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Background: National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of melanoma overdiagnosis in the context of rising incidence without a corresponding rise in mortality. Objective: To characterize 10- and 50-year trends in melanoma incidence and mortality. Methods: Multicenter, population-based epidemiologic study utilizing the Rochester Epidemiology Project for Olmsted County, Minnesota residents diagnosed with melanoma from 01/01/1970 to 12/21/2020. Age- and sex-adjusted incidence and disease-specific mortality are calculated. Results: Two thousand three hundred ten primary cutaneous melanomas were identified. Current age- and sex-adjusted incidence rates increased 11.1-fold since 1970s (P

Abstract Background Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. Methods We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton’s tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. Results Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. Conclusions Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

Environmental sustainability is now being continuously researched in almost all areas of humankind. This study investigated the impact of environmental sustainability disclosures (proxy by renewable energy disclosures, Greenhouse Gas Emissions disclosures, and waste management disclosures) on the returns on equity of sampled Quoted Nigerian Financial Institutions. Purposely, Fourteen Quoted Nigerian Financial Institutions on the Nigerian Exchange Group were taken as the sample size for this study. The study spanned a period of 9 years from 2013 to 2021. The analysis was carried out using panel data and employing multiple regression models to assess the relationships between the variables using secondary data collated from the annual reports of Quoted Nigerian Financial Institutions. The findings of the study reveal that the impact of renewable energy disclosures (with coefficient estimate = -0.19295, t-value = -1.41 and p-value = 0.16), Greenhouse Gas Emissions disclosures (with coefficient estimate = -0.16105 & the t-value = -1.18 p-value = 0.239, and waste management disclosures (with coefficient estimate = 0.124013, the t-value of 1 and p-value = 0.317) on returns on equity is not significant. This study concluded that the relationship between return on equity and environmental sustainability variables disclosures (proxy by Renewable Energy Disclosure and Greenhouse Gas Emissions) is unrelated.

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

Abstract The first reports that auxins promoted root formation in cuttings and that indole-3-butyric acid (IBA) was a particularly effective treatment date from the early 1930s. Since its introduction into horticultural practice, the focus on improvements in the rooting of plants has been largely on the proper use of auxins to enhance adventitious rooting (AR) as well as to increase the range of plants where it can be effective. In this review, we focus on new ideas that might build on what is known about auxin induction of AR. We explore what the evolution in chemical biology has opened through novel high-throughput screening tools to explore auxin regulation of plant development and what it might add to our understanding and potential to produce new tools for the manipulation of AR. The potential for using stronger auxin analogues, alternative indolealkanoic acids, compounds that alter β-oxidation of IBA and other indolealkanoic acids, auxin conjugates, inhibitors of auxin conjugation, inhibitors of endogenous auxin biosynthesis, as well as other plant hormones and compounds that inhibit the production or mimic the effects of signals that might be involved in AR are all discussed. The expectation is that a summary of these advances in our understanding of the chemical biology important to AR might increase the use and exploration of new ideas for the improvement in the practical approaches to advance horticultural rooting methods.

Abstract We explore the effects of lower thermospheric water vapor deposited by launch vehicle plumes on polar mesospheric cloud (PMC) frequencies at 80°N. We use July‐averaged PMC frequencies from 2007 to 2022 from the Cloud Imaging and Particle Size (CIPS) instrument on NASA's Aeronomy of Ice in the Mesosphere (AIM) satellite. Launch sites worldwide are typically located near northern mid‐latitudes. Using the orbital launch record for the same time period, we find that the number of launches correlates with PMC frequencies with a coefficient of r = 0.60, which increases to r = 0.75 when only selecting launches from 2.5 to 21.5 local time (LT), indicating a weak LT dependence on global‐scale transport to 80°N. To support our findings, we use meridional winds from the Michelson Interferometer for Global High‐resolution Imaging experiment on NASA's Ionospheric Connection Explorer satellite and winds from the Horizontal Wind Model climatology to interpret the northward motion of air parcels at 105 km. We find the launch LT window that maximizes the correlation coefficient to be consistent with the expected maximum northward motion from the diurnal variation of mid‐latitude meridional winds. Comparisons with Microwave Limb Sounder satellite observations of upper mesospheric temperature and water vapor reveal a strong dependence of cloud frequency on water vapor (r = 0.86) but not on temperature (r = −0.26), indicating that water vapor is the primary source of PMC variability for the bright PMCs at 80°N. We therefore find that launch vehicle plumes originating primarily from northern mid‐latitudes modulate PMC frequency at 80°N in July.

