bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current opinion neurology: visual pathway biomarkers in Alzheimer's disease
Authors: Van Stavern Gregory P. 
Published: December 2019

Purpose of review
The incidence of Alzheimer's disease is increasing. Premortem diagnosis of Alzheimer's disease is now possible but require invasive and expensive testing such as PET amyloid beta binding and/or spinal fluid amyloid beta levels. There is a great need for minimally invasive and inexpensive biomarkers to allow for early diagnosis and intervention.

Recent findings
There has been a large volume of literature assessing ocular biomarkers for Alzheimer's disease. Much of the research to date has significant limitations, including sample size, variable diagnostic criteria for Alzheimer's disease, lack of biomarker assessment, and focus on patients with well established dementia. Work that is more recent has included individuals with early and preclinical Alzheimer's disease with biomarkers included in the design. These studies have shown consistent features of visual pathway involvement in Alzheimer's disease, even in the earliest and preclinical stages.

Summary
It is possible that in the future, ocular biomarkers (particularly retinal imaging techniques) may be part of a multimodality alogorithm screening for preclinical Alzheimer's disease, perhaps combined with other methods, such as blood-based biomarkers.
Utilization of Family Planning and Associated Factors among Reproductive Age Women with Disability in Arba Minch Town, Southern Ethiopia
Authors: Yesgat Yibeltal Mesfin , G/Meskel Feleke , Estifanous Wubshet , Gizachew Yordanos , Jemal Seid , Atnafu Natneal , Nuriye Keyirden 
Published: December 2019

ABSTRACTIntroductionglobally, one type of contraceptive was used by around 63 percent of women. Women with disabilities account for 10 percent of all women and make up three-quarters of the disabled people in low and middle-income countries.Objectiveto assess utilization of family planning and associated factors among reproductive-age women with disability group in Arba Minch town, southern Ethiopia from 1st March to April 15, 2019.Methodscommunity-based cross-sectional study with simple random sampling was used to select 4l8 reproductive age women with disabilities. Data were collected using a structured questionnaire and interview by eight trained females who completed grade twelve two of which communicate by speaking and sign language. Data were entered using Epi info 7 and exported to SPSS version 20 for analysis. A statically significant variable in the final model was declared by AOR, 95%CI and p-value <0.05.Resultin the current study family planning utilization among all reproductive-age women with disabilities was 33.7%. Family planning utilization was 2.2 times higher among those who have employed compared with those with not employed (AOR2.2 95% CI, 1.77-4.15). Women who had a positive attitude were 2.3 times more likely to use family planning than negative attitudes (AOR 2.3:95% CI, 1.21- 3.87). Besides these women who got married were almost four times more likely to use family planning methods than unmarried (AOR 3.9:95% CI, 2.31-6.63).ConclusionThe level of family planning utilization was low among reproductive women with disabilities and factors associated were attitude, marital status, & employed status, therefore governmental and non-governmental organization should promote for women with disabilities to change the attitude and creating job opportunities.
DrivAER: Identification of driving transcriptional programs in single-cell RNA sequencing data
Authors: Simon Lukas M. , Yan Fangfang , Zhao Zhongming 
Published: December 2019

AbstractSingle cell RNA sequencing (scRNA-seq) unfolds complex transcriptomic data sets into detailed cellular maps. Despite recent success, there is a pressing need for specialized methods tailored towards the functional interpretation of these cellular maps. Here, we present DrivAER, a machine learning approach that scores annotated gene sets based on their relevance to user-specified outcomes such as pseudotemporal ordering or disease status. We demonstrate that DrivAER extracts the key driving pathways and transcription factors that regulate complex biological processes from scRNA-seq data.
Mitral valve leaflet response to ischemic mitral regurgitation: From gene expression to tissue remodeling
Authors: Howsmon Daniel P. , Rego Bruno V. , Castillero Estibaliz , Ayoub Salma , Khalighi Amir H. , Gorman Robert C. , Gorman Joseph H. , Ferrari Giovanni , Sacks Michael S. 
Published: December 2019

AbstractAimsIschemic mitral regurgitation is frequently observed following myocardial infarction and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve leaflets actively remodel post–myocardial infarction, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. We sought to elucidate mitral valve remodeling post myocardial infarction at the tissue, cellular, and transcriptomic levels.Methods and ResultsThe mechanical behavior of ovine mitral valve leaflets pre– and 8 weeks post– myocardial infarction reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy mitral valves. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post–myocardial infarction. Assessment of the mitral valve interstitial cell nuclear aspect ratio, a metric of cellular deformation, revealed that they were on average rounder following myocardial infarction. RNA sequencing indicated that YAP-induced genes were elevated at 4 weeks post–myocardial infarction and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without ischemic mitral regurgitation at 4 weeks post–myocardial infarction. Additionally, RNA sequencing revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A.ConclusionsOur multiscale assessment revealed significant mechanical and microstructural changes due to myocardial infarction. RNA sequencing provided a baseline for global gene expression changes in response to myocardial infarction with and without ischemic mitral regurgitation and suggests YAP-induced mechanotransduction, altered expression of extracellular matrix–related genes, and recruitment of immune cells as mechanisms contributing to altered mitral valve biomechanics post–myocardial infarction.
Changes in subjective preference do not require dopamine signaling or the orbital frontal cortex
Authors: Lefner Merridee J. , Magnon Alexa P. , Gutierrez James M. , Lopez Matthew R. , Wanat Matthew J. 
Published: December 2019

