Hybrid Teamwork: What We Know and Where We Can Go From Here.

Hybrid teamwork, which describes any combination of one's work time spent across organizational and other (typically domestic) work settings, has become a critical aspect of modern work environments. However, despite the rising prevalence and technological support for hybrid teamwork, there is limited understanding of its impact at the team level. Although we still lack research that addresses the dynamic geographic configurations inherent to hybrid teamwork, we believe that much of the extant literature on virtual teamwork can inform our understanding and guide future research. Accordingly, this paper aims to advance knowledge on hybrid teamwork by defining its unique characteristics and critically reviewing three broad classes of theory from the virtual teams literature and their implications for understanding hybrid teamwork. Based on both contributions and limitations of these three theory classes, we conclude this paper by mapping out pressing questions to guide future research.

A clinical outcomes data archive for a comprehensive fetal diagnosis and treatment center.

INTRODUCTION: Data on near and long-term outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is important since physiologic and neurodevelopmental attributes do not manifest until childhood when multi-level factors influence health outcomes. Electronic health records (EHR) documentation structures are not designed for acquisition of key attributes, and changes over time and between-clinician differences can affect resultant output. Therefore, EHR derived datasets have limited ability to accurately characterize the clinical presentation and care trajectory of patients with congenital anomalies. Moreover, the fetus lacks a digital identity and requires relinking attributes documented in the maternal chart to those in the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Current data systems result in incomplete abstraction of variables that may confound, mediate, or moderate critical associations. Our objective was to develop and implement a prospective data capture platform to transform EHR data into an analytic-grade database for multi-purpose use. METHODS: A unified platform for longitudinal follow-up of maternal-child dyads named the Clinical Outcomes Data Archive (CODA) was constructed. CODA was designed using a data dictionary based on multidisciplinary input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated. Descriptive analyses were performed for data acquired between July 2022 - July 2023, and a comparison of studies before and after implementation of CODA is presented. CONCLUSION: 5,394,106 data points were validated for 7,662 patients across 12 conditions. 2% of data points were found to be unreliable or undocumented. 91% of data points were sourced from the EHR. 85% of condition-specific variables required manual chart abstraction. The study conducted with CODA contributed to 18 studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad.

Finding MeVO: Identifying Intracranial Medium-Vessel Occlusions at CT Angiography.

The development of methods to detect and treat intracranial large-vessel occlusions (LVOs) has revolutionized the management of acute ischemic stroke. CT angiography (CTA) of the head and neck is effective in depicting LVOs and widely used in the evaluation of patients who have had a stroke. Ongoing efforts are now focused on the potential to detect and treat intracranial medium-vessel occlusions (MeVOs), which by definition are smaller than LVOs and thus more difficult to detect with CTA. The authors review common and variant anatomies of medium-sized cerebral arteries and the appearance of a variety of MeVOs on CT angiograms. Possible pitfalls in MeVO detection include rare anatomic variants, calcified thrombi, and stump occlusions. Current recommendations for performing CTA and ancillary methods that might aid in MeVO detection are discussed. Understanding the relevant anatomy and the variety of appearances of MeVOs aids radiologists in identifying these occlusions, particularly in the setting of urgent stroke. ©RSNA, 2024 See the invited commentary by Ospel and Nguyen in this issue.

The TRIM-NHL RNA-binding protein Brain Tumor coordinately regulates expression of the glycolytic pathway and vacuolar ATPase complex.

The essential Drosophila RNA-binding protein Brain Tumor (Brat) represses specific genes to control embryogenesis and differentiation of stem cells. In the brain, Brat functions as a tumor suppressor that diminishes neural stem cell proliferation while promoting differentiation. Though important Brat-regulated target mRNAs have been identified in these contexts, the full impact of Brat on gene expression remains to be discovered. Here, we identify the network of Brat-regulated mRNAs by performing RNA sequencing (RNA-seq) following depletion of Brat from cultured cells. We identify 158 mRNAs, with high confidence, that are repressed by Brat. De novo motif analysis identified a functionally enriched RNA motif in the 3' untranslated regions (UTRs) of Brat-repressed mRNAs that matches the biochemically defined Brat binding site. Integrative data analysis revealed a high-confidence list of Brat-repressed and Brat-bound mRNAs containing 3'UTR Brat binding motifs. Our RNA-seq and reporter assays show that multiple 3'UTR motifs promote the strength of Brat repression, whereas motifs in the 5'UTR are not functional. Strikingly, we find that Brat regulates expression of glycolytic enzymes and the vacuolar ATPase complex, providing new insight into its role as a tumor suppressor and the coordination of metabolism and intracellular pH.

