bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral and brain signatures of substance use vulnerability in childhood
Authors: Rapuano Kristina M. , Rosenberg Monica D. , Maza Maria T. , Dennis Nicholas , Dorji Mila , Greene Abigail S. , Horien Corey , Scheinost Dustin , Constable R. Todd , Casey BJ 
Published: October 2020

AbstractThe prevalence of risky behavior such as substance use increases during adolescence; however, the neurobiological precursors to adolescent substance use remain unclear. Predictive modeling may complement previous work observing associations with known risk factors or substance use outcomes by developing generalizable models that predict early susceptibility. The aims of the current study were to identify and characterize behavioral and brain models of vulnerability to future substance use. Principal components analysis (PCA) of behavioral risk factors were used together with connectome-based predictive modeling (CPM) during rest and task-based functional imaging to generate predictive models in a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain & Cognitive Development (ABCD) study (NDA release 2.0.1). Dimensionality reduction (n=9,437) of behavioral measures associated with substance use identified two latent dimensions that explained the largest amount of variance: risk-seeking (PC1; e.g., curiosity to try substances) and familial factors (PC2; e.g., family history of substance use disorder). Using cross-validated regularized regression in a subset of data (Year 1 Fast Track data; n>1,500), functional connectivity during rest and task conditions (resting-state; monetary incentive delay task; stop signal task; emotional n-back task) significantly predicted individual differences in risk-seeking (PC1) in held-out participants (partial correlations between predicted and observed scores controlling for motion and number of frames [rp]: 0.07-0.21). By contrast, functional connectivity was a weak predictor of familial risk factors associated with substance use (PC2) (rp: 0.03-0.06). These results demonstrate a novel approach to understanding substance use vulnerability, which—together with mechanistic perspectives—may inform strategies aimed at early identification of risk for addiction.
Health Insurance Support on Maternal Health Care: Evidence from Survey Data in India
Authors: Ali Imtiyaz , Akhtar Saddaf Naaz , Chauhan Bal Govind , Malik Manzoor Ahmad , Singh Kapil Dev 
Published: October 2020

AbstractMaternal healthcare financing is key to the smooth functioning of maternal health systems in a country. In India, maternal healthcare persists as a significant public health issue. Adequate health insurance could transform the utilization of maternal health care services to prevent maternal consequences. This paper aims to examine the health insurance policies that cover maternal health and their performance in India. The unit-level social consumption data on health by the National Sample Survey Organizations (NSSO), conducted in India (2017-18), is used. Bi-variate analysis, logistic regression, and propensity scoring matching (PSM) are used to evaluate the coverage of health insurance coverage on women’s maternal health care utilization. Our findings suggest that spending on health insurance can benefit pregnant women, especially among the poor, without financial stress. The study has also minimized the financial burden and prevent high-risk pregnancy-related complications and consequences. Also, there is a need for proactive and inclusive policy development by the Government of India to promote more health insurance schemes in the public and private sectors. This can bring down the risk of maternal mortality and also boost the Indian economy in terms of a better quality of life in the long run, and the way towards more just and more egalitarian societies.HighlightsAround 14.1% of Indian women are covered with health insurance schemes.Muslim women have the lowest health insurance coverage in India.Women covered with health insurance schemes has showed significant contributor to the better utilization of full ANC and institutional delivery compared to uncovered women in India.A proactive and inclusive policy development is needed by the Government of India to promote more for health insurance schemes better quality of life in the long run.
COVID-19’s unfortunate events in schools: mitigating classroom clusters in the context of variable transmission
Authors: Tupper P. , Colijn C. 
Published: October 2020

