A concise update on the synthetic transformation of aurones via asymmetric cycloaddition, annulation, and Michael/Mannich reactions.

This review provides a comprehensive overview of the significance of aurone cores in organic chemistry, highlighting their crucial role as synthetic intermediates. With their innate electrophilic reactivity and convenient accessibility, aurone cores play a vital role in catalysing the development of novel methodologies and facilitating the creation of intricate compounds. The objective of this review is to present a current and insightful compilation that summarizes the progress in aurone synthetic transformations, focusing on diverse cycloaddition ([3 + 2], [4 + 2], [4 + 3], [10 + 2]) and annulation reactions.

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures.

Calcium (Ca2+ ) imaging reveals a variety of correlated firing in cultures of dissociated hippocampal neurons, pinpointing the non-synaptic paracrine release of glutamate as a possible mediator for such firing patterns, although the biophysical underpinnings remain unknown. An intriguing possibility is that extracellular glutamate could bind metabotropic receptors linked with inositol trisphosphate (IP3 ) mediated release of Ca2+ from the endoplasmic reticulum of individual neurons, thereby modulating neural activity in combination with sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA) and voltage-gated Ca2+ channels (VGCC). However, the possibility that such release may occur in different neuronal compartments and can be inherently stochastic poses challenges in the characterization of such interplay between various Ca2+ channels. Here we deploy biophysical modeling in association with Monte Carlo parameter sampling to characterize such interplay and successfully predict experimentally observed Ca2+ patterns. The results show that the neurotransmitter level at the plasma membrane is the extrinsic source of heterogeneity in somatic Ca2+ transients. Our analysis, in particular, identifies the origin of such heterogeneity to an intrinsic differentiation of hippocampal neurons in terms of multiple cellular properties pertaining to intracellular Ca2+ signaling, such as VGCC, IP3 receptor, and SERCA expression. In the future, the biophysical model and parameter estimation approach used in this study can be upgraded to predict the response of a system of interconnected neurons.

Recent trends in the prescription of opioids in the emergency department in patients with urolithiasis.

PURPOSE: Pain management is central in the treatment of urolithiasis. We aimed to estimate the impact of the 2017 Department of Health and Human Services declaration of an opioid crisis on prescribing patterns of opioids and NSAIDs in emergency department visits for urolithiasis. METHODS: The National Health Ambulatory Medical Care Survey (NHAMCS) was queried for emergency department visits of adults with a diagnosis of urolithiasis. The association between urolithiasis and narcotic and NSAIDs prescription patterns was evaluated and compared at pre-declaration (2014-2016) to post-declaration (2017-2018) periods. RESULTS: Opioids were prescribed in about 211 million (41.1%) out of 513 million emergency department visits, over a 5-year period. Diagnosis of urolithiasis accounted for 1.9% of the visits (6.0 million). The use of opioids was higher in urolithiasis (82.7%) compared to non-urolithiasis diagnosis (40.3%), as well as the use of multiple opioids per visit (p < 0.01 for all). There was an overall decrease in opioid prescriptions in the post-declaration period, - 4.3% for urolithiasis (p = 0.254) and - 5.6% for non-urolithiasis visits (p < 0.05). A decrease in the use of hydromorphone (- 47.5%. p < 0.001), an increase in the use of morphine (+ 59.7% p = 0.006), and an increase of 'other' opioids (+ 98.8%, p < 0.041), were observed. Opioids combined with NSAIDs comprised 72.6% of the opioid prescriptions and 62.3% of all analgesic prescriptions in visits with urolithiasis diagnosis. CONCLUSIONS: The use of opioids when managing urolithiasis decreased 4.3% after the crisis declaration; however, statistically are not different from pre-declaration numbers. Most often, opioids were prescribed with NSAIDs in urolithiasis patients.

An expeditious synthesis of 6,7-dihydrodibenzo[b,j][4,7] phenanthroline derivatives as fluorescent materials.

A rapid and efficient method has been developed for the synthesis of 13,14-dimethyl-6,7-dihydrodibenzo[b,j][4,7]phenanthroline derivatives (3a-d) through the Friedländer condensation of 2-aminoarylketone with 1,4-cyclohexanedione under solvent-free conditions using p-toluenesulphonic acid. The synthetic utility of compounds 3a, 3b, and 3c was demonstrated by synthesizing compounds 6a-kvia Suzuki coupling, 8 by Buchwald-Hartwig amination, and 9a-bvia NBS bromination. Significantly, the emission band corresponding to the π-π* electronic transition of compounds 3a, 6a, 6d, 6f, and 8 showed a redshift with increasing polarity of the solvents. Molar extinction coefficient (ε), Stoke's shift (Δ[italic small upsilon, Greek, macron]), and quantum yield (Φ f) were calculated for all these compounds.

