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In both a field study ( N  = 28,064) and a preregistered vignette experiment ( N  = 800), we find that more perceived structure in evaluation processes is associated with higher levels of belonging for employees. More structured evaluation processes increase perceptions of procedural justice and of genuine commitment to diversity, equity, and inclusion—both of which are tied to a greater sense of belonging. Managerial status moderates this relationship: managers report a greater sense of belonging than non-managers in organizations with less structured evaluations, but the gap between managers’ and non-managers’ sense of belonging narrows in organizations with more structured evaluations. However, more structured evaluation processes also reduce managers’ feelings of autonomy, suggesting that more structure is not unequivocally better. Our findings highlight the importance of perceptions of fairness and of organizational commitment to diversity, equity, and inclusion efforts in driving employees’ sense of belonging. Practically, organizations may want to invest in more structured evaluation processes to boost sense of belonging, while recognizing that the benefits of doing so may be largest for non-managerial employees.

Clinical trials support CRAFT's ability to engage both alcohol- and substance-using identified patients in treatment.

Neurofibromatosis involves activation of the RAS pathway. Inhibition of MEK, a component of the pathway, with selumetinib was performed in 50 children with inoperable disease. A total of 70% had a response, which was maintained in the majority for more than a year. Pain relief, improved function, and higher quality of life were also observed.

Patient-reported outcome measure (PROM) surveillance and collaborative care improve cancer symptom control. However, human resource requirements constrain their implementation and reach. Electronic health record (EHR) facilitation reduces resource needs and might allow population-level scaling. We aimed to assess the effect of EHR facilitation of PROM-directed collaborative care on clinical and health services outcomes. E2C2 was a cohort cluster-randomised, unblinded, stepped-wedge, pragmatic trial, in which we randomly assigned 15 clusters of medical oncology and haematology clinics in the USA sharing a common EHR, Epic, to five sequences to compare an intervention of remotely delivered electronic PROM (ePROM) symptom surveillance and EHR-facilitated collaborative care (ECC) management with a usual care (UC) control of ePROM surveillance alone. Sequences transitioned from the UC control to the ECC intervention state at 8-month intervals. All adult (aged ≥18 years) patients who received medical oncology or haematology care in a US multi-state health system were enrolled. All cancer stages, cancer types, and treatment phases were included, except for patients enrolled in hospice or with acute leukaemia. SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and energy deficit or fatigue) were assessed with 0–10-point numerical rating scales linked to clinical encounters. The prespecified co-primary outcomes were all post-baseline SPPADE scores, and clinically actionable scores (≥4/10), among participants who completed at least two ePROMs. The outcomes were assessed using multivariate regression of cluster-period mean SPPADE symptom scores against intervention exposure, baseline SPPADE scores, fixed-cluster, and secular time effects. The trial is registered at ClinicalTrials.gov (NCT03892967) and is now closed to recruitment. From March 28, 2019, to Jan 31, 2023, 50 207 patients were enrolled and administered ePROMs in association with oncology or haematology visits. In the analytical cohort of 24 874 participants, 10 390 (42%) were assigned ePROMS in both the ECC and UC periods. Of the 19 084 [77%] in the ECC group, 11 138 (58%) were female, 7946 (42%) were male, and 18189 (95%) were White; and of the 16 180 (65%) in the UC group, 9621 (60%) were female, 6559 (40%) were male, and 15468 (96%) were White. 21 153 (85%) participants reported one or more clinically actionable symptoms (defined as SPPADE score ≥4/10). In multivariate analyses, mean population joint SPPADE symptom burden favoured ECC periods (p=0·0055) with adjusted mean differences of –0·12 (95% CI –0·19 to –0·05) for anxiety, –0·08 (–0·15 to –0·01) for depression, –0·06 (–0·16 to 0·03) for fatigue, –0·04 (–0·14 to 0·07) for pain, 0·03 (–0·07 to 0·14) for physical function, and –0·07 (–0·16 to 0·02) for sleep. ECC benefit was also noted following actionable scores (p<0·0001) with adjusted mean differences of –0·10 (–0·17 to –0·03) for anxiety, –0·09 (–0·16 to –0·02) for depression, –0·09 (–0·18 to –0·01) for fatigue, 0·04 (–0·05 to 0·12) for pain, 0·07 (–0·03 to 0·17) for physical function, and –0·02 (–0·10 to 0·07) for sleep. Centralised EHR-facilitated, symptom surveillance and collaborative care management are more beneficial than symptom surveillance alone in reducing the population burden of SPPADE symptoms in oncology patients. US National Institutes of Health.

