bluuebunny/crossref_metadata_2025_split huggingface dataset:
389 A CME virtual patient simulation activity evaluated the management of adults with atopic dermatitis
Authors: Dermer Shari J , Betz Briana , Bell Elaine , Guedj Philippe  , Chatterjee-Shin Piyali 
Published: June 2023

Abstract
Atopic dermatitis (AD) is an inflammatory skin disease with significant burden for patients. Individuals with moderate to severe AD frequently require treatment with systemic agents; however, this does not necessarily occur in clinical practice. This study was intended to evaluate the effect of online virtual patient simulation (VPS)-based CME in improving the management of moderate to severe AD. The educational intervention was designed to close gaps related to (i) underrecognition and undertreatment of patients with AD who would benefit from systemic agents and (ii) improve adoption of new therapies for moderate to severe AD. Case-based interventions in an online VPS platform allowed learners to interview patients via video, order tests, make diagnoses and order treatments supported by an extensive database matching the scope and depth of actual practice. Clinical decisions were analysed, and learners received immediate feedback in a short-form clinical guidance (CG) based on current evidence. Learners were permitted to modify their decisions post-CG. Pre- to post-CG decisions were compared using a McNemar’s test with P &lt; 0.05 as significant. The intervention launched on March 4, 2022, and data were collected through June 2022. We report on data from n = 188 dermatologists and n = 130 allergists who participated in two virtual cases. Significant performance-based improvements were made in Case 1 and Case 2 as a result of education (%pre vs. %post, Case1 and %pre vs. %post, Case2). Assessing appropriateness of systemic AD therapy: ordering evaluation of itch with the NRS (61% vs. 71% and 58% vs. 68%); assessing BSA affected (70% vs. 78% and 70% to 80%); evaluating IGA (39% vs. 54% and 65% vs. 70% [ns]); and asking about itch, sleep and ability to function in daily activities (88% vs. 92% and 91% vs. 99%).Diagnosing moderate to severe AD: 47% vs. 58% and 54% vs. 62%.Selecting an evidence-based AD treatment: start FDA-approved IL-4 receptor blocker (18% vs. 47% and 23% vs. 35%); other treatment choices were topical corticosteroids, topical calcineurin inhibitors, crisaborole, systemic immunosuppressants, systemic steroids, JAK inhibitors (upadacitinib and abrocitinib) and tralokinumab.
This study demonstrated that immediate feedback provided in short-form clinical guidance in a VPS that immerses and engages specialists in an authentic and practical learning experience resulted in changes in performance relating to assessing and treating virtual patients with moderate to severe AD. This initiative also revealed gaps in diagnosing moderate to severe AD, and in selecting evidence-based, FDA-approved systemic treatments. Future education is needed to close these gaps.
402 Efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: 16-week results from three randomized phase 3 clinical trials
Authors: Hebert Adelaide , Flohr Carsten , Chih-ho Hong H , Irvine Alan , Pierce Evangeline  , Elmaraghy Hany  , Xu Wen , Pillai Sreekumar  , Dawson Zach , Siegfried Elaine , Weidinger Stephan  
Published: June 2023

Abstract
Lebrikizumab, a high-affinity monoclonal antibody targeting IL-13, previously demonstrated clinical efficacy in adults and adolescents with atopic dermatitis (AD) in phase 3 trials. Here we evaluate 16-week efficacy outcomes of lebrikizumab in adolescent patients with moderate-to-severe AD from 3 randomized, double-blind, placebo-controlled phase 3 trials: ADvocate1, ADvocate2 and ADhere. Eligible adolescents (≥12 to &lt;18 years weighing ≥40 kg) were randomized 2 : 1 to subcutaneous lebrikizumab (loading doses of 500 mg at Baseline and Week 2 followed by 250 mg every 2 weeks) or placebo in ADvocate1&2 as monotherapy, and in combination with topical corticosteroids (TCS) in ADhere. Efficacy analyses at Week 16 included IGA (0,1) with ≥2-point improvement, EASI-75, and Pruritus NRS ≥4-point improvement. Adolescent data from ADvocate1 and ADvocate2 were pooled, and ADhere data were analysed separately. ADvocate2 and ADhere analyses were performed on a modified population, excluding 10 adolescent patients from a single site whose eligibility could not be confirmed. Combined adolescent 16-week results from ADvocate1 and ADvocate2 [lebrikizumab (n = 67) vs. placebo (n = 35)] were IGA (0,1) with ≥2-point improvement from baseline 46.6% vs. 14.3% (P &lt; 0.01), EASI-75 62.0% vs. 17.3% (P &lt; 0.001) and Pruritus NRS ≥4-point improvement from baseline 48.9% vs. 13.1% (P &lt; 0.01), respectively. The corresponding proportions in ADhere (lebrikizumab + TCS, n = 32; placebo + TCS, n = 14) were IGA (0,1) 57.3% vs. 28.6% (P = 0.071), EASI-75 88.0% vs. 57.1%, (P &lt; 0.05) and Pruritus NRS 45.8% vs. 13.8%, (P = 0.078), respectively. Lebrikizumab treatment with or without TCS demonstrated clinical efficacy in adolescents with moderate-to-severe AD.
416 Long-term efficacy of dupilumab in adults with moderate-to-severe atopic dermatitis: results from an open-label extension trial up to 5 years
Authors: Beck Lisa A , Bissonnette Robert , Deleuran Mette  , Nakahara Takeshi , Galus Ryszard  , Khokhar Faisal A , Coleman Anna  , Gherardi Guy  , Xiao Jing , Dingman Robert  , Xu Christine , Avetisova Elena  , Dubost-Brama Ariane , Shabbir Arsalan 
Published: June 2023

