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Transitory and sustained Cf0 effects: evidence from Swiss German
No full textIt is generally agreed that f0 following phonologically voiceless plosives is higher than after voiced plosives. Such consonant f0 (Cf0) effects have been reported in many languages. However, the phonetic basis of the ‘voiceless’ – ‘voiced’ distinction may differ between languages; for example, in English the distinction involves long-lag VOT in ‘voiceless’ plosives and short-lag VOT or prevoicing in ‘voiced’ plosives, while in Dutch the ‘voiceless’ plosives have short-lag VOT and the ‘voiced’ plosives are generally prevoiced. This study focuses on Swiss German, where neither long-lag VOT nor voicing is present: the primary difference between lenis (‘voiced’) and fortis (‘voiceless’) plosives lies in closure duration. Replicating Ladd and Schmid [Journal of Phonetics (2018), 71, 229–248], we show that both lenis and fortis plosives exhibit higher initial f0 followed by a brief fall, typical of ‘voiceless’ plosives in many languages. Using newer statistical methods (Generalised Additive Mixed Models), we also show that, during the latter part of the vowel beyond the initial f0 drop, overall f0 level is significantly higher after ‘fortis’ than after ‘lenis’ plosives. This suggests that two distinct but interacting Cf0 effects are involved. We discuss the relevance of this finding for future experimental work on Cf0
Enhancing single-cell ATAC sequencing with formaldehyde fixation, cryopreservation, and multiplexing for flexible analysis
No full textObjectiveThe need for freshly isolated cells in bulk or single cell ATAC-seq experiments creates considerable logistical barriers and increases susceptibility to batch effects. This makes it difficult to coordinate complex or longitudinal studies. Our goal was to develop a sample preservation strategy that overcomes these limitations, enabling consistent and high-quality chromatin accessibility profiling from archived samples.ResultsWe established a workflow that incorporates mild formaldehyde fixation prior to cryopreservation, preserving both bulk and single-cell ATAC-seq data quality at levels comparable to fresh samples in HepG2 cells. This protocol reliably maintains key data quality metrics, including signal-to-noise ratio and fragment distributions. Furthermore, the method is fully compatible with transposase-based sample multiplexing using custom Tn5 barcodes. To address barcode hopping inherent to multiplexing, we introduced a computational demultiplexing strategy based on fragment ratios, which accurately assigns single cells to their sample of origin. Our approach streamlines experimental logistics and ensures reproducibility across diverse and temporally dispersed samples, broadening the scope for ATAC-seq–based studies, including those in clinical research settings where coordinated sample collection is challenging
Orthodontic perspectives in the interdisciplinary management of pediatric obstructive sleep apnea
No full textPediatric obstructive sleep apnea (OSA) is a highly prevalent, multifactorial, and often underdiagnosed condition with significant consequences for cognitive and behavioral development. Early detection and timely multidisciplinary interventions are essential, particularly in children with craniofacial anomalies or syndromes associated with increased OSA risks, to prevent long-term complications. This narrative review explores the orthodontists’ role in the interdisciplinary management of pediatric OSA, focusing on early screening for craniofacial risk factors and implementing interceptive orthodontic interventions that support favorable airway development and growth modulation. Through early and frequent interaction with pediatric patients, orthodontists are well-positioned to identify clinical signs of airway-related abnormalities and craniofacial risk factors such as mandibular and maxillary retrognathism, maxillary constriction, and high-arched palatal vaults. Orthodontic interventions such as rapid maxillary expansion (RME), mandibular advancement, and myofunctional therapy may improve airway patency in selected cases. These approaches should be coordinated and integrated within the multidisciplinary team, including orthodontists, pediatricians, sleep specialists, ENT specialists, and speech-language pathologists. Furthermore, caregivers’ involvement and patients’ compliance are keys to success. Despite encouraging clinical observations, current evidence is limited by heterogeneity and a lack of long-term outcome data. Future research should prioritize well-designed prospective trials, explore the effectiveness of combined therapeutic strategies, and support the development of standard diagnostic protocols. Equally important is a stronger focus on early diagnosis and preventive measures to enhance patient outcomes and long-term treatment strategies. Integrating orthodontists into early OSA care is essential for optimizing outcomes and reducing long-term morbidity
Transforming growth factor‐β‐mediated fibrotic remodeling drives chronic kidney disease in methylmalonic aciduria and propionic aciduria - identification of a new therapeutic target
No full textPropionic aciduria (PA-uria) and methylmalonic aciduria (MMA-uria) are caused by defects in propionate catabolism. While chronic kidney disease (CKD) is a well-established complication in MMA-uria, renal involvement in PA-uria has only come into focus more recently, and the underlying mechanisms remain poorly understood. We investigated human renal epithelial cells from patients with PA-uria, MMA-uria, and healthy controls under metabolic stress, induced by methylmalonic acid, methylcitric acid, high-protein, or isoleucine/valine-enriched media. Proteomic profiling revealed significant enrichment of extracellular matrix (ECM)-related pathways in PA-uria cells. Both PA-uria and MMA-uria cells exhibited increased deposition of fibronectin and collagen fibers, which were further amplified under metabolic stress conditions. Transforming growth factor beta (TGF-β) signaling was identified as a key pro-fibrotic pathway. Pharmacological inhibition of the TGF-β receptor signaling normalized fibronectin and collagen deposition in both PA-uria and MMA-uria cells. Treatment with losartan, an angiotensin II type 1 receptor blocker known to modulate TGF-β signaling, also reversed the enhanced ECM deposition. This is the first study to mechanistically link ECM remodeling and TGF-β signaling to CKD pathogenesis in both PA-uria and MMA-uria. Our findings highlight fibrotic remodeling as a shared pathogenic feature and suggest that losartan, a widely available and well-tolerated drug, could be repurposed to mitigate renal fibrosis in these disorders
Integration of structured practical assessments into ultrasound training in the head and neck area
No full text
Novel numerical method for simultaneous design and control optimization of seasonal thermal energy storage systems
No full textBackgroundChild maltreatment (CM) is associated with deficits in cognitive development, particularly in core executive functioning (EF; cognitive flexibility, inhibitory control, working memory). However, due to limited meta-analytic evidence, it remains unclear whether CM dimensions (abuse, neglect) differentially relate to core EF development.ObjectiveWe conducted a pre-registered meta-analysis on studies comparing core EF performance between maltreated and nonmaltreated children and adolescents, examining CM dimensions, subtypes, sample-, and study-related characteristics as potential moderators.MethodsA systematic search in PsycINFO and PubMed (May 2022, updated March 2023) identified eligible peer-reviewed studies per pre-registered criteria. We conducted a multilevel mixed-effects meta-analysis, including subgroup analyses to explore EF domains and CM dimensions as moderators. Additional moderators (age, female ratio, CM subtypes, study quality) were examined via meta-regressions. Publication bias was assessed using funnel plots and Egger's test.Participants and settingWe included 59 studies with 92 effect sizes, comprising 13,022 individuals (MAge = 12.0 years, SD = 2.8; 50.2 % female)