Case Report: p40 phox deficiency underlying pediatric-onset systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40 phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells. Case presentation: We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE features including production of autoantibodies, hematologic manifestations, and hypocomplementemia, as well as chronic suppurative skin lesions and recurrent infections. Genetic analysis revealed biallelic pathogenic variants in NCF4 resulting in p40 phox deficiency. Comprehensive NADPH oxidase activity studies confirmed significantly decreased production of reactive oxygen species, confirming the cellular phenotype seen in p40 phox deficient patients. Conclusions: Here, we present a patient with pSLE harboring biallelic variants in NCF4. Our patient represents a unique clinical presentation of severe onset autoimmunity in the setting of a rare inborn error of immunity affecting NADPH oxidase activity. This case underscores the need to consider genetic causes of pSLE in cases of pre-pubertal onset and atypical disease.

Structure, Function, and Activity of Small Molecule and Peptide Inhibitors of Protein Arginine Methyltransferase 1.

Protein arginine N-methyltransferases (PRMT) are a family of S-adenosyl-l-methionine (SAM)-dependent enzymes that transfer methyl-groups to the ω-N of arginyl residues in proteins. PRMTs are involved in regulating gene expression, RNA splicing, and other activities. PRMT1 is responsible for most cellular arginine methylation, and its dysregulation is involved in many cancers. Accordingly, many groups have targeted PRMT1 using small molecules and peptide inhibitors. In this Perspective, we discuss the structure and function of selected peptide and small molecule inhibitors of PRMT1. We examine inhibitors that target the substrate arginyl peptide, SAM, or both binding sites, and the type of inhibition that results. Small molecules, and peptides that are bisubstrate, and/or PRMT transition state mimic inhibitors as well as inhibitors that alkylate PRMTs will be discussed. We define a structure-activity relationship for the aromatic/heteroaromatic N-methylethylenediamine inhibitors of PRMT1 and review current progress of PRMT1 inhibitors in clinical trials.

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells.

Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3+ T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models. Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial ( NCT05862012 ), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies.

Real-world impact of differences in the WHO and ICC classifications of non-Hodgkin lymphoma: a LEO Cohort Study analysis.

Recent introduction of two different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will impact <1% of non-Hodgkin lymphomas.

PDE4B Missense Variant Increases Susceptibility to Post-Traumatic Stress Disorder-Relevant Phenotypes in Mice.

Large-scale genome-wide association studies (GWAS) have associated intronic variants in PDE4B, encoding cAMP-specific phosphodiesterase-4B (PDE4B), with increased risk for post-traumatic stress disorder (PTSD), as well as schizophrenia and substance use disorders that are often comorbid with it. However, the pathophysiological mechanisms of genetic risk involving PDE4B are poorly understood. To examine the effects of PDE4B variation on phenotypes with translational relevance to psychiatric disorders, we focused on PDE4B missense variant M220T, which is present in the human genome as rare coding variant rs775201287. When expressed in HEK-293 cells, PDE4B1-M220T exhibited an attenuated response to a forskolin-elicited increase in the intracellular cAMP concentration. In behavioral tests, homozygous Pde4b M220T male mice with a C57BL/6JJcl background exhibited increased reactivity to novel environments, startle hyperreactivity, prepulse inhibition deficits, altered cued fear conditioning, and enhanced spatial memory, accompanied by an increase in cAMP signaling pathway-regulated expression of BDNF in the hippocampus. In response to a traumatic event (ten tone-shock pairings), neuronal activity was decreased in the cortex but enhanced in the amygdala and hippocampus of Pde4b M220T mice. At 24 hours post-trauma, Pde4b M220T mice exhibited increased startle hyperreactivity and decreased plasma corticosterone levels, similar to phenotypes exhibited by PTSD patients. Trauma-exposed Pde4b M220T mice also exhibited a slower decay in freezing at 15 days and 30 days post-trauma, demonstrating enhanced persistence of traumatic memories, similar to that exhibited by PTSD patients. These findings provide substantive mouse model evidence linking PDE4B variation to PTSD-relevant phenotypes, and thus highlight how genetic variation of PDE4B may contribute to PTSD risk.Significance Statement Human genetic studies have associated variants in the PDE4B gene, encoding the phosphodiesterase-4B (PDE4B) enzyme, with increased risk for post-traumatic stress disorder (PTSD) and other mental disorders that often occur with it. However, the underlying biological mechanisms of genetic risk involving PDE4B are poorly understood. To examine the effect of PDE4B variation on behaviors relevant to mental disorders, we studied male Pde4b M220T mice that carry a PDE4B variant (M220T), which is also present in humans. Pde4b M220T mice exhibited increased PTSD-like behavior in response to a traumatic event, as well as abnormal neuronal activity in the brain. Our findings provide substantive evidence linking PDE4B variation to PTSD-relevant behaviors, and thus highlight how genetic variation of PDE4B may contribute to PTSD risk.

