bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of MCI-to-AD progression with atrophy-weighted standard uptake value ratios of18F-Florbetapir PET
Authors: Fang Yu-Hua Dean , Perucho Jose U. , Chiu Sheng-Chieh , Lin Yun-Chi , McConathy Jonathan E. 
Published: March 2023

AbstractAccurate prediction of MCI-to-AD progression is an important yet challenging task. We introduce a new quantitative parameter: the atrophy-weighted standard uptake value ratio (awSUVR), defined as the PET SUVR divided by the hippocampal volume measured with MR, and evaluate whether it may provide better prediction of the MCI-to-AD progression. Materials and Methods: We used ADNI data to evaluate the prediction performances of the awSUVR against SUVR. 571, 363 and 252 18-F-Florbetaipir scans were selected based on criteria of conversion at the third, fifth and seventh year after the PET scans, respectively. Corresponding MR scans were segmented with Freesurfer and applied on PET for SUVR and awSUVR computation. We also searched for the optimal combination of target and reference regions. In addition to evaluating the overall prediction performances, we also evaluated the prediction for APOE4 carriers and non-carriers. For the scans with false predictions, we used 18-F-Flortaucipir scans to investigate the potential source of error. Results: awSUVR provides more accurate prediction than the SUVR in all three progression criteria. The 5-year prediction accuracy/sensitivity/specificity is 90/81/93% for awSUVR and 86/81/88% for SUV. awSUVR also yields good 3- and 7-year prediction accuracy/sensitivity/specificity of 91/57/96 and 92/89/93, respectively. APOE4 carriers generally are slightly more difficult to predict for the progression. False negative prediction is found to either due to a near-cutoff mis-classification or potentially non-AD dementia pathology. False positive prediction is mainly due to the slightly delayed progression than the expected progression time. Conclusion: We demonstrated with ADNI data that 18-F-Florbetapir SUVR weighted with hippocampus volume may provide good prediction power with over 90% accuracy in MCI-to-AD progression.
Regular deworming and seasonality are potential challenges but also offer opportunities for hookworm elimination
Authors: Lamptey Amanda NL , Larbi Irene A , Owusu Donkor Irene Ofei , Sumboh Jeffrey G , Ashong Yvonne , Osabutey Dickson , Cappello Michael , Adu-Gyasi Dennis , Konadu Dennis Gyasi , Asante Kwaku Poku , Koram Kwadwo A , Wilson Michael D 
Published: March 2023

AbstractThe global health community has targeted the elimination of neglected tropical diseases (NTDs) including soil-transmitted helminthiasis by 2030. The elimination strategy has not changed from that of control using regular mass drug administration (MDA) with albendazole, WASH and education. Already doubts have been expressed about this achievement, principally because drugs do not interrupt transmission. We report here the findings of a cohort study aimed to identify host modifiable and environmental factors associated with hookworm infection and reinfection in rural communities in Kintampo North Municipality, Ghana. Faecal samples of 564 consented participants were screened for intestinal parasites at baseline, 9 months and 24 months using the Kato-Katz method. At each time point, positive cases were treated with a single dose of albendazole (400 mg) and their samples were again screened 10-14 days post-treatment to record treatment failures. The hookworm prevalence at the three-time points was 16.7%, 9.22% and 5.3% respectively, whilst treatment failure rates were 17.25%, 29.03% and 40.9% respectively. The intensities of hookworm infection (in eggs per gram) at the time points were 138.3, 40.5 and 135, which showed a likely association with wet and dry seasons. We posit that the very low intensity of hookworm infections in humans during the dry season offers a window of opportunity for any intervention that could drastically reduce the community worm burden before the rainy season.
How long is the long COVID? a retrospective analysis of football players in two major European Championships
Authors: Miccinilli Sandra , Bravi Marco , Conti Giorgio , Bressi Federica , Sterzi Silvia , Santacaterina Fabio , Ciccozzi Massimo 
Published: March 2023

