bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrathecal Nicardipine for Cerebral Vasospasm Post Subarachnoid Hemorrhage – a Retrospective Analysis and Propensity-Based Comparison
Authors: Sadan Ofer , Waddel Hannah , Moore Reneé , Feng Chen , Mei Yajun , Pearce David , Kraft Jacqueline , Pimentel Cederic , Mathew Subin , Akbik Feras , Ameli Pouya , Taylor Alexis , Danyluk Lisa , Martin Kathleen S. , Garner Krista , Kolenda Jennifer , Pujari Amit , Asbury William , Jaja Blessing , Macdonald R. Loch , Cawley C. Michael , Barrow Daniel L. , Samuels Owen 
Published: September 2020

AbstractBackground and PurposeCerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, we describe our experience with intrathecal (IT) nicardipine for this indication.MethodsPatients admitted to Emory University Hospital Neuroscience ICU between 2012-2017 with non-traumatic SAH, either aneurysmal or idiopathic, were included in the analysis. This patient cohort was compared using a propensity-score model to patients in the SAH international trialist (SAHIT) repository who did not receive intrathecal nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events.ResultsThe analysis included 1,351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n=859) the treated group was younger (51.1±12.4 vs. 56.7±14.1, p<0.01), had a higher World Federation of Neurological Surgeons score (WFNS), modified Fisher grade, and more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs. 11.3%, p<0.01). Treatment with IT nicardipine decreased daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increase rate of bacterial ventriculitis (3.1% compared with 2.7%, p>0.1) yet higher rates of VP shunting were noted (19.9% vs. 8.8%, p<0.01). In a propensity score comparison to the SAHIT database, the odds ratio to develop DCI with IT nicardipine treatment was 0.61 with 95% CI[0.44-0.84], and to have a favorable functional outcome (mRS≤2) was 2.17[1.61-2.91].ConclusionsIT nicardipine was associated with improved outcome and reduced DCI compared with propensity matched controls. There was an increased need for permanent CSF diversion but no other safety issues. This data should be considered when selecting medications and treatments to study in future randomized controlled clinical trial for SAH.
Adjusting COVID-19 Reports for Countries’ Age Disparities: A Comparative Framework for Reporting Performances
Authors: Eryarsoy Enes , Delen Dursun , Davazdahemami Behrooz 
Published: September 2020

AbstractObjectivesThe COVID-19 outbreak has impacted distinct health care systems differently. While the rate of disease for COVID-19 is highly age-variant, there is no unified and age/gender-inclusive reporting taking place. This renders the comparison of individual countries based on their corresponding metrics, such as CFR difficult. In this paper, we examine cross-country differences, in terms of the age distribution of symptomatic cases, hospitalizations, intensive care unit (ICU) cases, and fatalities. In addition, we propose a new quality measure (called dissonance ratio) to facilitate comparison of countries’ performance in testing and reporting COVID-19 cases (i.e., their reporting quality).MethodsBy combining population pyramids with estimated COVID-19 age-dependent conditional probabilities, we bridge country-level incidence data gathered from different countries and attribute the variability in data to country demographics.ResultsWe show that age-adjustment can account for as much as a 22-fold difference in the expected number of fatalities across different countries. We provide case, hospitalization, ICU, and fatality breakdown estimates for a comprehensive list of countries. Also, a comparison is conducted between countries in terms of their performance in reporting COVID-19 cases and fatalities.ConclusionsOur research sheds light on the importance of and propose a methodology to use countries’ population pyramids for obtaining accurate estimates of the healthcare system requirements based on the experience of other, already affected, countries at the time of pandemics.
Take-Home Dosing Experiences among Persons Receiving Methadone Maintenance Treatment During COVID-19
Authors: Figgatt Mary C. , Salazar Zach , Day Elizabeth , Vincent Louise , Dasgupta Nabarun 
Published: September 2020