Impact of Skin Care Products on Phthalates and Phthalate Replacements in Children: the ECHO-FGS.

BACKGROUND: Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). OBJECTIVES: Our objective is to assess the associations between use of SCPs and children's urinary phthalate/replacement metabolite concentrations. METHODS: Children (4-8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children's SCP use in the past 24 h (n=906). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography-tandem mass spectrometry (n=630). We used linear regression to estimate the child's use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into "exposure profiles" that reflect discovered patterns of use for multiple SCPs. RESULTS: Children had lotions applied (43.0%) frequently, but "2-in-1" hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child's race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. DISCUSSION: We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children's exposure to developmental toxicants. https://doi.org/10.1289/EHP13937.

The Effect of Organic Semiconductor Electron Affinity on Preventing Parasitic Oxidation Reactions Limiting Performance of n-Type Organic Electrochemical Transistors.

A key challenge in the development of organic mixed ionic-electronic conducting materials (OMIEC) for high performance electrochemical transistors is their stable performance in ambient. When operating in aqueous electrolyte, potential reactions of the electrochemically injected electrons with air and water could hinder their persistence, leading to a reduction in charge transport. Here, the impact of deepening the LUMO energy level of a series of electron-transporting semiconducting polymers is evaluated, and subsequently rendering the most common oxidation processes of electron polarons thermodynamically unfavorable, on organic electrochemical transistors (OECTs) performance. Employing time resolved spectroelectrochemistry with three analogous polymers having varying electron affinities (EA), it is found that an EA below the thermodynamic threshold for oxidation of its electron polarons by oxygen significantly improves electron transport and lifetime in air. A polymer with a sufficiently large EA and subsequent thermodynamically unfavorable oxidation of electron polarons is reported, which is used as the semiconducting layer in an OECT, in its neutral and N-DMBI doped form, resulting in an excellent and air-stable OECT performance. These results show a general design methodology to avoid detrimental parasitic reactions under ambient conditions, and the benefits that arise in electrical performance.

Physical Activity and Sedentary Time in US Adults with and without Heart Failure: 2007-2018 NHANES.

OBJECTIVES: Current evidence describing physical activity (PA) and sedentary time (ST) in people with and without heart failure (HF) is limited. This study examines PA participation and ST in a nationally representative sample of US adults with and without self-reported HF. METHODS: The study sample (N = 21,633) included US adult (40 years old and older) participants from the 2007-2018 National Health and Nutrition Examination Survey. PA participation, ST, and HF status were assessed via a questionnaire. RESULTS: Compared with participants without HF (68%), 84% of participants with HF reported not meeting PA recommendations (P < 0.05). Compared with participants without HF (63%), 75% of participants with HF reported >4.5 hours/day of ST (P < 0.05). Unadjusted analysis suggests that participants with HF had 60% (P < 0.05) lower odds of reporting meeting PA recommendations when compared with those without HF. In a fully adjusted model, these odds were attenuated (odds ratio 0.74, P < 0.05). Similarly, unadjusted analysis illustrated those individuals with HF had 42% (P < 0.05) lower odds of reporting ≤4.5 hours/day of ST. In a fully adjusted model, these odds also were attenuated (odds ratio 0.66, P < 0.05). CONCLUSIONS: Our findings suggest that US adults with HF report significantly less PA and greater amounts of ST than those without HF.

Diagnosis of Gout as a Correlative Risk for Acute Myocardial Infarction in the Absence of Traditional Cardiovascular Risk Factors.

