bluuebunny/crossref_metadata_2025 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

Insects 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

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

Deep 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

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

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

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

Modeling 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

Leaf 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

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

Objective

Kinesiophobia 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.

Methods

This 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.

Results

There 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.

Conclusion

Despite 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.

Impact

Evaluating 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

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

Situated 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

This 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.
Is photosynthetic enhancement sustained through three years of elevated CO2 exposure in 175-year-old Quercus robur?
Authors: Gardner A , Ellsworth D S , Crous K Y , Pritchard J , MacKenzie A R
Published: July 2021

Current carbon cycle models attribute rising atmospheric CO2 as the major driver of the increased terrestrial carbon sink, but with substantial uncertainties. The photosynthetic response of trees to elevated atmospheric CO2 is a necessary step, but not the only one, for sustaining the terrestrial carbon uptake, but can vary diurnally, seasonally and with duration of CO2 exposure. Hence, we sought to quantify the photosynthetic response of the canopy-dominant species, Quercus robur, in a mature deciduous forest to elevated CO2 (eCO2) (+150 μmol mol−1 CO2) over the first 3 years of a long-term free air CO2 enrichment facility at the Birmingham Institute of Forest Research in central England (BIFoR FACE). Over 3000 measurements of leaf gas exchange and related biochemical parameters were conducted in the upper canopy to assess the diurnal and seasonal responses of photosynthesis during the 2nd and 3rd year of eCO2 exposure. Measurements of photosynthetic capacity via biochemical parameters, derived from CO2 response curves, (Vcmax and Jmax) together with leaf nitrogen concentrations from the pre-treatment year to the 3rd year of eCO2 exposure, were examined. We hypothesized an initial enhancement in light-saturated net photosynthetic rates (Asat) with CO2 enrichment of ≈37% based on theory but also expected photosynthetic capacity would fall over the duration of the study. Over the 3-year period, Asat of upper-canopy leaves was 33 ± 8% higher (mean and standard error) in trees grown in eCO2 compared with ambient CO2 (aCO2), and photosynthetic enhancement decreased with decreasing light. There were no significant effects of CO2 treatment on Vcmax or Jmax, nor leaf nitrogen. Our results suggest that mature Q. robur may exhibit a sustained, positive response to eCO2 without photosynthetic downregulation, suggesting that, with adequate nutrients, there will be sustained enhancement in C assimilated by these mature trees. Further research will be required to understand the location and role of the additionally assimilated carbon.
Potassium supply modulates Eucalyptus leaf water-status under PEG-induced osmotic stress: integrating leaf gas exchange, carbon and nitrogen isotopic composition and plant growth
Authors: de Souza Mateus Nikolas , Oliveira Ferreira Eric Victor , Florentino Antonio Leite , Vicente Ferraz Alexandre , Domec Jean-Christophe , Jordan-Meille Lionel , Bendassolli José Albertino , Moraes Gonçalves José Leonardo , Lavres José
Published: July 2021

The objective of this study was to quantify the effect of potassium (K) supply on osmotic adjustment and drought avoidance mechanisms of Eucalyptus seedlings growing under short-term water stress. The effects of K supply on plant growth, nutritional status, leaf gas exchange parameters, leaf water potential (Ψw), leaf area (LA), stomatal density (SD), leaf carbon (C) and nitrogen (N) isotopic compositions (δ13C and δ15N ‰) and leaf C/N ratio under polyethylene glycol (PEG)-induced water deficit were measured. Under both control (non-PEG) and osmotic stress (+PEG) conditions, K supply increased plant growth, boosting dry matter yield with decreased C/N leaf ratio and δ15N ‰ values. The +PEG significantly reduced LA, plant growth, dry matter yield, Ψw, number of stomata per plant and leaf gas exchange, relative to non-PEG condition. Potassium supply alleviated osmotic-induced alterations in Eucalyptus seedlings by better regulating leaf development as well as SD, thus improving the rate of leaf gas exchange parameters, mesophyll conductance to CO2 (lower δ13C ‰ values) and water use efficiency (WUE). Consequently, K-supplied plants under drought better acclimated to osmotic stress than K-deficient plants, which in turn induced lower CO2 assimilation and dry matter yield, as well as higher leaf δ13C ‰ and δ15N ‰ values. In conclusion, management practices should seek to optimize K-nutrition to improve WUE, photosynthesis-related parameters and plant growth under water deficit conditions.
Comparison of High Throughput Sequencing to Standard Protocols for Virus Detection in Berry Crops
Authors: Villamor D. E. V. , Keller K. E. , Martin R. R. , Tzanetakis I. E.
Published: July 2021