Abstract‘Sunk’ or unrecoverable costs impact proximal reward-based decisions across species. However, it is not known if these incurred costs elicit a long-lasting change in reward value. To address this, we identified the relative preference between different flavored food pellets in rats. Animals were then trained to experience the initially preferred reward after short delays and the initially less preferred reward after long delays. This training regimen enhanced the preference for the initially less desirable food reward. We probed whether this change in subjective preference involved dopamine signaling or the orbital frontal cortex (OFC) given that these neural systems contribute to reward valuation. Systemic dopamine receptor antagonism attenuated anticipatory responding during training sessions but did not prevent the change in reward preference elicited by incurred temporal costs. OFC lesions had no effect on anticipatory responding during training or on the change in reward preference. These findings collectively illustrate that the neural systems involved with economic assessments of reward value are not contributing to changes in subjective preference.
Enhanced post-traumatic headache-like behaviors and diminished contribution of peripheral CGRP in female rats following a mild closed head injury
Authors: Bree Dara , Mackenzie Kimberly , Stratton Jennifer , Levy Dan 
Published: December 2019

AbstractIntroductionFemales are thought to have increased risk of developing posttraumatic headache (PTH) following a traumatic head injury, or concussion. However, the processes underlying this susceptibility remain unclear. We previously explored the development of PTH-like pain behaviors in a novel rat model of mild closed head injury, along with the ability of sumatriptan and an anti-calcitonin-gene-related peptide monoclonal antibody to ameliorate these behaviors. Here, we explored the development of PTH-like behaviors and the effectiveness of these headache therapies in females subjected to the same head trauma protocol.MethodsAdult female Sprague Dawley rats were subjected to a mild closed head injury using a weight-drop device. Characterization of headache and pain related behaviors included assessment of changes in cutaneous cephalic and extracephalic tactile pain sensitivity, using von Frey monofilaments. Sensitivity to headache/migraine triggers was tested by examining the effect of systemic administration of a low-dose of glyceryl trinitrate (GTN). Treatments included acute systemic administration of sumatriptan and repeated systemic administration of a mouse anti-calcitonin-gene-related peptide monoclonal antibody. Serum levels of calcitonin-gene-related peptide were measured at various time points in females and males after the head injury.ResultsFemale rats subjected to a mild closed head injury developed cutaneous mechanical hyperalgesia, that was limited to the cephalic region, and was resolved 4 weeks later. Cephalic pain hypersensitivity was ameliorated by treatment with sumatriptan, but was resistant to an early and prolonged treatment with the anti-CGRP monoclonal antibody. Following the resolution of the head injury-evoked cephalic hypersensitivity, administration of GTN produced a renewed and pronounced cephalic and extracephalic pain hypersensitivity that was inhibited by sumatriptan, but only partially by the anti-CGRP treatment. CGRP serum levels were elevated in females but not in males at 7 days post head injury.ConclusionsDevelopment of PTH-like pain behaviors following a mild closed head injury, and responsiveness to treatment in rats is sexually dimorphic. When compared to males, female rats display a prolonged state of cephalic hyperalgesia, increased responsiveness to a headache trigger, and a poorer effectiveness of an early and prolonged anti-CGRP treatment. The increased risk of females to develop PTH may be linked to enhanced responsiveness of peripheral and/or central pain pathways and a mechanism independent of peripheral CGRP signaling.
Phylogeographic evidence that the distribution of cryptic euryhaline species in theGambusia punctataspecies group in Cuba was shaped by the archipelago geological history
Authors: García-Machado Erik , de Léon José L. Ponce , Gutiérrez-Costa María A. , Michel-Salzat Alice , Germon Isabelle , Casane Didier 
Published: December 2019

