bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-frequency oscillations reflect aberrant tone restoration during the auditory continuity illusion in schizophrenia
Authors: Wooldridge Joseph , Kaiser Mathis , Roa Romero Yadira , Riecke Lars , Keil Julian , Senkowski Daniel 
Published: July 2020

AbstractPatients with schizophrenia (ScZ) often show impairments in auditory information processing. These impairments have been related to clinical symptoms, such as auditory hallucinations. Some researchers have hypothesized that aberrant low-frequency oscillations contribute to auditory information processing deficits in ScZ. A paradigm for which modulations in low-frequency oscillations are consistently found in healthy individuals is the auditory continuity illusion (ACI), in which restoration processes lead to a perceptual grouping of tone fragments and a mask, so that a physically interrupted sound is perceived as continuous. We used the ACI paradigm to test the hypothesis that low-frequency oscillations play a role in aberrant auditory information processing in patients with ScZ (N = 23). Compared with healthy control participants we found that patients with ScZ show elevated continuity illusions of interrupted, partially-masked tones. Electroencephalography data demonstrate that this elevated continuity perception is reflected by diminished 3 Hz power. This suggests that reduced low-frequency oscillations relate to elevated restoration processes in ScZ. Our findings support the hypothesis that aberrant low-frequency oscillations contribute to altered perception-related auditory information processing in ScZ.
Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation
Authors: Brouns Sanne L. N. , van Geffen Johanna P. , Campello Elena , Swieringa Frauke , Spiezia Luca , van Oerle René , Provenzale Isabella , Verdoold Remco , Farndale Richard W. , Clemetson Kenneth J. , Spronk Henri M. H. , van der Meijden Paola E. J. , Cavill Rachel , Kuijpers Marijke J. E. , Castoldi Elisabetta , Simioni Paolo , Heemskerk Johan W. M. 
Published: July 2020

AbstractIn haemostasis and thrombosis, platelet, coagulation and anticoagulation pathways act together to produce fibrin-containing thrombi. We developed a microspot-based technique, in which we assessed platelet adhesion, platelet activation, thrombus structure and fibrin clot formation in real time using flowing whole blood. Microspots were made from distinct platelet-adhesive surfaces in the absence or presence of tissue factor, thrombomodulin or activated protein C. Kinetics of platelet activation, thrombus structure and fibrin formation were assessed by fluorescence microscopy. This work revealed: (1) a priming role of platelet adhesion in thrombus contraction and subsequent fibrin formation; (2) a surface-independent role of tissue factor, independent of the shear rate; (3) a mechanism of tissue factor-enhanced activation of the intrinsic coagulation pathway; (4) a local, suppressive role of the anticoagulant thrombomodulin/protein C pathway under flow. Multiparameter analysis using blood samples from patients with (anti)coagulation disorders indicated characteristic defects in thrombus formation, in cases of factor V, XI or XII deficiency; and in contrast, thrombogenic effects in patients with factor V-Leiden. Taken together, this integrative phenotyping approach of platelet–fibrin thrombus formation has revealed interaction mechanisms of platelet-primed key haemostatic pathways with alterations in patients with (anti)coagulation defects. It can help as an important functional add-on whole-blood phenotyping.
Glycosphingolipid expression at breast cancer stem cells after novel thieno[2,3-b]pyridine anticancer compound treatment
Authors: Marijan Sandra , Markotić Anita , Mastelić Angela , Režić-Mužinić Nikolina , Pilkington Lisa Ivy , Reynisson Johannes , Čulić Vedrana Čikeš 
Published: July 2020

AbstractGlycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells (non-CSC). We performed studies of viability, type of cell death, cancer stem cell percent and glycosphingolipid expression on CSC and non-CSC after treatment of MDA-MB-231 and MDA-MB-453 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1). Compound 1 was cytotoxic for both breast cancer cell lines and the majority of cells died by treatment-induced apoptosis. The percent of cancer stem cells and number of formed mammospheres was significantly lower. Glycosphingolipids IV6Neu5Ac-nLc4Cer and GalNAc-GM1b (IV3Neu5Ac-Gg5Cer) not reported previously, were identified in both CSCs and non-CSCs. IV6Neu5Ac-nLc4Cer had increased expression in both CSCs and non-CSCs of both cell lines after the treatment with 1, while GM3 (II3Neu5Ac-LacCer) had increased expression only on both cell subpopulations in MDA-MB-231 cell line. GalNAc-GM1b, Gb4Cer (GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer) and GM2 (II3Neu5Ac-GalNAcβ1-4Galβ1-4Glcβ1-1Cer) were increased only in CSCs of both cell lines while GD3 was decreased in CSC of MDA-MB-231 cell line. Due to its effect in reducing the percentage of cancer stem cells and number of mammospheres, and its influence upon several glycosphingolipid expressions, it can be concluded that compound 1 deserves attention as a potential new drug for triple-negative breast cancer therapy.
Magma diversity reflects recharge regime and thermal structure of the crust
Authors: Weber Gregor , Simpson Guy , Caricchi Luca 
Published: July 2020

AbstractThe chemistry of magmas erupted by volcanoes is a message from deep within the Earth’s crust, which if decrypted, can provide essential information on magmatic processes occurring at inaccessible depths. While some volcanoes are prone to erupt magmas of a wide compositional variety, others sample rather monotonous chemistries through time. Whether such differences are a consequence of physical filtering or reflect intrinsic properties of different magmatic systems remains unclear. Here we show, using thermal and petrological modelling, that magma flux and the thermal structure of the crust modulate diversity and temporal evolution of magma chemistry in mid to deep crustal reservoirs. Our analysis shows that constant rates of magma input leads to extractable magma compositions that tend to evolve from felsic to more mafic in time. Low magma injection rates into hot or deep crust produces less chemical variability of extractable magma compared to the injection of large batches in colder or shallower crust. Our calculations predict a correlation between magma fluxes and compositional diversity that resembles trends observed in volcanic deposits. Our approach allows retrieval of quantitative information about magma input and the thermal architecture of magmatic systems from the chemical diversity and temporal evolution of volcanic products.
Analysis of the “centrosome-ome” identifies MCPH1 deletion as a cause of centrosome amplification in human cancer
Authors: Denu Ryan A. , Burkard Mark E. 
Published: July 2020

AbstractThe centrosome is the microtubule organizing center of human cells and facilitates a myriad of cellular functions including organization of the mitotic spindle to ensure faithful chromosome segregation during mitosis, cell polarization and migration, and primary cilia formation. A numerical increase in centrosomes, or centrosome amplification (CA), is common in cancer and correlates with more aggressive clinical features and worse patient outcomes. However, the causes of CA in human cancer are unclear. Many previous studies have identified mechanisms of CA in cellulo, such as overexpression of PLK4, but it is unclear how often these are the primary mechanism in human disease. To identify a primary cause of CA, we analyzed The Cancer Genome Atlas (TCGA) genomic and transcriptomic data for genes encoding the 367 proteins that localize to the centrosome (the “centrosome-ome”). We identified the following candidates for primary causes of CA: gain-of-function alterations of CEP19, CEP72, CTNNB1, PTK2, NDRG1, SPATC1, TBCCD1; and loss-of-function alterations of CEP76, MCPH1, NEURL4, and NPM1. In cellulo analysis of these candidates revealed that loss of MCPH1/microcephalin caused the most robust increase in centriole number. MCPH1 deep gene deletions are seen in 5–15% of human cancers, depending on the anatomic site of the tumor. Mechanistic experiments demonstrated that loss of MCPH1 caused a CDK2-dependent increase in STIL levels at the centrosome to drive CA. We conclude that loss of MCPH1 is common in human cancer and is likely to be a cause of CA.
The potential interruptive effect of tinnitus-related distress on attention
Authors: Leong Sook Ling , Tchen Stephanie , Robertson Ian H. , Alsalman Ola , To Wing Ting , Vanneste Sven 
Published: July 2020

