algorithm

Addressing the challenges of non-unique decomposition outcomes and prolonged decomposition durations in the fault feature adaptive extraction algorithm based on tensor decomposition, this paper presents a novel algorithm called the adaptive variable sampling tensor singular spectrum decomposition (T-SSD) algorithm. The proposed approach centers on decomposing multichannel time series with adaptive sampling frequency, leveraging tensor singular value decomposition. Initially, the embedding dimension and the number of resampling points were optimized by power spectral density analysis and adaptive sampling algorithm. Subsequently, a third-order tensor is constructed based on the principle of tensor-tensor-preserving order multiplication, combining trajectory tensor construction and embedding dimension. Finally, the signal decomposition and reconstruction of multichannel component signals are achieved through adaptive sampling, interpolation, and complementary back steps. Experimental signal analysis indicates that this algorithm can better extract fault characteristics from signals compared to common signal processing algorithms. In comparison with the traditional T-SSD algorithm, this method significantly improves decomposition efficiency, particularly for low-frequency components. It effectively tackles the efficiency challenge caused by data redundancy, enabling the organic fusion and adaptive decomposition of multichannel signals.

A predictive model for stunting among children under the age of three.

In light of the global effort to eradicate stunting in childhood, the objective of this research endeavor was to assess the prevalence of stunting and associated factors, simultaneously construct and validate a risk prediction model for stunting among children under the age of three in Shenzhen, China. Using the stratified random sampling method, we selected 9,581 children under the age of three for research and analysis. The dataset underwent a random allocation into training and validation sets, adhering to a 8:2 split ratio. Within the training set, a combined approach of LASSO regression analysis and binary logistic regression analysis was implemented to identify and select the predictive variables for the model. Subsequently, model construction was conducted in the training set, encompassing model evaluation, visualization, and internal validation procedures. Finally, to assess the model's generalizability, external validation was performed using the validation set. A total of 684 (7.14%) had phenotypes of stunt. Utilizing a combined approach of LASSO regression and logistic regression, key predictors of stunting among children under three years of age were identified, including sex, age in months, mother's education, father's age, birth order, feeding patterns, delivery mode, average daily parent-child reading time, average time spent in child-parent interactions, and average daily outdoor time. These variables were subsequently employed to develop a comprehensive prediction model for childhood stunting. A nomogram model was constructed based on these factors, demonstrating excellent consistency and accuracy. Calibration curves validated the agreement between the nomogram predictions and actual observations. Furthermore, ROC and DCA analyses indicated the strong predictive performance of the nomograms. The developed model for forecasting stunt risk, which integrates a spectrum of variables. This analytical framework presents actionable intelligence to medical professionals, laying down a foundational framework and a pivot for the conception and execution of preemptive strategies and therapeutic interventions.

Epibiotic Bacteria Isolated from the Non-Indigenous Species Codium fragile ssp. fragile: Identification, Characterization, and Biotechnological Potential.

Due to their richness in organic substances and nutrients, seaweed (macroalgae) harbor a large number of epiphytic bacteria on their surfaces. These bacteria interact with their host in multiple complex ways, in particular, by producing chemical compounds. The released metabolites may have biological properties beneficial for applications in both industry and medicine. In this study, we assess the diversity of culturable bacterial community of the invasive alga Codium fragile ssp. fragile with the aim to identify key groups within this epiphytic community. Seaweed samples were collected from the Northern Tunisian coast. A total of fifty bacteria were isolated in pure culture. These bacterial strains were identified by amplification of the ribosomal intergenic transcribed spacer between the 16S and the 23S rRNA genes (ITS-PCR) and by 16S rRNA sequencing. Antimicrobial activity, biochemical, and antibiotic resistance profile characterization were determined for the isolates. Isolated strains were tested for their antimicrobial potential against human and fish bacterial pathogens and the yeast Candida albicans, using the in vitro drop method. About 37% of isolated strains possess antibacterial activity with a variable antimicrobial spectrum. Ba1 (closely related to Pseudoalteromonas spiralis), Ba12 (closely related to Enterococcus faecium), and Bw4 (closely related to Pseudoalteromonas sp.) exhibited strong antimicrobial activity against E. coli. The isolated strain Ba4, closely related to Serratia marcescens, demonstrated the most potent activity against pathogens. The susceptibility of these strains to 12 commonly used antibiotics was investigated. Majority of the isolates were resistant to oxacillin, cefoxitin, tobramycin, and nitrofurantoin. Ba7 and Ba10, closely related to the Vibrio anguillarum strains, had the highest multidrug resistance profiles. The enzymes most commonly produced by the isolated strains were amylase, lecithinase, and agarase. Moreover, nine isolates produced disintegration zones around their colonies on agar plates with agarolitic index, ranging from 0.60 to 2.38. This investigation highlighted that Codium fragile ssp. fragile possesses an important diversity of epiphytic bacteria on its surface that could be cultivated in high biomass and may be considered for biotechnological application and as sources of antimicrobial drugs.

