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Pathogenic variants in the transcription factor TP63 are associated with clinically overlapping syndromes including ectrodactyly-ectodermal dysplasia clefting (EEC) and ankyloblepharon-ectodermal defects-cleft lip/palate (AEC). T cell lymphopenia has rarely been described in individuals with TP63 variants and the cause of the T cell defect is unclear. Here, we present a case of a female infant born with TP63-related syndrome and profound T cell lymphopenia, first uncovered through newborn screening. Flow cytometry analysis revealed low CD4+ naïve T cells and nearly absent CD8+ T cells with intact B and NK cell compartments. A de novo heterozygous pathogenic variant c.1040 G>A (C347Y) in exon 8 of TP63 was identified. An artificial thymic organoid system, to assess the intrinsic ability of the patient's hematopoietic cells to develop into T cells, was performed twice using separate peripheral blood samples. Ex vivo T cell differentiation was evident with the artificial organoid system, suggesting that a thymic stromal cell defect may be the cause of the T cell lymphopenia. Consistent with this, interrogation of publicly available data indicated that TP63 expression in the human thymus is restricted to thymic epithelial cells. Based on these data, congenital athymia was suspected and the patient received an allogenic cultured thymus tissue implant (CTTI). This is the first report of suspected congenital athymia and attempted treatment with CTTI associated with TP63 variant. At 9 months post-implant, peripheral lymphocyte analysis revealed measurable T cell receptor excision circles and presence of CD4+ recent thymic emigrants suggestive of early thymopoiesis. She will continue regular monitoring to ensure restoration of T cell immunity. [ABSTRACT FROM AUTHOR]

Increased temperatures are altering rates of organic matter (OM) breakdown in stream ecosystems with implications for carbon (C) cycling in the face of global change. The metabolic theory of ecology (MTE) provides a framework for predicting temperature effects on OM breakdown, but differences in the temperature dependence of breakdown driven by different organismal groups (i.e., microorganisms vs. invertebrate detritivores) and litter species remain unresolved. Over two years, we conducted 12 60‐day leaf litterbag incubations in 20 headwater streams in the southern Appalachian Mountains (USA). We compared temperature dependence (as activation energy, Ea) between microbial and detritivore‐mediated breakdown, and between a highly recalcitrant (Rhododendron maximum) and a relatively labile (Acer rubrum) leaf species. Detritivore‐mediated breakdown had a higher Ea than microbial breakdown for both leaf species (Rhododendron: 1.48 > 0.56 eV; Acer: 0.97 > 0.29 eV), and Rhododendron breakdown had a higher Ea than Acer breakdown for both organismal groups. Similarly, the Ea of total (coarse‐mesh) Rhododendron breakdown was higher than the Ea of total Acer breakdown (0.89 > 0.52 eV). These effects for total breakdown were large, implying that the number of days to 95% mass loss would decline by 40% for Rhododendron and 26% for Acer between 12°C (our mean temperature value) and 16°C (+4°C, reflecting projected increases in global surface temperature due to climate change). Despite patterns in Ea, overall breakdown rates were higher for microbes than detritivores, and for Acer than Rhododendron over most of our temperature gradient. Additionally, the Ea for a subset of the microbial breakdown data declined from 0.40 to 0.22 eV when fungal biomass was included as a model predictor, highlighting the key role of fungi in determining the temperature dependence of litter breakdown. Our results imply that, as streams warm, routing of leaf litter C to detritivore‐mediated fates will increase faster than predicted by previous studies and MTE, especially for labile litter. As temperatures rise, earlier depletion of autumn‐shed, labile leaf litter combined with rapid breakdown rates of recalcitrant litter could exacerbate seasonal resource limitation and alter carbon storage and transport dynamics in temperate headwater stream networks. [ABSTRACT FROM AUTHOR]

Objectives: Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA. Methods: The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured. Results: The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task. Conclusions: Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition. [ABSTRACT FROM AUTHOR]

Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABAARs by promoting assembly of the postsynaptic gephyrin scaffold. Intriguingly, loss of Nlgn2 differentially affects subsets of GABAergic synapses, indicating that synapse-specific interactors and redundancies define its function, but the nature of these interactions remain poorly understood. Here we investigated how Nlgn2 function in hippocampal area CA1 is modulated by two proposed interaction partners, MDGA1 and MDGA2. We show that loss of MDGA1 expression, but not heterozygous deletion of MDGA2, ameliorates the abnormal cytosolic gephyrin aggregation, the reduction in inhibitory synaptic transmission and the exacerbated anxiety-related behaviour characterizing Nlgn2 knockout (KO) mice. Additionally, combined Nlgn2 and MDGA1 deletion causes an exacerbated layer-specific loss of gephyrin puncta. Given that both Nlgn2 and the MDGA1 have been correlated with many psychiatric disorders, our data support the notion that cytosolic gephyrin aggregation may represent an interesting target for novel therapeutic strategies. Analysis of inhibitory synapses in mouse hippocampus uncovers functional interactions between postsynaptic organizer proteins Neuroligin-2 and MDGA1 in regulating gephyrin aggregation, GABAergic synaptic transmission, and behavior. [ABSTRACT FROM AUTHOR]

Accurate assessment of post-stroke deficits is crucial in translational research. Recent advances in machine learning offer precise quantification of rodent motor behavior post-stroke, yet detecting lesion-specific upper extremity deficits remains unclear. Employing proximal middle cerebral artery occlusion (MCAO) and cortical photothrombosis (PT) in mice, we assessed post-stroke impairments via the Staircase test. Lesion locations were identified using 7 T-MRI. Machine learning was applied to reconstruct forepaw kinematic trajectories and feature analysis was achieved with MouseReach, a new data-processing toolbox. Lesion reconstructions pinpointed ischemic centers in the striatum (MCAO) and sensorimotor cortex (PT). Pellet retrieval alterations were observed, but were unrelated to overall stroke volume. Instead, forepaw slips and relative reaching success correlated with increasing cortical lesion size in both models. Striatal lesion size after MCAO was associated with prolonged reach durations that occurred with delayed symptom onset. Further analysis on the impact of selective serotonin reuptake inhibitors in the PT model revealed no clear treatment effects but replicated strong effect sizes of slips for post-stroke deficit detection. In summary, refined movement analysis unveiled specific deficits in two widely-used mouse stroke models, emphasizing the value of deep behavioral profiling in preclinical stroke research to enhance model validity for clinical translation. [ABSTRACT FROM AUTHOR]

