bluuebunny/crossref_metadata_2025_split huggingface dataset:
POU3F3‐related disorder: Defining the phenotype and expanding the molecular spectrum
Authors: Rossi Alessandra , Blok Lot Snijders , Neuser Sonja , Klöckner Chiara , Platzer Konrad , Faivre Laurence Olivier , Weigand Heike , Dentici Maria L. , Tartaglia Marco , Niceta Marcello , Alfieri Paolo , Srivastava Siddharth , Coulter David , Smith Lacey , Vinorum Kristin , Cappuccio Gerarda , Brunetti‐Pierri Nicola , Torun Deniz , Arslan Mutluay , Lauridsen Mathilde F. , Murch Oliver , Irving Rachel , Lynch Sally A. , Mehta Sarju G. , Carmichael Jenny , Zonneveld‐Huijssoon Evelien , de Vries Bert , Kleefstra Tjitske , Johannesen Katrine M. , Westphall Ian T. , Hughes Susan S. , Smithson Sarah , Evans Julie , Dudding‐Byth Tracy , Simon Marleen , van Binsbergen Ellen , Herkert Johanna C. , Beunders Gea , Oppermann Henry , Bakal Mert , Møller Rikke S. , Rubboli Guido , Bayat Allan 
Published: May 2023

AbstractPOU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype–phenotype correlations in individuals with POU3F3‐related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA‐binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3‐related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype–phenotype correlations.
Explainability of neural networks for child language: Agent‐First strategy in comprehension of Korean active transitive construction
Authors: Shin Gyu‐Ho , Mun Seongmin 
Published: May 2023

AbstractThis study investigates how neural networks address the properties of children's linguistic knowledge, with a focus on the Agent‐First strategy in comprehension of an active transitive construction in Korean. We develop various neural‐network models and measure their classification performance on the test stimuli used in a behavioural experiment involving scrambling and omission of sentential components at varying degrees. Results show that, despite some compatibility of these models’ performance with the children's response patterns, their performance does not fully approximate the children's utilisation of this strategy, demonstrating by‐model and by‐condition asymmetries. This study's findings suggest that neural networks can utilise information about formal co‐occurrences to access the intended message to a certain degree, but the outcome of this process may be substantially different from how a child (as a developing processor) engages in comprehension. This implies some limits of neural networks on revealing the developmental trajectories of child language.Research Highlights
This study investigates how neural networks address properties of child language.
We focus on the Agent‐First strategy in comprehension of Korean active transitive.
Results show by‐model/condition asymmetries against children's response patterns.
This implies some limits of neural networks on revealing properties of child language.
Environmental and spatial determinants of fish community structure in an Afro‐tropical river ecosystem
Authors: Ugbor Ogechi Nnabuchi , Omoigberale Michael Osasele , Amoutchi Amien Isaac , Affian Kouadio , Mehner Thomas 
Published: May 2023

AbstractWe investigated the relative influence of local environmental and spatial factors in structuring the community composition of fish at 15 sampling sites along the longitudinal gradient of the Lower Niger River Basin (LNRB) in dry and rainy seasons using distance‐based redundancy analysis and variation partitioning analysis. We collected a total of 3807 fish specimens representing 42 species. Our result indicated that the fish community composition differed between the upper and lower regions of the river. The communities in the upper region is influenced by high‐nutrient concentrations, while downstream sites were characterized by high concentrations of suspended solids. Variation partitioning revealed higher contributions of spatial than environmental predictors on fish community composition, with a higher total predicted variance in dry season. The variations in the community composition between upper and lower region may be attributable to the differences in the nature of anthropogenic activities within the regions, which influenced the local conditions differently. Differences in flow dynamics between upper and lower regions as attributable to black and white floods in the LNRB modify the connectivity between sites. Dispersal among sites may be more limited downstream than in the upper region, particularly in the dry season, because damming in the upper region also interrupts the natural flood regime such that there are low water levels in the lower region, which spatially isolate fish communities at certain sampling sites. The relatively higher total predicted variance during dry season may be attributable to the temporal differences in abiotic conditions between sites, which may have influenced site level community composition and abundance differently.
Baseline long‐term potentiation‐like cortical plasticity is associated with longitudinal cortical thinning in healthy adults and in adults with bipolar disorder type II
Authors: Zak Nathalia , Moberget Torgeir , Bøen Erlend , Boye Birgitte , Rygvold Trine W. , Malt Ulrik F. , Andreassen Ole A. , Andersson Stein , Westlye Lars T. , Elvsåshagen Torbjørn 
Published: May 2023