We completed a comprehensive study comparing virus detection between high throughput sequencing (HTS) and standard protocols in 30 berry selections (12 Fragaria, 10 Vaccinium, and eight Rubus) with known virus profiles. The study examined temporal detection of viruses at four sampling times encompassing two growing seasons. Within the standard protocols, reverse transcription (RT) PCR proved better than biological indexing. Detection of known viruses by HTS and RT-PCR nearly mirrored each other. HTS provided superior detection compared with RT-PCR on a wide spectrum of variants and discovery of novel viruses. More importantly, in most cases in which the two protocols showed parallel virus detection, 11 viruses in 16 selections were not consistently detected by both methods at all sampling points. Based on these data, we propose a testing requirement of four sampling times over two growing seasons for berry and potentially other crops, to ensure that no virus remains undetected independent of titer, distribution, or other virus-virus or virus-host interactions.
Greenhouse Data Suggest That Growth Stage Impacts Phomopsis Stem Canker Severity Associated with Diaporthe gulyae on Sunflower (Helianthus annuus)
Authors: Guidini Renan , Braun Nathan , Korah Mammen , Marek Laura F. , Mathew Febina M.
Published: July 2021

Diaporthe gulyae Shivas et al. was initially described as causing Phomopsis stem canker of sunflower (Helianthus annuus L.) in the United States in 2010. In this study, the impact of growth stage on disease severity associated with D. gulyae in sunflower accessions was investigated in the greenhouse. One hundred thirty-nine accessions were inoculated with a single isolate of D. gulyae using the mycelium contact inoculation method at V4 to V6 (four to six true leaves) and R4 to R6 (inflorescence to ray flower wilting) growth stages. The experiment was conducted in a completely randomized design with six replications and repeated once. Disease severity was assessed at 14 days postinoculation using a 0-to-5 rating scale. A significant interaction between growth stage and accessions (P < 0.0001) was observed for disease severity (relative treatment effect [RTE]) caused by D. gulyae. Among the 139 accessions, 24, three, and two accessions had significantly lower RTE when inoculated at V4 to V6, R4 to R6, and both growth stages, respectively, upon comparing with the inbred susceptible check ‘HA 288’. This study suggests that accessions differ in their susceptibility to D. gulyae, possibly because of changes in resistance response during host development. Future studies on sunflower-D. gulyae interaction are warranted for developing commercial hybrids with resistance to the causal fungus.
Clinimetric Properties of Self-reported Disability Scales for Whiplash
Authors: Griffin Alexandra R. , Leaver Andrew M. , Arora Mohit , Walton David M. , Peek Aimie , Bandong Aila N. , Sterling Michele , Rebbeck Trudy
Published: July 2021

Objectives:

A core outcomes set (COS) for whiplash-associated disorders (WADs) has been proposed to improve consistency of outcome reporting in clinical trials. Patient-reported disability was one outcome of interest within this COS. The aim of this review was to identify the most suitable tools for measuring self-reported disability in WAD based on clinimetric performance.

Methods:

Database searches took place in 2 stages. The first identified outcome measures used to assess self-reported disability in WAD, and the second identified studies assessing the clinimetric properties of these outcome measures in WAD. Data on the study, population and outcome measure characteristics were extracted, along with clinimetric data. Quality and clinimetric performance were assessed in accordance with the Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN).

Results:

Of 19,663 records identified in stage 1 searches, 32 were retained following stage 2 searches and screening. Both the Whiplash Disability Questionnaire and Neck Disability Index performed well in reliability (intraclass correlation coefficient=0.84 to 0.98), construct validity (74% to 82% of hypotheses accepted), and responsiveness (majority of correlations in accordance with hypotheses). Both received Category B recommendations due to a lack of evidence for content validity.