Air quality sensor (AQS) networks are useful for mapping PM 2.5 (particles with a diameter of 2.5 µm or smaller) in urban environments, but quantitative assessment of the observed spatial and temporal variation is currently underdeveloped. This study introduces a new metric – the concentration similarity index (CSI) – to facilitate a quantitative and time-averaged comparison of the concentration–time profiles of PM 2.5 measured by each sensor within an air quality sensor network. Following development on a dataset with minimal unexplained variation and robust tests, the CSI function is used to represent an unbiased and fair depiction of the air quality variation within an area covered by a monitoring network. The measurement data is used to derive a CSI value for every combination of sensor pairs in the network, yielding valuable information on spatial variation in PM 2.5. This new method is applied to two separate AQS networks, in Dungarvan and in the city of Cork, Ireland. In Dungarvan there was a lower mean CSI value (x‾CSI, Dungarvan=0.61 , x‾CSI, Cork=0.71), indicating lower overall similarity between locations in the network. In both networks, the average diurnal plots for each sensor exhibit an evening peak in PM 2.5 concentration due to emissions from residential solid-fuel burning; however, there is considerable variation in the size of this peak. Clustering techniques applied to the CSI matrices identify two different location types in each network; locations in central or residential areas that experience more pollution from solid-fuel burning and locations on the edge of the urban areas that experience cleaner air. The difference in mean PM 2.5 between these two location types was 6 µgm-3 in Dungarvan and 2 µgm-3 in Cork. Furthermore, the examination of winter and summer months (January and May) indicates that higher PM 2.5 levels during periods of increased residential solid-fuel burning act as a major driver for greater differences (lower similarity indices) between locations in both networks, with differences in mean seasonal CSI values exceeding 0.25 and differences in mean seasonal PM 2.5 exceeding 7 µgm-3. These findings underscore the importance of including wintertime PM data in analyses, as the differences between locations is enhanced during periods when solid-fuel burning activities are at a peak. Additionally, the CSI method facilitates the assessment of the representativeness of the PM 2.5 measured at regulatory air quality monitoring locations with respect to population exposure, showing here that location type is more important than physical proximity in terms of similarity and spatial representativeness assessments. Applying the CSI in this manner can allow for the placement of monitoring infrastructure to be optimised. The results indicate that the population exposure to PM 2.5 in Dungarvan is moderately represented (x‾CSI=0.63) by the current regulatory monitoring location, and the regulatory monitoring location assessed in Cork represented the city-wide PM 2.5 levels well (x‾CSI=0.76). [ABSTRACT FROM AUTHOR]

Objective: Retrospectively evaluate multimodality imaging features of perinephric myxoid pseudotumor of fat (PMPTF). Methods: Institutional cases of PMPTF with CT, MRI and/or ultrasound evaluation from 1/1/2020 to 9/1/2023 were retrospectively reviewed. Patient demographics and clinical history were reviewed, and imaging features recorded. Results: 14 patients with pathologically-proven PMPTF were identified (11 M, 3 F; mean age 66.7 ± 17.0 years; range 40–87 years). Three patients (18%) had bilateral lesions; a total of 17 PMPTFs were reviewed. 15/17 (88%) were biopsy-proven; two cases were diagnosed by imaging only in patients with a contralateral biopsy-proven PMPTF. All evaluable specimens were negative for MDM2 amplification. 11/17 (65%) occurred in patients with renal disease, including 4/17 (24%) in patients with renal transplant. 100% (17/17) had CT, 11/17 (65%) MRI, and 6/17 (35%) ultrasound. The mean largest lesion dimension was 10.9 ± 4.6 cm (range 4.3–17.0 cm). Of cases involving native kidneys, 7/13 (54%) presented as multifocal perinephric masses and 5/13 (38%) as a solitary perinephric mass. All four transplant cases presented as infiltrative-appearing masses involving the renal sinus with lesser perinephric involvement. 14/17 (82%) lesions contained macroscopic fat on CT and MRI and 3/17 (18%) showed no macroscopic fat, all involving renal transplants. All cases with MRI demonstrated T2 hyperintensity with signal dropout on opposed-phase imaging. 11/13 (85%) PMPTF showed no or equivocal CT enhancement. Enhancement was better seen on MRI in all cases evaluated by both CT and MRI. Of the six PMPTFs imaged by ultrasound, four (67%) were heterogeneously hypoechoic and two (33%) had mixed regions of hypo-, iso- and hyperechogenicity relative to adjacent renal parenchyma. Conclusions: PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention. [ABSTRACT FROM AUTHOR]

Despite a wealth of research on the decision to notify police following victimization, there has been relative inattention to the role of a basic feature of crime: the tendency for individuals to offend in groups. Following this, the current research examines the influence of co-offending on the decision to notify police using information from the National Crime Victimization Survey. Results indicate that the co-offending is significantly and positively related to the likelihood of notification. Findings further indicate that this relationship is moderated by co-offender characteristics, such that young co-offenders and, to a lesser extent, male co-offenders are more likely than their counterparts to be reported to police. These results have important implications for understanding the invocation of both formal social control and disparities in these processes, indicating that co-offending not only has a direct effect on notification, but that it also changes the effect of offender characteristics on this decision. [ABSTRACT FROM AUTHOR]

Summary: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. Introduction: In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies. Methods: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients. Results: Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level. Conclusion: Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. [ABSTRACT FROM AUTHOR]

Gun violence, often characterized as a singular issue, is not one cohesive problem. Instead, it takes many forms resulting from the complex interplay of multiple factors. Outcomes of gun violence also vary significantly. They may be (a) physically non-injurious (a gun is brandished), (b) injurious but non-lethal, or (c) lethal. To understand and address gun violence effectively, it is essential to consider various risk factors for both non-lethal and lethal gun violence victimization, using a comprehensive, comparative framework. We present a novel comparative framework for better understanding gun violence, and for developing policy responses to this violence. We disaggregate gun violence into its various forms and propose a conceptualization of risk factors in discrete categories, each with important implications for policy intervention. While we emphasize the value of this framework for understanding and combatting interpersonal gun violence in America, the research and policy approaches discussed here should be equally applicable to other international contexts with gun violence as a serious public health issue as well. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases. Bronchopulmonary dysplasia and chronic obstructive pulmonary disease are marked by neutrophilic inflammation and microbial changes. Here, the authors show the efficacy of an inhaled live biotherapeutic in reducing inflammation and improving tissue structure across models of respiratory disease. [ABSTRACT FROM AUTHOR]