Facile One-Pot Synthesis of Functionalized Quinoline-Fused Fluorescent Dihydro/Spiro-quinazolinone Derivatives.

A facile and efficient method has been developed for the synthesis of quinoline-fused fluorescent dihydro/spiro-quinazolinones. A plausible mechanism involving an acid-mediated enaminone intermediate is provided. The reaction proceeded using p-toluene sulfonic acid as a green promoter. The methodology was successful in synthesizing various quinoline-appended spiro-quinazolinones 4a-o. The synthetic utility of compounds 4a-o was demonstrated by synthesizing compounds 6a-d via Suzuki coupling as a key reaction. Significantly, the π-π* electronic transition of compounds 4c and 4k showed a blue shift. The molar extinction coefficient (ε), Stoke's shift (Δu̅), and quantum yield (Φf)c were calculated for these derivatives (4c and 4k).

Impact of Supine Radiographs to Assess Curve Flexibility in the Treatment of Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The purpose of the study is to evaluate the role of supine radiographs in determining flexibility of thoracic and thoracolumbar curves. METHODS: Ninety operative AIS patients with 2-year follow-up from a single institution were queried and classified into MT structural and TL structural groups. Equations were derived using linear regression to compute cut-off values for MT and TL curves. Thresholds were externally validated in a separate database of 60 AIS patients, and positive and negative predictive values were determined for each curve. RESULTS: MT supine values were highly predictive of MT side-bending values (TL group: 0.63, P < 0.001; MT group: 0.66, P = 0.006). Similarly, TL supine values were highly predictive of TL side-bending values (TL group: 0.56, P = 0.001 MT group: 0.68, P = 0.001). From our derived equations, MT and TL curves were considered structural on supine films if they were ≥ 30° and 35°, respectively. Contingency table analysis of external validity sample showed that supine films were highly predictive of structurality of MT curve (Sensitivity = 0.91, PPV = 0.95, NPV = 0.81) and TL curve (Sensitivity = 0.77, PPV = 0.81, NPV = 0.94). ROC analysis revealed that the area under curve for MT structurality from supine films was 0.931 (SEM: 0.03, CI: 0.86-0.99, P < 0.001) and TL structurality from supine films was 0.922 (SEM: 0.03, CI- 0.84-0.98, P < 0.001). CONCLUSIONS: A single preoperative supine radiograph is highly predictive of side-bending radiographs to assess curve flexibility in AIS. A cut-off of ≥ 30° for MT and ≥ 35° for TL curves in supine radiographs can determine curve structurality.

Carbohydrate-to-Fiber Ratio, a Marker of Dietary Intake, as an Indicator of Depressive Symptoms.

OBJECTIVE: The aim of this study is to evaluate the association between a marker of dietary intake, the carbohydrate-to-fiber (CF) ratio, and moderate-to-severe depressive symptoms. DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey (NHANES) database from 2013-2016. PARTICIPANTS: Individuals 18 years and older were included. Participants with total energy intake outside of three standard deviations of the mean, pregnant or breastfeeding women, and those with missing data were excluded. MEASUREMENTS: The main independent variable, CF ratio, was generated using corresponding variables in NHANES and divided into quartiles. The main outcome was depressive symptoms using the Patient Health Questionnaire-9. Unadjusted and adjusted logistic regression analyses were used to calculate odds ratios and their corresponding 95% confidence interval (CI).  Results: Among all participants (n=9,728), 8.3% reported to have moderate-to-severe depressive symptoms (n=833). The highest proportion of depressive symptoms was reported in respondents in quartile 4 (Q4), with the highest CF ratio (13.0%; p<0.001). After adjustment, the odds of depressive symptoms significantly increased in Q4 of the CF ratio compared with Q1 (adjusted odds ratio 1.4, 95% CI 1.0-1.9). The prevalence of depressive symptoms significantly increased in females, lower federal poverty levels, non-married individuals, smokers, and hypertension patients.  Conclusion: This nationally representative sample suggests that a higher CF dietary intake ratio increases the risk of moderate-to-severe depressive symptoms. These results suggest that the CF ratio may help clinicians and patients evaluate their dietary risk for depressive symptoms. Further prospective studies are needed to validate this ratio as a dietary measurement.