AbstractThe precise neurobiological processes underlying cerebral cortical thinning in aging and psychiatric illnesses remain undetermined, yet aging‐ and synaptic dysfunction‐related loss of synapses are potentially important mechanisms. We used long‐term potentiation‐like plasticity of the visual evoked potential as an index of synaptic function in the cortex and hypothesized that plasticity at baseline would be negatively associated with future cortical thinning in healthy adults and in adults with bipolar disorder type II. Thirty‐two healthy adults and 15 adults with bipolar disorder type II underwent electroencephalography‐based measurement of visual evoked potential plasticity and 3T magnetic resonance imaging of the brain at baseline and a follow‐up brain scan on average 2.3 years later. The relationships between visual evoked potential plasticity at baseline and longitudinal cortical thickness changes were examined using Freesurfer and the Permutation Analysis of Linear Models tool. The analyses showed a negative association between the plasticity of the N1 visual evoked potential amplitude at baseline and thinning rate in the medial and lateral parietal and medial occipital cortices in healthy adults and in the right medial occipital cortex in the total sample of healthy adults and adults with bipolar disorder type II, indicating greater thinning over time in subjects with less N1 plasticity (pFWER < .05). Although preliminary, the results indicate an association between visual evoked potential plasticity and the future rate of cortical thinning in healthy adults and in bipolar disorder type II, supporting the hypothesis that cortical thinning might be related to synaptic dysfunction.
The fate and prospects of stem cell therapy in the treatment of hypoxic–ischemic encephalopathy
Authors: Luo Bo‐Yan , Zhou Hong‐Su , Sun Yi‐Fei , Xiao Qiu‐Xia , Chen Li , She Hong‐Qing , Wang Shi‐Feng , Yan Shan‐Shan , Chang Quan‐Yuan , He Yu‐Qi , Xiong Liu‐Lin 
Published: May 2023

AbstractHypoxic–ischemic encephalopathy (HIE) is a leading cause of long‐term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI‐induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic–ischemic encephalopathy (NHIE).
Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice
Authors: Contestabile Alessandro , Casarotto Giulia , Musardo Stefano , Espinosa Pedro , Maltese Federica , Jiang Yong‐hui , Bellone Camilla , Glangetas Christelle 
Published: May 2023

AbstractAnxiety disorders are the most prevalent co‐morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co‐occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours. Firstly, we characterize the developmental trajectories of locomotor, social behaviour and anxiety traits in a mouse model of ASD. We highlight that the anxiety phenotype is a late‐onset emerging phenotype in mice with a Shank3Δe4‐22 mutation. Consequently, we used an shRNA strategy to model Shank3 insufficiency in the bed nucleus of the stria terminalis (BNST), a brain region exerting a powerful control on anxiety level. We found that Shank3 downregulation in the anteromedial BNST (amBNST) induced anxiogenic effects and enhanced social avoidance after aversive social defeat. Associated with these behavioural defects, we showed alteration of glutamatergic synaptic functions in the amBNST induced by Shank3 insufficiency during adolescence. Our data strongly support the role of Shank3 in the maturation of amBNST, and its key role in anxiety control. Our results may further help to pave the road on a better understanding of the neuronal mechanisms underlying anxiety disorders implicated in ASDs.
Caveolinopathy: Clinical, histological, and muscle imaging features and follow‐up in a multicenter retrospective cohort
Authors: Berling Edouard , Verebi Camille , Venturelli Nadia , Vassilopoulos Stéphane , Béhin Anthony , Tard Céline , Michaud Maud , Villar Quiles Rocio Nur , Vicart Savine , Masingue Marion , Carlier Robert‐Yves , Romero Norma Beatriz , Lacene Emmanuelle , Leturcq France , Eymard Bruno , Laforêt Pascal , Stojkovic Tanya 
Published: May 2023

AbstractBackground and purposeCAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype.MethodsTwenty‐three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow‐up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow‐up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin‐3 Western blot analysis were also compiled.ResultsExercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin‐3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype–genotype correlation was evidenced.ConclusionsCaveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin‐3 immunostaining are pitfalls leading to misdiagnosis.
Improving brain and vascular health at the population level: Lessons from the Norwegian success story
Authors: Owolabi Mayowa O. 
Published: May 2023