AbstractThe mechanism through which tinnitus affects attention is unclear. This study examines whether distress mediates the relationship(s) between tinnitus and sustained, selective and executive attentions as well as response inhibition. Eighteen participants with tinnitus and fifteen controls completed the Counting Stroop, Vigilance and Stop Signal tasks. Tinnitus distress was assessed using the Tinnitus Questionnaire (TQ), severity of depressive mood states examined using the Beck Depression Inventory-II, and general distress assessed using the Hospital Anxiety and Depression Scale. Tinnitus participants had significantly slower reactions during the Vigilance task (F = 4.86, p = .035), and incongruent trials of the Cognitive Counting task (F = 3.45, p = .045) compared to controls. Tinnitus-related distress significantly mediated the effect of tinnitus in incongruent trials (TQ: Sobel test t = 1.73, p = .042) of the Cognitive Counting Task. Complaints of distress and concentration difficulties are common amongst tinnitus patients in clinical settings and these afflictions have been shown to negatively impact an individual’s quality of life. If confirmed in future studies, results suggest that distress may be an important factor in the causal mechanism between tinnitus and attention.
PfMAP-2 is essential for male gametogenesis in the malaria parasite Plasmodium falciparum
Authors: Hitz Eva , Balestra Aurélia C. , Brochet Mathieu , Voss Till S. 
Published: July 2020

AbstractIn malaria parasites, male gametogenesis is a proliferative stage essential for parasite transmission to the mosquito vector. It is a rapid process involving three rounds of genome replication alternating with closed endomitoses, and assembly of axonemes to produce eight flagellated motile microgametes. Studies in Plasmodium berghei have highlighted tight regulation of gametogenesis by a network of kinases. The P. berghei MAPK homologue PbMAP-2 is dispensable for asexual development but important at the induction of axoneme motility. However, in P. falciparum, causing the most severe form of human malaria, PfMAP-2 was suggested to be essential for asexual proliferation indicating distinct functions for MAP-2 in these two Plasmodium species. We here show that PfMAP-2 is dispensable for asexual growth but important for male gametogenesis in vitro. Similar to PbMAP-2, PfMAP-2 is required for initiating axonemal beating but not for prior DNA replication or axoneme formation. In addition, single and double null mutants of PfMAP-2 and the second P. falciparum MAPK homologue PfMAP-1 show no defect in asexual proliferation, sexual commitment or gametocytogenesis. Our results suggest that MAPK activity plays no major role in the biology of both asexual and sexual blood stage parasites up until the point of male gametogenesis.
Spectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan
Authors: Ramzan Memoona , Bashir Rasheeda , Salman Midhat , Mujtaba Ghulam , Sobreira Nara , Witmer P. Dane ,   Baylor-Hopkins Center for Mendelian Genomics, Naz Sadaf 
Published: July 2020

AbstractHearing loss affects 380 million people worldwide due to environmental or genetic causes. Determining the cause of deafness in individuals without previous family history of hearing loss is challenging and has been relatively unexplored in Pakistan. We investigated the spectrum of genetic variants in hearing loss in a cohort of singleton affected individuals born to consanguineous parents. Twenty-one individuals with moderate to severe hearing loss were recruited. We performed whole-exome sequencing on DNA samples from the participants, which identified seventeen variants in ten known deafness genes and one novel candidate gene. All identified variants were homozygous except for two. Eleven of the variants were novel, including one multi-exonic homozygous deletion inOTOA. A missense variant inESRRBwas implicated for recessively inherited moderate to severe hearing loss. Two individuals were heterozygous for variants inMYO7AandCHD7, respectively, consistent with de novo variants or dominant inheritance with incomplete penetrance as the reason for their hearing loss. Our results indicate that similar to familial cases of deafness, variants in a large number of genes are responsible for moderate to severe hearing loss in sporadic individuals born to consanguineous couples.
About lipid metabolism in Hermetia illucens (L. 1758): on the origin of fatty acids in prepupae
Authors: Hoc B. , Genva M. , Fauconnier M.-L. , Lognay G. , Francis F. , Caparros Megido R. 
Published: July 2020

