HTS384 NCI60: The Next Phase of the NCI60 Screen.

The NCI60 human tumor cell line screen has been in operation as a service to the cancer research community for over 30 years. The screen operated with 96-well plates, a 2-day exposure period to test agents, and, following cell fixation, a visible absorbance endpoint by the protein-staining dye sulforhodamine B. Here, we describe the next phase of this important cancer research tool, the HTS384 NCI60 screen. While the cell lines remain the same, the updated screen is performed with 384-well plates, a 3-day exposure period to test agents, and a luminescent endpoint to measure cell viability based upon cellular ATP content. In this study, a library of 1003 FDA-approved and investigational small molecule anticancer agents was screened by the two NCI60 assays. The datasets were compared with a focus on targeted agents with at least six representatives in the library. For many agents, including inhibitors of EGFR, BRAF, MEK, ERK, and PI3K, the patterns of GI50 values were very similar between the screens with strong correlations between those patterns within the dataset from each screen. However, for some groups of targeted agents, including mTOR, BET bromodomain, and NAMPRTase inhibitors, there were limited or no correlations between the two datasets, although the patterns of GI50 values and correlations between those patterns within each dataset were apparent. Beginning in January 2024, the HTS384 NCI60 screen became the free screening service of the National Cancer Institute to facilitate drug discovery by the cancer research community.

Management of Fibromyalgia: An Update.

Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management-namely duloxetine, milnacipran, pregabalin, and amitriptyline-which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.

Using Physiological Markers to Assess Comfort during Neuromuscular Electrical Stimulation Induced Muscle Contraction in a Virtually Guided Environment: Pilot Study for a Path toward Combating ICU-Acquired Weakness.

We assessed the feasibility of implementing a virtually guided Neuromuscular Electrical Stimulation (NMES) protocol over the tibialis anterior (TA) muscle while collecting heart rate (HR), Numeric Pain Rating Scale (NPRS), and quality of contraction (QoC) data. We investigated if HR, NPRS, and QoC differ ON and OFF the TA motor point and explored potential relationships between heart rate variability (HRV) and the NPRS. Twelve healthy adults participated in this cross-sectional study. Three NMES trials were delivered ON and OFF the TA motor point. HR, QoC, and NPRS data were collected. There was no significant difference in HRV ON and OFF the motor point (p > 0.05). The NPRS was significantly greater OFF the motor point (p < 0.05). The QoC was significantly different between motor point configurations (p < 0.05). There was no correlation between the NPRS and HRV (p > 0.05, r = -0.129). We recommend non-electrical methods of measuring muscle activity for future studies. The NPRS and QoC can be administered virtually. Time-domain HRV measures could increase the validity of the protocol. The variables should be explored further virtually to enhance the protocol before eventual ICU studies.

Confirmation and inheritance of glufosinate resistance in an Amaranthus palmeri population from North Carolina.

A putative glufosinate-resistant Amaranthus palmeri population was reported in 2015 in Anson County, North Carolina. The results from dose-response assays conducted in the field suggested plants were surviving lethal rates of glufosinate. Dose-response assays conducted in the glasshouse determined the Anson County accession exhibited reduced susceptibility to glufosinate compared to three glufosinate-susceptible populations. The LD50 values (210-316 g ai ha-1) for the Anson County population were always higher than the LD50 values (118-158 g ai ha-1) for the tested susceptible populations from the dose-response assays. Anson County plants that survived lethal glufosinate rates were reciprocally crossed with susceptible plants to create F1 genotypes and treated with a lethal rate of glufosinate (267 g ai ha-1; ascertained from glasshouse dose-response assay) to determine the distribution of injury and survival for each cross compared to a cross of susceptible parents. The distribution of injury was non-normal for the crosses containing an Anson County plant compared to the cross with a susceptible parent. Survival was 68%-84% for crosses containing an Anson County plant, whereas the survival was significantly reduced to 35% for the susceptible plant cross. Chi-square goodness of fit tests were used to test inheritance models to describe the responses of the genotypes. The resistant × susceptible crosses were best described with a heterozygous two loci with incomplete dominance model compared to the resistant × resistant cross that was best described with a heterozygous single locus with incomplete dominance model. The Anson County population has evolved resistance to glufosinate that is heritable and likely conferred by an oligogenic mechanism with incomplete dominance.

