bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Evolution of a Bark Beetle Odorant Receptor Clade Detecting Monoterpenoids of Different Ecological Origins
Authors: Hou Xiao-Qing , Yuvaraj Jothi Kumar , Roberts Rebecca E , Zhang Dan-Dan , Unelius C Rikard , Löfstedt Christer , Andersson Martin N 
Published: July 2021

AbstractInsects detect odors using an array of odorant receptors (ORs), which may expand through gene duplication. How and which new functions may evolve among related ORs within a species remain poorly investigated. We addressed this question by functionally characterizing ORs from the Eurasian spruce bark beetle Ips typographus, in which physiological and behavioral responses to pheromones, volatiles from host and nonhost trees, and fungal symbionts are well described. In contrast, knowledge of OR function is restricted to two receptors detecting the pheromone compounds (S)-(–)-ipsenol (ItypOR46) and (R)-(–)-ipsdienol (ItypOR49). These receptors belong to an Ips-specific OR-lineage comprising seven ItypORs. To gain insight into the functional evolution of related ORs, we characterized the five remaining ORs in this clade using Xenopus oocytes. Two receptors responded primarily to the host tree monoterpenes (+)-3-carene (ItypOR25) and p-cymene (ItypOR27). Two receptors responded to oxygenated monoterpenoids produced in larger relative amounts by the beetle-associated fungi, with ItypOR23 specific for (+)-trans-(1R, 4S)-4-thujanol, and ItypOR29 responding to (+)-isopinocamphone and similar ketones. ItypOR28 responded to the pheromone E-myrcenol from the competitor Ips duplicatus. Overall, the OR responses match well with those of previously characterized olfactory sensory neuron classes except that neurons detecting E-myrcenol have not been identified. The characterized ORs are under strong purifying selection and demonstrate a shared functional property in that they all primarily respond to monoterpenoids. The variation in functional groups among OR ligands and their diverse ecological origins suggest that neofunctionalization has occurred early in the evolution of this OR-lineage following gene duplication.
Targeting a noncanonical, hairpin-containing G-quadruplex structure from the MYCN gene
Authors: Yang Mo , Carter Sakereh , Parmar Shaifaly , Bume Desta D , Calabrese David R , Liang Xiao , Yazdani Kamyar , Xu Man , Liu Zhihui , Thiele Carol J , Schneekloth John S 
Published: July 2021

Abstract
The MYCN gene encodes the transcription factor N-Myc, a driver of neuroblastoma (NB). Targeting G-quadruplexes (G4s) with small molecules is attractive strategy to control the expression of undruggable proteins such as N-Myc. However, selective binders to G4s are challenging to identify due to the structural similarity of many G4s. Here, we report the discovery of a small molecule ligand (4) that targets the noncanonical, hairpin containing G4 structure found in the MYCN gene using small molecule microarrays (SMMs). Unlike many G4 binders, the compound was found to bind to a pocket at the base of the hairpin region of the MYCN G4. This compound stabilizes the G4 and has affinity of 3.5 ± 1.6 μM. Moreover, an improved analog, MY-8, suppressed levels of both MYCN and MYCNOS (a lncRNA embedded within the MYCN gene) in NBEB neuroblastoma cells. This work indicates that the approach of targeting complex, hybrid G4 structures that exist throughout the human genome may be an applicable strategy to achieve selectivity for targeting disease-relevant genes including protein coding (MYCN) as well as non-coding (MYCNOS) gene products.
DeepCOMBI: explainable artificial intelligence for the analysis and discovery in genome-wide association studies
Authors: Mieth Bettina , Rozier Alexandre , Rodriguez Juan Antonio , Höhne Marina M C , Görnitz Nico , Müller Klaus-Robert 
Published: July 2021