Abstract
Topical therapies often cannot sufficiently control moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease. Systemic immunosuppressants are not recommended for the long-term treatment of moderate-to-severe AD due to safety concerns. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, inhibiting the key drivers of type 2 inflammation. Data from the open-label extension (OLE) study, LIBERTY AD OLE, (NCT01949311) previously demonstrated acceptable safety and sustained efficacy of dupilumab in adult patients for up to 204 weeks (approximately 4 years). This study aims to assess the long-term efficacy and safety of dupilumab in adult patients with moderate-to-severe AD up to 5 years (the end of this OLE study). Adults (≥18 years) with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1 through phase 3) were enrolled into the long-term, multicenter OLE with a duration of up to 5 years. Initially, patients enrolled in the OLE were treated with 300-mg dupilumab weekly. In 2019, patients remaining in the study transitioned to dupilumab 300 mg every 2 weeks in alignment with the approved dupilumab dose regimen. Concomitant treatments for AD were permitted, including topical corticosteroids and topical calcineurin inhibitors. Data are presented as observed for the overall study population (n = 2677). Of the 2677 patients who enrolled, 2207 completed treatment up to Week 52, 362 up to Week 172 and 334 up to Week 260. The most common reason for study withdrawals during the OLE study period was dupilumab approval and commercialization in the patient’s country of enrollment [708 (51.3%)]. Fifty (1.9%) patients withdrew due to lack of efficacy. At the end of the study period, 88.9% of patients achieved a 75% reduction in Eczema Area and Severity Index (EASI) score from parent study baseline (PSBL) and 76.2% of patients achieved a 90% reduction in EASI score from PSBL. At Week 260, 66.5% of patients achieved a ≥4-point reduction in the Peak Pruritus Numerical Rating Scale score from PSBL. A total of 2276 (85.0%) patients reported treatment-emergent adverse events, and 101 (3.8%) patients discontinued treatment permanently due to reported adverse events. Dupilumab had an acceptable safety profile over 5 years of treatment. In this long-term (5 year/260 weeks) open-label study, dupilumab demonstrated robust efficacy substantiated by sustained improvement of AD signs and symptoms (including skin lesions and pruritus) in adult patients with moderate-to-severe AD. The safety profile was acceptable and consistent with the known safety profile observed in previous dupilumab placebo-controlled studies.
LGBTQ+ Affirmative State Care for Young People in Sweden: New Knowledge and Old Traditions
Authors: Carlström Charlotta , Andersson Catrine , Lindroth Malin 
Published: June 2023

Abstract
Young LGBTQ+ people are over-represented in various forms of state care. They experience hardships during their placements and staff competence in addressing specific needs among LGBTQ+ youth is lacking. In this article, we investigate whether and how LGTBQ+ issues are considered and described in digital marketing for state care providers. The material consists of the homepages of residential care homes and secure state care institutions, which we analyse using critical discourse analysis. The results show that LGBTQ+ issues are largely invisible. Of the approximately 1,000 existing state care providers, only twenty stated that they worked with or had competence in LGBTQ+ issues. Among these, no secure state care institution offered LGBTQ+ competence at the time of the study. The descriptions of how care providers work with LGBTQ+ issues are characterised by heteronormativity where there is a mix of two types of language on the homepages regarding LGBTQ+ youth; on the one hand, a heteronormative, traditional description based on a binary understanding of gender; and, on the other, an LGBTQ+ inclusive language is used. However, the LGBTQ+ affirmative language has been imposed upon the traditional rather than being integrated into it, which comes across as superficial and unclear.
Post-transcriptional microRNA repression of PMP22 dose in severe Charcot-Marie-Tooth disease type 1
Authors: Pipis Menelaos , Won Seongsik , Poh Roy , Efthymiou Stephanie , Polke James M , Skorupinska Mariola , Blake Julian , Rossor Alexander M , Moran John J , Munot Pinki , Muntoni Francesco , Laura Matilde , Svaren John , Reilly Mary M 
Published: June 2023