Comparative Effects of Advanced Footwear Technology in Track Spikes and Road-Racing Shoes on Running Economy.

PURPOSE: Determine the effects of advanced footwear technology (AFT) in track spikes and road-racing shoes on running economy (RE). METHODS: Four racing shoes (3 AFT and 1 control) and 3 track spikes (2 AFT and 1 control) were tested in 9 male distance runners on 2 visits. Shoes were tested in a random sequence over 5-minute trials on visit 1 (7 trials at 16 km·h-1; 5-min rest between trials) and in the reverse/mirrored order on visit 2. Metabolic data were collected and averaged across visits. RESULTS: There were significant differences across footwear conditions for oxygen consumption (F = 13.046; P < .001) and energy expenditure (F = 14.710; P < .001). Oxygen consumption (in milliliters per kilogram per minute) in both the first AFT spike (49.1 [1.7]; P < .001; dz = 2.1) and the other AFT spike (49.3 [1.7]; P < .001; dz = 1.7) was significantly lower than the control spike (50.2 [1.6]), which represented a 2.1% (1.0%) and 1.8% (1.0%) improvement in RE, respectively, for the AFT spikes. When comparing the subjects' most economic shoe by oxygen consumption (49.0 [1.5]) against their most economic spike (49.0 [1.8]), there were no statistical differences (P = .82). Similar statistical conclusions were made when comparing energy expenditure (in watts per kilogram). CONCLUSIONS: AFT track spikes improved RE ∼2% relative to a traditional spike. Despite their heavier mass, AFT shoes resulted in similar RE as AFT spikes. This could make the AFT shoe an attractive option for longer track races, particularly in National Collegiate Athletic Association and high school athletics, where there are no stack-height rules.

The contributions of social network support and reciprocity to posttraumatic stress symptoms across time among parents and caregivers impacted by the ABC Day Care Center fire in Hermosillo, Mexico.

In 2009, a fire occurred in the ABC Day Care Center in Hermosillo, Mexico, that killed and injured many children who were in attendance that day. This study investigated the association between the posttraumatic stress symptoms (PTSS) of socially connected parents and caregivers whose children were affected by the fire. Parents and caregivers of the children who were in attendance the day of the fire were interviewed 8-11 months and 20-23 months postfire. Linear network autocorrelation modeling was used to test for autocorrelations of the outcome variable count of PTSS within different configurations of the network of caregivers. No significant network effects appeared in models from the first interview period, but effects did appear in the second period, specifically in the three models in which network ties consisted of "receive informational support" (.220), "give and receive emotional support" (.167), and "give and receive both informational and emotional support" (.213). The findings suggest that in these three network configurations, as relationships grew in strength from the first interview to the second, the level of one's own PTSS was more comparable to the level of PTSS of one's social connections. Two theoretical mechanisms that may explain this result are homophily and social influence.

Trends in the relationship between suicide behaviors and obesity among adolescents in the United States from 1999 to 2019.

Previous studies indicate that obesity is a risk factor of suicide behaviors among adolescents. Whether this association has remained consistent during the ongoing obesity epidemic remains unknown. The time trends of the obesity-suicide association were examined using the 1999-2019 biannual Youth Risk Behavior Survey data (n = 161,606). Prevalence odds ratio of suicide behaviors among adolescents with obesity (vs. adolescents with no obesity) for each survey year and time trends using National Cancer Institute Joinpoint regression analysis was calculated. For each year post-baseline, there was a significant increase of prevalence odds ratio of 1.4 (1.2-1.6)-1.6 (1.3-2.0) for suicide ideation, 1.3 (1.1-1.7) -1.7 (1.4-2.0) for plan, and 1.3 (1.0-1.7) -1.9 (1.5-2.4) for an attempt, except for the 2013 survey for attempt (1.19 [0.9-1.6]). Significant positive trends were found from1999 to 2019 for ideation and plan, with biannual %-changes of + 0.92 and + 1.22%, respectively. Adolescents with obesity have consistently higher odds of engaging in suicide behaviors than their peers without obesity since the beginning of the United States obesity epidemic, and this association grew stronger as the obesity epidemic continued.

First-passage-time statistics of growing microbial populations carry an imprint of initial conditions.