AbstractStroke, dementia and ischemic heart disease are a triple threat which combined are the leading causes of death and disability globally. Fortunately, the three diseases share similar risk factors along the vascular cascade which can be targeted for primordial and primary prevention. In Norway, during 1990–2019, the age‐standardised incidence rates decreased significantly for dementia by −5.4%, ischemic heart disease by −30.0%, and stroke by −35.3%. This was possible because Norway ensured equitable income for her citizens, and committed sufficient funds to universal health coverage while implementing a semi‐decentralized and responsive health system with robust primary health care. This included monitoring the burden of the triple threat and their cardinal risk factors; ensuring primordial, primary and secondary preventive interventions; implementing acute care for ischemic heart disease and stroke; and ensuring interdisciplinary rehabilitation and chronic care for the triple threat. Overall, all countries will need to develop national strategies for combating the triple threat within the context of sustainable development goals with adequate allocation and utilization of resources.
Probationary precarity? Differential inclusion among post‐graduation work permit‐holders in Canada
Authors: Vosko Leah F. 
Published: May 2023

AbstractIn high‐income receiving states, educational visa‐holders are routinely cast as beneficiaries of immigration systems prioritizing well‐trained workers. Promising pathways to permanent residency, Canada's Post‐Graduation Work Permit Program (PGWPP), an expanding stream of its new International Mobility Program, is a case in point. Yet there is a dearth of scholarly analysis of program design and its effects on visa‐holders. Addressing this lacuna, this article examines the PGWPP through a multi‐method approach focusing on the interface between program requirements, distinctions between doors of entry with attention to criteria for accessing permanent residency, country of origin, and gender. Underlining the porosity of entry categories, contributing to multiple doors through which educational migrants must pass to secure permanent residency, it reveals that PGWP‐holders experience “probationary precarity” – a concept devised to capture labour market insecurities permit‐holders endure.
RETRACTED: Effect of endoscopic loop ties in acute appendicitis on wound infection rate: A meta‐analysis
Authors: Ding Hongling , Li Yong 
Published: May 2023

AbstractA meta‐analysis study to measure the consequence of endoscopic loop ties (ELT) in acute appendicitis (AA) on wound infection rate. A comprehensive literature inspection till February 2023 was applied and 2765 interrelated studies were reviewed. The 27 chosen studies enclosed 15 093 subjects with AA in the chosen studies' starting point, 7141 of them were ELT, and 7952 were open surgery. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the effect of ELT in AA on wound infection rate by the dichotomous and continuous styles and a fixed or random model. Open surgery had a significantly higher postoperative surgical site wound infection (SSWI). (OR, 1.41; 95% CI, 1.09–1.83, P = 0.009) with low heterogeneity (I2 = 34%) compared to ELT in AA subjects. Although no significant difference was detected between open surgery and ELT in intra‐abdominal abscess rate (OR, 0.88; 95% CI, 0.56–1.40, P = 0.59) with moderate heterogeneity (I2 = 51%) in AA subjects. Open surgery had a significantly higher postoperative SSWI, however, no significant difference was found in intra‐abdominal abscess rate compared to ELT in AA subjects. However, caused by the small sample sizes of several chosen studies for this meta‐analysis, care must be exercised when dealing with its values.
Vertical stratification of ant assemblages varies along a latitudinal gradient in Brazilian savanna
Authors: Vasconcelos Heraldo L. , Neves Karen C. , Andersen Alan N. 
Published: May 2023

