bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Human Immunodeficiency Virus Infections Linked in Genetic Clusters But Disconnected in Partner Tracing
Authors: Pasquale Dana K. , Doherty Irene A. , Miller William C. , Leone Peter A. , Sampson Lynne A. , Ledford Sue Lynn , Sebastian Joseph , Dennis Ann M.
Published: November 2019

Background

Successful partner notification can improve community-level outcomes by increasing the proportion of persons living with human immunodeficiency virus (HIV) who are linked to HIV care and virally suppressed, but it is resource intensive. Understanding where HIV transmission pathways may be undetected by routine partner notification may help improve case finding strategies.

Methods

We combined partner notification interview and HIV sequence data for persons diagnosed with HIV in Wake County, NC in 2012 to 2013 to evaluate partner contact networks among persons with HIV pol gene sequences 2% or less pairwise genetic distance. We applied a set of multivariable generalized estimating equations to identify correlates of disparate membership in genetic versus partner contact networks.

Results

In the multivariable model, being in a male-male pair (adjusted odds ratio [AOR], 16.7; P = 0.01), chronic HIV infection status (AOR, 4.5; P < 0.01), and increasing percent genetic distance between each dyad member's HIV pol gene sequence (AOR, 8.3 per each 1% increase, P < 0.01) were all associated with persons with HIV clustering but not being identified in the partner notification network component. Having anonymous partners or other factors typically associated with risk behavior were not associated.

Conclusions

Based on genetic networks, partnerships which may be stigmatized, may have occurred farther back in time or may have an intervening partner were more likely to be unobserved in the partner contact network. The HIV genetic cluster information contributes to public health understanding of HIV transmission networks in these settings where partner identifying information is not available.
Point-of-Care Ultrasound to Assess Gastric Content
Authors: Moake Matthew M. , Jackson Benjamin F. , Presley Bradley C.
Published: November 2019

Gastric ultrasound (US) is a growing modality within the point-of-care ultrasound (POCUS) field. It provides the ability to directly measure an individual patient's gastric content and has potential use as both a clinical and a research tool. Here, we review the historical development of current gastric US models and their clinical application within the field of general anesthesia, describe the US findings and technique for using POCUS to assess gastric content, and discuss the current and potential applications of gastric POCUS within the emergency department.
An Intervention to Increase Knowledge and Utilization of the Low Risk Ankle Rule Among Pediatric Emergency Department Providers
Authors: Loftus Kirsten V. , Gittelman Michael A. , FitzGerald Michael , Pomerantz Wendy J.
Published: November 2019

Objectives

The Low Risk Ankle Rule (LRAR) can assist pediatric emergency department providers in reducing radiographs without missing significant fractures. Most providers are unaware of this tool. This study sought to educate providers about the LRAR then determine their self-reported use immediately and 2 months after education.

Methods

A web-based survey was e-mailed to providers at one large pediatric emergency department. The survey assessed knowledge and use of the rule. Clinical scenarios, in which radiographs were not indicated, helped determine radiograph ordering practices. After a brief LRAR tutorial, respondents were requeried about radiograph ordering practices along with likelihood of future LRAR use. At 2 months, radiograph ordering was again assessed using the same scenarios; interim LRAR use was also determined.

Results

Response rates on the initial and follow-up surveys were 61.4% and 96.2%, respectively. A minority (20%) had heard of the LRAR. Providers initially reported ordering radiographs on 84% of ankle injuries and 82.5% ordered radiographs in the scenario. Immediately after education, only 32% ordered a radiograph in the scenario; 85% reported that they would use the tool consistently. At 2 months, there was no significant change in radiograph ordering practices (79.5% vs 84%). In the interim, 30% reported using the rule at least once.

Conclusions

Most pediatric emergency department providers were unfamiliar with the LRAR. After a brief tutorial, most providers reported that planning to use the tool and self-reported radiograph ordering was significantly reduced; however, at 2 months, clinical practice was unaffected. Further work to implement the tool into practice is necessary.
Association of In Utero HIV Exposure With Obesity and Reactive Airway Disease in HIV-Negative Adolescents and Young Adults
Authors: Fourman Lindsay T. , Pan Chelsea S. , Zheng Isabel , Gerard Marisa E. , Sheehab Asia , Lee Hang , Stanley Takara L. , Grinspoon Steven K.
Published: November 2019

Background:

HIV-negative individuals with in utero HIV exposure represent an emerging population, exceeding 18 million people worldwide. Long-term clinical outcomes among HIV-exposed uninfected (HEU) individuals into adolescence and young adulthood remain unknown.

Setting:

US academic health system.

