A high-throughput behavioral screening platform for measuring chemotaxis by C. elegans.

Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made small molecules (SMs) that are harmful and must be avoided from those that are beneficial and should be sought. This ability to classify chemical cues as a function of their value is fundamental to olfaction and represents a capacity shared by many animals, including humans. Here, we present an efficient platform based on multiwell plates, liquid handling instrumentation, inexpensive optical scanners, and bespoke software that can efficiently determine the valence (attraction or repulsion) of single SMs in the model nematode, Caenorhabditis elegans. Using this integrated hardware-wetware-software platform, we screened 90 plant SMs and identified 37 that attracted or repelled wild-type animals but had no effect on mutants defective in chemosensory transduction. Genetic dissection indicates that for at least 10 of these SMs, response valence emerges from the integration of opposing signals, arguing that olfactory valence is often determined by integrating chemosensory signals over multiple lines of information. This study establishes that C. elegans is an effective discovery engine for determining chemotaxis valence and for identifying natural products detected by the chemosensory nervous system.

Cataract surgery utilization in Parkinson's disease: the english longitudinal survey on ageing.

PURPOSE: Older adults with Alzheimer's disease are less likely to be offered cataract surgery than the general population, but these disparities have not been examined in the context of other neurodegenerative disorders such as Parkinson's disease (PD). METHODS: Using data from the English Longitudinal Study on Ageing (ELSA), an ongoing, longitudinal population-based survey of older adults in England, we examined the relationship between PD and cataract surgery among adults 50 and older. We used logistic regression to measure the association between PD and history of cataract surgery at baseline. In longitudinal analyses of subjects with no history of cataract surgery at time of enrollment, we used semiparametric, discrete-time proportional hazards models to model the incidence of cataract surgery as a function of PD and other time-dependent covariates. Models were adjusted for demographic variables, self-reported comorbidities, and measures of daily activity limitation. RESULTS: We included data from 19,241 eligible ELSA respondents, of whom 231 (1.2%) reported a diagnosis of PD. PD was positively associated with a history of self-reported cataract surgery at baseline (OR 3.66, 95% CI: 2.55-5.26), but this did not remain significant after adjusting for confounders (OR 1.22, 95% CI: 0.75-1.98). Among subjects with no history of cataract surgery at baseline, PD was also not associated with incident cataract surgery (adjusted HR 1.32, 95% CI: 0.86-2.02). CONCLUSION: Unlike Alzheimer's disease, people with PD were no less likely to receive cataract surgery compared to those without PD.

Plant Metabolic Network 15: A resource of genome-wide metabolism databases for 126 plants and algae.

To understand and engineer plant metabolism, we need a comprehensive and accurate annotation of all metabolic information across plant species. As a step towards this goal, we generated genome-scale metabolic pathway databases of 126 algal and plant genomes, ranging from model organisms to crops to medicinal plants (https://plantcyc.org). Of these, 104 have not been reported before. We systematically evaluated the quality of the databases, which revealed that our semi-automated validation pipeline dramatically improves the quality. We then compared the metabolic content across the 126 organisms using multiple correspondence analysis and found that Brassicaceae, Poaceae, and Chlorophyta appeared as metabolically distinct groups. To demonstrate the utility of this resource, we used recently published sorghum transcriptomics data to discover previously unreported trends of metabolism underlying drought tolerance. We also used single-cell transcriptomics data from the Arabidopsis root to infer cell type-specific metabolic pathways. This work shows the quality and quantity of our resource and demonstrates its wide-ranging utility in integrating metabolism with other areas of plant biology.

Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma.

Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.

Patterns of storage, use, and disposal of opioids among cancer outpatients.

PURPOSE: Improper storage, use, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our objective was to determine the patterns of storage, utilization, and disposal of opioids among cancer outpatients. PATIENTS AND METHODS: We surveyed 300 adult cancer outpatients receiving opioids in our supportive care center and collected information regarding opioid use, storage, and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye-opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or losing opioids; unsafe storage was defined as storing opioids in plain sight. RESULTS: The median age was 57 years. CAGE was positive in 58 of 300 patients (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28 (9%) locked their opioids. CAGE-positive patients (p = .007) and those with a history of illicit drug use (p = .0002) or smoking (p = .03) were more likely to lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or losing (17%) their opioids. Patients who were never married or single (odds ratio: 2.92; 95% confidence interval: 1.48-5.77; p = .006), were CAGE positive (40% vs. 21%; p = .003), or had a history of illicit drug use (42% vs. 23%; p = .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused opioids at home. CONCLUSION: A large proportion of cancer patients improperly and unsafely use, store, and dispose of opioids, highlighting the need for establishment of easily accessed patient education and drug take-back programs.