Frustrative Nonreward: Behavior, Circuits, Neurochemistry, and Disorders.

The surprising omission or reduction of vital resources (food, fluid, social partners) can induce an aversive emotion known as frustrative nonreward (FNR), which can influence subsequent behavior and physiology. FNR is an integral mediator of irritability/aggression, motivation (substance use disorders, depression), anxiety/fear/threat, learning/conditioning, and social behavior. Despite substantial progress in the study of FNR during the twentieth century, research lagged in the later part of the century and into the early twenty-first century until the National Institute of Mental Health's Research Domain Criteria initiative included FNR and loss as components of the negative valence domain. This led to a renaissance of new research and paradigms relevant to basic and clinical science alike. The COVID-19 pandemic's extensive individual and social restrictions were correlated with increased drug and alcohol use, social conflict, irritability, and suicide, all potential consequences of FNR. This article highlights animal models related to these psychiatric disorders and symptoms and presents recent advances in identifying the brain regions and neurotransmitters implicated.

Performance replication of the Hospital Mental Health Risk Screen in ethnoracially diverse U.S. patients admitted through emergency care.

BACKGROUND: Patients admitted to hospitals after emergency care for injury or acute illness are at risk for later mental health problems. The American College of Surgeons Committee on Trauma Standards for care of injured patients call for mental health risk screening, and the Hospital Mental Health Risk Screen (HMHRS) accurately identified at-risk patients in a developmental study that included patients from five ethnoracial groups. Replication of these findings is essential, because initial positive results for predictive screens can fail to replicate if the items were strongly related to outcomes in the development sample but not in a new sample from the population the screen was intended for. STUDY DESIGN: Replication of the predictive performance of the 10-item HMHRS was studied prospectively in ethnoracially diverse patients admitted after emergency care for acute illness or injury in three hospitals across the U.S. RESULTS: Risk screen scores and follow-up mental health outcomes were obtained for 452 of 631 patients enrolled (72%). A cut score of 10 on the HMHRS correctly identified 79% of the patients who reported elevated levels of depression, anxiety, and PTSD symptoms two months post-admission (sensitivity) and 72% of the patients whose symptoms were not elevated (specificity). HMHRS scores also predicted well for patients with acute illness, for patients with injuries, and for patients who reported an Asian American/Pacific Islander, Black, Latinx, Multirace, or White identity. CONCLUSIONS: Predictive performance of the HMHRS was strong overall and within all five ethnoracial subgroups. Routine screening could reduce suffering and health care costs, increase health and mental health equity, and foster preventive care research and implementation. The performance of the HMHRS should be studied in other countries and in other populations of recent trauma survivors, such as survivors of disaster or mass violence.

What are the public health benefits of community-based education in dentistry? A scoping review.

Aim To examine what is known about the public health benefits of community-based education in dentistry.Method A scoping review was conducted using a modified Arksey and O'Malley framework. Database searches were undertaken on PubMed, Medline via Ovid, CINAHL via EBSCO and ERIC, and a grey literature search was undertaken on OpenGrey, Medlar, BASE and the British Library. Reference lists of included studies were also searched. Although no formal quality assessment was undertaken, observations on methodological rigour were recorded.Results In total, 31 studies from nine countries met the inclusion criteria. Most were from high-income countries. Methodologies of included studies varied: quantitative (n = 17); qualitative (n = 5); mixed methods (n = 6); and reviews (n = 3). Several potential public health benefits were reported: increased access to dental services (including improvements in their availability, affordability, acceptability, accessibility, and accommodation); improved awareness/health literacy of students and communities; and improved clinical outcomes. The overall quality of the evidence was low and had little community engagement.Conclusion Notwithstanding the methodological limitations of the included studies, several potential public health benefits have been associated with community-based education in dentistry. Rigorously designed, methodologically appropriate research is needed, which should include engagement with communities.

Unexpected westward range shifts in European forest plants link to nitrogen deposition.

Climate change is commonly assumed to induce species' range shifts toward the poles. Yet, other environmental changes may affect the geographical distribution of species in unexpected ways. Here, we quantify multidecadal shifts in the distribution of European forest plants and link these shifts to key drivers of forest biodiversity change: climate change, atmospheric deposition (nitrogen and sulfur), and forest canopy dynamics. Surprisingly, westward distribution shifts were 2.6 times more likely than northward ones. Not climate change, but nitrogen-mediated colonization events, possibly facilitated by the recovery from past acidifying deposition, best explain westward movements. Biodiversity redistribution patterns appear complex and are more likely driven by the interplay among several environmental changes than due to the exclusive effects of climate change alone.

