bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bouncing the network: A dynamical systems model of auditory–vestibular interactions underlying infants’ perception of musical rhythm
Authors: Tichko Parker , Kim Ji Chul , Large Edward W. 
Published: February 2021

AbstractPrevious work suggests that auditory–vestibular interactions, which emerge during bodily movement to music, can influence the perception of musical rhythm. In a seminal study on the ontogeny of musical rhythm, Phillips‐Silver and Trainor (2005) found that bouncing infants to an unaccented rhythm influenced infants’ perceptual preferences for accented rhythms that matched the rate of bouncing. In the current study, we ask whether nascent, diffuse coupling between auditory and motor systems is sufficient to bootstrap short‐term Hebbian plasticity in the auditory system and explain infants’ preferences for accented rhythms thought to arise from auditory–vestibular interactions. First, we specify a nonlinear, dynamical system in which two oscillatory neural networks, representing developmentally nascent auditory and motor systems, interact through weak, non‐specific coupling. The auditory network was equipped with short‐term Hebbian plasticity, allowing the auditory network to tune its intrinsic resonant properties. Next, we simulate the effect of vestibular input (e.g., infant bouncing) on infants’ perceptual preferences for accented rhythms. We found that simultaneous auditory–vestibular training shaped the model's response to musical rhythm, enhancing vestibular‐related frequencies in auditory‐network activity. Moreover, simultaneous auditory–vestibular training, relative to auditory‐ or vestibular‐only training, facilitated short‐term auditory plasticity in the model, producing stronger oscillator connections in the auditory network. Finally, when tested on a musical rhythm, models which received simultaneous auditory–vestibular training, but not models that received auditory‐ or vestibular‐only training, resonated strongly at frequencies related to their “bouncing,” a finding qualitatively similar to infants’ preferences for accented rhythms that matched the rate of infant bouncing.
The use of attention to maintain information in working memory: A developmental investigation of spontaneous refreshing in school‐aged children
Authors: Vergauwe Evie , Besch Vincent , Latrèche Caren , Langerock Naomi 
Published: February 2021

AbstractThe capacity of working memory is limited and undergoes important developmental changes during childhood. One proposed reason for the expansion of working memory capacity during childhood is the emergence and increased efficiency of active maintenance mechanisms, such as that of refreshing. Refreshing is a proposed mechanism to keep information active in working memory by bringing memory items back into the focus of attention. One prevalent view is that the spontaneous use of refreshing emerges around the age of 7 and becomes more efficient during middle childhood and beyond. Using a novel approach to examine refreshing in children in Experiment 1, we show, against common conceptions, that simply giving free time in a basic working memory task does not lead to spontaneous refreshing in 9–12‐year‐old children. Instead, their focus of attention appears to linger on the last‐presented memory item, even when ample time for refreshing is provided. Experimentally imposing the use of refreshing in Experiment 2, however, showed that children in this age range are able to switch their focus of attention away from the last‐presented item in switch to another memory item. Thus, the current study uncovers that children in middle childhood do not always spontaneously switch attention away from the last‐presented memory item to refresh the entire list, even though they are able to switch attention away from the last‐presented memory item when instructed to do so. The theoretical implications of these findings are discussed.
Kidney organoids: Research in developmental biology and emerging applications
Authors: Shimizu Tatsuya , Yamagata Kunihiro , Osafune Kenji 
Published: February 2021

AbstractKidney organoids generated from human pluripotent stem cells (hPSCs) have drastically changed the field of stem cell research on human kidneys within a few years. They are self‐organizing multicellular structures that contain nephron components such as glomeruli and renal tubules in most cases, but hPSC‐derived ureteric buds, the progenitors of collecting ducts and ureters, can also form three‐dimensional organoids. Today's challenges facing human kidney organoids are further maturation and anatomical integrity in order to achieve a complete model of the developing kidneys and ultimately a complete adult organ. Since chronic kidney disease (CKD) and impaired kidney function are an increasing burden on public health worldwide, there is an urgent need to develop effective treatments for various renal conditions. In this regard, hPSC‐derived kidney organoids may impact medicine by providing new translational approaches. The unique ability of kidney organoids derived from disease‐specific hPSCs to reproduce human diseases caused by genetic alterations may help provide the next generation of kidney disease models. Recent advances in the field of kidney organoid research have been generally accompanied by progress in developmental biology and other technological breakthroughs. In this review, we consider the current trends in kidney organoid technology, especially focusing on the relationship to the study of human kidney development, and discuss the remaining hurdles and prospects in regenerating human kidney structures beyond organoids.
Fenfluramine as antiseizure medication for epilepsy
Authors: Gogou Maria , Cross J Helen 
Published: February 2021