People can use their sense of hearing for discerning thermal properties, though they are for the most part unaware that they can do so. While people unequivocally claim that they cannot perceive the temperature of pouring water through the auditory properties of hearing it being poured, our research further strengthens the understanding that they can. This multimodal ability is implicitly acquired in humans, likely through perceptual learning over the lifetime of exposure to the differences in the physical attributes of pouring water. In this study, we explore people's perception of this intriguing cross modal correspondence, and investigate the psychophysical foundations of this complex ecological mapping by employing machine learning. Our results show that not only can the auditory properties of pouring water be classified by humans in practice, the physical characteristics underlying this phenomenon can also be classified by a pre-trained deep neural network. [ABSTRACT FROM AUTHOR]

The Hate Crime Statistics Act (HCSA) of 1990 requires the federal government to publicly release official hate crime statistics annually; the HCSA does not, however, mandate that local agencies submit hate crime reports to the government in the first place. Although research has evaluated the reporting of hate crime statistics in a dichotomous fashion (compliance vs. noncompliance), the current study suggests that the consistent and invariable reporting of zero hate crimes in a particular jurisdiction over time is unlikely and thus better conceptualized as a third response strategy: ceremonious compliance. We examine this strategy as a potentially unique institutional behavior, structured by local political and historical contexts, including discursive differences in the identification of hate crime as an important social problem, and localized histories of racial oppression. This research then uses multilevel multinomial logistic regression models to estimate variation in the likelihood of differential compliance strategies (i.e., true compliance, ceremonious compliance, noncompliance), according to several political and historical factors, including Republican vote share, location in the Confederate South, and historical lynchings. Findings reveal that political and historical contexts are important predictors of agency responses to hate crime, with a particular tendency toward ceremonious compliance in Republican‐leaning locales. [ABSTRACT FROM AUTHOR]

Objectives: While extant research has largely framed prejudicial attitudes as a precursor to hate crime offending, the current research considers the possibility that negative outgroup attitudes may also be an important consequence of hate crime victimization as well. Methods: Using survey data from 3,183 respondents across the United States, this research employs a series of regression models to examine the relationship between hate crime victimization and three different types of prejudicial attitudes: anti-Asian xenophobia, anti-Hispanic xenophobia, and anti-Black prejudice. Results: Results indicate that hate crime victimization is significantly and positively associated with all three prejudicial attitudes, such that those who experienced a hate crime are more likely to report higher levels of anti-Asian xenophobia (b =.455; p <.001), anti-Hispanic xenophobia (b =.408; p <.001), and anti-Black prejudice (b =.360; p <.001). Results also indicate that these patterns are both offender race-specific and stronger for more recent victimization, compared to less recent victimization. Conclusions: When interpreting these results within a pattern matching framework, we argue that they suggest important initial evidence that prejudice may not be just a precursor to hate crime offending, but also a possible consequence of hate crime victimization, thus implying a potentially cyclical relationship between intergroup offending and victimization that should be the subject of future research. [ABSTRACT FROM AUTHOR]

Background/Aims: Athletic trainers are often the point person when sports‐related traumatic dental injuries (TDIs) occur. The aim of this study was to assess knowledge levels of the management of TDIs among athletic trainers in the Midwest United States, as well as evaluate variables that may influence knowledge levels. Material and Methods: A survey was sent to athletic trainers licensed in Minnesota, Nebraska, and Iowa. The survey included 28 multiple‐choice and fill in the blank questions split into three sections. The three sections included background, emergency management of TDIs, and opinion questions. Results: Of the participants, 100% recalled receiving medical first aid training. However, only 71% recalled receiving formal training on emergency management of dental injuries. Although 75% were confident in managing a dental injury, over 63% of participants scored less than 70% in the knowledge score section. Majority of the participants (98.4%) reported that they believe training on the management of TDIs is important. Athletic trainers working with contact sports were more likely to have experienced managing TDIs more recently than those working in noncontact sports. Conclusions: This study shows the gaps in knowledge among athletic trainers pertaining to management of TDIs and emphasizes the importance of sports community having adequate education on emergency management of such dental injuries. [ABSTRACT FROM AUTHOR]

Bergofungin D is a helical peptide of the peptaibol family consisting of 14 amino acids, six of which are the helix inducer aminoisobutyric acid (Aib). In the second third of the sequence, a hydroxyproline causes a bending of the helix and a disruption of the hydrogen bond network, and Aib7 is the only amino acid in this region involved in the hydrogen bond network. Therefore, modification of this residue can serve as a probe to monitor the effect of introducing amino acid substitutions on this more fragile helical turn. To validate this approach, we simplified the original bergofungin D by reducing the number of non‐classical amino acids, replacing the (R)‐isovaleric acid by its enantiomer or an Aib and the hydroxyproline with a proline, respectively, without affecting its secondary structure. Within the modified structure, we replaced Aib7‐Aib8 by its 1,2,3‐triazolodipeptide equivalent or Aib7 by a serine or a dehydrobutyrine. We have reported and analyzed five crystal structures, three of which are new, demonstrating the usefulness of the modified bergofungin D as a probe for monitoring the introduction of amino acid substitutions within a helical structure. [ABSTRACT FROM AUTHOR]

An editorial is presented on the 2023 European Society of Cardiology (ESC) Guidelines for the Management of Acute Coronary Syndromes (ACS). Topics include the comprehensive management approach from admission to long-term care, the emphasis on a person-centered approach including symptom recognition and patient education, and the recommendations for antithrombotic therapy and long-term treatment strategies.

The graphene adjustable-barriers phototransistor is an attractive novel device for potential high speed and high responsivity dual-band photodetection. In this device, graphene is embedded between the semiconductors silicon and germanium. Both n-type and p-type Schottky contacts between graphene and the semiconductors are required for this device. While n-type Schottky contacts are widely investigated, reports about p-type Schottky contacts between graphene and the two involved semiconductors are scarce. In this study, we demonstrate a p-type Schottky contact between graphene and p-germanium. A clear rectification with on–off ratios of close to 103 (±5 V) and a distinct photoresponse at telecommunication wavelengths in the infrared are achieved. Further, p-type silicon is transferred to or deposited on graphene, and we also observe rectification and photoresponse in the visible range for some of these p-type Schottky junctions. These results are an important step toward the realization of functional graphene adjustable-barrier phototransistors. [ABSTRACT FROM AUTHOR]