AbstractDeep learning has revolutionized data science in many fields by greatly improving prediction performances in comparison to conventional approaches. Recently, explainable artificial intelligence has emerged as an area of research that goes beyond pure prediction improvement by extracting knowledge from deep learning methodologies through the interpretation of their results. We investigate such explanations to explore the genetic architectures of phenotypes in genome-wide association studies. Instead of testing each position in the genome individually, the novel three-step algorithm, called DeepCOMBI, first trains a neural network for the classification of subjects into their respective phenotypes. Second, it explains the classifiers’ decisions by applying layer-wise relevance propagation as one example from the pool of explanation techniques. The resulting importance scores are eventually used to determine a subset of the most relevant locations for multiple hypothesis testing in the third step. The performance of DeepCOMBI in terms of power and precision is investigated on generated datasets and a 2007 study. Verification of the latter is achieved by validating all findings with independent studies published up until 2020. DeepCOMBI is shown to outperform ordinary raw P-value thresholding and other baseline methods. Two novel disease associations (rs10889923 for hypertension, rs4769283 for type 1 diabetes) were identified.
Highly Selective Partial Neurectomies for Spasticity: A Single-Center Experience
Authors: Mahan Mark A , Eli Ilyas , Hamrick Forrest , Abou-Al-Shaar Hussam , Shingleton Robert , Tucker Balun Kara , Edgley Steven R 
Published: July 2021

Abstract

BACKGROUND
Sedating antispastic medications and focal therapies like botulinum toxin are the most common therapies for spasticity but are temporary and must be performed continuously for a principally static neurological insult. Alternatively, highly selective partial neurectomies (HSPNs) may reduce focal spasticity more permanently.

OBJECTIVE
To quantify the change in spasticity after HSPN and assess patient satisfaction.

METHODS
We retrospectively reviewed the records of patients with upper- and/or lower-extremity spasticity treated with HSPN from 2014 to 2018. Only cases with a modified Ashworth scale (MAS) score independently determined by a physical therapist were included. Pre- and postoperative MAS, complications, and patient satisfaction were evaluated.

RESULTS
The 38 patients identified (24 male, 14 female; mean age 49 yr) underwent a total of 88 procedures for focal spasticity (73% upper extremity, 27% lower extremity). MAS scores were adjusted to a 6-point scale for evaluation. The mean preoperative and final postoperative follow-up adjusted MAS scores were 3.6 and 1.7, respectively (P < .001), which represents average MAS less than 1+. Positive, neutral, and worse results were described by 91%, 6%, and 3% of patients, respectively. Four patients requested revision surgery. No perioperative complications were encountered.

CONCLUSION
This is the first North American series to analyze HSPN for spasticity and the only series based on independent evaluation results. HSPN surgery demonstrated objective short- and long-term reduction in spasticity with minimal morbidity and excellent patient satisfaction.
Longitudinal Cost Profiles of Pipeline Embolization Device Versus Stent-Assisted Coiling in Propensity-Matched Unruptured Small Anterior Circulation Aneurysms
Authors: Salem Mohamed M , Salih Mira , Nwajei Felix , Williams Natalie , Thomas Ajith J , Moore Justin M , Ogilvy Christopher S 
Published: July 2021

Abstract

BACKGROUND
The cost profiles of stent-assisted coiling (SAC) vs Pipeline embolization device (PED) in small unruptured anterior circulation aneurysms have not been studied.

OBJECTIVE
To compare the 2 modalities cost profiles in a propensity-matched cohort controlling for potential technical complexity confounders including size and location.

METHODS
Patients treated with either SAC or PED at our institution were identified. Following propensity-score algorithm, 46 patients, 23 in each group were matched. The procedural and follow-up costs in each group were analyzed and compared.

RESULTS
Median maximal aneurysm size in the SAC and PED cohort were 5.3 vs 5.1 mm, respectively. Costs of access guide materials were significantly higher in the SAC group (P < .01). The average implant cost was not significantly different between the SAC and PED cohorts (

13973.2 ±

2886.2 vs

14,760.7 ±

3782.1, respectively; P = .43). Similarly, total procedural costs were not different (

18341.5 ± 4104 vs

17484.3 ± 2914.1, respectively, P = .42). Although there were significantly more total follow-ups (P = .02) and longer follow-up duration (P = .01) in SAC cohort, no significant difference in follow-up costs between the 2 groups was identified (

20557 ±

9247 vs

18958 ±

9171.9, P = .56). Overall cost was similar between the SAC (

38898.9 ±

9645.5) and PED groups (

36442.4 ±

9076) (P = .38).

