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Purpose Autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) is a promising treatment modality for glioblastomas. The purpose of this study was to investigate the potential utility of multiparametric MRI-based prediction model in evaluating treatment response in glioblastoma patients treated with DCVax-L. Methods Seventeen glioblastoma patients treated with standard-of-care therapy + DCVax-L were included. When tumor progression was suspected and repeat surgery was being contemplated, we sought to ascertain the number of cases correctly classified as true progression (TP) + mixed response or pseudoprogression (PsP) from multiparametric MRI-based prediction model using histopathology/mRANO criteria as ground truth. Multiparametric MRI model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI-derived parameters. A comparison of overall survival (OS) was performed between patients treated with standard-of-care therapy + DCVax-L and standard-of-care therapy alone (external controls). Additionally, Kaplan-Meier analyses were performed to compare OS between two groups of patients using PsP, Ki-67, and MGMT methylation status as stratification variables. Results Multiparametric MRI model correctly predicted TP + mixed response in 72.7% of cases (8/11) and PsP in 83.3% (5/6) with an overall concordance rate of 76.5% with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.54; p = 0.026). DCVax-L-treated patients had significantly prolonged OS than those treated with standard-of-care therapy (22.38 ± 12.8 vs. 13.8 ± 9.5months, p = 0.040). Additionally, glioblastomas with PsP, MGMT methylation status, and Ki-67 values below median had longer OS than their counterparts. Conclusion Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

Individuals with prediabetes and diabetes are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Whether ASCVD or HF is more likely to occur first in these populations within different race-sex groups is unknown.Determine the competing risk for the first cardiovascular event by subtype in Black and White men and women with prediabetes and diabetes.Individual-level data from adults without ASCVD or HF were pooled from 6 population-based cohorts. We estimated the competing cumulative incidences of ASCVD, HF, and non-cardiovascular death as the first event in middle-aged (40-59 years) and older (60-79 years) adults, stratified by race and sex, with normal fasting plasma glucose (FPG100 mg/dL), prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥126 mg/dL or on antihyperglycemic agents) at baseline. Within each race-sex group, we estimated risk (aHR) of ASCVD, HF, and non-cardiovascular death in adults with prediabetes and diabetes relative to adults with normoglycemia after adjusting for cardiovascular risk factors.In 40,117 participants with 638,910 person-years of follow-up, 5,781 cases of incident ASCVD and 3,179 cases of incident HF occurred. In middle-aged adults with diabetes, competing cumulative incidence of ASCVD as first event was higher than HF in White men (35.4% vs. 11.6%), Black men (31.6% vs. 15.1%), and White women (24.3% vs 17.2%), but not in Black women (26.4% vs 28.4%). Within each group, aHR of ASCVD and HF was significantly higher in adults with diabetes compared with adults with normal FPG. Findings were largely similar in middle-aged adults with prediabetes and older adults with prediabetes or diabetes.Black women with diabetes are more likely to develop HF as their first CVD event, while individuals with diabetes from other race-sex groups are more likely to present first with ASCVD. These results can inform tailoring primary prevention therapies for either HF- or ASCVD-specific pathways based on individual-level risk.

Selective upcycling of polyolefin waste has been hampered by the relatively high temperatures that are required to cleave the carbon-carbon (C–C) bonds at reasonably high rates. We present a distinctive approach that uses a highly ionic reaction environment to increase the polymer reactivity and lower the energy of ionic transition states. Combining endothermic cleavage of the polymer C–C bonds with exothermic alkylation reactions of the cracking products enables full conversion of polyethylene and polypropylene to liquid isoalkanes (C 6 to C 10 ) at temperatures below 100°C. Both reactions are catalyzed by a Lewis acidic species that is generated in a chloroaluminate ionic liquid. The alkylate product forms a separate phase and is easily separated from the reactant catalyst mixture. The process can convert unprocessed postconsumer items to high-quality liquid alkanes with high yields.