Magnetic diffusion in solar atmosphere produces measurable electric fields.

The efficient release of magnetic energy in astrophysical plasmas, such as during solar flares, can in principle be achieved through magnetic diffusion, at a rate determined by the associated electric field. However, attempts at measuring electric fields in the solar atmosphere are scarce, and none exist for sites where the magnetic energy is presumably released. Here, we present observations of an energetic event using the National Science Foundation's Daniel K. Inouye Solar Telescope, where we detect the polarization signature of electric fields associated with magnetic diffusion. We measure the linear and circular polarization across the hydrogen Hε Balmer line at 397 nm at the site of a brightening event in the solar chromosphere. Our spectro-polarimetric modeling demonstrates that the observed polarization signals can only be explained by the presence of electric fields, providing conclusive evidence of magnetic diffusion, and opening a new window for the quantitative study of this mechanism in space plasmas.

BLU-945, a potent and selective next-generation EGFR TKI, has antitumor activity in models of osimertinib-resistant non-small-cell lung cancer.

Introduction: Despite the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), most patients with non-small-cell lung cancer (NSCLC) eventually develop resistance to these agents. Notably, EGFR_C797S mutations confer resistance to the third-generation EGFR-TKI osimertinib and no approved post-osimertinib targeted pharmacology options are currently available. BLU-945 is a novel, reversible, and orally available next-generation EGFR-TKI that selectively targets EGFR-activating (EGFRm) and resistance mutations (including EGFR_C797S) with nanomolar potency while sparing wild-type EGFR in vitro. Methods: In vitro activity of BLU-945 as a single agent and in combination with osimertinib was tested in engineered EGFR-mutant cell lines as well as patient-derived cells and patient-derived organoids. In vivo activity was evaluated in osimertinib-resistant patient-derived xenograft mouse models. Three patient cases from the global, first-in-human, phase I/II SYMPHONY trial (NCT04862780) demonstrating the clinical efficacy of BLU-945 were reported. Results: In vitro BLU-945 demonstrated inhibited cell viability and growth of EGFR-mutant/osimertinib-resistant cell lines. BLU-945 demonstrated in vivo tumor shrinkage in osimertinib-resistant models of NSCLC (osimertinib second line: EGFR_L858R/C797S and third line: EGFR_ex19del/T790M/C797S and L858R/T790M/C797S) both as monotherapy and in combination with osimertinib. BLU-945 also demonstrated tumor shrinkage in patients from the SYMPHONY trial. Conclusion: Our findings demonstrate the preclinical and early clinical activity of BLU-945 in EGFRm NSCLC progressing on previous EGFR-TKIs.

The influence of body mass index on biomarkers of cellular senescence in older adults.

Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index (BMI). After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity BMI categories by linear regression in both cohorts (all p < 0.05). These results highlight the influence of BMI on circulating concentrations of senescence biomarkers.

Atrial Flutter and Sick Sinus Syndrome.

BACKGROUND: Sick sinus syndrome (SSS) is a common condition resulting in reduced quality of life, syncope, and pacemaker (PPM) implantation, but predictors have not been elucidated. While atrial arrhythmias are frequently associated with SSS, we hypothesized that atrial flutter (AFL) would strongly predict SSS given shared relationships with right atrial, and particularly crista terminalis, fibrosis. OBJECTIVE: To assess the impact of AFL on the occurrence of SSS and associated syncope and PPM implantation. METHODS: Healthcare databases were used to identify adults aged ≥ 18 years receiving hospital-based care in California in 2005-2019. ICD codes were used to identify diagnoses and procedures. Patients were classified based on the presence of AFL and atrial fibrillation (AF). Cox proportional hazard models adjusting for demographics and co-morbidities were employed. RESULTS: We included 29,357,609 individuals (54% females, mean age 46 years), 101,243 with AFL alone, 1,674,680 with AF alone, and 284,547 with AF and AFL. After adjustment for age, sex, race and ethnicity, and co-morbidities, AF, AFL, and both arrhythmias were each associated with increased risk of SSS and associated syncope and PPM implantation (all p<0.001). In the population with AF, an additional AFL diagnosis conferred a higher risk of developing SSS (hazard ratio [HR]1.62, 95% confidence interval [CI] 1.59-1.64), syncope (HR 1.63, 1.54-1.72) and PPM implantation (HR 1.74, 1.70-1.79). CONCLUSION: AFL is associated with an increased risk of incident SSS and its adverse consequences, especially in patients with co-existing AF. AFL may be useful for risk stratification strategies to predict, prevent, and treat SSS.