Background: End‐of‐life (EOL) care patterns may differ by physician age given differences in how physicians are trained or changes associated with aging. We sought to compare patterns of EOL care delivered to older Americans according to physician age. Methods: We conducted a cross‐sectional study of a 20% sample of Medicare fee‐for‐service beneficiaries aged ≥66 years who died in 2016–2019 (n = 487,293). We attributed beneficiaries to the physician who had >50% of primary care visits during the last 6 months of life. We compared beneficiary‐level outcomes by physician age (<40, 40–49, 50–59, or ≥60) in two areas: (1) advance care planning (ACP) and palliative care; and (2) high‐intensity care at the EOL. Results: Beneficiaries attributed to younger physicians had slightly higher proportions of billed ACP (adjusted proportions, 17.1%, 16.1%, 15.5%, and 14.0% for physicians aged <40, 40–49, 50–59, and ≥60, respectively; p‐for‐trend adjusted for multiple comparisons <0.001) and palliative care counseling or hospice use in the last 180 days of life (64.5%, 63.6%, 61.9%, and 60.8%; p‐for‐trend <0.001). Similarly, physicians' younger age was associated with slightly lower proportions of emergency department visits (57.4%, 57.0%, 57.4%, and 58.1%; p‐for‐trend <0.001), hospital admissions (51.2%, 51.1%, 51.4%, and 52.1%; p‐for‐trend <0.001), intensive care unit admissions (27.8%, 27.9%, 28.2%, and 28.3%; p‐for‐trend = 0.03), or mechanical ventilation or cardiopulmonary resuscitation (14.2, 14.9%, 15.2%, and 15.3%; p‐for‐trend <0.001) in the last 30 days of life, and in‐hospital death (20.2%, 20.6%, 21.3%, and 21.5%; p‐for‐trend <0.001). Conclusions: We found that differences in patterns of EOL care between beneficiaries cared for by younger and older physicians were small, and thus, not clinically meaningful. Future research is warranted to understand the factors that can influence patterns of EOL care provided by physicians, including initial and continuing medical education. [ABSTRACT FROM AUTHOR]

Pretrial assessments are criticized for inherent biases. We conduct research in Kentucky to assess the predictive validity and differential prediction by sex of one pretrial assessment, the Public Safety Assessment (PSA). Our research is unique because we find equal base rates by sex for missing a court date, which allows us to assess for error rate balance by sex. We find the PSA to have predictive validity within acceptable ranges for the criminal legal field. The analyses show a lack of evidence of predictive bias for any arrest or missing a court date, and we find equal error rates for five different error measures. The analyses contribute to methodological debates about how to measure predictive bias with assessments. [ABSTRACT FROM AUTHOR]

In many European countries with plentiful forest resources, novel forest‐based businesses play a key role in the transition from our current fossil‐based economy towards a circular bioeconomy. For example, kraft lignin, a by‐product from the pulping industry, is produced in large amounts globally. To date, however, it is still only offered on the market by a small number of pulping companies. The successful innovation diffusion of related new technologies and businesses requires establishing a collective effort among multiple societal actors to motivate the sharing of value creation processes. In this paper, potential innovation diffusion pathways are modeled and simulated by means of an agent‐based approach (Biorefinery Products Innovation Diffusion model, BioPID). The paper investigates the conditions needed to encourage the diffusion of kraft lignin innovations as a (partial) replacement for fossil‐based feedstock in selected applications. The results reveal the basic mechanisms behind potential innovation diffusion pathways. The major barriers were found to be the high level of uncertainty surrounding the additional costs arising in lignin processing, the small number of lignin providers, and the presence of relatively homogeneous pricing strategies based on opportunity and basic preparation costs. The analysis of two product categories revealed different patterns in terms of innovation diffusion and potential greenhouse gas emissions. A novelty of BioPID is that it allows for iterative technology evaluation and technology foresight analysis of biorefinery projects (e.g., by combining techno‐economic, socio‐technical, and environmental aspects). This produces knowledge for diverse stakeholders involved in the lignin innovation ecosystem, thus enabling better communication on shared values and furthering innovation diffusion. [ABSTRACT FROM AUTHOR]

In this study, the resistive switching phenomena in TiN/Ti/HfO2/Ti metal–insulator–metal stacks is investigated, mainly focusing on the analysis of set and reset transitions. The electrical measurements in a wide temperature range reveal that the switching transitions require less voltage (and thus, less energy) as temperature rises, with the reset process being much more temperature sensitive. The main conduction mechanism in both resistance states is Space-charge-limited Conduction, but the high conductivity state also shows Schottky emission, explaining its temperature dependence. Moreover, the temporal evolution of these transitions reveals clear differences between them, as their current transient response is completely different. While the set is sudden, the reset process development is clearly non-linear, closely resembling a sigmoid function. This asymmetry between switching processes is of extreme importance in the manipulation and control of the multi-level characteristics and has clear implications in the possible applications of resistive switching devices in neuromorphic computing. [ABSTRACT FROM AUTHOR]

This paper introduces out-of-focus spatial map imaging (SMI) as a detection method for magnetic deflection of molecular/cluster beams, using Nam(NH3)n to illustrate its capabilities. This method enables imaging of the complete spatial distribution, simplifying measurements and allowing for cluster-size-resolved analysis by shifting away from traditional in-focus SMI conditions. Incorporating out-of-focus SMI with TOF-MS and velocity map imaging into a single setup allows for direct assessment of clusters' magnetic moments without needing to pre-select velocities. Key findings include a slower relaxation for Na(NH3)4 compared to Na(NH3)3 and Na(NH3)5, unexpectedly high deflection for larger clusters up to Na(NH3)9, hinting at changes in cluster dynamics as the first solvation shell closes. The study also covers the first measurements of Na2(NH3)1 and Na3(NH3)n, showing distinct deflection behaviors and underscoring the improved capabilities of the new detection method. [ABSTRACT FROM AUTHOR]

The Kyrenia Ship, found off the north coast of Cyprus, is a key vessel in the history of scientific underwater excavations and in the history of Greek shipbuilding. The first volume of the site's final publication appeared in 2023 and provides detailed archaeological information tightly constraining the dating of the ship. A very specific date range is proposed: ca. 294–290 BCE, but is based on a less than certain reading of one coin recovered from the ship. While there is clear benefit to finding high-precision dates for the Kyrenia Ship and its rich assemblage using independent scientific dating (combined with Bayesian chronological modeling), efforts to do so proved more challenging and complex than initially anticipated. Strikingly, extensive radiocarbon dating on both wooden materials from the ship and on short-lived contents from the final use of the ship fail to offer dates using the IntCal20 calibration curve—the current Northern Hemisphere radiocarbon calibration curve at the time of writing—that correspond with the archaeological constraints. The issue rests with a segment of IntCal20 ca. 350–250 BCE reliant on legacy pre-AMS radiocarbon data. We therefore measured new known-age tree-ring samples 350–250 BCE, and, integrating another series of new known-age tree-ring data, we obtained a redefined and more accurate calibration record for the period 433–250 BCE. These new data permit a satisfactory dating solution for the ship and may even indicate a date that is a (very) few years more recent than current estimations. These new data in addition confirm and only very slightly modify the dating recently published for the Mazotos ship, another Greek merchant ship from the southern coast of Cyprus. Our work further investigated whether ship wood samples impregnated with a common preservative, polyethylene glycol (PEG), can be cleaned successfully, including a known-age test. [ABSTRACT FROM AUTHOR]