Discussion:

This review identified the Neck Disability Index and Whiplash Disability Questionnaire as the most appropriate patient-reported outcome measures (PROMs) for assessing self-reported disability in WAD based on moderate to high-quality evidence for sufficient reliability, construct validity and responsiveness. However, the content validity of these PROMs has yet to be established in WAD, and until this is undertaken, it is not possible to recommend 1 PROM over the other for inclusion in the WAD COS.
Adult Auditory Brainstem Implant Outcomes and Three-Dimensional Electrode Array Position on Computed Tomography
Authors: Egra-Dagan Dana , van Beurden Isabeau , Barber Samuel R. , Carter Christine L. , Cunnane Mary E. , Brown M. Christian , Herrmann Barbara S. , Lee Daniel J.
Published: July 2021

Objectives:

Factors contributing to auditory brainstem implant (ABI) outcomes are poorly understood. The aims of this study are to (1) characterize ABI electrode array position on postoperative imaging and (2) determine if variability in position is related to perceptual outcomes.

Design:

Retrospective cohort study. Subjects were selected from the adult ABI recipient population at Massachusetts Eye and Ear. Postoperative three-dimensional (3D) computed tomography (CT) reconstruction of the head was used to measure ABI array position in 20 adult ABI recipients (17 with Neurofibromatosis Type 2 (NF2) and three non-NF2 recipients). Three-dimensional electrode array position was determined based on angles from the horizontal using posterior and lateral views and on distances between the proximal array tip superiorly from the basion (D1), laterally (D2P) and posteriorly (D2L) from the midline. Array position was correlated with perceptual data (in 15 of the 20 recipients who used their ABI). Perceptual data included the number of electrodes that provided auditory sensation, location and type of side effects, level of speech perception (from no sound to open-set word recognition of monosyllables) and the amount of charge required for auditory perception.

Results:

Although the 3D orientation of the ABI array exhibited a variety of angles, all arrays were posteriorly tilted from the lateral view and most were medially tilted from the posterior view. ABI position relative to the basion from posterior showed mean distances of 1.71 ± 0.42 and 1.1 ± 0.29 cm for D1 and D2, respectively, and a mean D2 of 1.30 ± 0.45 cm from the lateral view. A strong linear negative correlation was found between the number of active electrodes and the distance of the proximal array tip laterally from the basion (D2P; rs = −0.73, p = 0.006) when measured in the posterior view. Although side effects were experienced in all recipients and varied in type and location across the array, electrodes in the middle part of the array tended to elicit auditory sensations while the proximal and distal tips of the array tended to elicit nonauditory side effects. Arrays with and without low charge thresholds appeared to generally overlap in position. However, the two recipients with the best (open-set) speech perception had low charge thresholds and had arrays that were tilted superiorly in the posterior view.

Conclusion:

ABI recipients with better speech perception appear to share a profile of arrays that are tilted superiorly as compared to recipients with lower speech perception levels. These ABI recipients have a high number of active electrodes (10 or more) and require less electrical charge on individual electrodes to achieve optimal stimulation.
Important Factors for Retrograde Nailing Through Total Knee Arthroplasty: A Cadaveric Study
Authors: Lentine Brandon , Tarka Mitchell , Nelms Nathaniel J. , Russell Sheila , Schottel Patrick C. , Blankstein Michael
Published: July 2021

Objectives:

Evaluate how total knee arthroplasty (TKA) implant design, femoral component size, and preoperative knee range of motion affect retrograde femoral nailing.

Methods:

Cadaveric specimens were prepared for TKA with a single radius (SR) or medial pivot (MP) design and tested with cruciate retaining (CR), cruciate substituting (CS), and posterior stabilizing (PS) 9-mm liners. Knee extension identified the minimum flexion required to pass an opening reamer without impinging on TKA components. The angle between the reamer path and the femoral shaft was calculated from lateral fluoroscopic images.

Results:

In SR TKA, the average flexion required was 70, 71, and 82 degrees for CR, CS, and PS, respectively. The required flexion in PS was significantly greater (P = 0.03). In MP TKA, the average flexion required was 74, 84, and 123 degrees for CR, CS, and PS, respectively. The required flexion was significantly greater in CS and PS designs (P < 0.0001). Femoral component size did not affect the minimum flexion required. The entry reamer resulted in 9.2 (SR) and 12.5 (MP) degrees of apex anterior deviation.

