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Electrohydraulic forming (EHF) is a high-speed forming technique that utilizes plasma-driven hydraulic pressure to deform metal sheets. It offers the advantages of high-speed forming while eliminating the need for conventional forming dies. However, the conventional EHF method (C-EHF) requires manual installation of thin wires to initiate electrical discharge, resulting in lengthy preparation times, inconsistent forming results, and asymmetric deformations. To address these limitations, this study proposes and experimentallyfi validates a novel wire-free approach, termed Wireless EHF (W-EHF). Under identical experimental conditions, W-EHF was compared to C-EHF based on their ability to achieve comparable forming heights. The results showed that W-EHF significantly outperformed C-EHF in terms of symmetry, repeatability, and time efficiency. W-EHF maintained near-perfect symmetry with aspect ratios close to 1.0 across the entire forming height, and the deviation of the center point demonstratedexcellent consistency. Preparation time was reduced from an average of 20.6 minutes (CEHF) to just 3.2 minutes (W-EHF), and each additional discharge in the W-EHF process required only 0.3 minutes, highlighting its suitability for continuous operations. Accordingly, the findings of this study confirm that the W-EHF method offers enhanced process efficiency and greater potential for industrial application compared to the conventional approach, making it a promising alternative for high-speed sheet metal forming processes.

Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcription factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene expression profiles (i.e., mosaic expression patterns), it has been challenging to identify the additional factors complementing the transcriptional regulation. We aimed to identify the transcriptional regulators involved in the regulation of mTEC development and self-peptide expression in an unbiased and genome-wide manner. We used ATAC footprinting analysis as an indirect approach to identify transcription factors involved in the gene expression regulation in mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs). Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF, and PEA3 subfamily of the ETS transcription factor family and members of the Krüppel-like family of transcription factors play a role in the transcriptional regulation of genes involved in late mTEC development and promiscuous gene expression.

Using the latest HadGHCND daily temperature dataset, global trends in observed summertime heatwaves and annually calculated warm spells for 1950–2011 are analysed via a multi‐index, multi‐aspect framework. Three indices that separately focus on maximum temperature (TX90pct), minimum temperature (TN90pct) and average temperature (EHF) were studied with respect to five characteristics of event intensity, frequency and duration. Despite which index is employed, increases in heatwave/warm spell intensity, frequency and duration are found. Furthermore, TX90pct and TN90pct trends are larger and exhibit more significance for warm spells, implying that non‐summer events are driving annual trends over some regions. Larger increases in TN90pct aspects relative to EHF and TX90pct are also observed. While qualitative information on event trends is similar across the indices, quantitative values vary. This result highlights the importance of employing the most appropriate index when assessing the impact of sustained extreme temperature events. Key Points Global heatwaves have increased in frequency, intensity and duration Non‐summer events are driving annual changes Nighttime heatwaves have increased faster than daytime and daily‐average events

IntroductionHeadache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce.Material and methodsWe searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8–18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted.ResultsOut of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall [95%CI: 9–14%], 8% for migraine without aura (MwoA) [95%CI: 5–12%], 3% for migraine with aura (MwA) [95%CI:2–4%] and 17% for tension-type headache (TTH) [95% CI: 12–23%]. The pooled prevalence of overall primary headache in children and adolescents was 62% [95% CI: 53–70%], with prevalence in females and males of 38% [95% CI: 16–66%] and 27% [95% CI: 11–53%] respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking.ConclusionWe found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.

Migraine is a complex brain disorder explained by the interaction of genetic and environmental factors. In monogenic migraines, including familial hemiplegic migraine and migraine with aura associated with hereditary small-vessel disorders, the identified genes code for proteins expressed in neurons, glial cells, or vessels, all of which increase susceptibility to cortical spreading depression. The study of monogenic migraines has shown that the neurovascular unit plays a prominent role in migraine. Genome-wide association studies have identified numerous susceptibility variants that each result in only a small increase in overall migraine risk. The more than 180 known variants belong to several complex networks of “pro-migraine” molecular abnormalities, which are mainly neuronal or vascular. Genetics has also highlighted the importance of shared genetic factors between migraine and its major co-morbidities, including depression and high blood pressure. Further studies are still needed to map all of the susceptibility loci for migraine and then to understand how these genomic variants lead to migraine cell phenotypes.