CONCLUSION
In small unruptured anterior circulation aneurysms (excluding anterior communicating artery aneurysms) matched for technical complexity confounders, SAC and PED offer an overall equivalent economic cost profile. Postprocedural noninvasive imaging was more frequent in the SAC group. However, follow-up costs and total costs were not significantly different.
Acute Brain Activation Patterns of High- Versus Low-Frequency Stimulation of the Anterior Nucleus of the Thalamus During Deep Brain Stimulation for Epilepsy
Authors: Middlebrooks Erik H , Jain Ayushi , Okromelidze Lela , Lin Chen , Westerhold Erin M , O'Steen Chad A , Ritaccio Anthony L , Quiñones-Hinojosa Alfredo , Tatum William O , Grewal Sanjeet S 
Published: July 2021

Abstract

BACKGROUND
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an increasingly utilized treatment of drug-resistant epilepsy. To date, the effect of high-frequency stimulation (HFS) vs low-frequency stimulation (LFS) in ANT DBS is poorly understood.

OBJECTIVE
To assess differences in the acute effect of LFS vs HFS in ANT DBS utilizing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI).

METHODS
In this prospective study of 5 patients with ANT DBS for epilepsy, BOLD activation and deactivation were modeled for 145-Hz and 30-Hz ANT stimulation using an fMRI block design. Data were analyzed with a general linear model and combined via 2-stage mixed-effects analysis. Z-score difference maps were nonparametrically thresholded using cluster threshold of z > 3.1 and a (corrected) cluster significance threshold of P = .05.

RESULTS
HFS produced significantly greater activation within multiple regions, in particular the limbic and default mode network (DMN). LFS produced minimal activation and failed to produce significant activation within these same networks. HFS produced widespread cortical and subcortical deactivation sparing most of the limbic and DMN regions. Meanwhile, LFS produced deactivation in most DMN and limbic structures.

CONCLUSION
Our results show that HFS and LFS produce substantial variability in both local and downstream network effects. In particular, largely opposing effects were identified within the limbic network and DMN. These findings may serve as a mechanistic basis for understanding the potential of HFS vs LFS in various epilepsy syndromes.
Distribution models using semi-structured community science data outperform unstructured-data models for a data-poor species, the Plain Tyrannulet
Authors: Gorleri Fabricio C , Hochachka Wesley M , Areta Juan I 
Published: July 2021

AbstractModeling the distribution of a data-poor species is challenging due to a reliance on unstructured data that often lacks relevant information on sampling and produces coarse-resolution outputs of varying accuracy. Data on sampling effort associated with higher-quality, semi-structured data derived from some community science programs can be used to produce more precise models of distribution, albeit at a cost of using fewer data. Here, we used semi-structured data to model the seasonal ranges of the Plain Tyrannulet (Inezia inornata), a poorly known Austral–Neotropical migrant, and compared predictive performance to models built with the full unstructured dataset of the species. By comparing these models, we examined the relatively unexplored tradeoff between data quality and data quantity for modeling of a data-sparse species. We found that models using semi-structured data outperformed unstructured-data models in the predictive accuracy metrics (mean squared error, area under the curve, kappa, sensitivity, and specificity), despite using only 30% of the available detection records. Moreover, semi-structured models were more biologically accurate, indicating that the tyrannulet favors arboreal habitats in dry and hot lowlands during the breeding season (Chaco region) and is associated with proximity to rivers in tropical and wet areas during the nonbreeding season (Pantanal, Beni, and southwest Amazonia). We demonstrate that more detailed insights into distributional patterns can be gained from even small quantities of data when the data are analyzed appropriately. The use of semi-structured data promises to be of wide applicability even for data-poor bird species, helping refine information on distribution and habitat use, needed for effective assessments of conservation status.
The leaf meristem enigma: The relationship between the plate meristem and the marginal meristem
Authors: Tsukaya Hirokazu 
Published: July 2021