OBJECTIVES: We aimed to study the impact of gout as a correlative risk factor in the incidence of acute myocardial infarction (AMI) among patients without known MI risk factors. Our study population was obtained from the National Inpatient Sample (NIS) 2011-2018 using the International Classification of Diseases, Ninth and Tenth Revisions. METHODS: This study included patients without cardiovascular disease (CVD), and various outcomes were compared among patients with and without gout. Cohorts were weighted using an algorithm provided by the NIS, which allows for national estimates. Our primary endpoint was the odds of developing an MI, and secondary endpoints were adverse hospital events and length of stay. In total, 117,261,842 patients without CVD risk factors were included in this study, 187,619 (0.16%) of whom had a diagnosis of gout. RESULTS: Patients without CVD risk factors who had gout were older and more likely to be male compared with patients without gout. Among patients without CVD risk factors, the odds of having an AMI were significantly higher in those with gout compared with those without, even after adjusting for chronic nonsteroidal anti-inflammatory drug and oral steroid use. Moreover, patients without CVD risk factors and with gout were more likely to develop acute renal failure, acute thromboembolic event, shock, acute gastrointestinal bleed, and arrhythmia compared with those without gout. Furthermore, patients without CVD risk factors who were admitted with gout had higher mortality compared with those without gout. CONCLUSIONS: In our study, we found that patients without risk factors for AMI who had gout were more likely to develop AMI compared with those without gout. Furthermore, the same patients were more likely to develop other adverse outcomes. Even with proper management, these individuals should be monitored closely for coronary events.

Enhanced aqueous formation and neutralization of fine atmospheric particles driven by extreme cold.

The prevailing view for aqueous secondary aerosol formation is that it occurs in clouds and fogs, owing to the large liquid water content compared to minute levels in fine particles. Our research indicates that this view may need reevaluation due to enhancements in aqueous reactions in highly concentrated small particles. Here, we show that low temperature can play a role through a unique effect on particle pH that can substantially modulate secondary aerosol formation. Marked increases in hydroxymethanesulfonate observed under extreme cold in Fairbanks, Alaska, demonstrate the effect. These findings provide insight on aqueous chemistry in fine particles under cold conditions expanding possible regions of secondary aerosol formation that are pH dependent beyond conditions of high liquid water.

Risk of Incident Melanoma Among Individuals With Low-Count Monoclonal B-Cell Lymphocytosis.

PURPOSE: Chronic lymphocytic leukemia (CLL)-phenotype monoclonal B-cell lymphocytosis (MBL) is a premalignant condition that is roughly 500-fold more common than CLL. It is unknown whether the two-fold increased risk of developing melanoma associated with CLL extends to individuals with MBL. METHODS: Using the Mayo Clinic Biobank, we identified participants who were 40 years or older with no previous hematological malignancies, who resided in the 27 counties around Mayo Clinic, and who had available biospecimens for screening. Eight-color flow cytometry was used to screen for MBL. Individuals with MBL were classified as low-count MBL (LC-MBL) or high-count MBL on the basis of clonal B-cell percent. Incident melanomas were identified using International Classification of Diseases codes and confirmed via medical records review. Cox regression models were used to estimate hazard ratios (HRs) and 95% CI. RESULTS: Of the 7,334 participants screened, 1,151 were identified with a CD5-positive MBL, of whom 1,098 had LC-MBL. After a median follow-up of 3.2 years (range, 0-13.5), 131 participants developed melanoma, of whom 36 individuals were positive for MBL. The estimated 5-year cumulative incidence of melanoma was 3.4% and 2.0% among those with and without MBL, respectively. After adjusting for age, sex, and history of previous melanoma, individuals with MBL exhibited a 1.86-fold (95% CI, 1.25 to 2.78) risk of melanoma. This elevated risk persisted when analysis was restricted to those without a history of melanoma (HR, 2.05 [95% CI, 1.30 to 3.23]). Individuals with LC-MBL had a 1.92-fold (95% CI, 1.29 to 2.87) increased risk of developing melanoma overall and a 2.74-fold increased risk (95% CI, 1.50 to 5.03) of melanoma in situ compared with those without MBL. CONCLUSION: LC-MBL is associated with an approximately two-fold increased risk of melanoma overall and a 2.74-fold increased risk of melanoma in situ.

Methane fluxes in tidal marshes of the conterminous United States.