Fenfluramine hydrochloride has classically been described as acting pharmacologically through a serotonergic mechanism. Therefore, it was initially used as an anorectic drug, given that impaired serotonin homeostasis may be associated with increased food intake. Although positive results were documented, cardiovascular concerns resulted in its temporary withdrawal. Nevertheless, a novel role in patients with epilepsy was later suggested by isolated clinical observations. The wide application of genetic testing allowed the classification (predominantly as Dravet syndrome) of patients in whom benefit was seen, while with the development of zebrafish models, its antiepileptic properties were confirmed at a molecular level. Data from randomized clinical trials have shown a beneficial effect of fenfluramine, as an adjunct therapy, on seizure control for children with Dravet syndrome, though there is still uncertainty about the impact on neurodevelopment in these patients. No signs of heart valve disease have been documented to date. Long‐term and appropriately designed clinical studies will verify whether fenfluramine is a therapeutic agent of high importance, living up to the promise shown so far.
What this paper adds

Fenfluramine is a very promising repurposed therapy specifically for seizures in Dravet syndrome.

The long‐term effect of fenfluramine on neurodevelopmental prognosis requires further investigation.
Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose‐ranging study
Authors: Wölnerhanssen Bettina K. , Drewe Jürgen , Verbeure Wout , le Roux Carel W. , Dellatorre‐Teixeira Ludmilla , Rehfeld Jens F. , Holst Jens J. , Hartmann Bolette , Tack Jan , Peterli Ralph , Beglinger Christoph , Meyer‐Gerspach Anne C. 
Published: February 2021

AbstractAimTo determine whether a dose‐dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon‐like peptide‐1 [aGLP‐1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol.Materials and MethodsTwelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13C‐sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo‐controlled, double‐blind, cross‐over trial. Blood samples and breath samples (13C‐sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated.ResultsWe found (a) a dose‐dependent stimulation of CCK, aGLP‐1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose‐dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting.ConclusionsSolutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol‐containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.
Global analysis reveals an environmentally driven latitudinal pattern in mushroom size across fungal species
Authors: Bässler Claus , Brandl Roland , Müller Jörg , Krah Franz S. , Reinelt Arthur , Halbwachs Hans 
Published: February 2021

AbstractAlthough macroecology is a well‐established field, much remains to be learned about the large‐scale variation of fungal traits. We conducted a global analysis of mean fruit body size of 59 geographical regions worldwide, comprising 5340 fungal species exploring the response of fruit body size to latitude, resource availability and temperature. The results showed a hump‐shaped relationship between mean fruit body size and distance to the equator. Areas with large fruit bodies were characterised by a high seasonality and an intermediate mean temperature. The responses of mutualistic species and saprotrophs were similar. These findings support the resource availability hypothesis, predicting large fruit bodies due to a seasonal resource surplus, and the thermoregulation hypothesis, according to which small fruit bodies offer a strategy to avoid heat and cold stress and therefore occur at temperature extremes. Fruit body size may thus be an adaptive trait driving the large‐scale distribution of fungal species.
Paternal age negatively affects sperm production of the progeny
Authors: Vuarin Pauline , Lesobre Loïc , Levêque Gwènaëlle , Saint Jalme Michel , Lacroix Frédéric , Hingrat Yves , Sorci Gabriele 
Published: February 2021

AbstractParental age has profound consequences for offspring’s phenotype. However, whether patrilineal age affects offspring sperm production remains unknown, despite the importance of sperm production for male reproductive success in species facing post‐copulatory sexual selection. Using a longitudinal dataset on ejaculate attributes of the houbara bustard, we showed that offspring sired by old fathers had different age‐dependent trajectories of sperm production compared to offspring sired by young fathers. Specifically, they produced less sperm (−48%) in their first year of life, and 14% less during their lifetime. Paternal age had the strongest effect, with weak evidence for grandpaternal or great grandpaternal age effects. These results show that paternal age can affect offspring reproductive success by reducing sperm production, establishing an intergenerational link between ageing and sexual selection.
Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data
Authors: Kanber Baris , Vos Sjoerd B. , de Tisi Jane , Wood Tobias C. , Barker Gareth J. , Rodionov Roman , Chowdhury Fahmida Amin , Thom Maria , Alexander Daniel C. , Duncan John S. , Winston Gavin P. 
Published: February 2021