Topical tranexemic acid reduces intra-operative blood loss and transfusion requirements in spinal deformity correction in patients with adolescent idiopathic scoliosis.

PURPOSE: To evaluate the effectiveness of the use of topical tranexamic acid (tTXA) in spinal deformity correction in AIS patients METHODS: Sixty consecutive operative AIS patients were reviewed from a single institution and divided into two groups with similar demographics. Standardized peri-operative blood salvage techniques were utilized in all 60 patients. In the latter 30 patients, tTXA soaked sponges (1 g mixed in 500 ml Normal Saline) was utilised for wound packing during the entire surgical procedure compared to dry sponges as used in the former 30 patients. Both the groups were compared for the magnitude of deformity corrected, EBL per level fused, total EBL, blood transfused, drain output and peri-operative events. RESULTS: Sixty AIS patients (mean age 14.4 yrs, 43 females, mean BMI 21.5, mean levels 10.7) were included. Both groups achieved similar change in Coronal Cobb correction. The EBVL (Estimated blood volume loss) % lost in the topical TXA group was 38% less than the control group (11.2 vs. 18.3%, p = 0.006). Similarly, the EBL/level was significantly lower in the topical TXA group (41 ± 30 ml vs. 57 ± 26 ml, p = 0.03). Three of 30 patients in the control group required at least 1 unit of blood transfusion, whereas only 1 patient in the topical TXA group required transfusion (10 vs. 3.3%, p = 0.001). No differences were noted in post-operative drain output, change in hemoglobin levels, and peri-operative complication rates. CONCLUSION: When used as an adjunct to the conventional blood salvage techniques in spinal deformity correction procedures, the use of tTXA resulted in reduced operative blood loss, and blood transfusion requirements.

Mu Rhythm during Standing and Walking Is Altered in Children with Unilateral Cerebral Palsy Compared to Children with Typical Development.

Background: Rehabilitation in cerebral palsy (CP) seeks to harness neuroplasticity to improve movement, including walking, yet cortical activation underlying gait is not well understood. Methods: We used electroencephalography (EEG) to compare motor related cortical activity, measured by mu rhythm, during quiet standing and treadmill walking in 10 children with unilateral CP and 10 age- and sex-matched children with typical development (TD). Peak mu band frequency, mu rhythm desynchronization (MRD), and gait related intra- and inter-hemispheric coherence were examined. Results: MRD during walking was observed bilaterally over motor cortex in both cohorts but peak mu band frequency showing MRD was significantly lower in CP compared to TD. Coherence during quiet standing between motor and frontal regions was significantly higher in the non-dominant compared to dominant hemisphere in CP with no hemispheric differences in TD. Conclusions: EEG-based measures should be further investigated as clinical biomarkers for atypical motor development and to assess rehabilitation effectiveness.

Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

Publisher Correction: Evidence of radial Weibel instability in relativistic intensity laser-plasma interactions inside a sub-micron thick liquid target.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background pressure effects on MeV protons accelerated via relativistically intense laser-plasma interactions.

We present how chamber background pressure affects energetic proton acceleration from an ultra-intense laser incident on a thin liquid target. A high-repetition-rate (100 Hz), 3.5 mJ laser with peak intensity of [Formula: see text] impinged on a 450 nm sheet of flowing liquid ethylene glycol. For these parameters, we experimentally demonstrate a threshold in laser-to-proton conversion efficiency at background pressures [Formula: see text], wherein the overall energy in ions [Formula: see text] increases by an order of magnitude. Proton acceleration becomes increasingly efficient at lower background pressures and laser-to-proton conversion efficiency approaches a constant as the vacuum pressure decreases. We present two-dimensional particle-in-cell simulations and a charge neutralization model to support our experimental findings. Our experiment demonstrates that high vacuum is not required for energetic ion acceleration, which relaxes target debris requirements and facilitates applications of high-repetition rate laser-based proton accelerators.

Evaluating the My Life self-determination model for older youth in foster care: Establishing efficacy and exploring moderation of response to intervention.