ABSTRACTObjectivesthe goal of this study was to investigate the correlation between SARS-CoV-2 infection and muscle injuries among a large sample of professional soccer players.MethodsA retrospective cohort study was conducted on professional soccer players from the Serie A and LaLiga leagues during the 2019-2020 and 2020-2021 football seasons. The players were divided into two groups based on whether they contracted the Sars-CoV-2 infection (C+) or not (C-) during the 2020/2021 season. Data collection was conducted using the Transfermarkt24 site.ResultsIn the 2019-2020 both championships showed non-significant differences in the average number of muscular injuries between the C+ group and the C- group (Serie A: p=0.194; 95%CI: - 0.044 to 0.215, LaLiga p=0.915; 95%CI: -0.123 to 0.137). In the 2020-2021 the C+ group had a significantly higher number of muscular injuries compared to the C- group in both championships (Serie A: p<0.001; 95%CI 0.731 to 1.038; LaLiga: p<0.001; 95%CI: 0.773 to 1.054). Multiple linear regression analysis confirmed that belonging to C+ in the season 2020/2021 was the variable that most strongly influenced the probability of having a muscle injury in both championships. Survival analysis revealed a hazard ratio of 3.73 (95%CI 3.018 to 4.628) and of 5.14 (95% CI 3.200 to 8.254) for Serie A and LaLiga respectively.ConclusionsThis retrospective cohort study revealed a significant association between SARS-CoV-2 infection and increased risk of muscle injury, emphasizing the importance of carefully considering the infection in the decision-making process for determining athletes’ readiness to return to sport.
Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis
Authors: Bernou Corentin , Mouthon Marc-André , Daynac Mathieu , Kortulewski Thierry , Demaille Benjamin , Barroca Vilma , Couillard-Despres Sébastien , Dechamps Nathalie , Ménard Véronique , Bellenger Léa , Antoniewski Christophe , Chicheportiche Alexandra , Boussin François D. 
Published: March 2023

SummaryThe lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.
Economic and social determinants of health disparities in India: A systematic review of sleep literature
Authors: Zoukal Sofia , Cordova Gabriel Zarate , Etindele Sosso Faustin Armel 
Published: March 2023

AbstractAmong multiple determinants affecting sleep health, there is people socioeconomic status (SES), a multidimensional concept of an individual’s social, economic and ecological position associated to public health inequalities at different levels. No systematic review on the relation between SES and sleep health has been previously conducted in India. Following Prisma protocol, seven articles were selected. Findings revealed that all studies were cross-sectional. The combined number of participants is N=12,746 participants, composed of 81.15% of adults (n=10,343), 10.56% of children (n=1346) and 8.29% of adolescents (n=1057). The smallest sample was N=268 and the larger was N=7017. The socioeconomic determinants the most reported by authors were perceived SES/composite indices, education, income and employment/occupation. The most reported sleep disturbances were obstructive sleep apnea (OSA), insomnia, restless legs syndrome (RLS) and sleep quality. Higher SES (specifically high education and high income) was associated on one hand in adults, with insomnia and a lower risk for OSA; and on the other hand, in adolescents, with poor quality of sleep and shorter sleep duration. Unemployment was significantly associated with insomnia and risk for pediatric OSA (specifically maternal employment). These findings are coherent with the conceptual socioeconomic model of sleep health published by Etindele Sosso et al. and one previous ecological model of sleep published by Grandner et al., both explaining the relationship between SES and sleep disparities. More studies on the subject and more longitudinal research are necessary to support public health programs related to sleep health disparities in India.
An O-GlcNAc transferase pathogenic variant that affects pluripotent stem cell self-renewal
Authors: Omelková Michaela , Fenger Christina Dühring , Murray Marta , Hammer Trine Bjørg , Pravata Veronica M. , Bartual Sergio Galan , Czajewski Ignacy , Bayat Allan , Ferenbach Andrew T. , Stavridis Marios P. , van Aalten Daan M. F. 
Published: March 2023

AbstractO-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. InbornOGTgenetic variants were recently shown to mediate a novel type of Congenital Disorder of Glycosylation (OGT-CDG) which is characterized by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Yvariant which co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Yshow decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4, Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome.Summary statementWe show that the C921Y O-GlcNAc transferase variant found in patients with intellectual disability leads to a defect in pluripotent stem cell self-renewal and decreased levels of stem cell markers.
An extra-circadian function for human CLOCK in the neocortex
Authors: Liu Yuxiang , Fontenot Miles R. , Kulkarni Ashwinikumar , Khandelwal Nitin , Park Seon-Hye E. , Douglas Connor , Harper Matthew , Xu Pin , Gupta Nisha , Gibson Jay R. , Takahashi Joseph S. , Konopka Genevieve 
Published: March 2023