Methane (CH4) is a potent greenhouse gas (GHG) with atmospheric concentrations that have nearly tripled since pre-industrial times. Wetlands account for a large share of global CH4 emissions, yet the magnitude and factors controlling CH4 fluxes in tidal wetlands remain uncertain. We synthesized CH4 flux data from 100 chamber and 9 eddy covariance (EC) sites across tidal marshes in the conterminous United States to assess controlling factors and improve predictions of CH4 emissions. This effort included creating an open-source database of chamber-based GHG fluxes (https://doi.org/10.25573/serc.14227085). Annual fluxes across chamber and EC sites averaged 26 ± 53 g CH4 m-2 year-1, with a median of 3.9 g CH4 m-2 year-1, and only 25% of sites exceeding 18 g CH4 m-2 year-1. The highest fluxes were observed at fresh-oligohaline sites with daily maximum temperature normals (MATmax) above 25.6°C. These were followed by frequently inundated low and mid-fresh-oligohaline marshes with MATmax ≤25.6°C, and mesohaline sites with MATmax >19°C. Quantile regressions of paired chamber CH4 flux and porewater biogeochemistry revealed that the 90th percentile of fluxes fell below 5 ± 3 nmol m-2 s-1 at sulfate concentrations >4.7 ± 0.6 mM, porewater salinity >21 ± 2 psu, or surface water salinity >15 ± 3 psu. Across sites, salinity was the dominant predictor of annual CH4 fluxes, while within sites, temperature, gross primary productivity (GPP), and tidal height controlled variability at diel and seasonal scales. At the diel scale, GPP preceded temperature in importance for predicting CH4 flux changes, while the opposite was observed at the seasonal scale. Water levels influenced the timing and pathway of diel CH4 fluxes, with pulsed releases of stored CH4 at low to rising tide. This study provides data and methods to improve tidal marsh CH4 emission estimates, support blue carbon assessments, and refine national and global GHG inventories.

Covalent Triazine-Based Frameworks with Ru-tda Based Catalyst Anchored via Coordination Bond for Photoinduced Water Oxidation.

Light-induced water splitting (hν-WS) for the production of hydrogen as a solar fuel is considered a promising sustainable strategy for the replacement of fossil fuels. An efficient system for hν-WS involves a photoactive material that, upon shining light, is capable of separating and transferring charges to catalysts for the hydrogen and oxygen evolution processes. Covalent triazine-based frameworks (CTFs) represent an interesting class of 2D organic light-absorbing materials that have recently emerged thanks to their tunable structural, optical and morphological properties. Typically, catalysts (Cat) are metallic nanoparticles generated in situ after photoelectroreduction of metal precursors or directly drop-casted on top of the CTF material to generate Cat-CTF assemblies. In this work, the synthesis, characterization and photocatalytic performance of a novel hybrid material, Ru-CTF, is reported, based on a CTF structure featuring dangling pyridyl groups that allow the Ru-tda (tda is [2,2':6',2'"-terpyridine]-6,6'"-dicarboxylic acid) water oxidation catalyst (WOC) unit to coordinate via covalent bond. The Ru-CTF molecular hybrid material can carry out the light-induced water oxidation reaction efficiently at neutral pH, reaching values of maximum TOF of 17 h-1 and TONs in the range of 220 using sodium persulfate as a sacrificial electron acceptor.

Normative Neuroimaging Library: Designing a Comprehensive and Demographically Diverse Dataset of Healthy Controls to Support Traumatic Brain Injury Diagnostic and Therapeutic Development.

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and socioeconomic categories. Clinicians can only use the results of imaging scans to support their decision-making if they know how the results for their patient compare with a normative standard. This potential for utilizing magnetic resonance imaging (MRI) in TBI diagnosis motivated the American College of Radiology and Cohen Veterans Bioscience to create a reference database of healthy individuals with neuroimaging, demographic data, and characterization of psychological functioning and neurocognitive data that will serve as a normative resource for clinicians and researchers for development of diagnostics and therapeutics for TBI and other brain disorders. The goal of this article is to introduce the large, well-curated Normative Neuroimaging Library (NNL) to the research community. NNL consists of data collected from ∼1900 healthy participants. The highlights of NNL are (1) data are collected across a diverse population, including civilians, veterans, and active-duty service members with an age range (18-64 years) not well represented in existing datasets; (2) comprehensive structural and functional neuroimaging acquisition with state-of-the-art sequences (including structural, diffusion, and functional MRI; raw scanner data are preserved, allowing higher quality data to be derived in the future; standardized imaging acquisition protocols across sites reflect sequences and parameters often recommended for use with various neurological and psychiatric conditions, including TBI, post-traumatic stress disorder, stroke, neurodegenerative disorders, and neoplastic disease); and (3) the collection of comprehensive demographic details, medical history, and a broad structured clinical assessment, including cognition and psychological scales, relevant to multiple neurological conditions with functional sequelae. Thus, NNL provides a demographically diverse population of healthy individuals who can serve as a comparison group for brain injury study and clinical samples, providing a strong foundation for precision medicine. Use cases include the creation of imaging-derived phenotypes (IDPs), derivation of reference ranges of imaging measures, and use of IDPs as training samples for artificial intelligence-based biomarker development and for normative modeling to help identify injury-induced changes as outliers for precision diagnosis and targeted therapeutic development. On its release, NNL is poised to support the use of advanced imaging in clinician decision support tools, the validation of imaging biomarkers, and the investigation of brain-behavior anomalies, moving the field toward precision medicine.