Limited rigorous research has been conducted to evaluate the impact of interventions designed to promote the successful transitions of young people exiting foster care. The current study builds on previous experimental evaluations of the My Life Model (MLM) for self-determination enhancement, which demonstrated effectiveness in improving educational and transition-to-adulthood outcomes for youth in foster care with disabilities, including those with mental health challenges. The model features one-on-one youth-directed coaching and near-peer mentoring to increase self-determination and goal achievement. The current study was the first to test the impact of the model with a diverse population-based cohort of youth aged 16.5-18.5 in foster care (N=293), including those with and without disabilities, on key model outcome indicators of self-determination and self-efficacy. This study also explored potential moderation by disability status, trauma symptoms, placement stability, and placement restrictiveness. Findings show that, compared to the randomized control group, the treatment group had greater post-intervention and one-year follow-up gains on several indicators of self-determination. Moderation analysis demonstrated no difference in intervention effectiveness for youth with or without disabilities, suggesting the universality of this approach. Findings also suggest that foster youth participants with low-to-average risks in terms of placement stability, placement restrictiveness, and traumatic stress levels seem to benefit most from the intervention, although youth who are at higher risk due to low placement stability, high placement restriction, and high traumatic stress still showed some benefit of participating in the intervention on some measures. My Life is one of only a few intervention models with experimental evidence of effectiveness with older youth in foster care. This validation study establishes that the approach has benefits for both youth with and without disabilities, as well as providing the first information available on the influence of critical barriers facing many youth in care.

High-Throughput DNA Assembly Using Yeast Homologous Recombination.

Yeast homologous recombination is a reliable, low-cost, and efficient method for DNA assembly. Using homology regions as short as 24 base pairs, constructs of up to 12 unique parts can be assembled into a diverse range of vectors. The simplicity and robustness of this protocol make it amenable to laboratory automation and high-throughput operations. Here we describe a high-throughput protocol to generate DNA parts through PCR, assemble them into a vector via yeast transformation, and "shuttle" the resulting plasmid constructs into E. coli for storage and propagation. Though this protocol is intended for high-throughput workflows, it can be easily adapted for bench-scale DNA assembly.

Highly Multiplexed, Semiautomated Nextera Next-Generation Sequencing (NGS) Library Preparation.

High-throughput, inexpensive DNA sequencing is an essential component of large-scale DNA assembly operations. Using traditional and acoustic liquid-handling robotics, Illumina's Nextera Tagmentation reactions can be miniaturized and paired with custom PCR index primers to produce highly multiplexed NGS libraries for pooled sequencing. This chapter describes a high-throughput protocol that enables the simultaneous sequencing of thousands of DNA constructs in a single sequencing run at a dramatically reduced cost compared to bench-top methods.

Evidence of radial Weibel instability in relativistic intensity laser-plasma interactions inside a sub-micron thick liquid target.

Super-intense laser plasma interaction has shown great promise as a platform for next generation particle accelerators and sources for electron, x-rays, ions and neutrons. In particular, when a relativistic intense laser focus interacts with a thin solid density target, ionized electrons are accelerated to near the speed of light (c) within an optical cycle and are pushed in the forward and transverse directions away from focus, carrying a significant portion of the laser energy. These relativistic electrons are effectively collisionless, and their interactions with the ions and surrounding cold electrons are predominantly mediated by collective electromagnetic effects of the resulting currents and charge separation. Thus, a deeper understanding of subsequent high energy ions generated from various mechanisms and their optimization requires knowledge of the relativistic electron dynamics and the fields they produce. In addition to producing MV/m quasi-static fields, accelerating the ions and confining the majority of the electrons near the bulk of the laser target, these relativistic electron currents are subject to plasma instabilities like the Weibel instability as they propagate through the thermal population in the bulk target. In this work, we present high temporal (100 fs) and spatial (1 µm) resolution shadowgraphy video capturing relativistic radial ionization front expansion and the appearance of filamentation radiating from the laser spot within a sub-micron thick liquid sheet target. Filamentation within the region persists for several picoseconds and seeds the eventual recombination and heating dynamics on the nanosecond timescale. A large scale three-dimensional particle-in-cell (PIC) simulation of the interaction revealed the presence of strong magnetic fields characteristic of Weibel Instability, and corroborated the relativistic radial expansion of the ionization front, whose speed was determined to be 0.77c. Both the experimental and simulation results strongly point towards the target field ionization and the outward expanding hot electron current as the cause of the radial expansion.

Barriers to Participation in Therapeutic Clinical Trials as Perceived by Community Oncologists.