AbstractAimArboreal and ground‐dwelling species experience distinct microclimates, have contrasting thermal tolerances and thus may be expected to respond differentially to geographic climatic gradients. We tested this idea by evaluating if the degree of vertical stratification of savanna ant assemblages varies along a latitudinal climatic gradient, and by determining how compositional dissimilarities within each stratum varies across increased geographical and climatic distances.LocationBrazil.TaxonAnts.MethodsWe sampled ants foraging on the ground or in trees at 32 sites. Species were classified according to their main foraging stratum, as arboreal, ground‐dweller or strata generalist. We used linear models to evaluate the effects of latitude and sampling stratum on species richness, and the effect of latitude on the proportion of species typical from trees or from the ground in different sampling strata. The influence of geographic and climatic distances on the compositional differences between assemblages from the same stratum was assessed using regression on distance matrices.ResultsSpecies richness on the ground increased with latitude significantly faster than in trees. The turnover of species between strata was lower at lower latitudes, where there were proportionally more strata generalists and species typical from the ground stratum foraging in trees. Consequently, the compositional dissimilarity between vertical strata decreased with decreasing latitude. Despite that, the dissimilarities between vertical strata were, on average, as great or even greater than the dissimilarities between assemblages from the same stratum across the horizontal space.Main ConclusionsWe found support for the idea that climatic variation across latitude had different effects on arboreal compared with ground‐foraging assemblages. Overall, our results suggest that as Brazilian savanna becomes hotter and drier as forecast under climate change, ant assemblages may become not only less diverse, notably on the ground, but also more homogeneous vertically.
EGFR marks a subpopulation of dermal mesenchymal cells highly expressing IGF1 which enhances hair follicle regeneration
Authors: Chen Min , Xu Zaoxu , Chen Yu , Yang Qingyang , Lu Ruiqing , Dong Yankai , Li Xiaosong , Xie Jundong , Xu Ren‐He , Jia Haidong , Kang Yan , Wu Yaojiong 
Published: May 2023

AbstractThe skin harbours transcriptionally and functionally heterogeneous mesenchymal cells that participate in various physiological activities by secreting biochemical cues. In this study, we aimed to identify a new subpopulation of dermal mesenchymal cells that enhance hair follicle regeneration through a paracrine mechanism. Integrated single‐cell RNA sequencing (scRNA‐seq) data analysis revealed epidermal growth factor receptor (EGFR) as a marker of distinct fibroblast subpopulation in the neonatal murine dermis. Immunofluorescence staining and fluorescence‐activated cell sorting (FACS) were used to validate the existence of the cell population in Krt14‐rtTA‐H2BGFP mouse. The difference of gene expression between separated cell subpopulation was examined by real‐time PCR. Potential effect of the designated factor on hair follicle regeneration was observed after the application on excisional wounds in Krt14‐rtTA‐H2BGFP mouse. Immunofluorescence staining demonstrated the existence of dermal EGFR+ cells in neonatal and adult mouse dermis. The EGFR+ mesenchymal population, sorted by FACS, displayed a higher expression level of Igf1 (insulin‐like growth factor 1). Co‐localisation of IGF1 with EGFR in the mouse dermis and upregulated numbers of hair follicles in healed wounds following the application of exogenous IGF1 illustrated the contribution of EGFR+ cells in promoting wound‐induced hair follicle neogenesis. Our results indicate that EGFR identifies a subpopulation of dermal fibroblasts that contribute to IGF1 promotion of hair follicle neogenesis. It broadens the understanding of heterogeneity and the mesenchymal cell function in skin and may facilitate the potential translational application of these cells.
Effect of rapamycin on lysosomal accumulation in a CRISPR/Cas9‐based cellular model of VPS13A deficiency
Authors: Tornero‐Écija A. R. , Navas M. A. , Muñoz‐Braceras S. , Vincent O. , Escalante R. 
Published: May 2023

AbstractVPS13A is a lipid transfer protein localized at different membrane contact sites between organelles, and mutations in the corresponding gene produce a rare neurodegenerative disease called chorea‐acanthocytosis (ChAc). Previous studies showed that VPS13A depletion in HeLa cells results in an accumulation of endosomal and lysosomal markers, suggesting a defect in lysosomal degradation capacity leading to partial autophagic dysfunction. Our goal was to determine whether compounds that modulate the endo‐lysosomal pathway could be beneficial in the treatment of ChAc. To test this hypothesis, we first generated a KO model using CRISPR/Cas9 to study the consequences of the absence of VPS13A in HeLa cells. We found that inactivation of VPS13A impairs cell growth, which precludes the use of isolated clones due to the undesirable selection of edited clones with residual protein expression. Therefore, we optimized the use of pool cells obtained shortly after transfection with CRISPR/Cas9 components. These cells are a mixture of wild‐type and edited cells that allow a comparative analysis of phenotypes and avoids the selection of clones with residual level of VPS13A expression after long‐term growth. Consistent with previous observations by siRNA inactivation, VPS13A inactivation by CRISPR/Cas9 resulted in accumulation of the endo‐lysosomal markers RAB7A and LAMP1. Notably, we observed that rapamycin partially suppressed the difference in lysosome accumulation between VPS13A KO and WT cells, suggesting that modulation of the autophagic and lysosomal pathway could be a therapeutic target in the treatment of ChAc.