Abstract
Copy number variation (CNV) may lead to pathological traits, and Charcot-Marie-Tooth disease type 1A (CMT1A), the commonest inherited peripheral neuropathy, is due to a genomic duplication encompassing the dosage-sensitive PMP22 gene. MicroRNAs act as repressors on post-transcriptional regulation of gene expression and in rodent models of CMT1A, overexpression of one such microRNA (miR-29a) has been shown to reduce the PMP22 transcript and protein level.
Here we present genomic and functional evidence, for the first time in a human CNV-associated phenotype, of the 3′ untranslated region (3′-UTR)-mediated role of microRNA repression on gene expression.
The proband of the family presented with an early-onset, severe sensorimotor demyelinating neuropathy and harboured a novel de novo deletion in the PMP22 3′-UTR. The deletion is predicted to include the miR-29a seed binding site and transcript analysis of dermal myelinated nerve fibres using a novel platform, revealed a marked increase in PMP22 transcript levels. Functional evidence from Schwann cell lines harbouring the wild-type and mutant 3′-UTR showed significantly increased reporter assay activity in the latter, which was not ameliorated by overexpression of a miR-29a mimic.
This shows the importance of miR-29a in regulating PMP22 expression and opens an avenue for therapeutic drug development.
Artificial intelligence and the public arena
Authors: Jungherr Andreas , Schroeder Ralph 
Published: June 2023

Abstract
The public arena relies on artificial intelligence (AI) to ever greater degrees. Media structures hosting the public arena—such as Facebook, TikTok, Twitter, and YouTube—increasingly rely on AI-enabled applications to shape information environments, autonomously generate content, and communicate with people. These applications affect the public arena’s functions: make society visible to itself and provide spaces for the formation of publics and counterpublics. We offer a framework that allows for the conceptualization and empirical examination of AI’s structural impact on the public arena. Based on this perspective, we argue that the growing uses of AI will lead to a strengthening of intermediary structures that can exercise a greater degree of control over the public arena. In addition, the data-driven nature of most AI-applications threatens to push challenges to the political status quo out of sight and obstruct the assessability of AI-enabled interventions.
Host use by 2 sibling species of bogus yucca moths in relation to plant hardness and saponin content
Authors: Luna Diego , Mohanbabu Neha , Johnson Josiah , Althoff David M 
Published: June 2023

Abstract
Plant defenses allow plants to deter or kill their insect herbivores and are considered to be a major driver of host use for herbivorous insects in both ecological and evolutionary time. Many closely related species of insect herbivores differ in their ability to respond to plant defenses and in some cases are specialized to specific plant species. Here we tested whether both mechanical and chemical plant defenses are a major factor in determining the host range of 2 sibling species of Prodoxid bogus yucca moths, Prodoxus decipiens (Riley) and Prodoxus quinquepunctellus (Chambers) that feed within the inflorescence stalk of Yucca species. These 2 moth species have separate suites of host plant species, yet narrowly overlap geographically and share 1 Yucca species, Y. glauca. We surveyed the lignin and cellulose content, the force required to the puncture the stalk tissue, and saponin concentration across 5 Yucca species used as hosts. Lignin, cellulose concentrations, and stalk hardness differed among Yucca species but did not correlate with host use patterns by the moths. Saponin concentrations in the stalk tissue were relatively low for yuccas (&lt;1%) and did not differ among species. The results suggest that these moth species should be able to use each other’s hosts for egg deposition. Additional factors such as larval development or competition among larvae for feeding space may serve to keep moth species from expanding onto plants used by its sibling species.
The Political Economy of Peacekeeping: Civil–Military Resource Substitution through International Brokerage
Authors: Sakib Nazmus , Rahman Md Muhibbur 
Published: June 2023

Abstract
What effects does participation in peacekeeping operations (PKO) have on the participating countries’ civil–military resource allocation? Answering this question can widen our understanding of state motivations to contribute to the United Nations PKOs by incorporating the civil–military dynamic. We argue that contributing states can substitute part of their domestic military expenditures with external resources. Governments act as brokers between domestic military interests and international sources of rent, a process which we call civil–military resource substitution through international brokerage. By doing so, governments can (i) reduce part of the bottom-up demands for increased military spending (i.e., salaries and allowances) and (ii) outsource critical resources to meet military organizational priorities (i.e., training, weapons, perks for the military elite, and so on). Using cross-national statistical analysis, we find that the UN PKO contributing states allocate fewer resources to the defense sector than the non-contributing states, and higher troop-contributing states are likely to allocate fewer resources to the defense sector than the lower-contributing or non-contributing states. The implications point to a much wider role of the UN peacekeeping missions than what is previously understood and demonstrate their impacts beyond the host countries.
Impact of 1,6-hexanediol on Schizosaccharomyces pombe genome stability
Authors: Jones Chance E , Forsburg Susan L 
Published: June 2023