Abstract Establishing marine species distributions is essential for guiding management and can be estimated by identifying potential favorable habitat at a population level and incorporating individual‐level information (e.g., movement constraints) to inform realized space use. In this research, we applied a combined modeling approach to tracking data of adult female and juvenile South American sea lions (Otaria flavescens; n = 9) from July to November 2011 to make habitat predictions for populations in northern Chile. We incorporated topographic and oceanographic predictors with sea lion locations and environmentally based pseudo‐absences in a generalized linear model for estimating population‐level distribution. For the individual approach, we used a generalized linear mixed‐effects model with a negative exponential kernel variable to quantify distance‐dependent movement from the colony. Spatial predictions from both approaches were combined in a bivariate color map to identify areas of agreement. We then used a GIS‐based risk model to characterize bycatch risk in industrial and artisanal purse‐seine fisheries based on fishing set data from scientific observers and artisanal fleet logs (2010–2015), the bivariate sea lion distribution map, and criteria ratings of interaction characteristics. Our results indicate population‐level associations with productive, shallow, low slope waters, near to river‐mouths, and with high eddy activity. Individual distribution was restricted to shallow slopes and cool waters. Variation between approaches may reflect intrinsic factors restricting use of otherwise favorable habitat; however, sample size was limited, and additional data are needed to establish the full range of individual‐level distributions. Our bycatch risk outputs identified highest risk from industrial fisheries operating nearshore (within 5 NM) and risk was lower, overall, for the artisanal fleet. This research demonstrates the potential for integrating potential and realized distribution models within a spatial risk assessment and fills a gap in knowledge on this species' distribution, providing a basis for targeting bycatch mitigation outreach and interventions.

The University of Southern Mississippi has developed the coastal CUBEnet environment. Coastal CUBEnet is a high-resolution, coastal ocean sensor, modeling, and data sharing web-based network that provides the environmental intelligence needed to support the complex modeling of the interlinked processes in the northern Gulf of Mexico. With near-real time data delivery via a common infrastructure, CUBEnet uses state of the art sensors to provide a set of networked measurements systems, visualization tools, and model developments to gain an understanding of the Gulf of Mexico’s marine environments. CUBEnet is also a mechanism for improved human engagement with Gulf of Mexico resources and provides stake holders with the data needed to make informed coastal, environmental, and economic decisions. The Coastal CUBEnet’s data environment utilizes both stationary and uncrewed mobile systems and high-resolution distributed sensors to create a networked platform across the northern coastal Gulf of Mexico. CUBEnet’s modeling environment has developed an implementation of The Coupled Ocean Atmosphere Wave Sediment Transport (COAWST) Model for the Mississippi Bight region that has been applied to investigate shore to shelf advective exchange processes, and their influence on coastal water quality conditions that support the region’s prolific marine ecosystem. CUBEnet’s modeling environment provides prototype modeling applications that are supported by real-time observations of key coastal environmental variables. CUBEnet’s Web accessible visualization tools provide parameter fields and vertical profiles from hydrodynamic models and field observations. Nowcasts and forecast results are available for the Eastern LA coastline, MS coastline, Mobile Bay, and the West coast of Florida.

Background: During Mohs surgery for melanoma, evidence has demonstrated that many surgeons opt for smaller initial margins than traditionally recommended (0.5 cm for in situ and 1 cm for invasive). Literature regarding surgical outcomes based on initial margin is sparse. Objective: To determine differences in disease-specific survival of melanoma after Mohs micrographic surgery for varied initial surgical margins. Methods: A literature search was conducted on February 14, 2022, from MEDLINE via PubMed (1946-present), Embase (1974-present), Central (1991-present), and Scopus (1960-present). The primary outcome was disease-specific mortality. Results: Nineteen studies were included for final analysis. The overall disease-specific mortality rate of melanoma in all included studies was 0.5% (CI, 0.1-0.8; P, .010). Disease-specific mortality for 1 to 5, 5, and 6 to 10 mm categories were 0.4% (CI, 0.0-0.9; P, .074), 0.7% (CI, 0.2-1.3; P, .2-1.3), and 0.4% (CI, –0.9 to 1.8; P, .524), respectively. None of the variances across initial margin categories were statistically significant. Limitations: Early-stage melanomas have low overall mortality rates. In our associated article, initial margins of 5 to 10 mm were shown to have the lowest rates of local recurrence. Conclusions: In this systematic review and meta-analysis, melanoma-specific mortality was not significantly impacted by the initial surgical margin taken during Mohs micrographic surgery.

Faculty from two universities in Florida and Ohio designed, developed, and implemented programs to work with youth from their respective service regions to support college and career readiness initiatives. Both programs were directed by university faculty and utilized university resources to support K-12 students' career development skills. In this paper, we examine the programs' designs, implementations, and results; we include feedback from students, school personnel, and local stakeholders. Attentive to results and the relevant literature, we hope to ignite a long-term discussion on how universities can create effective outreach programs that help support student transitions from high school to college, or directly into a career.

This article explores the planning and implementation process for a community partnership school for a historically low-performing elementary school using an asset-based community development approach. We offer insights into the community needs assessment process that enabled four key community partners to identify needs and projects for the school and surrounding community. The community partnership school draws its strength from four local organizations assimilating their expertise and resources on focal areas for community engagement. Beyond organizational resources, the partners also developed local networks and resources that could be useful for the community. Building on the asset-based community development model, insights and challenges are presented for others seeking to employ a similar approach to mobilize assets for student success and community engagement.