AbstractWidespread school closures occurred during the COVID-19 pandemic. Because closures are costly and damaging, many jurisdictions have since reopened schools with control measures in place. Early evidence indicated that schools were low risk and children were unlikely to be very infectious, but it is becoming clear that children and youth can acquire and transmit COVID-19 in school settings and that transmission clusters and outbreaks can be large. We describe the contrasting literature on school transmission, and argue that the apparent discrepancy can be reconciled by heterogeneity, or “overdispersion” in transmission, with many exposures yielding little to no risk of onward transmission, but some unfortunate exposures causing sizeable onward transmission. In addition, respiratory viral loads are as high in children and youth as in adults, pre- and asymptomatic transmission occur, and the possibility of aerosol transmission has been established. We use a stochastic individual-based model to find the implications of these combined observations for cluster sizes and control measures. We consider both individual and environment/activity contributions to the transmission rate, as both are known to contribute to variability in transmission. We find that even small heterogeneities in these contributions result in highly variable transmission cluster sizes in the classroom setting, with clusters ranging from 1 to 20 individuals in a class of 25. None of the mitigation protocols we modeled, initiated by a positive test in a symptomatic individual, are able to prevent large transmission clusters unless the transmission rate is low (in which case large clusters do not occur in any case). Among the measures we modeled, only rapid universal monitoring (for example by regular, onsite, pooled testing) accomplished this prevention. We suggest approaches and the rationale for mitigating these “unfortunate events”, even if they are expected to be rare.
Aging Reduces EEG Markers of Recognition Despite Intact Performance: Implications for Forensic Memory Detection
Authors: Hellerstedt Robin , Moccia Arianna , Brunskill Chloe M. , Bowman Howard , Bergström Zara M. 
Published: October 2020

AbstractERP-based forensic memory detection is based on the logic that guilty suspects will hold incriminating knowledge about crimes they have committed, and therefore should show parietal ERP positivities related to recognition when presented with reminders of their crimes. We predicted that such forensic memory detection might however be inaccurate in older adults, because of changes to recognition-related brain activity that occurs with aging. We measured both ERPs and EEG oscillations associated with episodic old/new recognition and forensic memory detection in 30 younger (age < 30) and 30 older (age > 65) adults. EEG oscillations were included as a complementary measure which is less sensitive to temporal variability and component overlap than ERPs. In line with predictions, recognition-related parietal ERP positivities were significantly reduced in the older compared to younger group in both tasks, despite highly similar behavioural performance. We also observed ageing-related reductions in oscillatory markers of recognition in the forensic memory detection test, while the oscillatory effects associated with episodic recognition were similar across age groups. This pattern of results suggests that while both forensic memory detection and episodic recognition are accompanied by ageing-induced reductions in parietal ERP positivities, these reductions may be caused by non-overlapping mechanisms across the two tasks. Our findings suggest that EEG-based forensic memory detection tests are invalid in older populations, limiting their practical applications.
The possible anti-inflammatory activity of macrolide antibiotics in male albino rat models
Authors: Hamed Mohamed , Abdelmonem Esmail , Zayed Mahmoud , Shaban Sameh , Khashab Iman El , Abu-El-Azm Soheir 
Published: October 2020

SummaryRecently, there has been increasing evidence on the use of macrolide antibiotics in treatment of chronic inflammatory diseases through mechanisms distinct from their antibacterial activity. The key desired effect lies somewhere between these two therapeutic potentials and has not been identified yet. The aim of the present study was to evaluate the anti-inflammatory activity of the macrolide antibiotic azithromycin in formaldehyde induced arthritis and carrageenan induced air pouch in albino rats in comparison to the anti-rheumatic drug meloxicam. Results of Formaldehyde induced arthritis revealed that pretreatment of animals with a single daily dose of either azithromycin (10, 20 and 40 mg/kg) or meloxicam (4 mg/kg) for 15 days produced a significant reduction in inflammation size. Histopathological study showed that Formaldehyde produced marked inflammatory cell infiltration, congestion of blood vessels and soft tissue edema which were attenuated by azithromycin in dose dependent manner. The radiological study revealed that azithromycin attenuates soft tissue edema, periarticular bone resorption, narrowing of joint spaces and joint deformities induced by formaldehyde. This effect was marked with 40mg/kg azithromycin pre-treatment. In carrageenan, induced air pouch, results demonstrate that group of animals pretreated with azithromycin (10, 20 and 40 mg/kg) or meloxicam (4 mg/kg) for 6 days significantly attenuated the mean increase in total leukocyte count in air pouch exudate. In conclusion, the present work showed that azithromycin has antiinflammatory activity in the models tested and suggests that it can exert therapeutics effects independent of its anti-bacterial activity. Also, the anti-inflammatory effect of azithromycin was potent and even comparable to that of meloxicam.
The data-index: an author-level metric that values impactful data and incentivises data sharing
Authors: Hood Amelia S C , Sutherland William J 
Published: October 2020