Conclusions:

When performing retrograde nailing through either of these TKA designs with a 12-mm opening reamer, at least 70 degrees of knee flexion is required to avoid damage to the polyethylene liner or femoral component. PS implants require significantly more flexion with both TKA designs. Femoral component size did not affect the flexion requirement. Approximately a 10-degree deviation exists between the reamer path and femoral shaft.
Preseptal cellulitis, intraocular inflammatory reaction and corneal persistent epithelial defect as side effects of avapritinib
Authors: García Caride Sara , Marquina Gloria , Díaz Valle David
Published: July 2021

Avapritinib is a tyrosine kinase inhibitor currently being investigated on clinical trials for the treatment of unresectable or metastatic gastrointestinal stromal tumour (GIST). It has been recently approved by the Food and Drug Administration and the European Medicines Agency for the treatment of unresectable or metastatic GIST harbouring PDGFRa Exon 18 mutation and by the European Medicines Agency for the treatments of unresectable or metastatic GIST harbouring the PDGFRa D842V mutation. We report a clinical case of a 76-year-old female, diagnosed with a stage IV GIST, treated with avapritinib 300 mg once daily. through compassionate use who experienced an intraocular side effect not previously reported avapritinib. She developed preseptal cellulitis on her right eye following 2 months of treatment with avapritinib and, subsequently evolved to an intraocular inflammatory reaction and persistent corneal epithelial defect. The treatment with avapritinib was stopped and the patient received corticosteroid and corneal regenerating agents. The symptoms resolved within 1 month and the patient has remained on stable disease at two subsequent adjusted avapritinib doses (100 mg once daily) for over 1 year.
Tyrosine kinase inhibitors-associated pyoderma gangrenosum, a systematic review of published case reports
Authors: Khoshnam-Rad Niloofar , Gheymati Azin , Jahangard-Rafsanjani Zahra
Published: July 2021

Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the reported evidence of pyoderma gangrenosum associated with the use of these drugs. A systematic electronic literature search of PubMed and Embase was conducted. In these databases, search terms describing pyoderma gangrenosum were combined with TKIs. Fifteen case reports (eight cases associated with sunitinib, two with imatinib, two with ibrutinib, one with gefitinib, one with pazopanib, and one with dabrafenib and trametinib) were identified over the 14 years. The average Naranjo score of these cases is 6.6, which indicates a probable adverse drug reaction. Pyoderma gangrenosum is a probable and reversible drug reaction associated with some TKIs. Detailed medical history can help to prompt diagnosis of drug-induced pyoderma gangrenosum. Clinicians should be aware of TKI-associated pyoderma gangrenosum when caring for the skin of oncologic patients undergoing therapy with kinase inhibitors.
Evaluation of nuclear PGAM2 value in hepatocellular carcinoma prognosis
Authors: Li Yi-Ran , Chen Jin-Dong , Zhu Yu-Yao , Li Ju-Tang , Jin Guang-Zhi , Jin Ri-Ming
Published: July 2021

Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan–Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan–Meier analyses of 178 HCC samples revealed that nuclear PGAM2’s high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2’s high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.
Anlotinib treatment in elderly patients with unresectable or metastatic soft tissue sarcoma: a retrospective study
Authors: Zhang Xin-Yao , Liu Jie , Deng Yao-Tiao , Jiang Yu
Published: July 2021