AbstractPurposeMethadone maintenance treatment is a life-saving treatment for people with opioid use disorders (OUD). The coronavirus pandemic (COVID-19) introduces many concerns surrounding access to opioid treatment. In March 2020, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued guidance allowing the expansion of take-home methadone doses. We sought to describe changes to treatment experiences from the perspective of persons receiving methadone at outpatient treatment facilities for OUD.MethodsWe conducted an in-person survey among 104 persons receiving methadone from three clinics in central North Carolina. Surveys collected information on demographic characteristics, methadone treatment history, and experiences with take-home methadone doses in the context of COVID-19 (i.e., before and since March 2020).ResultsBefore COVID-19, the clinic-level percent of participants receiving any amount of days’ supply of take-home doses at each clinic varied ranged from 56% to 82%, while it ranged from 78% to 100% since COVID-19. The clinic-level percent of participants receiving a take-homes days’ supply of a week or longer (i.e., ≥6 days) since COVID-19 ranged from 11% to 56%. Of the 87 participants who received take-homes since COVID-19 began, only four reported selling their take-home doses.ConclusionsOur study found variation in experiences of take-home dosing by clinic and little diversion of take-home doses. While SAMSHA guidance should allow expanded access to take-home doses, adoption of these guidelines may vary at the clinic level. The adoption of these policies should be explored further, particularly in the context of benefits to patients seeking treatment for OUD.
Intraluminal thrombus effect on the progression of abdominal aortic aneurysms by using a multistate continuous-time Markov chain model
Authors: Zhang Liangliang , Zambrano Byron A. , Choi Jongeun , Lee Whal , Baek Seungik , Lim Chae Young 
Published: September 2020

AbstractObjectiveRecent studies reported the intraluminal thrombus (ILT) among others strongly affects abdominal aortic aneurysms (AAA) expansion rates. Thus, we investigate characteristics of ILT with AAA expansion.MethodsWe applied homogeneous multistate continuous-time Markov chain models to longitudinal data of 26 Korean AAA patients as a retrospective clinical study. We considered four states of AAA and maximal thickness of ILT (maxILT), fraction of wall area covered by ILT (areafrac) and fraction of ILT volume (volfrac) as possible covariates.ResultsBased on likelihood-ratio statistics, areafracis the most significant biomarker and maxILTis the second most significant. Besides, within AAAs that developed an ILT layer, we found that an AAA expands relatively fast at an early stage but the rate goes slower once AAA reaches in a large size.ConclusionResults recommends surgical intervention when any patient with areafracmore than 60% or maxILTmore than 30mm. Although this recommendation should be considered with caution given the limited sample size, one can use the proposed model as a tool to find such recommendations with their own data.
Age affects temporal response, but not durability, to serial ketamine infusions for treatment refractory depression
Authors: Pennybaker Steven , Roach Brian J , Fryer Susanna L , Badathala Anusha , Wallace Art W , Mathalon Daniel H , Marton Tobias F 
Published: September 2020

AbstractBackgroundKetamine is a rapid-acting treatment for patients with treatment refractory depression (TRD), however treatment responses are often transient and ketamine’s antidepressant action lacks robust clinical durability. Little is known about which patient characteristics are associated with faster or more durable ketamine responses. Ketamine’s antidepressant mechanism is proposed to involve modulation of glutamatergic signaling leading to long term potentiation (LTP) and synaptogenesis, and these neuroplasticity pathways have been shown to be attenuated with older age. We therefore investigated the impact of patient age on the speed and durability of ketamine’s antidepressant effects in veterans receiving serial intravenous ketamine infusions for TRD.MethodsBeck Depression Inventory (BDI-II) scores from 49 veterans receiving six ketamine infusions (twice weekly) were examined from a retrospective case series. Percent change in BDI-II scores across the infusion series were assessed with respect to patient age using a mixed-linear model. Follow-up analyses examined the age x infusion number interaction effect at each assessment time point. To assess treatment durability, BDI-II change scores three weeks following the sixth infusion were correlated with age.ResultsThere was a significant age x infusion number interaction (F=3.01, p=.0274) across the six infusions. Beta estimates at each infusion showed a significant effect of age at infusion #4 (B=.88% +/-.29%, t=3.02, p=. 004) and a trend towards significance at infusion #5 (B=.62% +/-.31%, t=1.95, p=.057). There was no significant correlation between percent change in BDI-II and age at three-week follow-up.ConclusionsOlder age is associated with an altered trajectory of antidepressant response across serial ketamine infusions, with a model-predicted difference of 8.8% less improvement in BDI-II score for each decade in age mid-way through the infusion course. In contrast, antidepressant durability at three-week follow-up was not related to age. These data suggest age is an important moderating factor of patient response to ketamine, and that differing mechanisms may underlie speed and durability of ketamine’s antidepressant activity.
Peri-adolescent THC exposure does not lead to anxiety-like behavior in adult mice
Authors: Sestan-Pesa Matija , Shanabrough Marya , Horvath Tamas L. , Miletta Maria Consolata 
Published: September 2020