AbstractLeaf organogenesis is governed by the spatiotemporal activity of the leaf meristem, which has far greater mitotic activity than the shoot apical meristem. The two types of leaf meristems, the plate meristem and the marginal meristem, are distinguished by the location and longevity of their cell proliferative activity. Most leaf lamina outgrowth depends on the plate meristem. The presence of the marginal meristem was a matter of debate in classic anatomy, but recent genetic analyses of leaf growth in Arabidopsis thaliana confirmed its short-lived activity. Several genes key for the regulation of the two meristem types have been identified, and at least superficially, the systems appear to function independently, as they are regulated by different transcription factors and microRNAs. However, many of the details of these regulatory systems, including how the expression of these key factors is spatially regulated, remain unclear. One major unsolved question is the relationship between the plate meristem and the marginal meristem. Here, I present an overview of our current understanding of this topic and discuss questions that remain to be answered.
Effect of Manual Therapy Interventions on Range of Motion Among Individuals with Myofascial Trigger Points: A Systematic Review and Meta-Analysis
Authors: Guzmán-Pavón María José , Cavero-Redondo Iván , Martínez-Vizcaíno Vicente , Torres-Costoso Ana Isabel , Reina-Gutiérrez Sara , Álvarez-Bueno Celia 
Published: July 2021

Abstract

Objective
Patients with myofascial trigger points (MTPs) frequently manifest restricted range of motion (ROM) during physical evaluation. Multiple manual therapy interventions have been developed for the treatment of MTPs, but their effect on ROM has not been clarified through a systematic review and meta-analysis. Thus, this systematic review aimed to assess the effect of manual therapy interventions on ROM among individuals with MTPs.

Methods
A systematic search was conducted in PubMed, Web of Science, Cochrane, Scopus, and Clinical Trials.gov. Articles analyzing the effect of manual therapy interventions on ROM were included. The risk of bias was assessed with the Cochrane Risk of Bias (RoB) 2 tool. The DerSimonian-Laird method was used to compute the pooled effect size (ES) and its 95% confidence interval (95% CI) for ROM.

Results
A total of 13 randomized controlled trials were included in this systematic review and meta-analysis. The pooled ES for ROM was 0.52 (95% CI: 0.42–0.63). The pooled ES for ROM evaluated in centimeters was 0.36 (95% CI: 0.14–0.59), and the pooled ES for ROM evaluated in degrees was 0.57 (95% CI: 0.47–0.68).

Conclusion
Manual therapy interventions may be an effective approach for improving ROM among individuals with MTPs.
The Impact of the Degree of Kinesiophobia on Recovery in Patients With Achilles Tendinopathy
Authors: Alghamdi Nabeel Hamdan , Pohlig Ryan T , Lundberg Mari , Silbernagel Karin Grävare 
Published: July 2021

AbstractObjectiveKinesiophobia has been proposed to influence recovery in individuals with Achilles tendinopathy. However, whether there are differences in outcomes in individuals with different levels of kinesiophobia is unknown. The purpose of this study was to compare the characteristics of patients at baseline and recovery over time in individuals with Achilles tendinopathy and various levels of kinesiophobia.MethodsThis study was a secondary analysis of a prospective observational cohort study of 59 individuals with Achilles tendinopathy. The participants were divided into 3 groups on the basis of scores on the Tampa Scale for Kinesiophobia (TSK) (those with low TSK scores [≤33; low TSK group], those with medium TSK scores [34–41; medium TSK group], and those with high TSK scores [≥42; high TSK group]). All participants were evaluated with self-reported outcomes, clinical evaluation, tendon morphology, viscoelastic property measurements, and a calf muscle endurance test at baseline, 6 months, and 12 months. No treatment was provided throughout the study period.ResultsThere were 16 participants (8 women) in the low TSK group (age = 51.9 [SD = 15.3] years, body mass index [BMI] = 24.3 [22.3–25.4]), 28 participants (13 women) in the medium TSK group (age = 52.7 [SD = 15.2] years, BMI = 26.4 [22.5–30.8]), and 15 participants (8 women) in the high TSK group (age = 61.1 [SD = 11.1] years, BMI = 28.1 [25.2–33.6]). Among the groups at baseline, the high TSK group had significantly greater BMI and symptom severity and lower quality of life. All groups showed significant improvement over time for all outcomes except tendon viscoelastic properties and tendon thickening when there was an adjustment for baseline BMI. The high and medium TSK groups saw decreases in kinesiophobia at 6 months, but there was no change for the low TSK group.ConclusionDespite the high TSK group having the highest BMI and the worse symptom severity and quality of life at baseline, members of this group showed improvements in all of the outcome domains similar to those of the other groups over 12 months.ImpactEvaluating the degree of kinesiophobia in individuals with Achilles tendinopathy might be of benefit for understanding how they are affected by the injury. However, the degree of kinesiophobia at baseline does not seem to affect recovery; this finding could be due to the patients receiving education about the injury and expectations of recovery.
Effect of statins on the prevention of recurrent thrombosis in thrombotic antiphospholipid syndrome
Authors: Kwon Oh Chan , Park Yong-Beom , Park Min-Chan 
Published: July 2021