Cancer treatment with anti–PD-1 immunotherapy can cause central nervous system immune-related adverse events (CNS-irAEs). The role of microglia in anti–PD-1 immunotherapy–induced CNS-irAEs is unclear. We found that anti–PD-1 treatment of mice caused morphological signs of activation and major histocompatibility complex (MHC) class II up-regulation on microglia. Functionally, anti–PD-1 treatment induced neurocognitive deficits in mice, independent of T cells, B cells, and natural killer cells. Instead, we found that microglia mediated these CNS-irAEs. Single-cell RNA sequencing revealed major transcriptional changes in microglia upon anti–PD-1 treatment. The anti–PD-1 effects were mediated by anti–PD-1 antibodies interacting directly with microglia and were not secondary to peripheral T cell activation. Using a proteomics approach, we identified spleen tyrosine kinase (Syk) as a potential target in activated microglia upon anti–PD-1 treatment. Syk inhibition reduced microglia activation and improved neurocognitive function without impairing anti-melanoma effects. Moreover, we analyzed CNS tissue from a patient cohort that had received anti–PD-1 treatment. Imaging mass cytometry revealed that anti–PD-1 treatment of patients was associated with increased surface marker expression indicative of microglia activation. In summary, we identified a disease-promoting role for microglia in CNS-irAEs driven by Syk and provide an inhibitor-based approach to interfere with this complication after anti–PD-1 immunotherapy. Editor's summary: Immune checkpoint inhibitors targeting PD-1 and CTLA-4 have revolutionized cancer treatment, but these powerful treatments come at a cost. A subset of patients who receive these therapies develop immune-related adverse events (irAEs). These irAEs can affect multiple tissues, including the central nervous system (CNS). Here, Vinnakota et al. studied the CNS after PD-1 blockade in mice with and without tumors. The authors observed activation of microglia that was associated with behavioral changes. Preventing microglial activation with an inhibitor of Syk improved neurocognitive functions in mice cotreated with PD-1 blockade. Finally, the authors showed that CNS tissue from patients who received PD-1 blockade also had evidence of microglial activation. Together, these data suggest both a cause of CNS-irAEs and a potential therapeutic approach. —Courtney Malo [ABSTRACT FROM AUTHOR]

There has been much progress on mononuclear chromium(III) complexes featuring luminescence and photoredox activity, but dinuclear chromium(III) complexes have remained underexplored in these contexts until now. We identified a tridentate chelate ligand able to accommodate both meridional and facial coordination of chromium(III), to either access a mono‐ or a dinuclear chromium(III) complex depending on reaction conditions. This chelate ligand causes tetragonally distorted primary coordination spheres around chromium(III) in both complexes, entailing comparatively short excited‐state lifetimes in the range of 400 to 800 ns in solution at room temperature and making photoluminescence essentially oxygen insensitive. The two chromium(III) ions in the dimer experience ferromagnetic exchange interactions that result in a high spin (S=3) ground state with a coupling constant of +9.3 cm−1. Photoinduced energy transfer from the luminescent ferromagnetically coupled dimer to an anthracene derivative results in sensitized triplet‐triplet annihilation upconversion. Based on these proof‐of‐principle studies, dinuclear chromium(III) complexes seem attractive for the development of fundamentally new types of photophysics and photochemistry enabled by magnetic exchange interactions. [ABSTRACT FROM AUTHOR]

Classical photochemistry requires nanosecond excited-state lifetimes for diffusion-controlled reactions. Excited radicals with picosecond lifetimes have been implied by numerous photoredox studies, and controversy has arisen as to whether they can actually be catalytically active. We provide direct evidence for the elusive pre-association between radical ions and substrate molecules, enabling photoinduced electron transfer beyond the diffusion limit. A strategy based on two distinct light absorbers, mimicking the natural photosystems I and II, is used to generate excited radicals, unleashing extreme reduction power and activating C(sp2)―Cl and C(sp2)―F bonds. Our findings provide a long-sought mechanistic understanding for many previous synthetically-oriented works and permit more rational future photoredox reaction development. The newly developed excitation strategy pushes the current limits of reactions based on multi-photon excitation and very short-lived but highly redox active species. Classical photochemistry requires nanosecond excited-state lifetimes for diffusion-controlled reactions. Here the authors provide direct evidence for the elusive pre-association between radical ions and substrate molecules, enabling photoinduced electron transfer beyond the diffusion limit. [ABSTRACT FROM AUTHOR]

The conversion of forestlands to alternative land uses is a growing worldwide concern, given the wide range of provisioning and regulating ecosystem services (ES) provided by forests. We applied a scenario-based land-use/land-cover (LULC) projection technique integrating societal preferences, conservation policies, and socio-economic factors to the Upper Flint River Watershed in the Atlanta, Georgia (USA) metropolitan area. We employed the InVEST modeling toolset to assess the impact of anticipated LULC changes on ES under each development scenario. Our simulations projected a consistent conversion from Deciduous/Mixed Forests to either Urban or Evergreen forests across all scenarios, leading to a significant decline in ES. We quantified the economic impacts of this ES loss, conservatively estimated as representing millions of dollars per year under a Business as Usual scenario in just carbon and water services alone. Integrating social and policy drivers into our projection approach yielded policy-relevant results and identified the need for conservation policy instruments to protect forested ecosystems with higher conservation values. Existing conservation policies are unlikely to stem the loss of important ES, and there may be a need to consider more aggressive policies to prevent further degradation of watersheds, such as the one analyzed here. [ABSTRACT FROM AUTHOR]