Palliative chemotherapy can improve outcomes in most patients with advanced soft tissue sarcoma (STS), but the treatment of elderly patients remains a challenge because of older age, comorbidities and poor performance status. This study retrospectively analyzed the efficacy and safety of the multi-targeted tyrosine kinase inhibitor anlotinib in elderly patients with advanced STS. Eligible patients included those of age at least 60 years, diagnosed with unresectable or metastatic STS, and treated with at least one cycle of anlotinib between June 2018 and September 2020 in our center. Clinical characteristics, treatment response, survival status and adverse events were analyzed by reviewing medical records. The median age of 35 eligible patients was 65 (range, 61–85) years, and the median Charlson Comorbidity Index score was 8 (range, 4–11). Anlotinib as first-line systemic treatment was in 24 (68.6%) patients, and as second-line or third-line treatment in the remaining 11 (31.4%) patients. The objective response rate was 8.6%. The median progression-free survival was 5.5 [95% confidence interval (CI), 1.4–9.6] months and the median overall survival was 14.3 (95% CI, 9.6–19.0) months. Thirteen (37.1%) patients developed at least one grade 3/4 adverse event during anlotinib treatment. Our findings suggest that anlotinib treatment has promising efficacy and an acceptable toxicity profile in elderly patients with unresectable or metastatic STS. Prospective controlled trials are needed to compare the safety and efficacy of anlotinib and chemotherapy as first-line treatment in elderly patients with advanced STS.
Updates on the diagnosis, current and future therapeutic options in Merkel-cell carcinoma
Authors: Turshudzhyan Alla , Hadfield Matthew , Grant-Kels Jane
Published: July 2021

Merkel-cell carcinoma (MCC) is a rare and extremely aggressive nonmelanocytic cutaneous neuroendocrine carcinoma. Historically, it has been associated with limited therapy options and poor prognosis. While its incidence has been rising over the last two decades, recent discoveries and a better understanding of its pathogenesis, viral association and immunologic features have allowed for the emergence of new therapies. Surgical excision with or without radiotherapy remains the first-line therapy for primary lesions without evidence of metastatic disease. The majority of MCC cases are regrettably diagnosed at advanced stages and oftentimes require systemic therapy. There have been several significant advances in the treatment of MCC in the last decade. Among these have been the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death ligand-1 (PDL-1). Despite recent success of immunotherapy, nearly 50% of patients diagnosed with MCC still succumb to the disease. Fortunately, there has been a number of new targeted therapies that hold great promise. Among them are phosphatidylinositide-3kinase (Pl3K) inhibitors, adoptive T-cell immunotherapy, activated NK-92 cells infusions and therapeutic vaccines. Additional emerging therapeutic targets include cellular ubiquitin-specific processing protease 7 (Usp7) that restricts viral replication and IFN genes (STING), activation of which promotes an antitumor inflammatory response.
Differences in menopausal symptoms and female sexual function by region and ethnicity in West Texas and Central Arizona: a cross-sectional survey
Authors: Prairie Beth A. , Kling Juliana M. , Buras Matthew R. , Butterfield Richard J. , Jenkins Marjorie
Published: July 2021

Objective:

To evaluate menopausal symptoms and sexual problems in Hispanic and non-Hispanic women in two Southwest areas.

Methods:

An anonymous survey including the Green Climacteric Scale (GCS), Female Sexual Function Index (FSFI), and demographics was distributed to English and Spanish-speaking women age 40 to 60 in Scottsdale, Arizona, and West Texas. FSFI for sexually active women and GCS scores for the Hispanic and non-Hispanic women in Texas were analyzed with multivariable analysis and compared between Texas and Arizona for Non-Hispanic participants.

Results:

Predominantly non-Hispanic women (70%), average age 51.5 (SD = 7.25) completed questionnaires (199 West Texas, 163 Scottsdale). A majority of sexually active women (88%) were found to be at risk of sexual dysfunction. Within the Texas cohort, GCS score was estimated to be 3.49 points lower (less symptoms) in Hispanic versus non-Hispanic participants [95% CI −6.58 to −0.40, P = 0.03], and FSFI score was estimated to be 2.31 points lower (more symptoms) in Hispanic versus non-Hispanic participants [95% CI −4.49 to −0.14, P = 0.04]. Among non-Hispanic women, GCS scores were lower (less symptoms) in Texas versus Arizona by 10.25 points [95% CI −14.83 to −5.66, P < 0.01], while FSFI scores were higher overall (less symptoms) in Texas by 3.65 points [95% CI 0.53-6.77), P = 0.02]. All FSFI and GCS scores were adjusted for multiple variables.

Conclusions:

In a group of menopausal women from the Southwest, most reported symptoms were consistent with FSD, and the degree of sexual problems appeared to be greater in the Hispanic participants from Texas.

Video Summary:

http://links.lww.com/MENO/A781.