The continued threat of emerald ash borer (Agrilus planipennis; EAB) to North American ash trees (Fraxinus spp.) has necessitated the use of systemic insecticide treatments as a primary control strategy against EAB in urban centers. Altered tree phenology due to systemic insecticides could mediate nontarget effects on other insect species, such as seed weevils or leaf-feeders, but whether such injections alter phenological events has not been studied. This study assessed the effects of systemic injections of emamectin benzoate or azadirachtin relative to untreated controls on the spring and fall phenology of mature green ash trees in Saint Paul, MN, USA from fall 2017 to spring 2019. EAB was first detected in this area in 2009. Trees showed minor, visible signs of EAB infestation at study initiation, but not mortality. We examined six phenological events: bud swelling, budburst, flowering, leaf out, leaf color change, and leaf abscission using a visual survey protocol. The timing of phenological events was similar across the different treatments for all but two of events; budburst and flowering. Budburst and flowering occurred 7 d and 5 d earlier, respectively, in treated trees than untreated trees. Given symptoms observed, we posit that delays in these events in untreated trees were due to infestations of EAB and the treatments of emamectin benzoate or azadiractin simply preserved the original phenology. The results from this study suggest that systemic insecticides may mitigate changes in ash tree phenology such as delayed leaf out that may be early symptoms of emerald ash borer.

Voluntary Feed Intake (VFI) and Average Daily Gain (ADG) of three rabbit breeds fed on pigeon pea (PP), cowpea (CoP) and soybean (SB) as sources of protein for growing rabbits were determined. Flemish Giant (FG), California Black (CB) and New Zealand White (NZW)) were fed soybean (Glycine max), pigeon pea (Cajunus cajan) and cowpea (Vigna unguiculata) as protein sources in the ration. Eighteen rabbits weaned at six weeks of age were used for each breed (a total of 54 rabbits) out of which six of them were assigned to Ration 1 (containing 31.6% SB), six rabbits to ration 2 (containing 72% CoP) and the last six to Ration 3 (containing 70.18% PP). The rabbits were randomly assigned to fifty four cages in a 3 x 3 factorial experiment. The three legume grains were roasted before rations were compounded. Raw Legume Grains (RaLG), Roasted Legume Grains (RoLG) and the three Rations (1, 2 and 3) were analyzed for tannin content (TC). TC was significantly (p

Background: Social and psychosocial factors are associated with cardiovascular health (CVH). Our objective was to examine the contributions of individual-level social and psychosocial factors to racial and ethnic differences in population CVH in the NHANES (National Health and Nutrition Examination Surveys) 2011 to 2018, to inform strategies to mitigate CVH inequities. Methods: In NHANES participants ages ≥20 years, Kitagawa-Blinder-Oaxaca decomposition estimated the statistical contribution of individual-level factors (education, income, food security, marital status, health insurance, place of birth, depression) to racial and ethnic differences in population mean CVH score (range, 0–14, accounting for diet, smoking, physical activity, body mass index, blood pressure, cholesterol, blood glucose) among Hispanic, non-Hispanic Asian, or non-Hispanic Black adults compared with non-Hispanic White adults. Results: Among 16 172 participants (representing 255 million US adults), 24% were Hispanic, 12% non-Hispanic Asian, 23% non-Hispanic Black, and 41% non-Hispanic White. Among men, mean (SE) CVH score was 7.45 (2.3) in Hispanic, 8.71 (2.2) in non-Hispanic Asian, 7.48 (2.4) in non-Hispanic Black, and 7.58 (2.3) in non-Hispanic White adults. In Kitagawa-Blinder-Oaxaca decomposition, education explained the largest component of CVH differences among men (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.36 [0.04] points higher in Hispanic, 0.24 [0.04] points lower in non-Hispanic Asian, and 0.23 [0.03] points higher in non-Hispanic Black participants; P P P Conclusions: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.