The use of a validated tool for risk assessment to inform hospital discharge, combined with rapid follow-up, led to a lower risk of death or hospitalization for cardiovascular causes within 30 days among patients with acute heart failure.

Despite widespread use of statins to reduce low-density lipoprotein cholesterol (LDL-C) and associated atherosclerotic cardiovascular risk, many patients do not achieve sufficient LDL-C lowering due to muscle-related side effects, indicating novel treatment strategies are required. Bempedoic acid (ETC-1002) is a small molecule intended to lower LDL-C in hypercholesterolemic patients, and has been previously shown to modulate both ATP-citrate lyase (ACL) and AMP-activated protein kinase (AMPK) activity in rodents. However, its mechanism for LDL-C lowering, efficacy in models of atherosclerosis and relevance in humans are unknown. Here we show that ETC-1002 is a prodrug that requires activation by very long-chain acyl-CoA synthetase-1 (ACSVL1) to modulate both targets, and that inhibition of ACL leads to LDL receptor upregulation, decreased LDL-C and attenuation of atherosclerosis, independently of AMPK. Furthermore, we demonstrate that the absence of ACSVL1 in skeletal muscle provides a mechanistic basis for ETC-1002 to potentially avoid the myotoxicity associated with statin therapy. Statins are lipid-lowering drugs that prevent cardiovascular disease but tolerability is limited by severe side effects in muscles. Here the authors elucidate a liver-specific activation mechanism for bempedoic acid, a novel cholesterol-lowering drug, and show how it effectively reduces LDL-C and atherosclerotic burden in mice, but does not cause myotoxicty.

Plexiform neurofibroma is a complication of the NF1 mutation in neurofibromatosis that results in overactivity of the RAS pathway. Selumetinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, induced tumor regressions in a majority of patients. Neurofibromatosis type 1 is a common genetic disorder that is characterized by multiple manifestations including tumors of the nervous system. 1 , 2 Plexiform neurofibromas develop in 20 to 50% of persons with neurofibromatosis type 1 and can cause substantial complications including pain, functional impairment, disfigurement, and malignant transformation. 3 – 7 Most plexiform neurofibromas are diagnosed in early childhood and grow most rapidly during this period. 8 , 9 Complete surgical resection of these tumors is often not feasible, and regrowth of the tumor after incomplete surgical resection has been observed. 10 , 11 The NF1 product neurofibromin functions as a negative regulator of RAS activity. Lack . . .

Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.

College Football carries a strong social, cultural, and economic importance in the United States with teams, universities, the public and others leveraging social media and the online sphere to promote and discuss events and happenings. In our study, we quantify the mentions and underlying public sentiment of online posts related to American College Football originating in the 2019–2023 seasons on social and news media in the United States. We complement this with an analysis of how team performance clustered into conference levels relates to social media data using ordinary least squares. We find the impact of the 2020 season, which had pandemic-induced schedule adjustments, was felt across the sports landscape, but impacted different conferences in diverse ways. We further observe that public sentiment during the season tends to be higher in Power Five conferences that have a lower winning percentage. Additionally, our results suggest that the COVID season corresponds to decreased mentions. The effect on sentiment is less clear, but we more generally find that the winning percentage (positively) predicts sentiment.