Methods:

In this observational cohort study, we leveraged a patient data registry to identify 50 HEU adolescents and young adults. We also identified 141 HIV-unexposed controls that were matched to HEU subjects up to 3:1 on age of last encounter (±2 years), birthdate (±5 years), sex, race/ethnicity, and zip code. All subjects were born since January 1, 1990, with medical records available into adolescence and young adulthood. Primary outcomes were most recent body mass index (BMI) z-score and presence of reactive airway disease (RAD). Records were manually reviewed to extract health information.

Results:

Fifty HEU adolescents and young adults (18 ± 3 years, 54% men) and 141 matched controls (19 ± 3 years, 54% men) were compared. HEU individuals had a higher BMI z-score (1.12 ± 1.08 vs. 0.73 ± 1.09, P = 0.03) and an increased prevalence of obesity (42% vs. 22%, P = 0.009) compared with controls. HEU subjects also had a higher prevalence of RAD vs. controls (40% vs. 23%, P = 0.03). These differences persisted on adjusting for demographic, socioeconomic, maternal, and birth-related factors. Maternal prenatal CD4+ T-cell count was inversely associated with BMI z-score among HEU adolescents (r = −0.47, P = 0.01).

Conclusions:

HEU adolescents and young adults exhibited a heightened prevalence of obesity and RAD compared with HIV-unexposed controls. Additional studies are needed to optimize care for the expanding population of HEU individuals transitioning to adulthood.
A Third-Generation Adaptive Statistical Iterative Reconstruction for Contrast-Enhanced 4-Dimensional Dual-Energy Computed Tomography for Pancreatic Cancer
Authors: Ohira Shingo , Kanayama Naoyuki , Wada Kentaro , Washio Hayate , Karino Tsukasa , Ueda Yoshihiro , Inui Shoki , Miyazaki Masayoshi , Koizumi Masahiko , Teshima Teruki
Published: November 2019

Objectives

The objective of this study was to assess the objective and subjective qualities of the contrast-enhanced 4-dimensional dual-energy computed tomography using adaptive statistical iterative reconstruction (ASiR) and ASiR-V.

Methods

The virtual monochromatic images at 60 keV were reconstructed using filtered back projection, ASiR, and ASiR-V (10%–100%) for 14 patients with pancreatic cancer. The contrast-to-noise ratio (CNR) was calculated, and the subjective measurements were compared based on a 5-point score scale.

Results

The ASiR-V yielded a significantly higher CNR than ASiR (P < 0.05). The subjective image quality (peak) was significantly improved (P < 0.01) with ASiR (50%) (3.8, 3.5, and 4.0; overall image quality, tumor delineation, and noise, respectively) and with ASiR-V (50%) (3.9, 3.5, and 4.2, respectively) compared with the filtered back projection (3.2, 3.2, and 3.0, respectively).

Conclusions

The ASiR-V yielded higher CNR than ASiR and provided the highest subjective scores regarding the overall image quality.
Diabetic Foot Ulcer Patients' Uncertainty Regarding Their Prognosis
Authors: Lee Ye-Na , Chang Sung Ok
Published: November 2019

PURPOSE:

The purpose of this qualitative study was to identify the subjective patient perspectives toward the uncertainty regarding diabetic foot ulcer (DFU) prognosis.

DESIGN:

Q-methodology, which is a qualitative method for analyzing subjective viewpoints, was used.

SUBJECTS AND SETTING:

Forty patients with DFUs who were admitted to the diabetic wound center of a university hospital in Seoul, South Korea.

METHODS:

Data were collected on the subjective viewpoint of patients regarding their DFU prognosis uncertainty and analyzed by the software program PQMethod 2.35 using a principal component analysis and varimax rotation.

RESULTS:

This study revealed 4 factors characterizing patient subjective experience related to DFU prognosis: confusion from a lack of knowledge, concerns about a negative future, overdependence on information, and expectations for a positive outlook about favorable results.

CONCLUSION:

The findings of this study suggest various intervention methods for patients with DFU facing uncertainty about their prognosis based on the 4 viewpoints identified. The identification of the factor causing uncertainty and integration of all uncertainty factors are expected to be used as the basis for reducing patients' uncertainty and helping nurses care for patients more effectively.
Hierarchy processing in human neurobiology: how specific is it?
Authors: Friederici Angela D.
Published: November 2019