Targeting CGRP has proved to be efficacious, tolerable, and safe to treat migraine; however, many patients with migraine do not benefit from drugs that antagonize the CGRPergic system. Therefore, this review focuses on summarizing the general pharmacology of the different types of treatments currently available, which target directly or indirectly the CGRP receptor or its ligand. Moreover, the latest evidence regarding the selectivity and site of action of CGRP small molecule antagonists (gepants) and monoclonal antibodies is critically discussed. Finally, the reasons behind non-responders to anti-CGRP drugs and rationale for combining and/or switching between these therapies are addressed.

Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. The burden of disease on individuals and societies is significant due to high costs and comorbidities. In the Third Edition of the International Classification of Headache Disorders, medication-overuse headache is recognized as a separate secondary entity next to mostly primary headache disorders, although many clinicians see the disease as a sole complication of primary headache disorders. In this review, we explore the historical background of medication-overuse headache, its epidemiology, phenomenology, pathophysiology and treatment options. The review explores relevant unanswered questions and summarizes the current debates in medication-overuse headache.

BackgroundMigraine is a highly prevalent and disabling neurological disorder which is commonly linked with a broad range of psychiatric comorbidities, especially among subjects with migraine with aura or chronic migraine. Defining the exact nature of the association between migraine and psychiatric disorders and bringing out the pathophysiological mechanisms underlying the comorbidity with psychiatric conditions are relevant issues in the clinical practice.MethodsA systematic review of the most relevant studies about migraine and psychiatric comorbidity was performed using “PubMed”, “Scopus”, and “ScienceDirect” electronic databases from 1 January 1998 to 15 July 2018. Overall, 178 studies met our inclusion criteria and were included in the current review.ResultsAccording to the most relevant findings of our overview, the associations with psychiatric comorbidities are complex, with a bidirectional association of major depression and panic disorder with migraine. Importantly, optimizing the pharmacological and non-pharmacological treatment of either migraine or its psychiatric comorbidities might help clinicians to attenuate the burden of both these conditions.ConclusionsThe available data highlight the need for a comprehensive evaluation of psychiatric disorders in migraine in order to promote an integrated model of care and carefully address the burden and psychosocial impairment related to psychiatric comorbidities in migraine.

BackgroundThere is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective.MethodsThe review was based on a primary literature search on the PubMed using the search terms “migraine and exercise”.ResultsLow levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise.ConclusionIn conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.

The association between migraine and cognitive function has been studied during the last decade, however, this relationship is not well established. As migraine prevalence is highest between the ages of 30–40, aligning with some of our most productive years, we must understand cognitive changes within this disorder. Cognitive impairment potentially limits social and professional interactions, thus negatively impacting quality of life. Therefore, we will review the relationship between prevalent migraine and cognition. Cognitive dysfunction has been reported to be the second largest cause of disability, after pain, in migraine patients. While subjective patient reports on cognition consistently describe impairment, findings for objective neuropsychological assessments vary. Many studies report worse cognitive performance in the ictal phase compared to controls, which can persist into the postictal period, although whether this continues in the interictal period has been understudied. There is limited consensus as to whether cognition differs in migraine with aura versus migraine without aura, and while many studies do support cognitive impairment in chronic migraine, it remains uncertain as to whether this is more debilitating than the cognitive difficulties experienced by those with episodic migraine. To date, objective assessment of neurological abnormalities that may underlie cognitive impairment through neuroimaging has been underutilized. There is limited consensus as to whether cognitive impairment is a characteristic specific to migraine, whether it is driven by a combination of factors including co-morbidities such as anxiety, depression, or vascular dysfunction, treatment, or whether it is a more general characteristic of pain disorders. Overall, increasing numbers of studies support cognitive impairment in migraine patients. Future studies should consider longitudinal study designs to assess cognition across different migraine phases and subtypes of the disorder, including migraine with aura and chronic migraine, as well as controlling for important confounders such as treatment use.