AbstractAlthough increasingly targeted in animal nutrition, black soldier fly larvae or prepupae (BSF, Hermetia illucens L. 1758) require the characterization and modulation of their fatty acid profile to become fully integrated within the feed sector. This improvement will only be possible by the understanding of underlaying biochemical pathways of fatty acid synthesis in BSF. In this study, we hypothesized a labelling of de novo synthesized fatty acids in BSF by the incorporation of deuterated water (D2O) in their feed. Three batches of fifty larvae were reared on two diets with different polyunsaturated fatty acid profiles moistened with 40% of H2O or D2O: chicken feed or 40% of chicken feed and 60% of flax cake. Although the occurrence of D2O in insect feed increased the larval development time and decreased prepupal weight, it was possible to track the biosynthesis of fatty acids through deuterium labelling. Some fatty acids (decanoic, lauric or myristic acid) were exclusively present in their deuterated form while others (palmitic, palmitoleic or oleic acid) were found in two forms (deuterated or not) indicating that BSF can partially produce these fatty acids via biosynthesis pathways and not only by bioaccumulation from the diet. These results suggest the importance of carbohydrates as a source of acetyl-CoA in the constitution of the BSF fatty acid profile but also the potential importance of specific enzymes (e.g. thioesterase II or Δ12 fat2 desaturase) in BSF fatty acid metabolism. Finally, nearly no deuterated polyunsaturated fatty acids were found in BSF fed with deuterium confirming that BSF is not able to produce these types of fatty acids. Despite the high levels of linolenic acid in flax-enriched diets, BSF will simply bioaccumulate around 13% of this fatty acid and will metabolize approximately two-thirds of it into saturated fatty acids as lauric or myristic acid.
Subliminal determinants of cue-guided choice
Authors: Garofalo Sara , Sagliano Laura , Starita Francesca , Trojano Luigi , di Pellegrino Giuseppe 
Published: July 2020

AbstractBy anticipating potential rewards, external cues can guide behavior to achieve a goal. Whether the conscious elaboration of these cues is necessary to elicit cue-guided choices is still unknown. The goal of the present study is to test whether the subliminal presentation of a visual cue previously paired with a reward is sufficient to bias responses that can lead to the same or a similar reward. To this aim, three experiments compared the subliminal and supraliminal presentation of reward-associated cues during a Pavlovian-to-Instrumental Transfer task. In line with previous evidence, results showed that the supraliminal presentation of reward-associated Pavlovian cues biased participant’s choice towards motivationally similar rewards (general transfer) as well as towards rewards sharing the precise sensory-specific properties of the cue (outcome-specific transfer). In striking contrast, subliminal cues biased choice only towards motivationally similar rewards (general transfer). Taken together, these findings suggest that cue-guided choices are modulated by the level of perceptual threshold (i.e., subliminal vs supraliminal) of reward-associated cues. Although conscious elaboration of the cue is necessary to guide choice towards a specific reward, subliminal processing is still sufficient to push towards choices sharing the motivational properties of the cue. Implications for everyday life, clinical conditions, and theoretical accounts of cue-guided choices are discussed.
The understanding of congruent and incongruent referential gaze in 17-month-old infants: an eye-tracking study comparing human and robot
Authors: Manzi F. , Ishikawa M. , Di Dio C. , Itakura S. , Kanda T. , Ishiguro H. , Massaro D. , Marchetti A. 
Published: July 2020