In exponential population growth, variability in the timing of individual division events and environmental factors (including stochastic inoculation) compound to produce variable growth trajectories. In several stochastic models of exponential growth we show power-law relationships that relate variability in the time required to reach a threshold population size to growth rate and inoculum size. Population-growth experiments in E. coli and S. aureus with inoculum sizes ranging between 1 and 100 are consistent with these relationships. We quantify how noise accumulates over time, finding that it encodes-and can be used to deduce-information about the early growth rate of a population.

The Role of Location in the Spread of SARS-CoV-2: Examination of Cases and Exposed Contacts in South Texas, Using Social Network Analysis.

OBJECTIVE: This study sought to better understand the types of locations that serve as hubs for the transmission of COVID-19. METHODS: Contact tracers interviewed individuals who tested positive for SARS-CoV-2 between November 2020 and March 2021, as well as the people with whom those individuals had contact. We conducted a 2-mode social network analysis of people by the types of places they visited, focusing on the forms of centrality exhibited by place types. RESULTS: The most exposed locations were grocery stores, commercial stores, restaurants, commercial services, and schools. These types of locations also have the highest "betweenness," meaning that they tend to serve as hubs between other kinds of locations since people would usually visit more than 1 location in a day or when infected. The highest pairs of locations were grocery store/retail store, restaurant/retail store, and restaurant/grocery store. Schools are not at the top but are 3 times in the top 7 pairs of locations and connected to the 3 types of locations in those top pairs. CONCLUSIONS: As the pandemic progressed, location hotspots shifted between businesses, schools, and homes. In this social network analysis, certain types of locations appeared to be potential hubs of transmission.

Durability of Near-Complete Skin Clearance in Patients with Psoriasis Using Systemic Biologic Therapies: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Near-complete skin clearance has become a rapidly achievable treatment goal for patients with psoriasis receiving systemic biologic therapies. However, real-world evidence for durability of near-complete skin clearance and risk factors associated with loss of near-complete skin clearance is limited. METHODS: This study described durability of near-complete skin clearance (≥ 90% improvement in Psoriasis Area and Severity Index from initiation; PASI90) and identified clinical factors or patient characteristics associated with loss of PASI90 among patients with psoriasis from the CorEvitas Psoriasis Registry (April 2015-August 2021). Included patients had PASI > 5 at biologic initiation and achieved PASI90 at approximately 6 months from initiation (index). A Kaplan-Meier estimate described time to loss of treatment response over 24 months follow-up from index. Proportional hazards regression was used to identify independent predictors of loss of treatment response. RESULTS: This study included 687 patient initiations (instances of patients initiating a biologic). Following achievement of PASI90, treatment response was maintained in more than half of patient initiations (54%). Treatment response was maintained at 6, 12, and 18 months from index in an estimated 73% (95% [confidence interval] CI 70-77%), 60% (95% CI 56-63%), and 50% (95% CI 47-54%) of patient initiations, respectively. Adjusted hazards regression suggested non-White race, full-time employment, greater body weight, concomitant psoriatic arthritis, prior use of biologics, and clinically meaningful skin symptoms were associated with loss of treatment response. CONCLUSIONS: Among real-world patients with psoriasis who achieved PASI90 with biologic therapy, about one-quarter lost response at 6 months, and half lost response at 18 months. Prior use of a biologic therapy and clinically meaningful skin symptoms at index, including itch and skin pain, were associated with loss of treatment response. Therefore, dermatologists may consider focusing on patient-reported symptoms as part of any intervention designed to reduce the likelihood of loss of response to biologic therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to almost clear skin for many people. However, there is limited information available about how long almost clear skin can be maintained with biologic medications, and what predicts who is likely to lose it. To explore these questions, we examined a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and the medications they take. Out of every 100 patients, 54 maintained almost clear skin and stayed on their original medication for 2 years after first having almost clear skin. Out of every 100 patients, 73, 60, and 50 maintained almost clear skin and remained on their original medication at 6, 12, and 18 months after they had achieved this response. The results indicated that patients who were not White, worked full time, previously used a biologic medication, or had itchy and/or painful skin after they had achieved almost-clear skin were more likely to change their medication and/or no longer have almost-clear skin. These results suggest that dermatologists may consider focusing on patient-reported characteristics when deciding how to treat their patients, to reduce the likelihood that they lose their response to the medication they are prescribed.