AbstractAuthor-level metrics are a widely used measure of scientific success. The h-index, and its variants, measure publication output (number of publications) and impact (number of citations), and these are often used to allocate funding or jobs. Here we argue that the emphasis on publication output and impact hinders progress in the fields of ecology and evolution as it disincentivises two fundamental practices: generating long-term datasets and sharing data. We describe a new author-level metric, the data-index, which values dataset output and impact and promotes generating and sharing data as a result. It is designed to complement other metrics of scientific success, as scientific contributions are diverse and our value system should reflect that. Future work should focus on designing alternative metrics that value our wider merits, such as communicating our research, informing policy, mentoring other scientists, and providing open-access code and tools.
Partial epithelial-to-mesenchymal transition is prognostic and associates with Slug in head and neck cancer
Authors: Schinke Henrik , Pan Min , Akyol Merve , Zhou Jiefu , Kranz Gisela , Libl Darko , Simon Florian , Canis Martin , Baumeister Philipp , Gires Olivier 
Published: October 2020

ABSTRACTTherapy resistance leading to local recurrence and metastases remains highly problematic in head and neck squamous cell carcinomas (HNSCC). Single cell RNA-sequencing defined a partial epithelial-to-mesenchymal transition (p-EMT) signature associated with metastases in HNSCC. However, the prognostic value of the p-EMT signature and potential drivers of p-EMT in HNSCC remain unclear. Here, single sample scoring of molecular phenotypes (Singscoring) served to establish clinical p-EMT-Singscores that were significantly associated with nodal metastases and predicted overall survival in two independent HNSCC cohorts. p-EMT-Singscores correlated most strongly with EMT transcription factor (EMT-TF) Slug.In vitro, Slug promoted p-EMT, enhanced invasion, and resistance to irradiation. In patients, Slug protein levels in tumors predicted disease-free survival and its peripheral expression at the interphase to tumor-microenvironment was significantly increased in recurring patients. Thus, p-EMT represents a novel clinical risk-predictor that impacts on HNSCC patients’ outcome and is partly controlled by Slug.
nMAT3 is an essential maturase splicing factor required for holo-complex I biogenesis and embryo-development inArabidopsis thalianaplants
Authors: Shevtsov-Tal Sofia , Best Corinne , Matan Roei , Chandran Sam Aldrin , Brown Gregory G. , Ostersetzer-Biran Oren 
Published: October 2020

SummaryGroup II introns are large catalytic RNAs that are particularly prevalent in the organelles of terrestrial plants. In angiosperm mitochondria, group II introns reside in the coding-regions of many critical genes, and their excision is essential for respiratory-mediated functions. Canonical group II introns are self-splicing and mobile genetic elements, consisting of the catalytic intron-RNA and its cognate intron-encoded endonuclease factor (i.e.maturase, Pfam-PF01348). Plant organellar introns are extremely degenerate, and lack many regions that are critical for splicing, including their related maturase-ORFs. The high degeneracy of plant mitochondrial introns was accompanied during evolution by the acquisition of ‘host-acting’ protein cofactors. These include several nuclear encoded maturases (nMATs) and various other splicing-cofactors that belong to a diverse set of RNA-binding families,e.g.RNA helicases (Pfam-PF00910), Mitochondrial Transcription Termination Factors (mTERF, Pfam-PF02536), Plant Organelle RNA Recognition (PORR, Pfam-PF11955), and Pentatricopeptide repeat (PPR, Pfam-PF13812) proteins. Previously, we established the roles of MatR and three nuclear-maturases, nMAT1, nMAT2, and nMAT4, in the splicing of different subsets of mitochondrial introns in Arabidopsis. The function of nMAT3 (AT5G04050) was found to be essential during early embryogenesis. Using a modified embryo-rescue method, we show thatnMAT3-knockout plants are strongly affected in the splicing ofnad1introns i1, i3 and i4 in Arabidopsis mitochondria. The embryo-defect phenotype is tightly associated with complex I biogenesis defects. Functional complementation ofnMAT3restored the splicing defects and altered embryogenesis phenotypes associated with thenmat3mutant-line.
High-throughput transcriptomics and benchmark concentration modeling for potency ranking of per- and polyfluoroalkyl substances (PFAS) in exposed human liver cell spheroids
Authors: Reardon A.J.F. , Rowan-Carroll A. , Ferguson S.S. , Leingartner K. , Gagne R. , Kuo B. , Williams A. , Lorusso L. , Bourdon-Lacombe J.A. , Carrier R. , Moffat I. , Yauk C.L. , Atlas E. 
Published: October 2020