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Because of their abundance and high emissions rates, small reservoirs (< 0.01 km2) can be important emitters of the greenhouse gases carbon dioxide and methane. However, emissions estimates from small reservoirs have lagged those of larger ones, and efforts to characterize small reservoir emissions have largely overlooked variations in emissions pathways, times, and locations. We intensively sampled four small reservoirs in Georgia, USA, during the summer to quantify the contribution and spatiotemporal variability of different emissions pathways (CO2 and CH4 diffusion, CH4 ebullition). We used these data to evaluate the efficiency and accuracy of different sampling schemes. Every emissions pathway was dominant in one reservoir on one sampling day, and excluding ebullition caused misestimation between −89% and −15% of the total flux. Sampling only once daily caused misestimation between −78% and 45%, but sampling twice or just after dawn (07:00 h) reduced error. Sampling four or fewer locations caused misestimation between −85% and 366%, and our results indicated that 6–20 sampling locations may be needed for reasonable accuracy. The floating aquatic macrophyte Wolffia sp. (duckweed) appeared to exert control over emissions variability, and the consequences of not accounting for variability were greater in a duckweed‐covered reservoir. Our results indicate that sampling only at 10:00 h (modal sampling time of prior efforts) may lead to the erroneous conclusion that reservoirs with high photosynthetic biomass are CO2 sinks rather than sources. Improving estimation accuracy by accounting for within‐reservoir variation in emissions will facilitate more strategic management of these abundant, anthropogenic ecosystems. [ABSTRACT FROM AUTHOR]

It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the litter birth weight phenotype (LBWP) in sows, thereby impacting the BW of entire litters, but the biological and molecular pathways behind this phenomenon are largely unknown. The aim of this study was to investigate the differential gene expression in placental tissues at day 30 of gestation between low LBWP (LLBWP) vs. high LBWP (HLBWP) sows from a purebred Large White maternal line. Using mRNA sequencing, we found 45 differentially expressed genes (DEGs) in placental tissues of LLBWP and HLBWP sows. Furthermore, (GO) enrichment of upregulated DEGs predicted that there were two biological processes significantly related to cornification and regulation of cell population proliferation. To better understand the molecular interaction between cell proliferation and cornification, we conducted transcriptional factor binding site (TFBS) prediction analysis. The results indicated that a highly significant TFBS was located at the 5′ upstream of all four upregulated genes (CDSN, DSG3, KLK14, KRT17), recognized by transcription factors EGR4 and FOSL1. Our findings provide novel insight into how transcriptional regulation of two different biological processes interact in placental tissues of LLBWP sows. [ABSTRACT FROM AUTHOR]

Background: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)). Methods: We recruited 77 patients with relapsing–remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse. Results: After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029). Conclusions: Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone. [ABSTRACT FROM AUTHOR]

A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin's origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants. [ABSTRACT FROM AUTHOR]

All mitochondria import >95% of their proteins from the cytosol. This process is mediated by protein translocases in the mitochondrial membranes, whose subunits are generally highly conserved. Most eukaryotes have two inner membrane protein translocases (TIMs) that are specialized to import either presequence‐containing or mitochondrial carrier proteins. In contrast, the parasitic protozoan Trypanosoma brucei has a single TIM complex consisting of one conserved and five unique subunits. Here, we identify candidates for new subunits of the TIM or the presequence translocase‐associated motor (PAM) using a protein–protein interaction network of previously characterized TIM and PAM subunits. This analysis reveals that the trypanosomal TIM complex contains an additional trypanosomatid‐specific subunit, designated TbTim15. TbTim15 is associated with the TIM complex, lacks transmembrane domains, and localizes to the intermembrane space. TbTim15 is essential for procyclic and bloodstream forms of trypanosomes. It contains two twin CX9C motifs and mediates import of both presequence‐containing and mitochondrial carrier proteins. While the precise function of TbTim15 in mitochondrial protein import is unknown, our results are consistent with the notion that it may function as an import receptor for the non‐canonical trypanosomal TIM complex. [ABSTRACT FROM AUTHOR]

The elucidation of novel bonding situations at heavy p-block elements has greatly advanced recent efforts to access useful reactivity at earth-abundant main-group elements. Molecules with unsaturated bonds between heavier, electropositive elements and lighter, electronegative elements are often highly polarized and competent in small-molecule activations, but the reactivity of these molecules may be quenched by self-association of monomers to form oligomeric species where the polar, unsaturated groups are assembled in a head-to-tail fashion. In this Frontier, we discuss the synthetic strategies employed to isolate monomeric σ2,λ3-stibinidene chalcogenides (RSbCh) and monomeric σ4,λ5-stibine chalcogenides (R3SbCh). These classes of molecules each feature polarized antimony–chalcogenide bonds (Sb = Ch/Sb+–Ch−). We highlight how the synthesis and isolation of these molecules has led to the discovery of novel reactivity and has shed light on fundamental aspects of inorganic structure and bonding. Despite these advances, there are critical aspects of this chemistry that remain underdeveloped and we provide our perspective on yet-unrealized synthetic targets that may be achieved with the continued development of the strategies described herein. [ABSTRACT FROM AUTHOR]

Background: A low technology emanator device for slowly releasing vapour of the volatile pyrethroid transfluthrin was recently developed in Tanzania that provides robust protection against night biting Anopheles and Culex vectors of malaria and filariasis for several months. Here these same emanator devices were assessed in Dar es Salaam city, as a means of protection against outdoor-biting Aedes (Stegomia) aegypti, the most important vector of human arboviruses worldwide, in parallel with similar studies in Haiti and Brazil. Methods: A series of entomological experiments were conducted under field and semi-field conditions, to evaluate whether transfluthrin emanators protect against wild Ae. aegypti, and also compare the transfluthrin responsiveness of Ae. aegypti originating from wild-caught eggs to established pyrethroid-susceptible Ae. aegypti and Anopheles gambiae colonies. Preliminary measurements of transfluthrin vapour concentration in air samples collected near treated emanators were conducted by gas chromatography-mass spectrometry. Results: Two full field experiments with four different emanator designs and three different transfluthrin formulations consistently indicated negligible reduction of human landing rates by wild Ae. aegypti. Under semi-field conditions in large cages, 50 to 60% reductions of landing rates were observed, regardless of which transfluthrin dose, capture method, emanator placement position, or source of mosquitoes (mildly pyrethroid resistant wild caught Ae. aegypti or pyrethroid-susceptible colonies of Ae. aegypti and An. gambiae) was used. Air samples collected immediately downwind from an emanator treated with the highest transfluthrin dose (15g), contained 12 to 19 μg/m3 transfluthrin vapour. Conclusions: It appears unlikely that the moderate levels of pyrethroid resistance observed in wild Ae. aegypti can explain the modest-to-undetectable levels of protection exhibited. While potential inhalation exposure could be of concern for the highest (15g) dose evaluated, 3g of transfluthrin appears sufficient to achieve the modest levels of protection that were demonstrated entomologically. While the generally low levels of protection against Aedes reported here from Tanzania, and from similar entomological studies in Haiti and Brazil, are discouraging, complementary social science studies in Haiti and Brazil suggest end-users perceive valuable levels of protection against mosquitoes. It therefore remains unclear whether transfluthrin emanators have potential for protecting against Aedes vectors of important human arboviruses. [ABSTRACT FROM AUTHOR]