Although human and non-human animals share a number of perceptual and cognitive abilities, they differ in their ability to process hierarchically structured sequences. This becomes most evident in the human capacity to process natural language characterized by structural hierarchies. This capacity is neuroanatomically grounded in the posterior part of left Broca's area (Brodmann area (BA) 44), located in the inferior frontal gyrus, and its dorsal white matter fibre connection to the temporal cortex. Within this neural network, BA 44 itself subserves hierarchy building and the strength of its connection to the temporal cortex correlates with the processing of syntactically complex sentences. Whether these brain structures are also relevant for other human cognitive abilities is a current debate. Here, this question will be evaluated with respect to those human cognitive abilities that are assumed to require hierarchy building, such as music, mathematics and Theory of Mind. Rather than supporting a domain-general view, the data indicate domain-selective neural networks as the neurobiological basis for processing hierarchy in different cognitive domains. Recent cross-species white matter comparisons suggest that particular connections within the networks may make the crucial difference in the brain structure of human and non-human primates, thereby enabling cognitive functions specific to humans.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
The syntax–semantics interface in animal vocal communication
Authors: Suzuki Toshitaka N. , Wheatcroft David , Griesser Michael
Published: November 2019

Syntax (rules for combining words or elements) and semantics (meaning of expressions) are two pivotal features of human language, and interaction between them allows us to generate a limitless number of meaningful expressions. While both features were traditionally thought to be unique to human language, research over the past four decades has revealed intriguing parallels in animal communication systems. Many birds and mammals produce specific calls with distinct meanings, and some species combine multiple meaningful calls into syntactically ordered sequences. However, it remains largely unclear whether, like phrases or sentences in human language, the meaning of these call sequences depends on both the meanings of the component calls and their syntactic order. Here, leveraging recently demonstrated examples of meaningful call combinations, we introduce a framework for exploring the interaction between syntax and semantics (i.e. the syntax-semantic interface) in animal vocal sequences. We outline methods to test the cognitive mechanisms underlying the production and perception of animal vocal sequences and suggest potential evolutionary scenarios for syntactic communication. We hope that this review will stimulate phenomenological studies on animal vocal sequences as well as experimental studies on the cognitive processes, which promise to provide further insights into the evolution of language.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
A taxonomy for vocal learning
Authors: Tyack Peter L.
Published: November 2019

Humans and songbirds learn to sing or speak by listening to acoustic models, forming auditory templates, and then learning to produce vocalizations that match the templates. These taxa have evolved specialized telencephalic pathways to accomplish this complex form of vocal learning, which has been reported for very few other taxa. By contrast, the acoustic structure of most animal vocalizations is produced by species-specific vocal motor programmes in the brainstem that do not require auditory feedback. However, many mammals and birds can learn to fine-tune the acoustic features of inherited vocal motor patterns based upon listening to conspecifics or noise. These limited forms of vocal learning range from rapid alteration based on real-time auditory feedback to long-term changes of vocal repertoire and they may involve different mechanisms than complex vocal learning. Limited vocal learning can involve the brainstem, mid-brain and/or telencephalic networks. Understanding complex vocal learning, which underpins human speech, requires careful analysis of which species are capable of which forms of vocal learning. Selecting multiple animal models for comparing the neural pathways that generate these different forms of learning will provide a richer view of the evolution of complex vocal learning and the neural mechanisms that make it possible.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Becoming human: human infants link language and cognition, but what about the other great apes?
Authors: Novack Miriam A. , Waxman Sandra
Published: November 2019

Human language has no parallel elsewhere in the animal kingdom. It is unique not only for its structural complexity but also for its inextricable interface with core cognitive capacities such as object representation, object categorization and abstract rule learning. Here, we (i) review recent evidence documenting how (and how early) language interacts with these core cognitive capacities in the mind of the human infant, and (ii) consider whether this link exists in non-human great apes—our closest genealogical cousins. Research with human infants demonstrates that well before they begin to speak, infants have already forged a link between language and core cognitive capacities. Evident by just three months of age, this language–cognition link unfolds in a rich developmental cascade, with each advance providing the foundation for subsequent, more precise and more powerful links. This link supports our species' capacity to represent and convey abstract concepts and to communicate beyond the immediate here and now. By contrast, although the communication systems of great apes are sophisticated in their own right, there is no conclusive evidence that apes establish reference, convey information declaratively or pass down communicative devices via cultural transmission. Thus, the evidence currently available reinforces the uniqueness of human language and the power of its interface to cognition.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
What can animal communication teach us about human language?
Authors: Fishbein Adam R. , Fritz Jonathan B. , Idsardi William J. , Wilkinson Gerald S.
Published: November 2019

Language has been considered by many to be uniquely human. Numerous theories for how it evolved have been proposed but rarely tested. The articles in this theme issue consider the extent to which aspects of language, such as vocal learning, phonology, syntax, semantics, intentionality, cognition and neurobiological adaptations, are shared with other animals. By adopting a comparative approach, insights into the mechanisms and origins of human language can be gained. While points of agreement exist among the authors, conflicting viewpoints are expressed on several issues, such as the presence of proto-syntax in animal communication, the neural basis of the Merge operation, and the neurogenetic changes necessary for vocal learning. Future comparative research in animal communication has the potential to teach us even more about the evolution, neurobiology and cognitive basis of human language.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Towards a new taxonomy of primate vocal production learning
Authors: Fischer Julia , Hammerschmidt Kurt
Published: November 2019