PURPOSE: Despite considerable research on the barriers to enrollment in cancer therapeutic trials, few studies have elicited barriers from the perspective of community physicians, who provide the majority of cancer care. The purpose of this study was to characterize barriers to and facilitators of cancer therapeutic trials as perceived by oncologists in community practices. METHODS: Twenty semistructured interviews were conducted with oncologists at six community sites affiliated with City of Hope National Medical Center from March to June 2018. Responses were recorded digitally and transcribed. Data were analyzed using qualitative content analysis. RESULTS: Of the 20 participants, 4 (20%) were women, 13 (65%) had > 10 years of practice experience, and 16 (80%) reported that < 5% of their patients were enrolled in a therapeutic trial. Participants identified four system-level barriers: lack of appropriate trials for community-based settings, insufficient infrastructure support, restrictive eligibility criteria, and financial limitations; three physician-level barriers: lack of awareness of available trials, lack of knowledge of trial details, and lack of time; and two patient-level barriers: patient burden and negative beliefs/attitudes toward research. Efforts aimed to increase trial availability, clinical trial support personnel, and physician knowledge were identified as major facilitators. CONCLUSION: Community oncologists face numerous complex, multifaceted barriers to cancer therapeutic trial enrollment. Although expanding clinical research beyond the academic setting allows access to a larger and more diverse patient population, increasing generalizability and relevance of trial findings, there remains a substantial need for new strategies to improve cancer research delivery in the community.

Conjunctival Melanoma: Features and Outcomes Based on the Fitzpatrick Skin Type in 540 Patients at a Single Ocular Oncology Center.

PURPOSE: To determine the association of Fitzpatrick skin type (FST) with conjunctival melanoma. METHODS: Retrospective case series of 540 patients with conjunctival melanoma to assess clinical features and outcomes per FST. RESULTS: The FST was Type I (n = 126, 23%), II (n = 337, 62%), III (n = 56, 10%), IV (n = 8, 2%), V (n = 12, 2%), and VI (n = 1, <1%). A comparison (FST I vs. II vs. III, IV, V, and VI) revealed Types I and II associated with older mean patient age (63.9 vs. 60.7 vs. 51.1 years, p < 0.001), greater percentage of female patients (68% vs. 44% vs. 42%, p < 0.001), lower frequency of complexion associated melanosis (1% vs. 2% vs. 13%, p < 0.001), smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p = 0.01), and less eyelid involvement (13% vs. 13% vs. 28%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by Types for visual acuity loss ≥3 lines, local tumor recurrence, exenteration, metastasis, or death. CONCLUSION AND RELEVANCE: Most patients with conjunctival melanoma show FST I or II, and this demonstrated no association with 5-year rate of vision loss, tumor recurrence, exenteration, metastasis, or death.

Are migratory waterfowl vectors of seagrass pathogens?

Migratory waterfowl vector plant seeds and other tissues, but little attention has focused on the potential of avian vectoring of plant pathogens. Extensive meadows of eelgrass (Zostera marina) in southwest Alaska support hundreds of thousands of waterfowl during fall migration and may be susceptible to plant pathogens. We recovered DNA of organisms pathogenic to eelgrass from environmental samples and in the cloacal contents of eight of nine waterfowl species that annually migrate along the Pacific coast of North America and Asia. Coupled with a signal of asymmetrical gene flow of eelgrass running counter to that expected from oceanic and coastal currents between Large Marine Ecosystems, this evidence suggests waterfowl are vectors of eelgrass pathogens.

Barriers to clinical trial enrollment of older adults with cancer: A qualitative study of the perceptions of community and academic oncologists.

OBJECTIVES: Oncologists can be one of the major barriers to older adult's participation in research. Multiple studies have described academic clinicians' concerns for not enrolling older adults onto trials. Although the majority of older adults receive their cancer care in the community, few studies have examined the unique challenges that community oncologists face and how they differ from oncologist-related barriers in academia. METHODS: Semi-structured interviews were conducted by telephone or face-to-face with 44 medical oncologists (24 academic-based and 20 community-based) at City of Hope from March to June 2018. Interviews explored oncologists' perceptions of barriers to clinical trial enrollment of older adults with cancer. Data were analyzed using qualitative content analysis. RESULTS: Of the 44 participants, 36% were women and 68% were in practice for >10 years. Among the entire sample, stringent eligibility criteria (n = 20) and oncologist concerns for treatment toxicities (n = 15) were the most commonly cited barriers. Compared to academic oncologists, community oncologists more often cited patient attitudes, beliefs, and understanding (n = 9 vs. n = 2) and caregiver burden (n = 6 vs. n = 0). In contrast, compared to community oncologists, academic oncologists more often cited oncologist bias (n = 10 vs. n = 3) and insufficient time/support (n = 4 vs. n = 1). CONCLUSIONS: Differences in perceptions among academic and community oncologists about trials suggest that barriers are multifaceted, complex, and vary by practice setting. Interventions to increase trial accrual among older adults with cancer may benefit from being tailored to address the unique barriers of different practice settings.