Source apportionment quantitatively links pollution to its source, but can be difficult to perform in areas like ports where emissions from ship and other port-related activities are intrinsically linked. Here we present the analysis of aerosol chemical speciation monitor (ACSM) data and combined organic and sulfate ion positive matrix factorization (PMF) during an intensive measurement campaign in Dublin Port. Two main types of ship emissions were identified by this technique: sulfate-rich (S-Ship) and organic-rich (O-Ship). The S-Ship emissions were attributed to heavy fuel oil use and are characterised by particles with standard V/Ni ratios from 2.7–3.9 and a large fraction of acidic sulfate aerosol. The O-Ship emissions were attributed to low-sulfur fuel types and were comprised mostly of organic aerosol (OA) with the V/Ni ratios ranging only from 0–2.3. O-Ship plumes occurred over three-times more frequently than S-Ship plumes during the measurement period. Ship plumes had PM1 concentrations in the range 4–252 µg m-3, with extreme concentrations usually lasting for 5–35 minutes. A third minor ship emission factor (X-Ship) was resolved by PMF, but not clearly attributable to any specific fuel type. Despite their short duration, shipping emission plumes were frequent and contributed to at least 28 % of PM1 (i.e. 14 % O-Ship, 12 % S-Ship, and 2 % X-Ship). Moreover, hydrocarbon-like organic aerosol (HOA) and black carbon could also originate, at least in part, from ship emissions and shipping related activities, suggesting that the shipping contribution to ambient PM is likely higher, with a maximum of 47 %. [ABSTRACT FROM AUTHOR]

We report the electrochemiluminescence (ECL) of a 3d6 Cr(0) complex ([Cr(LMes)3]; λem=735 nm) with comparable photophysical properties to those of ECL‐active complexes of 4d6 or 5d6 precious metal ions. The electrochemical potentials of [Cr(LMes)3] are more negative than those of [Ir(ppy)3] and render the [Cr(LMes)3]* excited state inaccessible through conventional co‐reactant ECL with tri‐n‐propylamine or oxalate. ECL can be obtained, however, through the annihilation route in which potentials sufficient to oxidise and reduce the luminophore are alternately applied. When combined with [Ir(ppy)3] (λem=520 nm), the annihilation ECL of [Cr(LMes)3] was greatly enhanced whereas that of [Ir(ppy)3] was diminished. Under appropriate conditions, the relative intensities of the two spectrally distinct emissions can be controlled through the applied potentials. From this starting point for ECL with 3d6 metal complexes, we discuss some directions for future development. [ABSTRACT FROM AUTHOR]

We report the electrochemiluminescence (ECL) of a 3d6 Cr(0) complex ([Cr(LMes)3]; λem=735 nm) with comparable photophysical properties to those of ECL‐active complexes of 4d6 or 5d6 precious metal ions. The electrochemical potentials of [Cr(LMes)3] are more negative than those of [Ir(ppy)3] and render the [Cr(LMes)3]* excited state inaccessible through conventional co‐reactant ECL with tri‐n‐propylamine or oxalate. ECL can be obtained, however, through the annihilation route in which potentials sufficient to oxidise and reduce the luminophore are alternately applied. When combined with [Ir(ppy)3] (λem=520 nm), the annihilation ECL of [Cr(LMes)3] was greatly enhanced whereas that of [Ir(ppy)3] was diminished. Under appropriate conditions, the relative intensities of the two spectrally distinct emissions can be controlled through the applied potentials. From this starting point for ECL with 3d6 metal complexes, we discuss some directions for future development. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death. However, the understanding of IRE's impact beyond the initiation of focal cell death in tumor tissue remains limited. In this study, we demonstrate that IRE triggers a unique mix of cell death pathways and orchestrates a shift in the local tumor microenvironment driven, in part, by reducing the myeloid-derived suppressor cell (MDSC) and regulatory T cell populations and increasing cytotoxic T lymphocytes and neutrophils. We further show that IRE drives induce cell cycle arrest at the G0/G1 phase in vitro and promote inflammatory cell death pathways consistent with pyroptosis and programmed necrosis in vivo. IRE-treated mice exhibited a substantial extension in progression-free survival. However, within a span of 14 days, the tumor immune cell populations reverted to their pre-treatment composition, which resulted in an attenuation of the systemic immune response targeting contralateral tumors and ultimately resulting in tumor regrowth. Mechanistically, we show that IRE augments IFN-γ signaling, resulting in the up-regulation of the PD-L1 checkpoint in pancreatic cancer cells. Together, these findings shed light on potential mechanisms of tumor regrowth following IRE treatment and offer insights into co-therapeutic targets to improve treatment strategies. [ABSTRACT FROM AUTHOR]

Many Confederate monuments were erected during the Jim Crow era, sending symbolic messages of intimidation and hostility to the Black population. Yet no studies have examined the relationship between contemporary Confederate memorialization and bias crime. Drawing from research on hate crime law compliance, we posit an inverse relationship between Confederate monuments and mobilization of hate crime law, such that compliance with hate crime laws will be lower in communities with memorialization, but that among complying agencies, anti-Black hate crime rates will be higher. To examine these relationships, we combined data from the Uniform Crime Report Hate Crime Statistics and the American Community Survey with Confederate monument data from the Southern Poverty Law Center. We conducted analyses predicting a) monument presence, b) agency non-compliance, and c) anti-Black hate crime. Results indicate that monuments are located in communities exemplifying a challenge to racial hierarchies: economically advantaged communities with larger Black populations. Regarding hate crime, analyses show that (1) the American South is associated with reduced compliance, and, (2) after accounting for compliance, Confederate memorialization is associated with increased anti-Black hate crime. These findings have implications for intergroup conflict and the impact of local symbolism on the formal mobilization of hate crime law. [ABSTRACT FROM AUTHOR]