An efficient behavioral screening platform classifies natural products and other chemical cues according to their chemosensory valence in C. elegans.

Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made small molecules (SMs) that are harmful and must be avoided from those that are beneficial and should be sought. This ability to classify chemical cues as a function of their value is fundamental to olfaction, and represents a capacity shared by many animals, including humans. Here, we present an efficient platform based on multi-well plates, liquid handling instrumentation, inexpensive optical scanners, and bespoke software that can efficiently determine the valence (attraction or repulsion) of single SMs in the model nematode, Caenorhabditis elegans. Using this integrated hardware-wetware-software platform, we screened 90 plant SMs and identified 37 that attracted or repelled wild-type animals, but had no effect on mutants defective in chemosensory transduction. Genetic dissection indicates that for at least 10 of these SMs, response valence emerges from the integration of opposing signals, arguing that olfactory valence is often determined by integrating chemosensory signals over multiple lines of information. This study establishes that C. elegans is an effective discovery engine for determining chemotaxis valence and for identifying natural products detected by the chemosensory nervous system.

Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting.

The transcription factor NRF2 plays an important role in many biological processes and is a promising therapeutic target for many disease states. NRF2 is highly expressed in the skin and is known to play a critical role in diabetic wound healing, a serious disease process for which treatment options are limited. However, many existing NRF2 activators display off-target effects due to their electrophilic mechanism, underscoring the need for alternative approaches. In this work, we investigated two recently described non-electrophilic NRF2 activators, ADJ-310 and PRL-295, and demonstrated their efficacy in vitro and in vivo in human keratinocytes and Leprdb/db diabetic mice. We also compared the downstream targets of PRL-295 to those of the widely used electrophilic NRF2 activator CDDO-Me by RNA sequencing. Both ADJ-310 and PRL-295 maintained human keratinocyte cell viability at increasing concentrations and maintained or improved cell proliferation over time. Both compounds also increased cell migration, improving in vitro wound closure. ADJ-310 and PRL-295 enhanced the oxidative stress response in vitro, and RNA-sequencing data showed that PRL-295 activated NRF2 with a narrower transcriptomic effect than CDDO-Me. In vivo, both ADJ-310 and PRL-295 improved wound healing in Leprdb/db diabetic mice and upregulated known downstream NRF2 target genes in treated tissue. These results highlight the non-electrophilic compounds ADJ-310 and PRL-295 as effective, innovative tools for investigating the function of NRF2. These compounds directly address the need for alternative NRF2 activators and offer a new approach to studying the role of NRF2 in human disease and its potential as a therapeutic across multiple disease states.

Does taking charge help or harm employees' promotability and visibility? An investigation from supervisors' status perspective.

Taking charge is an important form of proactive behavior that sustains organizational survival and success. Despite considerable research on how to encourage employees to take charge, little is known about whether and when supervisors will evaluate those who take charge as more or less promotable and visible. Building on and extending the theoretical notion of dyadic complementary fit, we propose that, compared with lower status-goal-striving supervisors, higher status-goal-striving supervisors regard those who take charge as helping enhance their status in the organization more (i.e., a dyadic fit condition) and subsequently evaluate these employees as more promotable and visible. In a vignette-based experiment using 175 U.S.-based supervisors (Study 1), a two-wave field survey among 143 supervisor-subordinate dyads in a hotel (Study 2), and a three-wave survey among 294 supervisor-subordinate dyads in various organizations and industries in China (Study 3), we find support for our predictions. The findings have important implications for proactivity theory and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Experimenting with a Prototype Interactive Narrative Game to Improve Knowledge and Beliefs for the HPV Vaccine.

Narratives can have a powerful impact on our health-related beliefs, attitudes, and behaviors. The human papillomavirus (HPV) vaccine can protect against human papillomavirus that leads to different types of cancers. However, HPV vaccination rates are low. This study explored the effectiveness of a narrative-based interactive game about the HPV vaccines as a method to communicate knowledge and perhaps create behavioral outcomes. We developed a serious storytelling game called Vaccination Vacation inspired by personal narratives of individuals who were impacted by the HPV. We tested the game using a randomized control study of 99 adult participants and compared the HPV knowledge and vaccine beliefs of the Gamer Group (who played the game, n = 44) and the Reader group (who read a vaccine information sheet, n = 55). We also evaluated the usability of the game. In addition to high usability, the interactive game slightly impacted the beliefs about the HPV vaccine over standard delivery of vaccine information, especially among those who never received the HPV vaccine. We also observed some gender-based differences in perception towards usability and the likelihood of frequently playing the game. A narrative-based game could bring positive changes to players' HPV-related health beliefs. The combination of more comprehensive HPV vaccine information with the narratives may produce a larger impact. Narrative-based games can be effectively used in other vaccine education interventions and warrant future research.