AbstractCore circadian-related proteins such as the transcription factor CLOCK are ubiquitously expressed and important for regulating molecular pathways underlying circadian rhythms. Previous work has suggested that CLOCK has evolved human neocortex-specific gene regulation and therefore may have extra-circadian functions. To test this in vivo, we generated a mouse model that recapitulates human cortical expression of CLOCK. The CLOCK humanized (HU) mice show enhanced cognitive flexibility, which is associated with the alteration in spatiotemporal expression of CLOCK. Cell type specific genomic profiling of HU mice identified upregulated genes related to dendritic growth and spine formation in excitatory neurons. Consistent with this result, we found that excitatory neurons in HU mice have increased complexity of dendritic branching and spine density, as well as a greater frequency of excitatory postsynaptic currents, suggesting an increase in neural connectivity. In contrast, CLOCK knockout in human induced pluripotent stem cell-induced neurons showed reduced complexity of dendrites and lower density of presynaptic puncta. Together, our data demonstrate that CLOCK evolved extra-circadian gains of function via altered spatiotemporal gene expression and these functions may underlie human brain specializations.
Permute-match tests: Detecting significant correlations between time series despite nonstationarity and limited replicates
Authors: Yuan Alex E. , Shou Wenying 
Published: March 2023

AbstractResearchers in fields from ecology to neuroscience analyze correlations between pairs of time series, often working with nonstationary data, wherein statistical properties change over time. This commonly involves a statistical test to determine whether an observed correlation is stronger than expected under the null hypothesis of independence. Testing for dependence between nonstationary time series with only one experimental replicate is exceedingly challenging. However, with many replicates, a nonparametric trial-swapping permutation test can be employed, comparing within-replicate correlations to between-replicate correlations. Although largely assumption-free, this test is severely limited by the number of replicates because its minimum achievablep-value is 1/n! wherenis the number of replicates. This curtails its applicability to many biomedical studies, wherenis frequently as low as 3, which would render significance thresholds like 0.05 unattainable. To address this, we propose modified permutation tests that can report lowerp-values of 2/nnor 1/nnwhen there is strong evidence of dependence. We prove that the tests guarantee a false positive rate at or below the significance level, as long as replicates come from independent and identical experiments. We demonstrate this approach by confirming the observation that groups of zebrafish swim faster when directionally aligned, using an existing dataset with 3 biological replicates.
Coupling microdroplet-based sample preparation, multiplexed isobaric labeling, and nanoflow peptide fractionation for deep proteome profiling of tissue microenvironment
Authors: Veličković Marija , Fillmore Thomas L. , Attah Kwame , Posso Camilo , Pino James C. , Zhao Rui , Williams Sarah M. , Veličković Dušan , Jacobs Jon M. , Burnum-Johnson Kristin E. , Zhu Ying , Piehowski Paul D. 
Published: March 2023

ABSTRACTThere is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity at a cell-type-specific level to better understand and predict the function of complex biological systems, such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverages due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (Microdroplet Processing in One pot for Trace Samples), the multiplexed isobaric labelling, and a nanoflow peptide fractionation approach. The integrated workflow allowed to maximize proteome coverage of laser-isolated tissue samples containing nanogram proteins. We demonstrated the deep spatial proteomics can quantify more than 5,000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 µm2) and reveal unique islet microenvironments.
Using Neural Style Transfer to study the evolution of animal signal design: A case study in an ornamented fish
Authors: Héjja-Brichard Yseult , Million Kara , Renoult Julien P , Mendelson Tamra C 
Published: March 2023

AbstractThe sensory drive hypothesis of animal signal evolution describes how animal communication signals and preferences evolve as adaptations to local environments. While classical approaches to testing this hypothesis often focus on preference for one aspect of a signal, deep learning techniques like generative models can create and manipulate stimuli without targeting a specific feature. Here, we used an artificial intelligence technique called neural style transfer to experimentally test preferences for color patterns in a fish. Findings in empirical aesthetics show that humans tend to prefer images with the visual statistics of the environment because the visual system is adapted to process them efficiently, making those images easier to process. Whether this is the case in other species remains to be tested. We therefore manipulated how similar or dissimilar male body patterns were to their habitats using the Neural Style Transfer (NST) algorithm. We predicted that males whose body patterns are more similar to their native habitats will be preferred by conspecifics. Our findings suggest that both males and females are sensitive to habitat congruence in their preferences, but to different extents, requiring additional investigation. Nonetheless, this study demonstrates the potential of artificial intelligence for testing hypotheses about animal communication signals.Highlights– Neural style transfer was used to test preferences for patterns in a colorful fish– Results trend in support of the processing bias hypothesis, a component of sensory drive– This study demonstrates the use of generative AI for animal behavioral studies
EZH2 represses mesenchymal genes and upholds the epithelial state of breast carcinoma cells
Authors: Gallardo Amador , López-Onieva Lourdes , Belmonte-Reche Efres , Fernández-Rengel Iván , Serrano-Prados Andrea , Molina Aldara , Sánchez-Pozo Antonio , Landeira David 
Published: March 2023