AbstractObjectiveTo compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.MethodsWe developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG.ResultsSeizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG.SignificanceComputational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.
The long and narrow path for novel cell‐based seafood to reduce fishing pressure for marine ecosystem recovery
Authors: Halpern Benjamin S. , Maier Jason , Lahr Heather J. , Blasco Gordon , Costello Christopher , Cottrell Richard S. , Deschenes Olivier , Ferraro Danielle M. , Froehlich Halley E. , McDonald Gavin G. , Millage Katherine D. , Weir Michael J. 
Published: February 2021

AbstractCell‐based seafood is an emerging novel food, with many start‐up companies aspiring for ocean conservation benefits through expanded market share that displaces wild‐caught seafood. However, the ability for cell‐based seafood to achieve this conservation outcome is often oversimplified and will rely on an extensive, and we find somewhat tenuous, chain of events. Here, we outline the technological, behavioural, market and ecological changes that must occur along this pathway, and conclude that fisheries recoveries and collateral ocean benefits are unlikely to result from cell‐based seafood technology. In particular, we detail nine necessary steps and argue that failure at any one step could hinder or even eliminate cell‐based seafood's conservation effects. We additionally draw comparisons to aquaculture and share broader lessons for other demand‐driven product interventions.
Cryptogamic ground covers as analogues for early terrestrial biospheres: Initiation and evolution of biologically mediated proto‐soils
Authors: Mitchell Ria L. , Strullu‐Derrien Christine , Sykes Dan , Pressel Silvia , Duckett Jeffrey G. , Kenrick Paul 
Published: February 2021

AbstractModern cryptogamic ground covers (CGCs), comprising assemblages of bryophytes (hornworts, liverworts, mosses), fungi, bacteria, lichens and algae, are thought to resemble early divergent terrestrial communities. However, limited in situ plant and other fossils in the rock record, and a lack of CGC‐like soils reported in the pre‐Silurian sedimentological record, have hindered understanding of the structure, composition and interactions within the earliest CGCs. A key question is how the earliest CGC‐like organisms drove weathering on primordial terrestrial surfaces (regolith), leading to the early stages of soil development as proto‐soils, and subsequently contributing to large‐scale biogeochemical shifts in the Earth System. Here, we employed a novel qualitative, quantitative and multi‐dimensional imaging approach through X‐ray micro‐computed tomography, scanning electron, and optical microscopy to investigate whether different combinations of modern CGC organisms from primordial‐like settings in Iceland develop organism‐specific soil forming features at the macro‐ and micro‐scales. Additionally, we analysed CGCs growing on hard rocky substrates to investigate the initiation of weathering processes non‐destructively in 3D. We show that thalloid CGC organisms (liverworts, hornworts) develop thin organic layers at the surface (<1 cm) with limited subsurface structural development, whereas leafy mosses and communities of mixed organisms form profiles that are thicker (up to ~ 7 cm), structurally more complex, and more organic‐rich. We term these thin layers and profiles proto‐soils. Component analyses from X‐ray micro‐computed tomography data show that thickness and structure of these proto‐soils are determined by the type of colonising organism(s), suggesting that the evolution of more complex soils through the Palaeozoic may have been driven by a shift in body plan of CGC‐like organisms from flattened and appressed to upright and leafy. Our results provide a framework for identifying CGC‐like proto‐soils in the rock record and a new proxy for understanding organism–soil interactions in ancient terrestrial biospheres and their contribution to the early stages of soil formation.
Body stoichiometry of heterotrophs: Assessing drivers of interspecific variations in elemental composition
Authors: Andrieux Benjamin , Signor Juliette , Guillou Vincent , Danger Michael , Jabot Franck 
Published: February 2021