Grafting metal cations to missing linker defect sites in zirconium-based metal-organic frameworks, such as UiO-66, produces a uniquely well-defined and homotopic catalytically active site. We present here the synthesis and characterization of a group of UiO-66-supported metal catalysts, M-UiO-66 (M = Ni, Co, Cu, and Cr), for the catalytic dimerization of alkenes. The hydrogen-deuterium exchange via deuterium oxide adsorption followed by infrared spectroscopy showed that the last molecular water ligand desorbs from the sites after evacuation at 300 °C leading to M(OH)-UiO-66 structures. Adsorption of 1-butene is studied using calorimetry and density functional theory techniques to characterize the interactions of the alkene with metal cation sites that are found active for alkene oligomerization. For the most active Ni-UiO-66, the removal of molecular water from the active site significantly increases the 1-butene adsorption enthalpy and almost doubles the catalytic activity for 1-butene dimerization in comparison to the presence of water ligands. Other M-UiO-66 (M = Co, Cu, and Cr) exhibit 1-3 orders of magnitude lower catalytic activities compared to Ni-UiO-66. The catalytic activities correlate linearly with the Gibbs free energy of 1-butene adsorption. Density functional theory calculations probing the Cossee-Arlman mechanism for all metals support the differences in activity, providing a molecular level understanding of the metal site as the active center for 1-butene dimerization.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2–3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2–4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non–AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding molecular profiling of gliomas.

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in May 2021. This summary describes how the vaccine worked in participants 12- to 15-years old. The part of the study described in the article is ongoing and expected to finish March 2023. This means that the final results may be different from the results included in this summary. What happened in this study? The part of the study described in this summary included participants 12- to 15-years old who had no serious health issues. The BNT162b2 vaccine had already been studied in participants 16 years of age or older. In this part of the study, the researchers wanted to find out: How effective and safe the vaccine was in participants 12- to 15-years old. What the immune response to the vaccine and the vaccine safety were like in 12- to 15-year-olds compared with 16- to 25-year-olds. How well the vaccine prevented SARS-CoV-2 infections in participants who received the vaccine compared to those who did not. This is also called efficacy of the BNT162b2 vaccine Half of the participants in this study received 2 injections of the BNT162b2 vaccine and half received 2 injections of a placebo in a muscle of the upper arm. The placebo looked like the BNT162b2 vaccine but did not have any active vaccine in it. What were the results? BNT162b2 had a favorable safety profile. The most common reactions were pain at the injection site, fatigue, and headache. None of the participants had serious reactions to the vaccine. The 12- to 15-year-old participants' immune system responses to the BNT162b2 vaccine were as good as or stronger than the 16- to 25-year-old participants' immune responses. The participants who received the BNT162b2 vaccine were less likely to get COVID-19 compared with the participants who got the placebo. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

Murphy and DeNisi (2021) suggest that the real-world effects of age stereotypes on personnel decisions are weak, null, or inconsistent. However, we know that both conscious and unconscious age stereotypes exist (Fiske, 2017; Posthuma & Campion, 2009), and both seem to affect people’s hiring decisions (Zaniboni et al., 2019). For instance, a field experiment in Sweden in which 6,000 fictitious resumes were sent to open positions found that applicants over 40 received fewer callbacks and that callbacks decreased with applicant age (Carlsson & Eriksson, 2019). Moreover, the implementation of age discrimination laws worldwide suggests that age discrimination is generally recognized as an issue for workers and job applicants. In this commentary, we draw on the attraction–selection–attrition (ASA) model to illustrate when age stereotypes do affect personnel decisions throughout the employee lifecycle, acting “under the radar” of current organizational research. Through this lens, we suggest new avenues and approaches to understand both the mechanisms by which stereotypes work and their true effects. In doing so, we provide theory-based recommendations for researchers to better uncover when and how age stereotypes do influence personnel decisions (see Table 1).

Background Many people with systemic lupus erythematosus (SLE) experience joint pain, swelling, and stiffness. These joint symptoms are associated with problems in physical functioning and work disability. We used survey data from adults with SLE to explore the burden and impact of joint symptoms. Methods SLE-UPDATE was a 2019 cross-sectional US survey of adults with SLE. We compared respondents with “currently active” joint symptoms’ and those “without currently active” joint symptoms. The active joint cohort comprised survey respondents who self-reported current “stiffness in joints” or “pain/swelling in joints” and who had moderate to severe joint pain (Worst Joint Pain Numeric Rating Scale [NRS] score ≥ 4). Respondents not fulfilling these criteria were included in the non-active joint cohort. Outcomes included frequency and severity of pain, patient-reported outcomes (LupusPRO™ and Work Productivity and Activity Impairment: Lupus [WPAI-Lupus]), satisfaction with current treatments, and importance of different treatment goals. Results More respondents in the active joint cohort (N = 285) than in the non-active joint cohort (N = 215) reported pain most or all the time over the preceding 7 days (77.5% vs. 32.1%, p < .0001), fibromyalgia (45% vs. 12%, p < .0001), and higher (worse) mean scores on the Worst Pain NRS (6.5 vs. 4.8, p < .0001) and Worst Joint Pain NRS (6.7 vs. 4.5, p < .0001). Mean Lupus PRO health-related quality of life (HRQoL) total score was lower (worse) in the active joint cohort (48.9 vs. 64.1, p < .0001). WPAI-Lupus scores indicated greater work productivity losses and activity impairment in the active joint cohort. More respondents in the active joint cohort than in the non-active joint cohort were neutral or not satisfied with current treatments and rated reducing pain as a “very important” treatment goal (26.7% vs. 18.1%). Conclusions Respondents with SLE and active joint manifestations in addition to having more pain report lower HRQoL and were less satisfied with their current treatments. Comorbid fibromyalgia may play a role in joint symptoms in patient with SLE joint manifestations. There is an unmet need for new therapeutic options to reduce joint symptom burden among patients with SLE.