SummaryEmerging studies support that the Polycomb Repressive Complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved across different types of carcinomas. By combining TGF-β-mediate reversible induction of epithelial to mesenchymal transition and pharmacological inhibition of EZH2 activity we demonstrate that EZH2 represses a large set of mesenchymal genes and favours the residence of breast cancer cells towards the more epithelial spectrum during EMT. In agreement, analysis of human patient samples support that EZH2 is required to efficiently repress mesenchymal genes in breast cancer tumours. Our results indicate that PRC2 operates through similar mechanisms in breast and lung cancer cells. We propose that PRC2-mediated direct transcriptional modulation of the mesenchymal gene expression program is a conserved molecular mechanism underlying cell dissemination across human carcinomas.
Perceptual learning of random acoustic patterns: Impact of temporal regularity and attention
Authors: Ringer Hanna , Schröger Erich , Grimm Sabine 
Published: March 2023

AbstractPerceptual learning is a powerful mechanism to enhance perceptual abilities and to form robust memory representations of previously unfamiliar sounds. Memory formation through repeated exposure takes place even for random and complex acoustic patterns devoid of semantic content. The current study sought to scrutinise how perceptual learning of random acoustic patterns is shaped by two potential modulators: temporal regularity of pattern repetition and listeners’ attention. To this end, we adapted an established implicit learning paradigm and presented short acoustic sequences that could contain embedded repetitions of a certain sound segment (i.e., pattern) or not. During each experimental block, one repeating pattern recurred across multiple trials, while the other patterns were presented in only one trial. During the presentation of sound sequences that contained either temporally regular or jittered within-trial pattern repetitions, participants’ attention was directed either towards or away from the auditory stimulation. Overall, we found a memory-related modulation of the event-related potential (ERP) and an increase in inter-trial phase coherence for patterns that recurred across multiple trials (compared to non- recurring patterns), accompanied by a performance increase in a (within-trial) repetition detection task when listeners attended the sounds. Remarkably, we show a memory-related ERP effect even for the first pattern occurrence per sequence when participants attended the sounds, but not when they were engaged in a visual distractor task. These findings suggest that learning of unfamiliar sound patterns is robust against temporal irregularity and inattention, but attention facilitates access to established memory representations upon first occurrence within a sequence.
Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23
Authors: Bloch Yehudi , Felix Jan , Merceron Romain , Provost Mathias , Symakani Royan Alipour , De Backer Robin , Lambert Elisabeth , Savvides Savvas N. 
Published: March 2023

AbstractCell-surface receptor complexes mediated by pro-inflammatory Interleukin-12 and -23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12:receptor interaction interfaces, in contrast to IL23:receptor complexes. Here we report cryo-EM structures of fully assembled IL-12/IL-23:receptor complexes comprising the complete extracellular segments of the cognate receptors. The structures reveal important commonalities but also surprisingly diverse features. Whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig-domain of their high affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell-membrane. Collectively, our findings will enable a cytokine-specific interrogation of IL-12 and IL-23 signaling in physiology and disease.
The FAAH inhibitor URB597 reduces cocaine seeking during conditioned punishment and withdrawal
Authors: Alegre-Zurano Laia , García-Baos Alba , Castro-Zavala Adriana , Martín-Sánchez Ana , Medrano Mireia , Gallego-Landin Ines , Valverde Olga 
Published: March 2023

ABSTRACTThe endocannabinoid system is prominently implicated in the control of cocaine reinforcement due to its relevant role in synaptic plasticity and neurotransmitter modulation in the mesocorticolimbic system. The inhibition of fatty acid amide hydrolase (FAAH), and the resulting increase in anandamide and other N-acylethanolamines, represents a promising strategy for reducing drug seeking. In the present study, we aimed to assess the effects of the FAAH inhibitor URB597 (1 mg/kg) on crucial features of cocaine addictive-like behaviour in mice. Therefore, we tested the effects of URB597 on acquisition of cocaine (0.6 mg/kg/inf) self-administration, compulsive-like cocaine intake and cue-induced drug-seeking behaviour during withdrawal. URB597 reduced cocaine intake under conditioned punishment while having no impact on acquisition. This result was associated to increased cannabinoid receptor 1 gene expression in the ventral striatum and medium spiny neurons activation in the nucleus accumbens shell. Moreover, URB597 reduced cue-induced drug-seeking behaviour during prolonged abstinence and prevented the withdrawal-induced increase in FAAH gene expression in the ventral striatum. In this case, URB597 decreased activation of medium spiny neurons in the nucleus accumbens core. Our findings evidence the prominent role of endocannabinoids in the development of cocaine addictive-like behaviours and support the potential of FAAH inhibition as a therapeutical target for the treatment of cocaine addiction.