The extent to which vocal learning can be found in nonhuman primates is key to reconstructing the evolution of speech. Regarding the adjustment of vocal output in relation to auditory experience (vocal production learning in the narrow sense), effects on the ontogenetic trajectory of vocal development as well as adjustment to group-specific call features have been found. Yet, a comparison of the vocalizations of different primate genera revealed striking similarities in the structure of calls and repertoires in different species of the same genus, indicating that the structure of nonhuman primate vocalizations is highly conserved. Thus, modifications in relation to experience only appear to be possible within relatively tight species-specific constraints. By contrast, comprehension learning may be extremely rapid and open-ended. In conjunction, these findings corroborate the idea of an ancestral independence of vocal production and auditory comprehension learning. To overcome the futile debate about whether or not vocal production learning can be found in nonhuman primates, we suggest putting the focus on the different mechanisms that may mediate the adjustment of vocal output in response to experience; these mechanisms may include auditory facilitation and learning from success.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Birdsong as a window into language origins and evolutionary neuroscience
Authors: Aamodt Caitlin M. , Farias-Virgens Madza , White Stephanie A.
Published: November 2019

Humans and songbirds share the key trait of vocal learning, manifested in speech and song, respectively. Striking analogies between these behaviours include that both are acquired during developmental critical periods when the brain's ability for vocal learning peaks. Both behaviours show similarities in the overall architecture of their underlying brain areas, characterized by cortico-striato-thalamic loops and direct projections from cortical neurons onto brainstem motor neurons that control the vocal organs. These neural analogies extend to the molecular level, with certain song control regions sharing convergent transcriptional profiles with speech-related regions in the human brain. This evolutionary convergence offers an unprecedented opportunity to decipher the shared neurogenetic underpinnings of vocal learning. A key strength of the songbird model is that it allows for the delineation of activity-dependent transcriptional changes in the brain that are driven by learned vocal behaviour. To capitalize on this advantage, we used previously published datasets from our laboratory that correlate gene co-expression networks to features of learned vocalization within and after critical period closure to probe the functional relevance of genes implicated in language. We interrogate specific genes and cellular processes through converging lines of evidence: human-specific evolutionary changes, intelligence-related phenotypes and relevance to vocal learning gene co-expression in songbirds.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Behaviour, biology and evolution of vocal learning in bats
Authors: Vernes Sonja C. , Wilkinson Gerald S.
Published: November 2019

The comparative approach can provide insight into the evolution of human speech, language and social communication by studying relevant traits in animal systems. Bats are emerging as a model system with great potential to shed light on these processes given their learned vocalizations, close social interactions, and mammalian brains and physiology. A recent framework outlined the multiple levels of investigation needed to understand vocal learning across a broad range of non-human species, including cetaceans, pinnipeds, elephants, birds and bats. Here, we apply this framework to the current state-of-the-art in bat research. This encompasses our understanding of the abilities bats have displayed for vocal learning, what is known about the timing and social structure needed for such learning, and current knowledge about the prevalence of the trait across the order. It also addresses the biology (vocal tract morphology, neurobiology and genetics) and evolution of this trait. We conclude by highlighting some key questions that should be answered to advance our understanding of the biological encoding and evolution of speech and spoken communication.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Syntax and compositionality in animal communication
Authors: Zuberbühler Klaus
Published: November 2019

Syntax has been found in animal communication but only humans appear to have generative, hierarchically structured syntax. How did syntax evolve? I discuss three theories of evolutionary transition from animal to human syntax: computational capacity, structural flexibility and event perception. The computation hypothesis is supported by artificial grammar experiments consistently showing that only humans can learn linear stimulus sequences with an underlying hierarchical structure, a possible by-product of computationally powerful large brains. The structural flexibility hypothesis is supported by evidence of meaning-bearing combinatorial and permutational signal sequences in animals, with sometimes compositional features, but no evidence for generativity or hierarchical structure. Again, animals may be constrained by computational limits in short-term memory but possibly also by limits in articulatory control and social cognition. The event categorization hypothesis, finally, posits that humans are cognitively predisposed to analyse natural events by assigning agency and assessing how agents impact on patients, a propensity that is reflected by the basic syntactic units in all languages. Whether animals perceive natural events in the same way is largely unknown, although event perception may provide the cognitive grounding for syntax evolution.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Next-generation sequencing of dsRNA is greatly improved by treatment with the inexpensive denaturing reagent DMSO
Authors: Wilcox Alexander H. , Delwart Eric , Díaz-Muñoz Samuel L.
Published: November 2019

