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Background The prevalence of type 2 diabetes (T2D) continues to rise in the United States and worldwide. Cognitive behavioral therapy (CBT) has been shown to improve glycemic control in patients with T2D, but broad implementation has been limited by inherent access and resource constraints. Digital therapeutics have the potential to overcome these obstacles. Hypothesis To describe the rationale and design of a trial evaluating the efficacy and safety of a digital therapeutic providing CBT to improve glycemic control in adults with T2D. Methods This randomized, controlled, multicenter, Phase 3 trial evaluates the hypothesis that BT‐001, an investigational digital therapeutic intended to help patients with T2D improve their glycemic control, on top of standard of care therapy, will lower hemoglobin A1c (HbA1c) compared to a control app across a broad range of patients in a real‐world setting. The study is designed to provide evidence to support FDA review of this device as a digital therapeutic. The intervention is provided within the digital application (app) and includes no person‐to‐person coaching. The primary endpoint is the difference in HbA1c change from baseline to 90 days for BT‐001‐allocated subjects compared with those assigned to the control app. Safety assessment includes adverse events and adverse device effects. The study incorporates pragmatic features including entirely remote conduct with at‐home visits for physical measures and blood sample collection. Conclusions This randomized, controlled trial evaluates a cognitive behavioral intervention delivered via smartphone app which has the potential to provide a scalable treatment option for patients with T2D.

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11c hi cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11c hi IgD + and IgD − subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11c hi B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11c hi B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD + and IgD − CD11c hi B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.

Facioscapulohumeral muscular dystrophy (FSHD) is a genetically dominant myopathy caused by mutations that disrupt repression of the normally silent gene, which encodes a transcription factor that has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a -knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53 dependence of DUX4 using various and models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4 does not lead to activation of the p53 pathway. DUX4 does lead to expression of the classic p53 target gene (p21) but in a p53-independent manner. Meta-analysis of 5 publicly available data sets of DUX4 transcriptional profiles in both human and mouse cells shows no evidence of p53 activation, and further reveals that is a mouse-specific target of DUX4. When the inducible DUX4 mouse model is crossed onto the -null background, we find no suppression of the male-specific lethality or skin phenotypes that are characteristic of the transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.

Measuring quality of care can transform care, but few tools exist to measure quality from the client’s perspective. The aim of this study was to create concordant clinician and client self-report quality-of-care scales in a sample of community mental health clinicians ( n  = 189) and clients ( n  = 469). The client scale had three distinct factors (Person-Centered Care, Negative Staff Interactions, and Inattentive Care), while the clinician scale had two: Person-Centered Care and Discordant Care. Both versions demonstrated adequate internal consistency and validity with measures related to satisfaction and the therapeutic relationship. These measures are promising, brief quality assessment tools.

We herein report a rare, probable exposure of a patient to phosphorus trifluoride gas. The objective of this case report is to highlight the potential exposure to phosphorus trifluoride gas and discuss the best management of it. A 48-year-old worker at a specialty gases laboratory was transported to the community Emergency Department (ED) in respiratory distress, presenting with peripheral cyanosis, an unobtainable oxygen saturation, chocolate-colored blood, and a Glasgow coma scale of 15. A non-rebreather was placed, poison control was contacted, and the patient was administered empiric methylene blue intravenously due to worsening cyanosis and respiratory distress. Upon arrival at the academic facility, the patient was no longer cyanotic and reported improvement of his symptoms. The patient's employer informed staff that a canister of phosphorus trifluoride gas in his workstation was found to be empty but should have been full. It was also discovered that a coworker left work early the same day with similar but milder symptoms. Hyperbaric oxygen therapy was considered; however, the patient was improving on oxygen via non-rebreather, and he had no other indications. Because the patient continued to require supplemental oxygen to maintain their oxygen saturation above 92%, he was admitted to the ICU and treated with prednisone daily for chemical pneumonitis. After 4 days, he successfully transitioned to room air without hypoxia. While exposures such as this do not occur frequently, it is important to maintain a broad differential and treatment plan as we continue to investigate the etiology and best treatment option.

Researcher innovation and leadership skills are fundamental for creating implementable solutions to pressing societal and market-based global problems. The Research to Innovation to Society (R2I2S) program is a transformative approach to graduate education, training students at the intersection of research, innovation, and leadership. In this article, we detail the design of the program and a 3-year exploratory investigation of its impact at one research university in the western United States. We found that, overall, students who participated in the program realized the value of thinking about their scientific research from a market-need perspective. Students had an enhanced interest in and understanding of societal and market insights related to their own and others’ research. Students also developed professional skills in communication, collaboration, and innovation, as well as entrepreneurial skills. We situate our findings in frameworks concerning the development of emerging professionals and argue for programming for STEM graduate students that extends the deep discipline knowledge-based model of professional development into one inclusive of leadership, communication, and innovation goals.

FSHD is a genetically dominant myopathy caused by mutations that disrupt repression of the normally silent DUX4 gene, which encodes a transcription factor that has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts, and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a p53 knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53-dependence of DUX4 using various in vitro and in vivo models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4 does not lead to activation of the p53 pathway. DUX4 does lead to expression of the classic p53 target gene, Cdkn1a (p21), however in a p53-independent manner. Meta analysis of 5 publicly available data sets of DUX4 transcriptional profiles in both human and mouse cells shows no evidence of p53 activation, and further reveals that Cdkn1a is a mouse-specific target of DUX4. When the inducible DUX4 mouse model is crossed onto the p53 null background, we find no suppression of the male-specific lethality or skin phenotypes that are characteristic of the DUX4 transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11c cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11c IgD and IgD subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11c B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11c B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD and IgD CD11c B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.

Staff burnout is widely believed to be problematic in mental healthcare, but few studies have linked burnout directly with quality of care. The purpose of this study was to examine the relationship between burnout and a newly developed scale for quality of care in a sample of community mental health workers ( N  = 113). The Self-Reported Quality of Care scale had three distinct factors (Client-Centered Care, General Work Conscientiousness, and Low Errors), with good internal consistency. Burnout, particularly personal accomplishment, and to a lesser extent depersonalization, were predictive of overall self-rated Quality of Care, over and above background variables.

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.