Rust fungi (Pucciniales) are a diverse group of plant pathogens in natural and agricultural systems. They pose ongoing threats to the diversity of native flora and cause annual crop yield losses. Agricultural rusts are predominantly managed with fungicides and breeding for resistance, but new control strategies are needed on non-agricultural plants and in fragile ecosystems. RNA interference (RNAi) induced by exogenous double-stranded RNA (dsRNA) has promise as a sustainable approach for managing plant-pathogenic fungi, including rust fungi. We investigated the mechanisms and impact of exogenous dsRNA on rust fungi through in vitro and whole-plant assays using two species as models, Austropuccinia psidii (the cause of myrtle rust) and Coleosporium plumeriae (the cause of frangipani rust). In vitro, dsRNA either associates externally or is internalized by urediniospores during the early stages of germination. The impact of dsRNA on rust infection architecture was examined on artificial leaf surfaces. dsRNA targeting predicted essential genes significantly reduced germination and inhibited development of infection structures, namely appressoria and penetration pegs. Exogenous dsRNA sprayed onto 1-year-old trees significantly reduced myrtle rust symptoms. Furthermore, we used comparative genomics to assess the wide-scale amenability of dsRNA to control rust fungi. We sequenced genomes of six species of rust fungi, including three new families (Araucariomyceaceae, Phragmidiaceae, and Skierkaceae) and identified key genes of the RNAi pathway across 15 species in eight families of Pucciniales. Together, these findings indicate that dsRNA targeting essential genes has potential for broad-use management of rust fungi across natural and agricultural systems.

Background: Oral squamous cell carcinoma (OSCC) is a disease typically seen in the elderly, with an established relationship with tobacco and/or alcohol abuse. However, the incidence of OSCC among young adults (defined in this study as ≤ 30 years old) is on the rise. Materials and Methods: With IRB approval, a retrospective search was performed at the University of Florida College of Dentistry Oral Pathology Biopsy Service database from 1994-to 2019 for all cases of OSCC affecting patients aged ≤ 30 years. Demographic data were recorded, and the slides were reviewed for diagnostic consensus. Results: Thirty-one of 3971 OSCC cases (0.76%) were identified. The data show a prominent increase over time. Male patients (54.83%) were more commonly affected. Their ages ranged from 8 to 30 years, with a mean age of 25 years. The lateral border of the tongue is the most frequent site of involvement. A wide spectrum of differential diagnoses were obtained, mostly consisting of reactive lesions. Symptoms were reported in 65.6% of the cases. The histological grades ranged from well to poorly differentiated. Conclusion: This study underscores the rarity of OSCC in children and young adults. This may potentially lead to a low clinical suspicion, misdiagnosis, and delay in treatment. Further longitudinal multicenter studies with detailed medical history, treatment, genotyping, and prognostic data may help to better understand the etiology of OSCC in young patients, aid in prevention, and improve outcomes.