dsRNA is the genetic material of important viruses and a key component of RNA interference-based immunity in eukaryotes. Previous studies have noted difficulties in determining the sequence of dsRNA molecules that have affected studies of immune function and estimates of viral diversity in nature. DMSO has been used to denature dsRNA prior to the reverse-transcription stage to improve reverse transcriptase PCR and Sanger sequencing. We systematically tested the utility of DMSO to improve the sequencing yield of a dsRNA virus (Φ6) in a short-read next-generation sequencing platform. DMSO treatment improved sequencing read recovery by over two orders of magnitude, even when RNA and cDNA concentrations were below the limit of detection. We also tested the effects of DMSO on a mock eukaryotic viral community and found that dsRNA virus reads increased with DMSO treatment. Furthermore, we provide evidence that DMSO treatment does not adversely affect recovery of reads from a ssRNA viral genome (influenza A/California/07/2009). We suggest that up to 50 % DMSO treatment be used prior to cDNA synthesis when samples of interest are composed of or may contain dsRNA.
Behavioral effects of multiple-dose oxytocin treatment in autism: A randomized, placebo-controlled trial with long-term follow-up
Authors: Bernaerts Sylvie , Boets Bart , Bosmans Guy , Steyaert Jean , Alaerts Kaat
Published: November 2019

Background

Intranasal administration of the ‘prosocial’ neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects are currently lacking.

Methods

Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of four weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after four weeks of treatment (approximately 24 hours after the last nasal spray administration), and at two follow-up sessions, four weeks and one year post-treatment.

Results

No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social responsiveness scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p= .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p= .19).

Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviours (p= .04) and reduced feelings of avoidance towards others (p= .03) in the oxytocin group compared to the placebo group, up to one month and even one year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of ‘vigor’ (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p= .03).

Conclusions

While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further.

Trial Registration

The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE).
Affective biases encoded by the central arousal systems dynamically modulate inequality aversion in human interpersonal negotiations
Authors: Murphy Daniel AJ , Harmer Catherine J , Browning Michael , Pulcu Erdem
Published: November 2019

Negotiating with others about how finite resources should be distributed is an important aspect of human social life. However, little is known about mechanisms underlying human social-interactive decision-making. Here, we report results from a novel iterative Ultimatum Game (UG) task, in which the proposer’s facial emotions and offer amounts were sampled probabilistically based on the participant’s decisions, creating a gradually evolving social-interactive decision-making environment. Our model-free results confirm the prediction that both the proposer’s facial emotions and the offer amount influence human choice behaviour. These main effects demonstrate that biases in facial emotion recognition also contribute to violations of the Rational Actor model (i.e. all offers should be accepted). Model-based analyses extend these findings, indicating that participants’ decisions are guided by an aversion to inequality in the UG. We highlight that the proposer’s facial responses to participant decisions dynamically modulate how human decision-makers perceive self–other inequality, relaxing its otherwise negative influence on decision values. In iterative games, this cognitive model underlies how offers initially rejected can gradually become more acceptable under increasing affective load, and accurately predicts 86% of participant decisions. Activity of the central arousal systems, assessed by measuring pupil size, encode a key element of this model: proposer’s affective reactions in response to participant decisions. Taken together, our results demonstrate that, under affective load, participants’ aversion to inequality is a malleable cognitive process which is modulated by the activity of the pupil-linked central arousal systems.
Neurovascular uncoupling in schizophrenia: A bimodal meta-analysis of brain perfusion and glucose metabolism
Authors: Sukumar Niron , Sabesan Priyadharshini , Anazodo Udunna , Palaniyappan Lena
Published: November 2019

SUKUMAR, N., S. Priyadharshini, U. Anazodo, L. Palaniyappan. Neurovascular uncoupling in schizophrenia: A bimodal meta-analysis of brain perfusion and glucose metabolism. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, XXXX. - The use of modern neuroimaging approaches has demonstrated resting-state regional cerebral blood flow (rCBF) to be tightly coupled to resting cerebral glucose metabolism (rCMRglu) in healthy brains. In schizophrenia, several lines of evidence point towards aberrant neurovascular coupling, especially in the prefrontal regions. To investigate this, we used Signed Differential Mapping to undertake a voxel-based bimodal meta-analysis examining the relationship between rCBF and rCMRglu in schizophrenia, as measured by Arterial Spin Labeling (ASL) and18Flurodeoxyglucose Positron Emission Tomography (FDG-PET) respectively. We used 19 studies comprised of data from 557 patients and 584 controls. Our results suggest that several key regions implicated in the pathophysiology of schizophrenia such as the frontoinsular cortex, dorsal ACC, putamen, and temporal pole show conjoint metabolic and perfusion abnormalities in patients. In contrast, discordance between metabolism and perfusion were seen in superior frontal gyrus and cerebellum, indicating that factors contributing to neurovascular uncoupling (e.g. inflammation, mitochondrial dysfunction, oxidative stress) are likely operates at these loci. Hybrid ASL-PET studies focusing on these regions could confirm our proposition.
Neural correlates of episodic memory modulated by temporally delayed rewards
Authors: Yoo Jungsun , Min Seokyoung , Lee Seung-Koo , Han Sanghoon
Published: November 2019