Application of validated size-exclusion chromatography method for physicochemical characterization of topical gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles.

The focus of current research work was to develop and validate size-exclusion chromatography method and develop and evaluate gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles (DEF-PEG-CNP) for topical delivery. Size-exclusion chromatography-based method was validated as per ICH guidelines. Effect of Carbopol® 974P and Transcutol® on the nanoparticles' permeation was studied by 3-level full factorial design of experiment. Gel formulations were characterized for viscosity, cohesive and adhesive force by texture analyzer, and drug permeation through pig ear and human skin. The analytical method was specific as no interference from solvent or excipients were observed and met preset criteria of validation with limit of quantification of 0.24 ± 0.00 µg/mL. The nanoparticles permeation, steady state flux, and retained drug were statistically (p < 0.05) affected by Carbopol® 974P and Transcutol® percentage in the gel formulations. The permeation, steady state flux, and retained nanoparticles from the gel formulations varied from 23.2 ± 2.5 % to 70.9 ± 113.3 %, 0.8 ± 0.3 to 6.6 ± 2.1 µg/cm2.h, and 5.6 ± 0.3 to 38.8 ± 8.8 µg/g, respectively. Permeation of the nanoparticles was 1.9 folds higher in pig skin compared to human skin. Immunofluorescence detected successful permeation of DEF-PEG-CNP particles into skin. In conclusion, the analytical method can quantify the nanoparticles from the gel formulation without interference, and gel formulation of the nanoparticles can permeate across the skin.

Efficient Ground-State Recovery of UV-Photoexcited p-Nitrophenol in Aqueous Solution by Direct and Multistep Pathways.

Nitroaromatic compounds are found in brown carbon aerosols emitted to the Earth's atmosphere by biomass burning, and are important organic chromophores for the absorption of solar radiation. Here, transient absorption spectroscopy spanning 100 fs-8 µs is used to explore the pH-dependent photochemical pathways for aqueous solutions of p-nitrophenol, chosen as a representative nitroaromatic compound. Broadband ultrafast UV-visible and infrared probes are used to characterize the excited states and intermediate species involved in the multistep photochemistry, and to determine their lifetimes under different pH conditions. The assignment of absorption bands, and the dynamical interpretation of our experimental measurements are supported by computational calculations. After 320 nm photoexcitation to the first bright state, which has 1ππ* character in the Franck-Condon region, and ultrafast (∼200 fs) structural relaxation in the adiabatic S1 state to a region with 1nπ* electronic character, the S1 p-nitrophenol population decays on a time scale of ∼12 ps. This decay involves competition between direct internal conversion to the S0 state (∼40%) and rapid intersystem crossing to the triplet manifold (∼60%). Population in the T1-state decays by excited-state proton transfer (ESPT) to the surrounding water and relaxation of the resulting triplet-state p-nitrophenolate anion to its S0 electronic ground state in ∼5 ns. Reprotonation of the S0-state p-nitrophenolate anion recovers p-nitrophenol in its electronic ground state. Overall recovery of the S0 state of aqueous p-nitrophenol via these competing pathways is close to 100% efficient. The experimental observations help to explain why nitroaromatic compounds such as p-nitrophenol resist photo-oxidative degradation in the environment.

The influence of sex on neuroimmune communication, pain, and physiology.

With the National Institutes of Health's mandate to consider sex as a biological variable (SABV), there has been a significant increase of studies utilizing both sexes. Historically, we have known that biological sex and hormones influence immunological processes and now studies focusing on interactions between the immune, endocrine, and nervous systems are revealing sex differences that influence pain behavior and various molecular and biochemical processes. Neuroendocrine-immune interactions represent a key integrative discipline that will reveal critical processes in each field as it pertains to novel mechanisms in sex differences and necessary therapeutics. Here we appraise preclinical and clinical literature to discuss these interactions and key pathways that drive cell- and sex-specific differences in immunity, pain, and physiology.

In the last decade, NIH-funded basic and clinical research studies have been mandated to include sex as a biological variable, and this has resulted in a boom of studies discovering sex differences. We know that females are more likely than males to develop chronic pain conditions and experience higher levels of pain for longer periods of time. Conditions that demonstrate this include migraine, arthritis, and peripheral neuropathy. Furthermore, these sex differences extend to surgical outcomes and are observable at the molecular, cellular, and systemic levels. Although pain perception pathways differ by sex, studies are also focusing on differences in the "conversation" between the immune system and the nervous system while addressing implications of sex hormones to gain a better understanding of the impact on pain, physiology, and behavior. Lifestyle factors such as diet and alcohol consumption also play a role in affecting the perception and impact of pain conditions. As this area of research continues to grow, the development and availability of sex-specific treatment options will grow and lead to improved patient outcomes and more effective pain management strategies.