AbstractThe main drivers of diversification of freshwater fishes in Cuba are not yet well understood. For example, salt tolerance was thought as the main factor involved in the diversification ofGambusia punctataspecies group in this archipelago. However, evidence from a recent DNA barcoding survey suggested the presence of cryptic species and no correlation between species delimitation and level of salinity. In this study, we analyzed the cryptic diversification ofG. punctataspecies group in Cuba, based on a comprehensive sampling of its distribution and including habitats with different salinity levels. We evaluated the patterns of molecular divergence of the samples by sequencing a set of mitochondrial DNA (mtDNA) regions and genotyping nine nuclear microsatellite loci. We also used cytochrome b gene (cytb) partial sequences and these microsatellite loci to analyze population structure inside putative species. Five mtDNA well-differentiated haplogroups were found, four of them also identified by the analysis of the microsatellite polymorphism which corresponds to two already recognized species,G. punctata, andG. rhizophorae, and three putative new species. The extent of hybrid zones between these groups is also described. In each group, populations inhabiting environments with contrasting salinity levels were identified, indicating a generalized trait not specific toG. rhizophorae. The geographic distribution of the groups suggested a strong association with major relict territories of the Cuban Archipelago that was periodically joined or split-up by changes in seawater levels and land uplifts. Salinity tolerance might have facilitated sporadic and long-distance oversea dispersal but did not prevent speciation in the Cuban archipelago.
Confluence of timing and reward biases in perceptual decision-making dynamics
Authors: Shinn Maxwell , Ehrlich Daniel , Lee Daeyeol , Murray John D. , Seo Hyojung 
Published: December 2019

AbstractAlthough the decisions of our daily lives often occur in the context of temporal and reward structures, the impact of such regularities on decision-making strategy is poorly understood. Here, to explore how temporal and reward context modulate strategy, we trained rhesus monkeys to perform a novel perceptual decision-making task with asymmetric rewards and time-varying evidence reliability. To model the choice and response time patterns, we developed a computational framework for fitting generalized drift-diffusion models (GDDMs) which flexibly accommodates diverse evidence accumulation strategies. We found that a dynamic urgency signal and leaky integration, in combination with two independent forms of reward biases, best capture behavior. We also tested how temporal structure influences urgency by systematically manipulating the temporal structure of sensory evidence, and found that the time course of urgency was affected by temporal context. Overall, our approach identified key components of cognitive mechanisms for incorporating temporal and reward structure into decisions.
Acute lymph node slices are a functional model system to study immunity ex vivo
Authors: Belanger Maura C. , Ball Alexander G. , Catterton Megan A. , Kinman Andrew W.L. , Anbaei Parastoo , Groff Benjamin D. , Melchor Stephanie J. , Lukens John R. , Ross Ashley E. , Pompano Rebecca R. 
Published: December 2019

AbstractThe lymph node is a highly organized and dynamic structure that is critical for facilitating the intercellular interactions that constitute adaptive immunity. Most ex vivo studies of the lymph node begin by reducing it to a cell suspension, thus losing the spatial organization, or fixing it, thus losing the ability to make repeated measurements. Live murine lymph node tissue slices offer the potential to retain spatial complexity and dynamic accessibility, but their viability, level of immune activation, and retention of antigen-specific functions have not been validated. Here we systematically characterized live murine lymph node slices as a platform to study immunity. Live lymph node slices maintained the expected spatial organization and cell populations while reflecting the 3D spatial complexity of the organ. Slices collected under optimized conditions were comparable to cell suspensions in terms of both 24-hr viability and inflammation. Slices responded to T cell receptor cross-linking with increased surface marker expression and cytokine secretion, in some cases more strongly than matched lymphocyte cultures. Furthermore, slices processed protein antigens, and slices from vaccinated animals responded to ex vivo challenge with antigen-specific cytokine secretion. In summary, lymph node slices provide a versatile platform to investigate immune functions in spatially organized tissue, enabling well-defined stimulation, time-course analysis, and parallel read-outs.
Value-related neuronal responses in the human amygdala during observational learning
Authors: Aquino Tomas G. , Minxha Juri , Dunne Simon , Ross Ian B. , Mamelak Adam N. , Rutishauser Ueli , O’Doherty John P. 
Published: December 2019

AbstractThe amygdala plays an important role in many aspects of social-cognition and reward-learning. Here we aimed to determine whether human amygdala neurons are involved in the computations necessary to implement learning through observation. We performed single-neuron recordings from the amygdalae of human neurosurgical patients (male and female) while they learned about the value of stimuli through observing the outcomes experienced by another agent interacting with those stimuli. We used a detailed computational modeling approach to describe patients’ behavior in the task. Then, using both population-level decoding and single neuron analyses we found evidence to implicate amygdala neurons in two key computations relevant for observational-learning: tracking the expected future reward associated with a given stimulus, and in tracking outcome values received by oneself or other agents. Encoding and decoding analyses suggested observational value coding in amygdala neurons occurred in a different subset of neurons than experiential value coding. Collectively, these findings support a key role for the human amygdala in the computations underlying the capacity for learning through observation.Significance statementSingle neuron studies of the human brain provide a unique window into the computational mechanisms of cognition. In this study, epilepsy patients implanted intracranially with depth microelectrodes performed an observational learning task. We measured activity bilaterally in the amygdala and found a representation for observational rewards as well as observational expected reward values. Additionally, the representation of self-experienced and observational values was performed by distinct subsets of amygdala neurons. This study thus provides a rare glimpse into the role of human amygdala neurons in social cognition.
DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis
Authors: Nassar Zeyad D. , Mah Chui Yan , Dehairs Jonas , Burvenich Ingrid J.G. , Irani Swati , Centenera Margaret M. , Shrestha Raj K. , Moldovan Max , Don Anthony S. , Scott Andrew M. , Horvath Lisa G. , Lynn David J. , Selth Luke A. , Hoy Andrew J. , Swinnen Johannes V. , Butler Lisa M. 
Published: December 2019