Neural Mechanisms of Learning and Consolidation of Morphologically Derived Words in a Novel Language: Evidence From Hebrew Speakers.

We examined neural mechanisms associated with the learning of novel morphologically derived words in native Hebrew speakers within the Complementary Learning Systems (CLS) framework. Across four sessions, 28 participants were trained on an artificial language, which included two types of morphologically complex words: linear (root + suffix) with a salient structure, and non-linear (root interleaved with template), with a prominent derivational structure in participants' first language (L1). A third simple monomorphemic condition, which served as baseline, was also included. On the first and fourth sessions, training was followed by testing in an fMRI scanner. Our behavioural results showed decomposition of both types of complex words, with the linear structure more easily learned than the non-linear structure. Our fMRI results showed involvement of frontal areas, associated with decomposition, only for the non-linear condition, after just the first session. We also observed training-related increases in activation in temporal areas specifically for the non-linear condition, which was correlated with participants' L1 morphological awareness. These results demonstrate that morphological decomposition of derived words occurs in the very early stages of word learning, is influenced by L1 experience, and can facilitate word learning. However, in contrast to the CLS framework, we found no support for a shift from reliance on hippocampus to reliance on cortical areas in any of our conditions. Instead, our findings align more closely with recent theories showing a positive correlation between changes in hippocampus and cortical areas, suggesting that these representations co-exist and continue to interact with one another beyond initial learning.

Lessons From the Change Healthcare Ransomware Attack.

This Viewpoint discusses responses to the Change Healthcare cyberattack, concerns about consolidations and acquisitions of health care companies and organizations, and the need to clarify cybersecurity priorities.

Facet-Engineered BiVO4 Photocatalysts for Water Oxidation: Lifetime Gain Versus Energetic Loss.

A limiting factor to the efficiency of water Oxygen Evolution Reaction (OER) in metal oxide nanoparticle photocatalysts is the rapid recombination of holes and electrons. Facet-engineering can effectively improve charge separation and, consequently, OER efficiency. However, the kinetics behind this improvement remain poorly understood. This study utilizes photoinduced absorption spectroscopy to investigate the charge yield and kinetics in facet-engineered BiVO4 (F-BiVO4) compared to a non-faceted sample (NF-BiVO4) under operando conditions. A significant influence of preillumination on hole accumulation is observed, linked to the saturation and, thus, passivation of deep and inactive hole traps on the BiVO4 surface. In DI-water, F-BiVO4 shows a 10-fold increase in charge accumulation (∼5 mΔOD) compared to NF-BiVO4 (∼0.5 mΔOD), indicating improved charge separation and stabilization. With the addition of Fe(NO3)3, an efficient electron acceptor, F-BiVO4 demonstrates a 30-fold increase in the accumulation of long-lived holes (∼45 mΔOD), compared to NF-BiVO4 (∼1.5 mΔOD) and an increased half-time, from 2 to 10 s. Based on a simple kinetic model, this increase in hole accumulation suggests that facet-engineering causes at least a 50-100 meV increase in band bending in BiVO4 particles, thereby stabilizing surface holes. This energetic stabilization/loss results in a retardation of OER relative to NF-BiVO4. This slower catalysis is, however, offset by the observed increase in density and lifetime of photoaccumulated holes. Overall, this work quantifies how surface faceting can impact the kinetics of long-lived charge accumulation on metal oxide photocatalysts, highlighting the trade-off between lifetime gain and energetic loss critical to optimizing photocatalytic efficiency.

Strategies to foster stakeholder engagement in residency coaching: a CFIR-Informed qualitative study across diverse stakeholder groups.