Antigen heterogeneity that results in tumor antigenic escape is one of the major obstacles to successful chimeric antigen receptor (CAR) T cell therapies in solid tumors including glioblastoma multiforme (GBM). To address this issue and improve the efficacy of CAR T cell therapy for GBM, we developed an approach that combines CAR T cells with inhibitor of apoptosis protein (IAP) antagonists, a new class of small molecules that mediate the degradation of IAPs, to treat GBM. Here, we demonstrated that the IAP antagonist birinapant could sensitize GBM cell lines and patient-derived primary GBM organoids to apoptosis induced by CAR T cell-derived cytokines, such as tumor necrosis factor. Therefore, birinapant could enhance CAR T cell-mediated bystander death of antigen-negative GBM cells, thus preventing tumor antigenic escape in antigen-heterogeneous tumor models

Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders.To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia.We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was0.001 with standard error0.001, indicating good discrimination and excellent calibration.The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

Sleep disturbance, including poor subjective sleep quality and insomnia disorder, is common in older adults and associated with increases in age-related morbidity risk. Accumulating evidence implicates inflammation as an underlying mechanism. In two complementary studies, we examined whether sleep disturbance is associated with activation of cellular and transcriptional mechanisms of inflammation in older adults.Study 1 examined whether healthy older adults with poor subjective sleep quality (n = 62), compared to those with good subjective sleep quality (n = 101), differed in monocytic production of interleukin (IL)-6 and/or tumor necrosis factor (TNF)-α following stimulation with lipopolysaccharide. Study 2 examined whether older adults with insomnia disorder (n = 17), compared to those without insomnia disorder (n = 25), differed in the regulation of transcription factors (TFs) related to immune activation (i.e., nuclear factor-κB/Rel family), sympathetic nervous system (SNS) activity (i.e., cAMP-response element-binding protein), hypothalamic-pituitary-adrenal (HPA) axis activity (i.e., glucocorticoid receptor) and anti-viral responses (i.e., interferon-regulatory factor/interferon-stimulated response element) assessed in peripheral blood mononuclear cells.In Study 1, older adults with poor subjective sleep quality, compared to those with good subjective sleep quality, showed higher percentages of stimulated monocytes producing IL-6 only (25.4 ± 16.8 % vs 20.4 ± 13.9 %; p 0.05, ηIn older adults, poor subjective sleep quality and insomnia diagnosis are associated with increases in monocytic cytokine production and changes in TF activity related to immune activation, SNS function, and HPA axis function. Activation of markers of cellular and transcriptional inflammation might contribute to the link between sleep disturbance and age-related morbidity risk.

Water resources in the West African Sudan Savannah are concentrated in fractured crystalline and sedimentary rock aquifers. Due to their low storage, these aquifers are vulnerable to changes in climate. This study assesses future temperature and precipitation trends in the Koumfab watershed of northern Togo. The impact of these future climate trends on surface water and the two types of fractured rock aquifers is also investigated. A fully integrated hydrologic model of the Koumfab watershed in Northern Togo is used to study the impact of climate change on water resources. Bias-corrected temperature and precipitation from four regional climate models (RCMs) and two greenhouse emissions scenarios are used as climate forcings for the integrated model. Climate projections from the four RCMs indicate a rise (1.4 −5.5 °C) in average temperature, from the control (1971–2000) to the future period (2031–2060). Projected precipitation follows two contrasting trends with some RCMs predicting an increase (by up to 14%) in mean annual precipitation, while others predict a decline (by up to −14%). These changes in precipitation and temperature will have a noticeable effect on groundwater levels and stream flow. The hydrologic model indicates a decline in groundwater levels for all future climate projections by 1.4−5.7 m. The decline in groundwater levels is not uniformly distributed in the two types of aquifers. The decline in the fractured sandstone aquifer will be four times greater than that of the fractured granodiorite/migmatite aquifer. Projected stream flow at the watershed outlet shows increasing (59 -332%) and decreasing trends (−39 −100%).

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual’s future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD. Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25–45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events. Results: We identified 45 methylation markers associated with cumulative CVH at false discovery rate P =4.7E-7–5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A , ABCG1 , and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1 , SOCS3 , and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly ( P =0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P =9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P =1.22E-05). Conclusions: Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.