AbstractPer- and polyfluoroalkyl substances (PFAS) are some of the most prominent organic contaminants in human blood. Although the toxicological implications from human exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are well established, data on lesser-understood PFAS are limited. New approach methodologies (NAMs) that apply bioinformatic tools to high-throughput data are being increasingly considered to inform risk assessment for data-poor chemicals. The aim of this investigation was to identify biological response potencies (i.e., benchmark concentrations: BMCs) following PFAS exposures to inform read-across for risk assessment of data-poor PFAS. Gene expression changes were measured in primary human liver cell microtissues (i.e., 3D spheroids) after 1-day and 10-day exposures to increasing concentrations of 23 PFAS. The cells were treated with four subgroups of PFAS: carboxylates (PFCAs), sulfonates (PFSAs), fluorotelomers, and sulfonamides. An established pipeline to identify differentially expressed genes and transcriptomic BMCs was applied. We found that both PFCAs and PFSAs exhibited a trend toward increased transcriptional changes with carbon chain-length. Specifically, longer-chain compounds (7 to 10 carbons) were more likely to induce changes in gene expression, and have lower transcriptional BMCs. The combined high-throughput transcriptomic and bioinformatic analyses supports the capability of NAMs to efficiently assess the effects of PFAS in liver microtissues. The data enable potency ranking of PFAS for human liver cell spheroid cytotoxicity and transcriptional changes, and assessment ofin vitrotranscriptomic points of departure. These data improve our understanding of the health effects of PFAS and will be used to inform read-across for human health risk assessment.
Evolution of diversity in metabolic strategies
Authors: Caetano R. A. , Ispolatov Y. , Doebeli M. 
Published: October 2020

AbstractUnderstanding the origin and maintenance of biodiversity is a fundamental problem. Many theoretical approaches have been investigating ecological interactions, such as competition, as potential drivers of diversification. Classical consumer-resource models predict that the number of coexisting species should not exceed the number of distinct resources, a phenomenon known as the competitive exclusion principle. It has recently been argued that including physiological tradeoffs in consumer-resource models can lead to violations of this principle and to ecological coexistence of very high numbers of species. Here we show that these results crucially depend on the functional form of the tradeoff. We investigate the evolutionary dynamics of resource use constrained by tradeoffs and show that if the tradeoffs are non-linear, the system either does not diversify, or diversifies into a number of coexisting species that does not exceed the number of resources. In particular, very high diversity can only be observed for linear tradeoffs.
Clarifying the relationship between body size and extinction risk in amphibians by complete mapping of model space
Authors: Cardillo Marcel 
Published: October 2020