INTRODUCTION: Coaching interventions in graduate medical education have proven successful in increasing technical and communication skills, reducing errors, and improving patient care. Effective stakeholder engagement enhances the relevance, value, and long-term sustainability of interventions, yet specific strategies for stakeholder engagement remain uncertain. The purpose of this article is to identify strategies to foster engagement of diverse stakeholder groups in coaching interventions. MATERIAL AND METHODS: We conducted 35 semi-structured interviews between November 2021 and April 2022 with purposively sampled key stakeholders that captured participants' perspectives on physicians' communication training needs, roles, and involvement in, as well as contextual factors, facilitators, barriers, and improvement strategies of the multi-departmental Communication Coaching Program at our institution. We utilized the Consolidated Framework of Implementation Research to guide data collection and analysis. An analytic approach relied on team-based thematic analysis with high inter-coder agreement between three raters (Cohen's kappa coefficient 0.83). Several validation techniques were used to enhance the credibility and trustworthiness of the study. RESULTS: Analysis of transcribed interviews with stakeholders directly involved in the Communication Coaching Program, including 10 residents, 10 faculty coaches, 9 medical education leaders, and 8 programmatic sponsors, revealed five key engagement strategies: (1) embrace collaborative design, (2) enable flexible adjustments and modifications, (3) secure funding, (4) identify champions, and (5) demonstrate outcomes. Additionally, a patient-centered approach to delivering the best possible patient care emerged as a primary objective that linked all stakeholder groups. DISCUSSION: Evaluating the experiences of key stakeholders in the Communication Coaching Program helped identify targetable strategies to facilitate participant engagement across all organizational levels. The analysis also revealed universal alignment around the importance of providing high-quality patient care. Insights from this work provide guidance for clinical training programs moving toward the implementation of coaching interventions.

Acute Cardiovascular Responses to the 100-Mile Western States Endurance Run.

Ultramarathon participation is growing in popularity and exposes runners to unique stressors including extreme temperatures, high altitude, and exceedingly long exercise duration. However, the acute effects of ultramarathon participation on the cardiovascular system are not well understood. PURPOSE: To determine the acute effects of trail ultramarathon participation on central artery stiffness and hemodynamics. METHODS: Forty-one participants (9F, 32M) participating in the 2023 Western States Endurance Run underwent measures of carotid-femoral pulse wave velocity (cf-PWV) and pulse wave analysis pre- and <1h post-race. Subendocardial viability ratio (SEVR) was calculated from central blood pressure (BP) waveforms. Serum was analyzed for creatine kinase (CK) activity as a measure of muscle damage. Normally distributed data are presented as mean±SD and non-normally distributed data are presented as median (interquartile range). RESULTS: Runners were middle-aged and generally lean (age=44±9 y, BMI=22.7±1.8 kg●m-2). There was no difference in cf-PWV from pre- to post-race (pre=6.4±1.0, post=6.2±0.85 m/s, p=0.104), a finding that persisted after adjusting for mean arterial pressure (p=0.563). Systolic and diastolic BP were lower post-race (pre=129/77±9/7, post=122/74±10/8 mmHg, ps<0.001). Augmentation index (AIx; pre=17.3±12.2, post=6.0±13.7%, p<0.001), AIx normalized to a heart rate of 75bpm (p=0.043), reflection magnitude (pre=55.5(49.0-60.8), post=45.5(41.8-48.8) %, p<0.001), and SEVR (pre=173.0(158.0-190.0), post=127.5(116.5-145.8) %, p<0.001) were reduced post-race. CK increased markedly from pre- to post-race (pre=111(85-162), post=11,973(5,049-17,954) U/L, p<0.001). CONCLUSIONS: Completing a 161-km trail ultramarathon does not affect central arterial stiffness and acutely reduces BP despite eliciting profound muscle damage. However, the reduced post-race SEVR suggests a short-term mismatch between myocardial work and coronary artery perfusion.

Evaporation from thin porous Coatings: Pore size effects and predictive equation for homogeneous coatings.

Evaporation of small water droplets on solids is hindered because surface tension pulls the droplet into a spherical cap that has a small perimeter. Our solution is to coat a solid with a very thin, porous layer into which the droplet flows to create a large-area disk with concomitant high rate of evaporation. We investigate evaporation by varying factors that have not been previously considered: pore size and distribution, contact angle, temperature, and relative humidity (RH).A larger pore size resulted in faster evaporation, which we explain through faster transport within the coating. Even faster evaporation occurred for a bilayer structure with small particles on the air side and larger particles on the solid side. The water advancing contact angle had an insignificant effect in the range from < 10° through to 60°.Our results for different pore sizes, temperature, humidity, and contact angle all collapse onto a single curve when appropriately normalized. This validates an equation that can be used for the evaporation from a homogeneous coating that depends only one empirical factor and the droplet volume. Since the volume is often user-controlled, we envisage that this equation can be used to predict evaporation and guide design of fast-drying coatings.