Complete Genome Sequence of Cycloclasticus sp. Strain PY97N, Which Includes Two Heavy Metal Resistance Genomic Islands.

We present the complete genome sequence of fluoranthene-consuming Cycloclasticus sp. strain PY97N. This strain has one circular chromosome with a G+C content of 42.06%. Moreover, two genomic islands were identified as putative conjugative elements. These genomic details are expected to inform our understanding of the remarkable catabolic capacities of organisms of the Cycloclasticus lineage.

Genome Sequence of a Marine Alkane Degrader, Alcanivorax sp. Strain 97CO-6.

Alcanivorax sp. strain 97CO-6 was isolated from a crude oil-consuming bacterial consortium, enriched from Yellow Sea sediments from China. Here, we present the draft genome of strain 97CO-6, which contains 3,253,423 bp, with a G+C content of 54.53%, as well as 2,931 protein-coding genes and 42 tRNAs.

Identifying factors associated with need for flexible ureteroscope repair: a Western Endourology STone (WEST) research consortium prospective cohort study.

Maintenance of flexible ureteroscopes can involve high costs and administrative burden. Instrument fragility necessitates eventual repair, rendering scopes inaccessible during refurbishment. We conducted a multi-institutional prospective cohort study to identify perioperative factors influencing flexible ureteroscope durability. Patients undergoing flexible ureteroscopy (URS) at six United States endourology centers were enrolled between August 2014 and June 2015. Surgeon self-reported concern and satisfaction with scope performance as well as upward and downward angles of deflection for each scope tip were measured before and after each procedure. The need for scope repair was determined by the operating surgeon at the time of the procedure and recorded. 424 URS cases using 74 flexible ureteroscopes were identified. Scope repair was required in 28 cases (6.6%) involving 26 scopes (35.1%). Upon univariate analysis, shorter patient height, absence of guidewire use, presence of a ureteral access sheath (UAS), longer procedure time, larger stone size, lithotrite type, surgeon training level, and self-reported concern were associated with scope repair. Upon multivariate analysis, UAS use (OR = 2.53, p = 0.005) and degree loss of scope upward flexion during a case (OR = 1.02, p = 0.03) increased the odds of a scope needing repair while the use of safety guidewire decreased the odds of a scope repair (OR = 0.50, p = 0.045). Lithotrite use and surgeon concern were associated with degree loss of scope upward flexion. The use of a UAS, absence of a safety guidewire, and the loss of upward ureteroscope flexion should be considered when evaluating means of optimizing reusable ureteroscope durability.

Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial.

CONTEXT: Dyspnea is one of the most distressing symptoms in patients with cancer, and often worsens with breakthrough episodes on exertion. We hypothesized that fentanyl given prophylactically may alleviate breakthrough dyspnea. OBJECTIVES: To determine the feasibility of conducting a randomized trial of subcutaneous fentanyl in patients with cancer, and examine the effects of fentanyl on dyspnea, walk distance, vital signs, and adverse events. METHODS: In this double-blind, randomized, controlled trial, we asked ambulatory patients with breakthrough dyspnea to perform a baseline six minute walk test (6MWT), and then assigned them to either subcutaneous fentanyl or placebo 15 minutes before a second 6MWT. We documented the change in dyspnea Numeric Rating Scale (NRS) score, walk distance, vital signs, and adverse events between the first and second 6MWT. RESULTS: A total of 20 patients were enrolled (1:1 ratio) without attrition. Comparison between baseline and second walk showed that fentanyl was associated with significant improvements in dyspnea NRS score at the end of the 6MWT (mean [95% CI] -1.8 [-3.2, -0.4]), dyspnea NRS score at rest of 15 minutes after drug administration (-0.9 [-1.8, -0.04]), Borg Scale fatigue score at the end of the 6MWT (-1.3 [-2.4, -0.2]), 6MWT distance (+37.2m [5.8, 68.6]), and respiratory rate (-2.4 [-4.5, -0.3]). Nonstatistically significant improvements also were observed in the placebo arm, with no difference between the two study arms. No significant adverse effects were observed. CONCLUSION: Prophylactic fentanyl was safe and improved dyspnea, fatigue, walk distance, and respiratory rate. We also observed a large placebo effect. Our results justify larger randomized controlled trials with higher fentanyl doses (clinicaltrials.gov registration: NCT01515566).