The Lazarus effect is a rare condition that happens when someone seemingly dead shows signs of life. The epidermal growth factor receptor (EGFR) represents a target in the fatal neoplasm glioblastoma (GBM) that through a series of negative clinical trials has prompted a vocal subset of the neuro-oncology community to declare this target dead. However, an argument can be made that the core tenets of precision oncology were overlooked in the initial clinical enthusiasm over EGFR as a therapeutic target in GBM. Namely, the wrong drugs were tested on the wrong patients at the wrong time. Furthermore, new insights into the biology of EGFR in GBM vis-à-vis other EGFR-driven neoplasms, such as non-small cell lung cancer, and development of novel GBM-specific EGFR therapeutics resurrects this target for future studies. Here, we will examine the distinct EGFR biology in GBM, how it exacerbates the challenge of treating a CNS neoplasm, how these unique challenges have influenced past and present EGFR-targeted therapeutic design and clinical trials, and what adjustments are needed to therapeutically exploit EGFR in this devastating disease.

Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and lead to atrial fibrillation (AF); however prior study findings have not been confirmed using objective measures for both SHS and AF events.We prospectively examined the association between SHS exposure and incident AF in 5731 participants, ages of 45-84 years and free of known AF and other cardiovascular diseases (CVD) at baseline (2000-2002), who were followed through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). SHS weekly exposure time was identified by self-report. Urine cotinine was collected in a cohort subset of 3237 current non-smoking cohort participants. AF events were identified using Medicare claims, hospital records, and 12‑lead electrocardiographic findings. A multivariable Cox proportional hazards regression analysis was used with simultaneous adjustment for demographic factors, educational level, health insurance status, active smoking status, tobacco pack-years, traditional CVD risk factors, depressive symptoms and medications.During a median follow-up of 14.0 years, 856 and 452 AF events were identified in the overall and the cohort subset, respectively. No association of SHS exposure time or urine cotinine with incident AF was observed. However, a higher AF risk with greater urine cotinine (8.53-442.0 ng/mL) compared with lower urine cotinine (≤7.07 ng/mL) was observed in never smokers [hazard ratios (HR) and 95% confidence intervals: 1.60 (1.16, 2.19)], but not in former smokers [HR: 0.88 (0.63, 1.23)] (p-value for multiplicative interaction: 0.009 and for additive interaction: 0.017, respectively).Objectively measured greater SHS exposure expressed by urine cotinine might be associated with 1.6-fold higher risk of incident AF in never smokers.

A diverse collection of dinosaur tracks and trackways preserved on a single bedding plane record activities of many animals over a very short time, possibly just a few days or less. The assemblage is exposed on a detached slab of siltstone from the Campanian–Maastrichtian St. Mary River Formation in southwestern Alberta, Canada. Members of four different groups of dinosaurs are identified as the makers of either isolated tracks, or trackways of varying lengths, and include inferred hatchling tyrannosaurids, medium and large ornithomimids, small and medium-sized ornithopods, and a small hadrosaurid. All but one of the seven trackways attributed to hatchling tyrannosaurids occur as codirectional, equally spaced pairs, but one pair walked in the opposite direction, albeit parallel, to the other two. The pair of ornithomimid trackways also appears to represent two animals walking at the same speed, in the same direction, and turning together. The trackway attributed to a medium-sized biped, possibly Parksosaurus warreni, is the first evidence for the presence of these dinosaurs in the environment recorded by the St. Mary River Formation.

Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. Results In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004–0.008) and 0.016 (0.010–0.023), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.024 (0.014–0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062–0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. Conclusion Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Particulate transport from surfaces governs a variety of phenomena including fungal spore dispersal, bioaerosol transmission, and self-cleaning. Here, we report a previously unidentified mechanism governing passive particulate removal from superhydrophobic surfaces, where a particle coalescing with a water droplet (∼10 to ∼100 μm) spontaneously launches. Compared to previously discovered coalescence-induced binary droplet jumping, the reported mechanism represents a more general capillary-inertial dominated transport mode coupled with particle/droplet properties and is typically mediated by rotation in addition to translation. Through wetting and momentum analyses, we show that transport physics depends on particle/droplet density, size, and wettability. The observed mechanism presents a simple and passive pathway to achieve self-cleaning on both artificial as well as biological materials as confirmed here with experiments conducted on butterfly wings, cicada wings, and clover leaves. Our findings provide insights into particle-droplet interaction and spontaneous particulate transport, which may facilitate the development of functional surfaces for medical, optical, thermal, and energy applications.