AbstractSeveral studies have shown that the human gaze, but not the robot gaze, has significant effects on infant social cognition and facilitate social engagement. The present study investigates early understanding of the referential nature of gaze by comparing—through the eye-tracking technique—infants’ response to human and robot’s gaze. Data were acquired on thirty-two 17-month-old infants, watching four video clips, where either a human or a humanoid robot performed an action on a target. The agent’s gaze was either turned to the target (congruent) or opposite to it (incongruent). The results generally showed that, independent of the agent, the infants attended longer at the face area compared to the hand and target. Additionally, the effect of referential gaze on infants’ attention to the target was greater when infants watched the human compared to the robot’s action. These results suggest the presence, in infants, of two distinct levels of gaze-following mechanisms: one recognizing the other as a potential interactive partner, the second recognizing partner's agency. In this study, infants recognized the robot as a potential interactive partner, whereas ascribed agency more readily to the human, thus suggesting that the process of generalizability of gazing behaviour to non-humans is not immediate.
Deep representation learning of electronic health records to unlock patient stratification at scale
Authors: Landi Isotta , Glicksberg Benjamin S. , Lee Hao-Chih , Cherng Sarah , Landi Giulia , Danieletto Matteo , Dudley Joel T. , Furlanello Cesare , Miotto Riccardo 
Published: July 2020

AbstractDeriving disease subtypes from electronic health records (EHRs) can guide next-generation personalized medicine. However, challenges in summarizing and representing patient data prevent widespread practice of scalable EHR-based stratification analysis. Here we present an unsupervised framework based on deep learning to process heterogeneous EHRs and derive patient representations that can efficiently and effectively enable patient stratification at scale. We considered EHRs of 1,608,741 patients from a diverse hospital cohort comprising a total of 57,464 clinical concepts. We introduce a representation learning model based on word embeddings, convolutional neural networks, and autoencoders (i.e., ConvAE) to transform patient trajectories into low-dimensional latent vectors. We evaluated these representations as broadly enabling patient stratification by applying hierarchical clustering to different multi-disease and disease-specific patient cohorts. ConvAE significantly outperformed several baselines in a clustering task to identify patients with different complex conditions, with 2.61 entropy and 0.31 purity average scores. When applied to stratify patients within a certain condition, ConvAE led to various clinically relevant subtypes for different disorders, including type 2 diabetes, Parkinson’s disease, and Alzheimer’s disease, largely related to comorbidities, disease progression, and symptom severity. With these results, we demonstrate that ConvAE can generate patient representations that lead to clinically meaningful insights. This scalable framework can help better understand varying etiologies in heterogeneous sub-populations and unlock patterns for EHR-based research in the realm of personalized medicine.
The Impact of Parkinson's Disease on Breath Pauses and Their Relationship to Speech Impairment: A Longitudinal Study
Authors: Darling-White Meghan , Huber Jessica E. 
Published: July 2020

Purpose
The purposes of this longitudinal study were to (a) examine the impact of Parkinson's disease (PD) progression on breath pause patterns and speech and linguistic errors and (b) determine the extent to which breath pauses and speech and linguistic errors contribute to speech impairment.

Method
Eight individuals with PD and eight age- and sex-matched control participants produced a reading passage on two occasions (Time 1 and Time 2) 3 years and 7 months apart on average. Two speech-language pathologists rated the severity of speech impairment for all participants at each time. Dependent variables included the location of each breath pause relative to syntax and punctuation as well as the number of disfluencies and mazes.

Results
At Time 1, there were no significant differences between the groups regarding breath pause patterns. At Time 2, individuals with PD produced significantly fewer breath pauses at major syntactic boundaries and periods as well as significantly more breath pauses at locations with no punctuation than control participants. Individuals with PD produced a significantly greater number of disfluencies than control participants at both time points. There were no significant differences between the groups in the number of mazes produced at either time point. Together, the number of mazes and the percentage of breath pauses at locations with no punctuation explained 50% of the variance associated with the ratings of severity of speech impairment.

Conclusion
These results highlight the importance of targeting both respiratory physiological and cognitive–linguistic systems in order to improve speech production in individuals with PD.