Disease burden among patients with atopic dermatitis treated with systemic therapy for 4-12 months: results from the CorEvitas Atopic Dermatitis Registry.

BACKGROUND: Real-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited. METHODS: Adult patients with AD in the CorEvitas AD registry (2020-2021) who received systemic therapies for 4-12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%-9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups. RESULTS: The study included 308 patients (BSA 0%-9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD®) was reported by 11% (BSA 0%-9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23). CONCLUSIONS: Patients with AD experience a high disease burden despite systemic treatment for 4-12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

This real-world study assessed clinical characteristics and overall disease burden in adult patients with atopic dermatitis (AD) who were receiving systemic therapy for 4­12 months.Patients reported greater involvement of back and anterior trunk, and lesions at difficult locations. Irrespective of body surface area involvement, patients continued to experience inadequate control of AD, varied disease severity, and impact on quality of life.The study provides potential evidence of suboptimal treatment and the need for effective treatment options for the management of AD. Besides clinical outcomes, treating dermatologists and dermatology practitioners should include patient-reported outcomes in routine clinical care to determine the best treatment options for their patients.

A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota.

The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome.

The effects of feeding dried browse leaves on rumen ammonia levels, methanogens and protozoa amplification of sheep in the Coastal Savannah of Ghana.

Tanniferous browse leaves are reported to inhibit methanogens and protozoa activity in the rumen, thus contributing to a reduction of methane emission. This study evaluated the influence of feeding dried browse leaves to sheep on rumen ammonia concentration, the base pair at which protozoa and methanogens were amplified and double stranded DNA concentration (dsDNA) from rumen fluid and faeces. The eight treatments were urea treated rice straw, Albizzia lebbek (AL), Moringa oleifera (MO), Millettia thonningii (MT), AL + MO, AL + MT, AL + MO + MT and MO + MT. After feeding 32 ram lambs for 3 months, one ram lamb on each of the eight experimental diets was randomly selected and slaughtered to obtain rumen fluid. Genomic DNAs were extracted from methanogen and protozoa strains obtained from rumen liquor and from faecal matter of sheep. Rumen ammonia was determined using spectrophotometer. Methanogens and protozoa from rumen fluid and faeces were amplified at 1100 base pair, 200-1100 base pair, 320-1100 base pair and 200-750 base pair respectively. Rumen ammonia concentration, dsDNA from rumen fluid and faeces ranged from 14.51 to 23.01 mg/dl, 65 to 900 µg/ml and 100 to 950 µg/g respectively. The rumen ammonia concentration met the requirements for efficient growth of microbes. The presence of methanogens and protozoa in the rumen fluid and in the faeces indicated that dried browse diets were able to inhibit the growth of both protozoa and methanogens in the rumen by eliminating them, and thus, were excreted in the faeces. Hence, feeding of dried browse leaves can contribute to lower methane emission.

Association of Obesity, Suicide Behaviors, and Psychosocial Wellness Among Adolescents in the United States.

BACKGROUND: Adolescents with obesity are more likely to exhibit suicide behaviors, but this association may be confounded by psychosocial stigma related to obesity. We examined whether the obesity is independently associated with suicide behaviors among United States adolescents, after adjusting for the psychosocial factors. METHODS: We analyzed data from 2019 Youth Risk Behavior Survey data (N = 13,871 United States adolescents) on recent (past year) suicide behavior (attempt, ideation, and plan); demographics (age, sex, and race/ethnicity); and psychosocial factors (feeling sad/hopeless, alcohol and illegal drug use, being bullied, and sexually abused). Participants were classified as having obesity (Y/N) per standardized percentiles. Logistic regression was employed to examine the association between obesity and suicide attempt, ideation, and plan, while adjusting for psychosocial covariates. RESULTS: The prevalence of suicide attempt, ideation, and plan was 8.90%, 18.75%, and 15.71%, respectively. Obesity prevalence was 15.5%. The odds of suicide attempt, ideation, and plan were 1.65 (1.30-2.11), 1.31 (0.89-1.61), and 1.27 (1.02-1.57), respectively, among those with obesity versus without obesity. DISCUSSION: Obesity is significantly associated with a suicide attempt, ideation, and plan among United States adolescents, even after adjusting for confounding psychosocial factors. Further research on the temporality and causality of this association is needed.