Abstract

Objective
To assess the effect of statins on the prevention of recurrent thrombosis in patients with thrombotic APS.

Methods
This retrospective cohort study included 184 patients with thrombotic APS. The effect of statins on recurrent thrombosis was investigated in the total study population and in an inverse probability of treatment weighting (IPTW)-adjusted population. Multivariable and IPTW-adjusted Cox proportional hazard regression analyses were performed on the total study population and the IPTW-adjusted population, respectively, to estimate the hazard ratios (HRs) with 95% CIs for recurrent thrombosis, according to the use of statins.

Results
Of the 184 patients, 103 (56.0%) received statins, while the other 81 (44.0%) did not. Recurrent thrombosis occurred in 22 (12.0%) patients during the mean observation period of 48.5 (34.9) months. In the multivariable Cox regression analyses, the use of statins was associated with a lower risk of recurrent thrombosis: (i) model 1 adjusted for risk factors of arterial and venous thrombosis, HR 0.24, 95% CI: 0.09, 0.63, P = 0.004; (ii) model 2 adjusted for the use of anticoagulants, antiplatelets and HCQ, HR 0.28, 95% CI: 0.10, 0.76, P = 0.012; and (iii) model 3 adjusted for the antiphospholipid autoantibody profile, HR 0.26, 95% CI: 0.10, 0.67, P = 0.005. The IPTW-adjusted Cox regression analysis also showed a lower risk of recurrent thrombosis with the use of statins (HR 0.28, 95% CI: 0.12, 0.65, P = 0.003).

Conclusion
Our data suggest that statins could be effective in reducing the risk of recurrent thrombosis in patients with thrombotic APS.
Emotion depends on context, culture and their interaction: evidence from effective connectivity
Authors: Pugh Zachary H , Choo Sanghyun , Leshin Joseph C , Lindquist Kristen A , Nam Chang S 
Published: July 2021

AbstractSituated models of emotion hypothesize that emotions are optimized for the context at hand, but most neuroimaging approaches ignore context. For the first time, we applied Granger causality (GC) analysis to determine how an emotion is affected by a person’s cultural background and situation. Electroencephalographic recordings were obtained from mainland Chinese (CHN) and US participants as they viewed and rated fearful and neutral images displaying either social or non-social contexts. Independent component analysis and GC analysis were applied to determine the epoch of peak effect for each condition and to identify sources and sinks among brain regions of interest. We found that source–sink couplings differed across culture, situation and culture × situation. Mainland CHN participants alone showed preference for an early-onset source–sink pairing with the supramarginal gyrus as a causal source, suggesting that, relative to US participants, CHN participants more strongly prioritized a scene’s social aspects in their response to fearful scenes. Our findings suggest that the neural representation of fear indeed varies according to both culture and situation and their interaction in ways that are consistent with norms instilled by cultural background.
Racial change and income tax policy in the US states
Authors: O’Brien Rourke , Travis Adam 
Published: July 2021

AbstractThis article examines the social correlates of US state income tax policy-making between 1980 and 2008. We focus on the three factors the existing research suggests that are relevant to redistributive policy-making: income structure, left power resources and racial composition. We employ a holistic measure of state income taxation—the dollar-weighted average marginal tax rate—that captures both the overall level of taxation as well as the distribution of tax incidence, key determinants of the redistributive effect of income tax policy. Our analyses examine within-state changes over time as estimated using both actual and fixed income distributions, which enables us to isolate real changes in tax policy from shifts in the income distribution. We find evidence that increases in the percentages of Black and Hispanic residents are associated with a decrease in average marginal tax rate on wage income. We situate these findings within the broader literature on the social determinants of redistributive policy-making.