AbstractFatty acid β-oxidation (FAO) is the main bioenergetic pathway in prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate therapeutic efficacy of targeting FAO in clinical prostate tumors cultured ex vivo, and identify DECR1, which encodes the rate-limiting enzyme for oxidation of polyunsaturated fatty acids (PUFAs), as robustly overexpressed in PCa tissues and associated with shorter relapse-free survival. DECR1 is a negatively-regulated androgen receptor (AR) target gene and, therefore, may promote PCa cell survival and resistance to AR targeting therapeutics. DECR1 knockdown in PCa cells selectively inhibited β-oxidation of PUFAs, inhibited proliferation and migration of PCa cells, including treatment resistant lines, and suppressed tumor cell proliferation in vivo. Mechanistically, targeting of DECR1 caused cellular accumulation of linoleic acid, enhanced mitochondrial oxidative stress and lipid peroxidation, and ferroptosis. These findings implicate PUFA oxidation via DECR1 as a previously unexplored facet of FAO that promotes survival of PCa cells.
Dispersal behaviour as the outcome and trigger of multilevel selection in a social spider
Authors: Vásárhelyi Zsóka , Pruitt Jonathan N. , Scheuring István 
Published: December 2019

AbstractThe facultatively social spider Anelosimus studiosus offers a unique opportunity for understanding how multilevel selection acts in natural populations. However, the importance of previous empirical studies are shaded by a conceptual debate about whether colony-level selection is truly present in these populations or not. Here we introduce a detailed individual based model, where practically all assumptions are supported by empirical data. The only element of the female A. studiosus life cycle missing from the literature is how maturing female spiders decide whether to disperse. This behavioural component we estimate with evolutionary simulations. This model is able to recapitulate the characteristic size and composition distributions of natural populations in different environments. The evolutionary simulations revealed that the optimal dispersal behaviour of a maturing female varies both with her ecological environment and behavioural phenotype. This finding is open for straightforward empirical testing. In agreement with empirical findings we have established parameter ranges where the population is prone to extinction without multiple-female nests. We propose that the dispersal behaviour of individuals is both the result and the prerequisite of multilevel selection in this species.
Effect of pretreatment with different MMP inhibitors on shear bond strength of composite to primary teeth dentin after six months of aging
Authors: Parsaie Zahra , Mohammadi Najmeh , Firouzmandi Maryam 
Published: December 2019

AbstractBackgroundloss of hybrid layer integrity compromises the resin-dentin bond stability. Subsequent release and activation of matrix metalloproteinase enzymes during dental restorative procedures or caries development are contributing factors to dentin-adhesive bond failure.AimTo investigate the effect of pre-treatment with different MMP inhibitors on the shear bond strength (SBS) of an etch-and-rinse adhesive (Adper Single Bond 2) to primary teeth dentin after six months of aging.MethodsSixty extracted anterior primary teeth, due to orthodontic reasons, were selected. A dentin block (6.0 mm × 6.0 mm × 2.0 mm) was obtained from each tooth. All the dentin blocks (n = 60) were pretreated for 60 s with either 0.01 M phosphate buffered saline (PBS, pH 7.2) in the control group, 2%: Chlorhexidine (CHX) solution, 2% Doxycycline (DO)solution and EDTA 17% after etching and before applying etch-and-rinse adhesive system (Adper Single Bond 2). Then composite was applied in clear teflon cylinders. The specimens were stored in artificial saliva for 6 months at 37°C and then the SBS values were determined with a universal testing machine. Representative samples were selected for visualization of the failure mode under stereomicroscope and SEM.ResultsNo statistically significant difference observed between the SBS of the EDTA group, DO group and the control group (P value>0.05). CHX showed significantly higher SBS values compared to the other groups of the study after six months(P value=0.011).ConclusionChlorhexidine significantly preserved the SBS of composite resin to deciduous dentin using etch and rinse adhesive Adper Single Bond 2 after 6 months of aging in artificial saliva.