AbstractAs marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illness, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gut and is important for feeding behavior. Recent studies have shown that ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) play important roles in mediating stress, as well as anxiety and, depression-like behaviors in animal models. Here, we investigated the effects of chronic Tetrahydrocannabinol (THC) administration during adolescence (P42-55), in GHSR (GHSR-/-) knockout mice and their wild type littermates in relation to anxiety-like behaviors. We found that continuous THC exposure during peri-adolescence did not lead to any significant alterations in anxiety-like behavior of male adult mice, regardless of genotype. These data indicate that in the presence of intact GHSR signaling, THC exposure during peri-adolescence has limited if any long term impact on anxiety-like behaviors in mice.
Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2in vitro
Authors: Drayman Nir , Jones Krysten A. , Azizi Saara-Anne , Froggatt Heather M. , Tan Kemin , Maltseva Natalia Ivanovna , Chen Siquan , Nicolaescu Vlad , Dvorkin Steve , Furlong Kevin , Kathayat Rahul S. , Firpo Mason R. , Mastrodomenico Vincent , Bruce Emily A. , Schmidt Madaline M. , Jedrzejczak Robert , Muñoz-Alía Miguel Á. , Schuster Brooke , Nair Vishnu , Botten Jason W. , Brooke Christopher B. , Baker Susan C. , Mounce Bryan C. , Heaton Nicholas S. , Dickinson Bryan C. , Jaochimiak Andrzej , Randall Glenn , Tay Savaş 
Published: September 2020

AbstractThere is an urgent need for anti-viral agents that treat SARS-CoV-2 infection. The shortest path to clinical use is repurposing of drugs that have an established safety profile in humans. Here, we first screened a library of 1,900 clinically safe drugs for inhibiting replication of OC43, a human beta-coronavirus that causes the common-cold and is a relative of SARS-CoV-2, and identified 108 effective drugs. We further evaluated the top 26 hits and determined their ability to inhibit SARS-CoV-2, as well as other pathogenic RNA viruses. 20 of the 26 drugs significantly inhibited SARS-CoV-2 replication in human lung cells (A549 epithelial cell line), with EC50 values ranging from 0.1 to 8 micromolar. We investigated the mechanism of action for these and found that masitinib, a drug originally developed as a tyrosine-kinase inhibitor for cancer treatment, strongly inhibited the activity of the SARS-CoV-2 main protease 3CLpro. X-ray crystallography revealed that masitinib directly binds to the active site of 3CLpro, thereby blocking its enzymatic activity. Mastinib also inhibited the related viral protease of picornaviruses and blocked picornaviruses replication. Thus, our results show that masitinib has broad anti-viral activity against two distinct beta-coronaviruses and multiple picornaviruses that cause human disease and is a strong candidate for clinical trials to treat SARS-CoV-2 infection.
Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis
Authors: Lee Heekyung , Wang Zitong , Zeger Scott , Gallagher Michela , Knierim James J. 
Published: September 2020

AbstractAge-related memory deficits are correlated with neural hyperactivity in the CA1 and CA3 regions of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between the normal tradeoff between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from male young and aged Long-Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite trend, with a decreasing gradient from proximal to distal CA3. Thus, CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared to young rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus, the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote bistable representations under certain conditions.
Climate change alters plant-herbivore interactions
Authors: Hamann Elena , Blevins Cameron , Franks Steven J. , Jameel M. Inam , Anderson Jill T. 
Published: September 2020

ABSTRACTPlant-herbivore interactions have evolved in response to co-evolutionary dynamics, along with selection driven by abiotic conditions. We examine how abiotic factors influence trait expression in both plants and herbivores to evaluate how climate change will alter this long-standing interaction. The paleontological record documents increased herbivory during periods of global warming in the deep past. In phylogenetically-corrected meta-analyses, we find that elevated temperatures, CO2concentration, drought stress and nutrient conditions directly and indirectly induce greater herbivore consumption, primarily in agricultural systems. Additionally, elevated CO2delays herbivore development, but increased temperatures accelerate development. For annual plants, higher temperatures, CO2, and drought stress increase foliar herbivory, and our meta-analysis suggests that greater temperatures and drought may heighten florivory in perennials. Human actions are causing concurrent shifts in CO2, temperature, precipitation regimes and nitrogen deposition, yet few studies evaluate interactions among these changing conditions. We call for additional multifactorial studies that simultaneously manipulate multiple climatic factors, which will enable us to generate more robust predictions of how climate change could disrupt plant-herbivore interactions. Finally, we consider how shifts in insect and plant phenology and distribution patterns could lead to ecological mismatches, and how these changes may drive future adaptation and coevolution between interacting species.
Decoding of attentional state using high-frequency local field potential is as accurate as using spikes
Authors: Prakash Surya S , Das Aritra , Kanth Sidrat Tasawoor , Mayo J. Patrick , Ray Supratim 
Published: September 2020