AbstractIn vertebrates, large body size is often a key diagnostic feature of species threatened with extinction. However, in amphibians the link between body size and extinction risk is highly uncertain, with previous studies suggesting positive, negative, u-shaped, or no relationship. Part of the reason for this uncertainty is “researcher degrees of freedom”: the subjectivity and selectivity in choices associated with model specification. Here I clarify the size – threat association in amphibians using Specification Curve Analysis, an analytical approach from the social sciences that attempts to minimize this problem by complete mapping of model space. I find strong support for prevailing negative associations between body size and threat status, the opposite of patterns typical in other vertebrates. This pattern is largely explained by smaller species having smaller geographic ranges, but smaller amphibian species also appear to lack some of the life-history advantages (e.g. higher reproductive output) that are often assumed to “protect” small species in other taxa. These results highlight the need for a renewed conservation focus on the smallest species of the world’s most threatened class of vertebrates, as aquatic habitats become increasingly degraded by human activity.
Cell-Type-Specific Decrease of the Intrinsic Excitability of Motor Cortical Pyramidal Neurons in Parkinsonism
Authors: Chen Liqiang , Daniels Samuel , Kim Yerim , Chu Hong-Yuan 
Published: October 2020

AbstractThe hypokinetic motor symptoms of Parkinson’s disease (PD) are closely linked with a decreased motor cortical output as a consequence of elevated basal ganglia inhibition. However, whether and how the loss of dopamine alters the cellular properties of motor cortical neurons in PD remains undefined. We induced parkinsonism in adult C57BL6 mice of both sexes by injecting neurotoxin, 6-hydroxydopamine, into the medial forebrain bundle. By usingex vivopatch-clamp recording and retrograde tracing approach, we found that the intrinsic excitability of pyramidal tract neurons (PTNs) in the motor cortical layer 5b was greatly decreased in parkinsonism; but the intratelencephalic neurons (ITNs) were not affected. The cell-type-specific intrinsic adaptations were associated with a depolarized threshold and broadened width of action potentials in PTNs. Moreover, the loss of midbrain dopaminergic neurons impaired the capability of M1 PTNs to sustain high-frequency firing, which could underlie their abnormal pattern of activity in the parkinsonian state. We also showed that the decreased excitability in parkinsonism was caused by an impaired function of both persistent sodium channels and the large conductance, Ca2+-activated K+channels. Acute activation of dopaminergic receptors failed to rescue the impaired intrinsic excitability of M1 PTNs in parkinsonian mice. Altogether, our data demonstrated a cell-type-specific decrease of the excitability of M1 pyramidal neurons in parkinsonism. Thus, intrinsic adaptations in the motor cortex, together with pathological basal ganglia inhibition, underlie the decreased motor cortical output in parkinsonian state and exacerbate parkinsonian motor deficits.Significance statementThe degeneration of midbrain dopaminergic neurons in Parkinson’s disease remodels the connectivity and function of cortico–basal ganglia–thalamocortical network. However, whether and how dopaminergic degeneration and the associated basal ganglia dysfunction alter motor cortical circuitry remain undefined. We found that pyramidal neurons in the layer 5b of the primary motor cortex (M1) exhibit distinct adaptations in response to the loss of midbrain dopaminergic neurons, depending on their long-range projections. Besides the decreased thalamocortical synaptic excitation as proposed by the classical model of Parkinson’s pathophysiology, these results, for the first time, show novel cellular and molecular mechanisms underlying the abnormal motor cortical output in parkinsonism.
Auditory Decisions in the Supplementary Motor Area
Authors: Morán Isaac , Perez-Orive Javier , Melchor Jonathan , Figueroa Tonatiuh , Lemus Luis 
Published: October 2020

AbstractIn human speech and communication across various species, recognizing and categorizing sounds is fundamental for the selection of appropriate behaviors. But how does the brain decide which action to perform based on sounds? We explored whether the premotor supplementary motor area (SMA), responsible for linking sensory information to motor programs, also accounts for auditory-driven decision making. To this end, we trained two rhesus monkeys to discriminate between numerous naturalistic sounds and words learned as target (T) or non-target (nT) categories. We demonstrated that the neural population is organized differently during the auditory and the movement periods of the task, implying that it is performing different computations in each period. We found that SMA neurons perform acoustic-decision-related computations that transition from auditory to movement representations in this task. Our results suggest that the SMA integrates sensory information while listening to auditory stimuli in order to form categorical signals that drive behavior.