When a stimulus is associated with an external reward, its chance of being consolidated into long-term memory is boosted via dopaminergic facilitation of long-term potentiation in the hippocampus. Given that higher temporal distance (TD) has been found to discount the subjective value of a reward, we hypothesized that memory performance associated with a more immediate reward will result in better memory performance. We tested this hypothesis by measuring both behavioral memory performance and brain activation using functional magnetic resonance imaging (fMRI) during memory encoding and retrieval tasks. Contrary to our hypothesis, both behavioral and fMRI results suggest that the TD of rewards might enhance the chance of the associated stimulus being remembered. The fMRI data demonstrate that the lateral prefrontal cortex, which shows encoding-related activation proportional to the TD, is reactivated when searching for regions that show activation proportional to the TD during retrieval. This is not surprising given that this region is not only activated to discriminate between future vs. immediate rewards, it is also a part of the retrieval-success network. These results provide support for the conclusion that the encoding-retrieval overlap provoked as the rewards are more delayed lead to better memory performance of the items associated with the rewards.
DeepSide: A Deep Learning Framework for Drug Side Effect Prediction
Authors: Uner Onur Can , Gokberk Cinbis Ramazan , Tastan Oznur , Cicek A. Ercument
Published: November 2019

Drug failures due to unforeseen adverse effects at clinical trials pose health risks for the participants and lead to substantial financial losses. Side effect prediction algorithms have the potential to guide the drug design process. LINCS L1000 dataset provides a vast resource of cell line gene expression data perturbed by different drugs and creates a knowledge base for context specific features. The state-of-the-art approach that aims at using context specific information relies on only the high-quality experiments in LINCS L1000 and discards a large portion of the experiments. In this study, our goal is to boost the prediction performance by utilizing this data to its full extent. We experiment with 5 deep learning architectures. We find that a multi-modal architecture produces the best predictive performance among multi-layer perceptron-based architectures when drug chemical structure (CS), and the full set of drug perturbed gene expression profiles (GEX) are used as modalities. Overall, we observe that the CS is more informative than the GEX. A convolutional neural network-based model that uses only SMILES string representation of the drugs achieves the best results and provides 13.0% macro-AUC and 3.1% micro-AUC improvements over the state-of-the-art. We also show that the model is able to predict side effect-drug pairs that are reported in the literature but was missing in the ground truth side effect dataset. DeepSide is available at http://github.com/OnurUner/DeepSide.
Mosaic metabolic ageing: Basal and standard metabolic rate age in opposite directions and independent of environmental quality, sex or lifespan in a passerine
Authors: Briga Michael , Verhulst Simon
Published: November 2019

Crucial to our understanding of the ageing process is identifying how traits change with age, which variables alter their ageing process and whether these traits associate with lifespan.

We here investigated metabolic ageing in zebra finches. We longitudinally monitored 407 individuals during six years and collected 3213 measurements of two independent mass-adjusted metabolic traits: basal metabolic rate (BMRm) at thermoneutral temperatures and standard metabolic rate (SMRm), which is the same as BMRmbut at ambient temperatures below thermoneutrality.

BMRmdecreasedlinearly with age, consistent with earlier reports. In contrast, SMRmincreasedlinearly with age. To the best of our knowledge, this is the first quantification of SMRmageing, and thereby of the contrast between SMRmand BMRmageing.

Neither metabolic rate nor metabolic ageing rate were associated with individual lifespan. Moreover, experimental manipulations of environmental quality that decreased BMRmand SMRmand shortened lifespan with 6 months (12%) did not affect the ageing of either metabolic trait. Females lived 2 months (4%) shorter than males, but none of the metabolic traits showed sex-specific differences at any age.

Our finding that ageing patterns of metabolic rate vary depending on the ambient temperature illustrates the importance of studying ageing in an ecologically realistic setting.