AbstractLocal field potentials (LFPs) in visual cortex are reliably modulated when the subject’s focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spiking activity. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spiking responses was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found that LFPs during neutral cueing were intermediate between cued and uncued conditions, and, for a single electrode, attention was more discriminable using high frequency (>30 Hz) LFP power than spikes. Surprisingly, spikes did not outperform LFPs even when discriminability was computed using multiple electrodes. These results constrain the spatial scale attention operates over and highlight the usefulness of LFPs in studying attention.
Pre-existing intratumoral CD8 T cells substantially contribute to control tumors following therapeutic anti-CD40 and polyI:C based vaccination
Authors: Stevens Aaron D. , Bullock Timothy N.J. 
Published: September 2020

ABSTRACTBackgroundDendritic cells are potently activated by the synergistic action of CD40 stimulation in conjunction with signaling through toll like receptors, subsequently activating antigen specific T cells. Cancer vaccines targeting the activation of dendritic cells in this manner show promise in murine models and are being developed for human cancer patients. While vaccine efficacy has been established, further investigation is needed to understand the mechanism of tumor control and how vaccination alters tumor infiltrating immune cells.MethodsMice bearing established murine melanoma tumors were vaccinated with agonist anti-CD40, polyI:C, and tumor antigen. Intratumoral T cell numbers, differentiation state, proliferation, and survival were assessed by flow cytometry. T cell effector function was measured both within the tumor and ex vivo by flow cytometry. T cell trafficking was blocked to examine changes to intratumoral T cells present at the time of vaccination.ResultsVaccination led to increased intratumoral T cell numbers and delayed tumor growth. Expansion of T cells and tumor control did not require trafficking of T cells from the periphery. The increase in intratumoral T cells was associated with an acute burst in proliferation but not changes in viability. Intratumoral T cells had lower PD-1 and Eomes expression but were less functional after vaccination on a per cell basis. However, the increased intratumoral T cell numbers yielded increased effector T cells per tumor.ConclusionsPre-infiltrated CD8 T cells are responsive to CD40/TLR-mediated vaccination and sufficient for vaccination to delay tumor growth when additional T cell trafficking is blocked. This indicates that the existing T cell response and intratumoral DC could be critical for vaccination efficacy. This also suggests that circulating T cells may not be an appropriate biomarker for vaccination efficacy.
Population and comparative genetics of thermotolerance divergence between yeast species
Authors: Abrams Melanie B. , Dubin Claire A. , AlZaben Faisal , Bravo Juan , Joubert Pierre M. , Weiss Carly V. , Brem Rachel B. 
Published: September 2020

ABSTRACTMany familiar traits in the natural world—from lions’ manes to the longevity of bristlecone pine trees—arose in the distant past, and have long since fixed in their respective species. A key challenge in evolutionary genetics is to figure out how and why species-defining traits have come to be. We used the thermotolerance growth advantage of the yeastSaccharomyces cerevisiaeover its sister speciesSaccharomyces paradoxusas a model for addressing these questions. Analyzing loci at which theS. cerevisiaeallele promotes thermotolerance, we detected robust evidence for positive selection, including amino acid divergence between the species and conservation withinS. cerevisiaepopulations. Since such signatures were particularly strong at the chromosome segregation geneESP1, we used this locus as a case study for focused mechanistic follow-up. Experiments revealed that, in culture at high temperature, theS. paradoxus ESP1allele conferred a qualitative defect in biomass accumulation and cell division relative to theS. cerevisiaeallele. Only genetic divergence in theESP1coding region mattered phenotypically, with no functional impact detectable from the promoter. Together, these data support a model in which an ancient ancestor ofS. cerevisiae, under selection to boost viability at high temperature, acquired amino acid variants atESP1and many other loci, which have been constrained since then. Complex adaptations of this type hold promise as a paradigm for interspecies genetics, especially in deeply diverged traits that may have taken millions of years to evolve.
Confirmatory evidence that healthy individuals can adaptively adjust prior expectations and interoceptive precision estimates
Authors: Smith Ryan , Kuplicki Rayus , Teed Adam , Upshaw Valerie , Khalsa Sahib S. 
Published: September 2020

AbstractTheoretical proposals have previously been put forward regarding the computational basis of interoception. Following on this, we recently reported using an active inference approach to 1) quantitatively simulate interoceptive computation, and 2) fit the model to behavior on a cardiac awareness task. In the present work, we attempted to replicate our previous results in an independent group of healthy participants. We provide evidence confirming our previous finding that healthy individuals adaptively adjust prior expectations and interoceptive sensory precision estimates based on task context. This offers further support for the utility of computational approaches to characterizing the dynamics of interoceptive processing.