A formally exact theory to construct nonreactive forcefields using linear regression to optimize bonded parameters.

This article derives theoretical foundations of force field functional theory (FFFT). FFFT studies topics related to the functional representation of nonreactive forcefields to achieve various desirable properties such as: (a) formal exactness of the forcefield's energy functional under certain conditions, (b) a formally exact ansatz separating the bonded potential energy from the nonbonded potential energy within a bonded cluster in a way that enables bonded parameters to be optimized using linear regression instead of requiring nonlinear regression, (c) the potential energy's continuous differentiability to various orders with respect to energetically accessible internal coordinate displacements within a subdomain defined by one electronic ground state, (d) forcefield design that guarantees the reference ground-state geometry is exactly reproduced as an equilibrium structure on the forcefield's potential energy landscape, (e) reasonably accurate and broadly applicable frugal model potentials, (f) computationally efficient embedded feature selection that identifies and removes unimportant forcefield terms, (g) well-designed methods to parameterize the forcefield from quantum-mechanically-computed and (optionally) experimental reference data, and (h) forcefields that approximately reproduce experimentally-measured properties. This article also introduces: (1) an angle-bending model potential that more accurately describes physical dynamics and is continuously differentiable to all orders with respect to internal coordinate displacements even when the bond angle is linear (i.e., θ = π (180°)) and (2) a first-principles-derived stretch potential that accurately describes short-range Pauli repulsion and the long-range bond dissociation energy. This new angle-bending potential gave good agreement to CCSD quantum-chemistry calculations for CaH2, CO2, H2O, HNO, Li2O, NO2, NS2, SF2, SiH2, and SO2 molecules. This new bond-stretch potential reproduced the first 12+ and 30+ vibrational energy levels of H2 and O2 molecules, respectively, within a few percent of experimental values. Studying the C-F bond stretch in C6F6 as an example, the new ansatz (item (b) above) reduced sensitivity of the optimized force constant's value to choice of nonbonded interaction parameters by an order of magnitude compared to the old ansatz. Normal mode analysis of optimized flexibility models for CO2, H2O, HNO, and SO2 molecules yielded vibrational transition frequencies within a few percent of experimental values. These results demonstrate advantages of this new approach.

New Linked Employee-Employer Data Show Workforce Composition Is Associated With Health Insurance Offers Among Small Employers.

Decades of research shows that small firms are much less likely to offer health insurance than large firms, but less is known about differences among small employers. We examine this issue using the Medical Expenditure Panel Survey-Insurance Component with Administrative Records (MEPS-ICAR), a unique employer-employee linked data set that is constructed by matching the Medical Expenditure Panel Survey-Insurance Component (MEPS-IC) to Internal Revenue Service administrative records and the Decennial Census. Multivariate analyses show that among firms with fewer than 50 workers, the probability that workers receive an insurance offer is positively associated with higher median workforce incomes, and conditional offers of dependent coverage increase when the majority of workers are married or from a family with at least three members. This first application of the MEPS-ICAR highlights the significance of workforce characteristics in shaping small employer insurance benefits and the data's usefulness for expanding analyses of policy changes, wage-benefit tradeoffs, and health insurance benefits.

The impact of mineralocorticoid and glucocorticoid receptor interaction on corticosteroid transcriptional outcomes.

The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are members of the steroid receptor subfamily of nuclear receptors. Their main function is to act as ligand-activated transcription factors, transducing the effects of corticosteroid hormones (aldosterone and glucocorticoids) by modulating gene expression. Corticosteroid signaling is essential for homeostasis and adaptation to different forms of stress. GR responds to glucocorticoids by regulating genes involved in development, metabolism, immunomodulation and brain function. MR is best known for mediating the effects of aldosterone, a key hormone controlling electrolyte and water homeostasis. In addition to aldosterone, MR binds glucocorticoids (cortisol and corticosterone) with equally high affinity. This ligand promiscuity has important repercussions to understand MR function, as well as glucocorticoid signaling. MR and GR share significant sequence and structural similarities, regulate overlapping sets of genes and are able to interact forming heteromeric complexes. However, the precise role of these heteromers in regulating corticosteroid-regulated transcriptional outcomes remains an open question. In this review, we examine the evidence supporting MR-GR heteromerization, the molecular determinants of complex formation and their possible role in differential regulation of transcription in different cellular contexts and ligand availability.