Dominantly acting variants in ATP6V1C1 and ATP6V1B2 cause a multisystem phenotypic spectrum by altering lysosomal and/or autophagosome function

The vacuolar H+-ATPase (V-ATPase) is a functionally conserved multimeric complex localized at the membranes of many organelles where its proton-pumping action is required for proper lumen acidification. The V-ATPase complex is composed of several subunits, some of which have been linked to human disease. We and others previously reported pathogenic dominantly acting variants in ATP6V1B2, the gene encoding the V1B2 subunit, as underlying a clinically variable phenotypic spectrum including dominant deafness-onychodystrophy (DDOD) syndrome, Zimmermann-Laband syndrome (ZLS), and deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures (DOORS) syndrome. Here, we report on an individual with features fitting DOORS syndrome caused by dysregulated ATP6V1C1 function, expand the clinical features associated with ATP6V1B2 pathogenic variants, and provide evidence that these ATP6V1C1/ATP6V1B2 amino acid substitutions result in a gain-of-function mechanism upregulating V-ATPase function that drives increased lysosomal acidification. We demonstrate a disruptive effect of these ATP6V1B2/ATP6V1C1 variants on lysosomal morphology, localization, and function, resulting in a defective autophagic flux and accumulation of lysosomal substrates. We also show that the upregulated V-ATPase function affects cilium biogenesis, further documenting pleiotropy. This work identifies ATP6V1C1 as a new gene associated with a neurodevelopmental phenotype resembling DOORS syndrome, documents the occurrence of a phenotypic continuum between ZLS, and DDOD and DOORS syndromes, and classify these conditions as lysosomal disorders.

Minimal dose resistance training enhances strength without affecting cardiac autonomic modulation in menopausal women: a randomized clinical trial

The proposition of a minimal dose of resistance training (RT) to elicit health benefits, encompassing physiological and psychological aspects, has garnered attention. While empirical investigations have demonstrated the efficacy of low-volume RT protocols in inducing adaptations such as enhanced strength and functional capacity, further exploration of the effects of this paradigm across a broader spectrum of variables is warranted. Thus, this study aimed to investigate the effects of minimal dose RT on strength and functional capacity, cardiac autonomic modulation, and hemodynamic parameters in menopausal women. Twenty-six women were randomly assigned to the training (TG: 63.2 ± 9.3 years) or control group (CG: 59.3 ± 7.6 years). Anthropometric measurements, strength and functional performance tests, cardiac autonomic assessment, and hemodynamic parameters were performed before and after four weeks of intervention. The TG performed the minimum dose RT twice weekly for four weeks (2 sets of 8–12 repetitions in three dynamic exercises, plus three 1-min isometric planks), and the CG had a weekly meeting with lectures and stretching. Two-way ANOVA with repeated measures was applied to each variable. Regarding time comparisons, there was a significant increase for LniRR (F = 4.78; ω2 = 0.046; p = 0.04), one repetition maximum (1RM) bench press (F = 8.06; ω2 = 0,013; p = 0.01), and 1RM leg press (F = 17.3; ω2 = 0,098; p < 0.01). There was a group*time interaction only for the index LnRMSSD (F = 5.11; ω2 = 0.042; p = 0.03), and 1RM bench press (F = 9.52; ω2 = 0,016; p = 0.01). No between-group main effect for any variable was found. The minimal dose RT protocol improved muscle strength, while cardiac autonomic and hemodynamic variables, as well as functional capacity, remained stable over 4 weeks in menopausal women.

Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network

Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.

Natural history of non-polyglutamine CACNA1A disease in Austria.

Non-polyglutamine CACNA1A variants underlie an extremely variable phenotypic spectrum encompassing developmental delay, hemiplegic migraine, epilepsy, psychiatric symptoms, episodic and chronic cerebellar signs. We provide our experience with the long-term follow-up of CACNA1A patients and their response to interval therapy. Patients with genetically confirmed non-polyglutamine CACNA1A disease were prospectively followed at the Center for Rare Movement Disorders of the Medical University of Innsbruck from 2004 to 2024. We recruited 41 subjects with non-polyglutamine CACNA1A disease, of which 38 (93%) familial cases. The mean age at the first examination was 35 ± 22years. Disease onset was in the childhood/adolescence in 31/41 patients (76%). Developmental delay and episodic symptoms were the first disease manifestation in 9/41 (22%) and 32/41 (78%) patients respectively. Chronic neurological signs encompassed a cerebellar syndrome in 35/41 (85%), which showed almost no progression during the observation period, as well as cognitive deficits in 9/20 (45%, MOCA test score < 26), psychiatric and behavioral symptoms in 11/41(27%). Seizures occurred in two patients concomitant to severe hemiplegic migraine. At the last visit, 27/41 patients (66%) required an interval prophylaxis (including acetazolamide, flunarizine, 4-aminopyridine, topiramate), which was efficacious in reducing the frequency and severity of episodic symptoms in all cases. In one patient in his 70ies with progressively therapy resistant hemiplegic migraine, treatment with the anti-CGRP antibody galcanezumab successfully reduced the frequency of migraine days from 4 to 1/month. Non-polyglutamine CACNA1A disease show an evolving age-dependent presentation. Interval prophylaxis is effective in reducing the burden of episodic symptoms.