Context: Research on emotional intelligence (EI) shows this concept's decades-long positive influence on well-being, self-efficacy, employability, and academic and professional achievement. Indeed, several studies have demonstrated that students with high EI have better grades and quality of life, as well as are more employable than students with low EI. By considering the two conceptualizations of EI as either an ability or personality trait, the present study investigates EI's influence on training achievement in initial vocational education and training (IVET). We posited that the two types of EI positively influence training achievement in a complementary way: Ability EI relates to achievement in theoretical training, while trait EI relates to achievement in practical training. Furthermore, these links are mediated by apprentices' engagement at school and in learning. Method: To test our hypotheses, 92 dual IVET health and social care apprentices in their last year of vocational school completed an online survey composed of validated scales measuring EI as an ability, EI as a personality trait, personality traits, and school engagement. The apprentices' grades were also obtained with their permission. Results: The findings confirmed our hypotheses and reflected EI's positive influence on training achievement. We observed that participants with high EI (as an ability and personality trait) obtained better grades than participants with lower EI. Moreover, our results showed that ability EI has a direct influence on achievement in theoretical health and social care training, while the link between trait EI and practical training is indirect and mediated by engagement in learning. Conclusion: The present study confirms EI's positive influence on school achievement in the VET context and further corroborates the important role that EI can play in dual IVET apprentices' achievement, particularly in the health and social sectors. This original study contributes to research on the VET system by placing EI among the skills necessary to ensure professional success. [ABSTRACT FROM AUTHOR]

Introduction: Responding to the need for innovative, multi-modal, nonpharmacological strategies in chronic low back pain (cLBP) care, this article presents the development and a mixed methods feasibility trial of a manualized Mindfulness-based Dance/Movement Therapy (M-DMT) program for cLBP. The 12-week program is designed as a group therapy, integrating mindfulness principles, creative/expressive dance and movement, and psychoeducational content focused on cLBP management. This holistic program seeks to cultivate nonjudgmental awareness of pain experiences, challenge maladaptive pain-related beliefs, enhance emotional well-being, foster social support, and promote effective coping strategies for the daily challenges associated with cLBP. Methods: The 12-week M-DMT intervention was administered to individuals with non-specific cLBP (N = 18, aged 51.7 ± 13.9 years, 72% female, 55% Black and 39% White). We assessed feasibility and acceptability through monitoring enrollment and retention rates, attendance, and adverse events. Moreover, we measured the intervention's credibility/expectancy, participants' perception of changes, and overall satisfaction. Additionally, we collected qualitative data, capturing participants' perspectives on the intervention's usefulness and perceived benefits. Specific benchmarks were established to gauge the successful feasibility and acceptability of the program. Results: The adherence rate stood at 80%, with a perfect retention rate of 100%. The study successfully met the benchmarks for treatment acceptability and satisfaction criteria, with 61% of participants reporting "feeling better" or a "great deal better" after the intervention. No adverse events were observed. Participants found the intervention enjoyable and reported that it provided effective tools for cLBP and related symptoms. Notably, participants reported a decrease in fear-avoidance behaviors, increased motivation for physical activity, and a boost in self-efficacy for pain management. Discussion: These encouraging findings establish a strong basis for considering the M-DMT intervention as a promising approach for cLBP management, warranting further investigation in larger-scale studies. [ABSTRACT FROM AUTHOR]

Air quality sensor (AQS) networks are useful for mapping PM2.5 in urban environments, but quantitative assessment of the observed spatial and temporal variation is currently under-developed. This study introduces a new metric – the Concentration Similarity Index (CSI) – to facilitate a quantitative and time-averaged comparison of the concentration‑time profiles of PM2.5 measured by each sensor within an air quality sensor network. Following development on a dataset with minimal unexplained variation and robust tests, the CSI function is ensured to represent an unbiased and fair depiction of the air quality variation within an area covered by a monitoring network. The measurement data is used to derive a CSI value for every combination of sensor pairs in the network, which can then be compared with others in the network, yielding valuable information on spatial variation in PM2.5. This new method is applied to two separate AQS networks in Dungarvan and Cork City, Ireland. Dungarvan yielded a lower mean CSI, indicating lower overall similarity between locations in the network, possibly due to the town's coastal location giving rise to higher variation within the network. In both networks, the average diurnal plots for each sensor exhibit an evening peak in PM2.5 concentration due to emissions from residential solid fuel burning, however, there is considerable variation in the size of this peak. Clustering techniques applied to the CSI matrices identify two different location types in each network; locations in central or residential areas which experience more pollution from sold fuel burning and locations on the edge of the urban areas which experience cleaner air. Furthermore, the examination of isolated data periods (January and May) indicates higher PM2.5 levels during periods of increased residential solid fuel burning act as a major driver for greater differences (lower similarity indices) between locations in both networks. Additionally, the CSI method facilitates the assessment of the representativeness of the PM2.5 measured at regulatory air quality monitoring locations with respect to population exposure, showing here that location type is more important than physical proximity in terms of similarity assessment. Applying the CSI in this manner can allow for the placement of monitoring infrastructure to be optimised. The findings of this work underscore the influence of solid fuel combustion as a local contributor to PM2.5 and the variation it can cause between the measurements at different monitoring locations in a network while also highlighting the importance of including wintertime PM data for accurate comparisons. The CSI method developed here could be a valuable tool for quantitative comparisons of air quality within a monitoring network, offering insights for further regulatory monitoring and exposure assessments. [ABSTRACT FROM AUTHOR]

Objective The purpose of this scoping review was to evaluate and characterize the scope of care for low back pain that falls under the specific label of manual therapy. Methods PubMed database, Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and SPORTDiscus were searched from journal inception through May 2022 for randomized controlled trials that investigated the treatment of low back pain using manual therapy. Terminology used to define manual therapy was extracted and categorized by using only the words included in the description of the intervention. An expert consultation phase was undertaken to gather feedback. Results One hundred seventy-six trials met final inclusion criteria, and 169 unique terms labeled as manual therapy for the treatment of low back pain were found. The most frequent terms were mobilization (29.0%), manipulation (16.0%), and thrust (6.4%). Eight percent of trials did not define or specify what type of manual therapy was used in the study. After removing duplicates, 169 unique terms emerged within 18 categories. Conclusions Manual therapy intervention labels used in low back pain trials are highly variable. With such variation, the heterogeneity of the intervention in trials is likely large, and the likelihood that different trials are comparing the same interventions is low. Researchers should consider being more judicious with the use of the term manual therapy and provide greater detail in titles, methods, and supplementary appendices in order to improve clarity, clinical applicability, and usefulness of future research. Impact The ability to interpret and apply findings from manual therapy–related research for low back pain is challenging due to the heterogeneity of interventions under this umbrella term. A clear use of terminology and description of interventions by researchers will allow for improved understanding for the role of manual therapy in managing back pain. [ABSTRACT FROM AUTHOR]