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We examine electronic and crystal structures of iron-based superconductorsLnFeAsO1-xHx(Ln= La, Sm) under pressure by means of x-ray absorption spectroscopy (XAS), x-ray emission spectroscopy (XES), and x-ray diffraction. In LaFeAsO the pre-edge peak on high-resolution XAS at the Fe-Kabsorption edge gains in intensity on the application of pressure up to 5.7 GPa and it saturates in the higher pressure region. VPS34-IN1 in vitro We found integrated-absolute difference values on XES forLn= La, corresponding to a spin state, decline on the application of pressure, and then it is minimized when theTcapproaches the maximum at around 5 GPa. In contrast, such the optimum value was not detected forLn= Sm. We reveal that the superconductivity is closely related to the lower spin state forLn= La unlike Sm case. We observed that As height from the Fe basal plane and As-Fe-As angle on the FeAs4tetrahedron forLn= La deviate from the optimum values of the regular tetrahedron in superconducting (SC) phase, which has been widely accepted structural guide to SC thus far. In contrast, the structural parameters were held near the optimum values up to ∼15 GPa forLn= Sm.Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI)-related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with the occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n = 62), the most common presentation was headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-ipilimumab (ipi) regimens, ipi has a stronger association with irH occurrence (P = 0.004) and a shorter time to irH development (P less then 0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24, 58 and 0% patients, respectively. High-dose steroids (HDS) or ICI discontinuation was not associated with hormonal recovery. In the non-irH group (n = 19), one patient had isolated central hypothyroidism and six had isolated central adrenal insufficiency. All remained on hormone therapy at the last follow-up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long-term follow-up to assess recovery is needed.Constitutive MAPK activation silences genes required for iodide uptake and thyroid hormone biosynthesis in thyroid follicular cells. Accordingly, most BRAFV600E papillary thyroid cancers (PTC) are refractory to radioiodide (RAI) therapy. MAPK pathway inhibitors rescue thyroid-differentiated properties and RAI responsiveness in mice and patient subsets with BRAFV600E-mutant PTC. TGFB1 also impairs thyroid differentiation and has been proposed to mediate the effects of mutant BRAF. We generated a mouse model of BRAFV600E-PTC with thyroid-specific knockout of the Tgfbr1 gene to investigate the role of TGFB1 on thyroid-differentiated gene expression and RAI uptake in vivo. Despite appropriate loss of Tgfbr1, pSMAD levels remained high, indicating that ligands other than TGFB1 were engaging in this pathway. The activin ligand subunits Inhba and Inhbb were found to be overexpressed in BRAFV600E-mutant thyroid cancers. Treatment with follistatin, a potent inhibitor of activin, or vactosertib, which inhibits both TGFBR1 and the activin type I receptor ALK4, induced a profound inhibition of pSMAD in BRAFV600E-PTCs. Blocking SMAD signaling alone was insufficient to enhance iodide uptake in the setting of constitutive MAPK activation. However, combination treatment with either follistatin or vactosertib and the MEK inhibitor CKI increased 124I uptake compared to CKI alone. In summary, activin family ligands converge to induce pSMAD in Braf-mutant PTCs. Dedifferentiation of BRAFV600E-PTCs cannot be ascribed primarily to activation of SMAD. However, targeting TGFβ/activin-induced pSMAD augmented MAPK inhibitor effects on iodine incorporation into BRAF tumor cells, indicating that these two pathways exert interdependent effects on the differentiation state of thyroid cancer cells.
In the United States, millions of adolescents report poor mental health, where 1 in 5 teenagers considers suicide. Reducing stigma and fostering peer support remains critical for positive mental health interventions and programs. Increasingly, digital mental health tools have emerged with great promise, leveraging social networks. Despite the potential, limited understanding of such comprehensive programs and their implementation exist.
The objective of this study investigates a piloted digital mental health training program (Be Present) for youth, specifically describing the impact on youth behavioral outcomes and user engagement and identifying high-risk youth in the early phases of prevention.
Eligibility included Ohio residents (aged 14 to 22 years) to be enrolled as either a Friend or a Peer Advocate. From May 1 to June 1, 2019, participants completed the Advocate training course, taking pretest and posttest surveys. Single-arm descriptive analyses measured youth outcomes (self-efficacy, intentionsearch, offering opportunity for substantial improvements for real-world digital mental health programs.
Simulation study results suggest that COVID-19 contact tracing apps have the potential to achieve pandemic control. Concordantly, high app adoption rates were a stipulated prerequisite for success. Early studies on potential adoption were encouraging. Several factors predicting adoption rates were investigated, especially pertaining to user characteristics. Since then, several countries have released COVID-19 contact tracing apps.
This study's primary aim is to investigate the quality characteristics of national European COVID-19 contact tracing apps, thereby shifting attention from user to app characteristics. The secondary aim is to investigate associations between app quality and adoption. Finally, app features contributing to higher app quality were identified.
Eligible COVID-19 contact tracing apps were those released by national health authorities of European Union member states, former member states, and countries of the European Free Trade Association, all countries with comparable legal standar.
In clinical research, important variables may be collected from multiple data sources. Physical pooling of patient-level data from multiple sources often raises several challenges, including proper protection of patient privacy and proprietary interests. We previously developed an SAS-based package to perform distributed regression-a suite of privacy-protecting methods that perform multivariable-adjusted regression analysis using only summary-level information-with horizontally partitioned data, a setting where distinct cohorts of patients are available from different data sources. We integrated the package with PopMedNet, an open-source file transfer software, to facilitate secure file transfer between the analysis center and the data-contributing sites. The feasibility of using PopMedNet to facilitate distributed regression analysis (DRA) with vertically partitioned data, a setting where the data attributes from a cohort of patients are available from different data sources, was unknown.
The objective oort clinical research in real-world settings.
Mindfulness meditation smartphone apps may improve mental health but lack evidence-based behavioral strategies to encourage their regular use for attaining mental health benefits. In October 2019, the Calm mindfulness meditation app introduced a mood check-in feature, but its effects on participation in meditation have yet to be tested.
The objective of this study was to investigate how a mood check-in feature impacts meditation behavior in Calm app subscribers.
This was a retrospective longitudinal analysis of mobile app usage data from a random sample of first-time subscribers to the Calm app (n=2600) who joined in summer 2018 or summer 2019. The mood check-in feature allows users to rate their mood using an emoji after completing a meditation session and displays a monthly calendar of their past mood check-ins. Regression analyses were used to compare the rate of change in meditation behavior before and after the introduction of mood check-ins and to estimate how usage of mood check-ins was associaterating mood check-ins to help better engage a wider range of users in app-based meditation, but more research is warranted.
Falls in older people commonly occur at home. link2 Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base.
The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions.
We searched the following databases from inception until January 31, 2020 PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool.
A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with healthcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.
Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.
Digital pill systems (DPSs), which comprise ingestible radiofrequency sensors integrated into a gelatin capsule that overencapsulates a medication, can directly measure ingestion events.
Teaching users to operate a DPS is vital to ensure the collection of actionable ingestion and adherence data. In this study, we aim to develop and pilot a training program, grounded in the Technology Acceptance Model, to instruct individuals on DPS operation.
A two-part training program, comprising in-person and text message-based components, was used with HIV-negative men who have sex with men with nonalcohol substance use, who had enrolled in a 90-day pilot demonstration study using the DPS to measure adherence to pre-exposure prophylaxis. We assessed the number of responses to text check-ins, the number and types of episodes where technical support was requested, the resolutions of such issues, and engagement with the program over the study period. link3 Participant feedback on the program was evaluated through qualitative user experience interviews.