AbstractAimThe aim was to document how body stoichiometry of heterotrophs varies globally and to assess phylogenetic, trophic, habitat and body mass drivers of this interspecific variation in elemental composition, focusing on carbon (C), nitrogen (N) and phosphorus (P).LocationWorld‐wide.Time period1930–2019.Major taxa studiedAmphibians, fishes (Actinopterygii), invertebrates, mammals, microbes and sauropsids (birds and reptiles).MethodsWe compiled from the scientific literature a global database of body elemental composition of heterotrophs in marine, freshwater and terrestrial realms. We used model selection and ANCOVAs to investigate the proportion of variance in elemental composition explained by taxonomic groups, diet, habitat and body mass. We assessed the phylogenetic signal in body stoichiometry using Blomberg's K and Pagel's λ statistics. We assessed the phylogenetic structure of interspecific variation in body stoichiometry using mixed models, with nested taxonomic levels as random factors. We finally assessed the covariations in elemental composition.ResultsOur database gathered 31,371 observations on 1,512 species. Body elemental composition was widely variable among species, with the four assessed drivers contributing significantly to this variation. Taxonomic group was the strongest contributor to interspecific variance for the stoichiometric traits studied, followed by habitat, diet and body mass. More precisely, C, N and P contents and C:N ratio were generally structured among classes, whereas the largest variations in C:P and N:P ratios were among families. This resulted in a significant but relatively modest phylogenetic signal. Finally, we found significant covariation among the three body elemental contents, resulting in taxonomic group‐specific C:N:P spectra.Main conclusionsOur global synthesis of body stoichiometry of heterotrophs revealed a strong interspecific variability that was only modestly explained by the species attributes investigated (body mass, habitat and diet). It also revealed that this taxonomically structured residual variation in body stoichiometry seemed to be constrained along taxonomic group‐specific elemental spectra.
Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status
Authors: Benzerdjeb Nazim , Tantot Juliet , Blanchet Christophe , Philouze Pierre , Mekki Yahia , Lopez Jonathan , Devouassoux‐Shisheboran Mojgan 
Published: February 2021

AimsOropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5–20% of p16‐positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC‐related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV‐driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC.Methods and resultsA total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16‐positive or p16‐negative/wild‐type patterns‐p53 (WT‐p53) cases (n = 63), DNA in‐situ hybridisation for high‐risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (n = 19). A significant association between TP53 mutation and pattern of p53 expression was found (WT‐p53, seven of 16, P < 0.001). The p16‐positive/WT‐p53 was significantly associated with HPV+ tumour status (p16‐positive/WT‐p53, 50 of 110, P < 0.001). Interestingly, a subset of p16‐positive OPSCC was unrelated to HPV (13.5%, eight of 59), and showed mutant‐type staining of p53 expression.ConclusionsThe p16 protein immunopositivity in conjunction with the mutant‐type pattern of p53 staining helped to reclassify a subset of p16‐positive OPSCC as OPSCC‐unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.
A laboratory study to test the responses of human dental pulp stem cells to extracts from three dental pulp capping biomaterials
Authors: Abou ElReash A. , Hamama H. , Grawish M. , Saeed M. , Zaen El‐Din A. M. , Shahin M. A. , Zhenhuan W. , Xiaoli X. 
Published: February 2021

AbstractAimThis laboratory study aimed to investigate the effects of three endodontic biomaterials; MTA‐HP, iRoot‐BP‐Plus and ACTIVA on the proliferation, adhesion and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs).MethodologyThe hDPSCs were isolated from the dental pulps of 21 patients scheduled for surgical extraction of their impacted third molars. The MTT assay was used for assessing cellular proliferation. Ninety‐six‐well plates were used and the experiment was repeated four times under the same condition and the assay was done in triplicate. Four groups were assigned in which the hDPSCs were cultured in complete media only and considered as negative control. Whilst in the 2nd, 3rd and 4th groups, the cells were treated with CM supplemented with 1.5 μl MTA‐HP (CM‐MTA, iRoot‐BP‐Plus (CM‐BP), and ACTIVA(CM‐AC) extracts, respectively. Attachment adhesion and growth morphology of hDPSCs were observed using SEM and the osteogenic differentiation assay was evaluated by Alizarin red stain test (ARS). The data of proliferation and osteogenic differentiation were analysed using two‐way ANOVA followed by Tukey’s post hoc multiple comparison test. A p‐value < 0.05 was considered significant to analyse the differences amongst the means of groups.ResultsBoth CM‐MTA and CM‐BP groups were associated with a significant increase in hDPSC proliferation in comparison with CM‐AC and CM groups (p = 0.001). hDPSCs exhibited a greater cellular attachment to iRoot‐BP‐Plus surfaces followed by MTA‐HP, whilst less attachment was observed in the ACTIVA group. Moreover, at day 7 there was a significant difference in formation of mineralizing nodules; CM‐BP, CM‐MTA and CM‐AC groups respectively (p = 0.001). Whilst there was no significance of difference between CM‐AC and CM groups (p > 0.05).ConclusionsIn a laboratory setting, ACTIVA, MTA‐HP and iRoot‐BP‐Plus promoted hDPSCs proliferation, mineralization and attachment, which may explain their in‐situ success as endodontic biomaterials.