Our results add to the mounting evidence that within an organism ageing is an asynchronous process.
A comprehensive online database for exploring ~20,000 public Arabidopsis RNA-Seq libraries
Authors: Zhang Hong , Zhang Fei , Feng Li , Jia Jinbu , Zhai Jixian
Published: November 2019

Application of Next Generating Sequencing (NGS) technology in transcriptome profiling has greatly improved our understanding of transcriptional regulation at genome-wide scale in the last decade, and tens of thousands of RNA-sequencing (RNA-seq) libraries have been produced by the research community. However, accessing such huge amount of RNA-seq data poses a big challenge for groups that lack dedicated bioinformatic personnel or expensive computational resources. Here, we introduce the Arabidopsis RNA-seq database (ARS), a free, web-accessible, and user-friendly to quickly explore expression level of any gene in 20,000+ publicly available Arabidopsis RNA-seq libraries.
S1P-S1PR1 activity controls VEGF-A signaling during lymphatic vessel development
Authors: Golding-Ochsenbein AM , Vidal S , Wilmering Wetter B , Guibourdenche C , Beerli C , Chang L , Leonhard S , Holway N , Seuwen K , Jurisic G
Published: November 2019

Sphingosine-1-phosphate (S1P), a lipid signaling molecule produced by endothelial cells, is required for development and homeostasis of blood vessels. However, its role during lymphatic vessel development is unclear. We show in murine newborns that pharmacologically enhanced S1P signaling increases VEGF-A-dependent LEC proliferation. In contrast, S1PR1 inhibition, mediated by the antagonist NIBR0213 or LEC-specific genetic deletion of S1pr1, promotes filopodia formation and vessel branching, independent of VEGF-A. To investigate the S1P and VEGF-A signaling crosstalk observed in vivo, we used LECs cultured in vitro. We demonstrate that S1P activates endogenous S1PR1 in a constitutive, autocrine manner. Importantly, S1P-S1PR1 activity was required for VEGF-A-induced LEC proliferation and strongly supported ERK1/2 activation and VEGFR-2 trafficking to the perinuclear area. In conclusion, S1P-S1PR1 signaling promotes VEGF-A-dependent LEC proliferation and limits migratory and filopodia-forming responses. Hence, S1P-S1PR1 signaling is required for balanced growth factor-induced lymphangiogenesis and correctly patterned lymphatic vessels during postnatal development.
Oxytocin Neurons Enable Social Transmission of Maternal Behavior
Authors: Carcea Ioana , Caraballo Naomi López , Marlin Bianca J. , Ooyama Rumi , Riceberg Justin S. , Mendoza Navarro Joyce M. , Opendak Maya , Diaz Veronica E. , Schuster Luisa , Alvarado Torres Maria I. , Lethin Harper , Ramos Daniel , Minder Jessica , Mendoza Sebastian L. , Hidema Shizu , Falkner Annegret , Lin Dayu , Mar Adam , Wadghiri Youssef Z. , Nishimori Katsuhiko , Kikusui Takefumi , Mogi Kazutaka , Sullivan Regina M. , Froemke Robert C.
Published: November 2019

Maternal care is profoundly important for mammalian survival, and non-biological parents can express it after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care by ensuring their nest presence, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin.

One Sentence Summary

Mother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.
RNA sequencing and lipidomic analysis of alveolar macrophages from normal and CD44 deficient mice
Authors: Dong Yifei , Arif Arif A. , Guo Jian , Ha Zongyi , Lee-Sayer Sally S. M. , Poon Grace F. T. , Dosanjh Manisha , Roskelley Calvin D. , Huan Tao , Johnson Pauline
Published: November 2019

Alveolar macrophages (AMs) are CD44 expressing cells that reside in the alveolar space where they maintain lung homeostasis by serving critical roles in immunosurveillance and lipid surfactant catabolism. AMs lacking CD44 are unable to bind the glycosaminoglycan, hyaluronan, which compromises their survival and leads to reduced numbers of AMs in the lung. Using RNA sequencing, lipidomics and multiparameter flow cytometry, we demonstrate that CD44-/- mice have impaired AM lipid homeostasis and increased surfactant lipids in the lung. CD44-/- AMs had increased expression of CD36, a lipid scavenger receptor, as well as increased intracellular lipid droplets, giving them a foamy appearance. RNA sequencing revealed the differential expression of genes associated with lipid efflux and metabolism in CD44-/- AMs. Lipidomic analysis showed increased lipids in both the supernatant and cell pellet extracted from the bronchoalveolar lavage of CD44-/- mice. Phosphatidylcholine species, cholesterol, oxidized phospholipids and levels of reactive oxygen species (ROS) were increased in CD44-/- AMs. Oxidized phospholipids were more cytotoxic to CD44-/- AMs and induced greater lung inflammation in CD44-/- mice. Reconstitution of CD44+/+ mice with CD44-/- bone marrow as well as adoptive transfer of CD44-/- AMs into CD44+/+ mice showed that lipid accumulation in CD44-/- AMs occurred irrespective of the lung environment, suggesting a cell intrinsic defect. Administration of colony stimulating factor 2 (CSF-2), a critical factor in AM development and maintenance, increased AM numbers in CD44-/- mice and decreased phosphatidylcholine levels in the bronchoalveolar lavage, but was unable to decrease intracellular lipid accumulation in CD44-/- AMs. Peroxisome proliferator-activated receptor gamma (PPARγ), downstream of CSF-2 signaling and a regulator of lipid metabolism, was reduced in the nucleus of CD44-/- AMs, and PPARγ inhibition in normal AMs increased their lipid droplets. Thus, CD44 deficiency causes defects in AMs that lead to abnormal lipid accumulation and oxidation, which exacerbates oxidized lipid-induced lung inflammation. Collectively, these findings implicate CD44 as a regulator of lung homeostasis and inflammation.
Automating parameter selection to avoid implausible biological pathway models
Authors: Magnano Chris S. , Gitter Anthony
Published: November 2019