A report on learning gains and student confidence after incorporating an enzyme purification and characterization course-based undergraduate experience.

Course-based undergraduate research experiences (CUREs) can provide undergraduate students access to research opportunities when student and faculty resources are limited. In addition to expanding research opportunities, CUREs may also be explored as a pedagogical tool for improving student learning of course content and laboratory skills, as well as improving meta-cognitive features such as confidence. We examined how a 6-week CURE in an upper-level undergraduate biochemistry lab affected student gains in content knowledge and confidence in scientific abilities, compared to a non-CURE section of the same course. We find that gains in content knowledge were similar between CURE and non-CURE sections, indicating the CURE does not negatively impact student learning. The CURE was associated with a statistically significant gain in student confidence, compared to non-CURE group. These results show that even a relatively short CURE can be effective in improving student confidence at scientific research skills, in addition to expanding access to research.

Small-world complex network generation on a digital quantum processor.

Quantum cellular automata (QCA) evolve qubits in a quantum circuit depending only on the states of their neighborhoods and model how rich physical complexity can emerge from a simple set of underlying dynamical rules. The inability of classical computers to simulate large quantum systems hinders the elucidation of quantum cellular automata, but quantum computers offer an ideal simulation platform. Here, we experimentally realize QCA on a digital quantum processor, simulating a one-dimensional Goldilocks rule on chains of up to 23 superconducting qubits. We calculate calibrated and error-mitigated population dynamics and complex network measures, which indicate the formation of small-world mutual information networks. These networks decohere at fixed circuit depth independent of system size, the largest of which corresponding to 1,056 two-qubit gates. Such computations may enable the employment of QCA in applications like the simulation of strongly-correlated matter or beyond-classical computational demonstrations.

Trends from 2005 to 2018 in child maltreatment outcomes with caregivers' substance use.

BACKGROUND: Caregivers' substance use is associated with child maltreatment. OBJECTIVE: Examine trends from 2005 to 2018 in percentages of three outcomes with caregivers' drug or alcohol use: child protective services (CPS) referrals, substantiated maltreatment reports, and foster care placements. PARTICIPANTS AND SETTING: 22 U.S. states that contributed child-level maltreatment outcomes and caregivers' substance use data to the National Child Abuse and Neglect Data System from 2005 to 2018. METHODS: Joinpoint regression was used to examine the average annual percent change (AAPC) in outcomes with caregivers' drug or alcohol use and to identify temporal changes. RESULTS: From 2005 to 2018, CPS referrals with caregivers' drug use increased (AAPC 2.33, p < .001), while referrals with alcohol use remained unchanged (AAPC -0.11, p = .92) (trend difference p = .04). Substantiated reports with caregivers' drug and alcohol use increased (AAPC drug use 3.63, p < .001, AAPC alcohol use 1.28, p = .03), with a greater increase observed with drug use (difference p = .03). Foster care placements with caregivers' drug use increased (AAPC 2.54, p < .001), while placements with alcohol use did not change (AAPC -1.22, p = .29), (difference p = .005). Within the study period, changes in trends with caregivers' drug use included increased substantiated reports from 2010 to 2018 (p < .001) and increased foster care placements from 2009 to 2018 (p < .001). With caregivers' alcohol use, CPS referrals and foster care placements decreased from 2007 to 2018 (all p < .001). CONCLUSIONS: Trends differed for outcomes with caregivers' drug versus alcohol use. Findings can inform policies to improve care for families affected by substance use.

Deflux Calcification Leading to Delayed Obstruction and Loss of Renal Function: A Case Report.

Dextranomer/hyaluronic acid (Deflux) has been widely used in the treatment of vesicoureteral reflux in the pediatric population. It has demonstrated acceptable early efficacy with minimal morbidity. Early complications from Deflux have been reported to occur in approximately 1% of cases. However, late complications from Deflux use, including calcification and delayed ureteral obstruction, are less well understood. We present the case of an asymptomatic 11 year old girl with severe ipsilateral hydroureteronephrosis, identified nearly 8 years after treatment. This case details a rare instance of loss of renal function after Deflux use in a patient with no apparent risk factors.