A common way to integrate and analyze large amounts of biological “omic” data is through pathway reconstruction: using condition-specific omic data to create a subnetwork of a generic background network that represents some process or cellular state. A challenge in pathway reconstruction is that adjusting pathway reconstruction algorithms’ parameters produces pathways with drastically different topological properties and biological interpretations. Due to the exploratory nature of pathway reconstruction, there is no ground truth for direct evaluation, so parameter tuning methods typically used in statistics and machine learning are inapplicable. We developed the pathway parameter advising algorithm to tune pathway reconstruction algorithms to minimize biologically implausible predictions. We leverage background knowledge in pathway databases to select pathways whose high-level structure resembles that of manually curated biological pathways. At the core of this method is a graphlet decomposition metric, which measures topological similarity to curated biological pathways. In order to evaluate pathway parameter advising, we compare its performance in avoiding implausible networks and reconstructing pathways from the NetPath database with other parameter selection methods across four pathway reconstruction algorithms. We also demonstrate how pathway parameter advising can guide construction of an influenza host factor network. Pathway parameter advising is method-agnostic; it is applicable to any pathway reconstruction algorithm with tunable parameters. Our pathway parameter advising software is available on GitHub athttps://github.com/gitter-lab/pathway-parameter-advisingand PyPI athttps://pypi.org/project/pathwayParameterAdvising/.
The influence of 2-aminoethoxydiphenyl borate on the electrical activity of the rat heart under hypoxia/reoxygenation conditions
Authors: Kharkovskaya Elena , Osipov Grigory V. , Mukhina Irina V.
Published: November 2019

The aim of the study was to apply the multi-electrode mapping method to investigate the effect of 2-aminoethoxydiphenyl borate (2-apb) on the electrical activity and vessels of the isolated rat heart under hypoxia/reoxygenation injury (H/R). To date, the ability to influence on the calcium currents and condition of gap junctions has been shown for 2-apb. Changes in the intracellular calcium concentration in the heart play the pivotal role in the development of H/R.

As a result, it was shown that 2-apb influences on the myocardial conduction velocity, sinus rhythm and coronary blood flow in the isolated rat heart. 2-apb caused heart fibrillation during normoxia but not under hypoxia, and attenuated the effect of the H/R on heart rate and vascular function.
Motor learning and transfer: from feedback to feedforward control
Authors: Maeda Rodrigo S. , Gribble Paul L. , Pruszynski J. Andrew
Published: November 2019

Previous work has demonstrated that when learning a new motor task, the nervous system modifies feedforward (ie. voluntary) motor commands and that such learning transfers to fast feedback (ie. reflex) responses evoked by mechanical perturbations. Here we show the inverse, that learning new feedback responses transfers to feedforward motor commands. Sixty human participants (34 females) used a robotic exoskeleton and either 1) received short duration mechanical perturbations (20 ms) that created pure elbow rotation or 2) generated self-initiated pure elbow rotations. They did so with the shoulder joint free to rotate (normal arm dynamics) or locked (altered arm dynamics) by the robotic manipulandum. With the shoulder unlocked, the perturbation evoked clear shoulder muscle activity in the long-latency stretch reflex epoch (50-100ms post-perturbation), as required for countering the imposed joint torques, but little muscle activity thereafter in the so-called voluntary response. After locking the shoulder joint, which alters the required joint torques to counter pure elbow rotation, we found a reliable reduction in the long-latency stretch reflex over many trials. This reduction transferred to feedforward control as we observed 1) a reduction in shoulder muscle activity during self-initiated pure elbow rotation trials and 2) kinematic errors (ie. aftereffects) in the direction predicted when failing to compensate for normal arm dynamics, even though participants never practiced self-initiated movements with the shoulder locked. Taken together, our work shows that transfer between feedforward and feedback control is bidirectional, furthering the notion that these processes share common neural circuits that underlie motor learning and transfer.