Abstract
Phase separation is a major mechanism of macromolecular condensation within cells. A frequently chosen tool for global disruption of phase separation via weak hydrophobic interactions is treatment with 1,6-hexanediol. This study evaluates the cytotoxic and genotoxic effects of treating live fission yeast with 1,6-hexanediol. We find that 1,6-hexanediol causes a drastic decrease in cell survival and growth rate. We also see a reduction in HP1 protein foci and increase in DNA damage foci. However, there is no evidence for increased genomic instability in two classically phase-separated domains, the heterochromatic pericentromere and the nucleolar rDNA repeats. This study reveals that 1,6-hexanediol is a blunt tool for phase separation inhibition and its secondary effects must be taken into consideration during its in vivo use.
Inferring the distributions of fitness effects and proportions of strongly deleterious mutations
Authors: Charmouh Anders P , Bocedi Greta , Hartfield Matthew 
Published: June 2023

Abstract
The distribution of fitness effects is a key property in evolutionary genetics as it has implications for several evolutionary phenomena including the evolution of sex and mating systems, the rate of adaptive evolution, and the prevalence of deleterious mutations. Despite the distribution of fitness effects being extensively studied, the effects of strongly deleterious mutations are difficult to infer since such mutations are unlikely to be present in a sample of haplotypes, so genetic data may contain very little information about them. Recent work has attempted to correct for this issue by expanding the classic gamma-distributed model to explicitly account for strongly deleterious mutations. Here, we use simulations to investigate one such method, adding a parameter (plth) to capture the proportion of strongly deleterious mutations. We show that plth can improve the model fit when applied to individual species but underestimates the true proportion of strongly deleterious mutations. The parameter can also artificially maximize the likelihood when used to jointly infer a distribution of fitness effects from multiple species. As plth and related parameters are used in current inference algorithms, our results are relevant with respect to avoiding model artifacts and improving future tools for inferring the distribution of fitness effects.
Ten health policy challenges for the next 10 years
Authors: Phillips Kathryn A , Marshall Deborah A , Adler Loren , Figueroa Jose , Haeder Simon F , Hamad Rita , Hernandez Inmaculada , Moucheraud Corrina , Nikpay Sayeh 
Published: June 2023

AbstractHealth policies and associated research initiatives are constantly evolving and changing. In recent years, there has been a dizzying increase in research on emerging topics such as the implications of changing public and private health payment models, the global impact of pandemics, novel initiatives to tackle the persistence of health inequities, broad efforts to reduce the impact of climate change, the emergence of novel technologies such as whole-genome sequencing and artificial intelligence, and the increase in consumer-directed care. This evolution demands future-thinking research to meet the needs of policymakers in translating science into policy. In this paper, the Health Affairs Scholar editorial team describes “ten health policy challenges for the next 10 years.” Each of the ten assertions describes the challenges and steps that can be taken to address those challenges. We focus on issues that are traditionally studied by health services researchers such as cost, access, and quality, but then examine emerging and intersectional topics: equity, income, and justice; technology, pharmaceuticals, markets, and innovation; population health; and global health.
Social determinants of health in Brazil during the COVID-19 pandemic: strengths and limitations of emergency responses
Authors: Lazzari Eduardo A , Paschoalotto Marco A C , Massuda Adriano , Rocha Rudi , Castro Marcia C 
Published: June 2023

Abstract
Economic crises often expose the most vulnerable to higher health risks and tend to exacerbate existing inequalities. The Social Determinants of Health (SDoH) framework illustrates many layers of inequalities that would affect outcomes of the COVID-19 pandemic. The impacts of emergency policy responses considering the SDoH framework are important for all sectors in policymaking. However, its assessment in Global South countries is limited, due to high informality rates and data availability. We address this gap using a unique dataset that allows for the analysis of occupational categories before and after the COVID-19 pandemic in Brazil, incorporating the emergency assistance provided in 2020. Results show that, although labor earnings fell 4% for the self-employed at each death from COVID-19, increasing unemployment and inactivity among the typically most vulnerable, those effects were offset by emergency policies, reducing poverty. Groups often considered less vulnerable, such as formal employees, had an increase. The policy responses to this shock served then as a leveler of previous SDoH, despite ignoring the health-risk gradient there is along the income distribution. A poverty rebound that ensued after the sudden discontinuation of those policies is a lesson for future crises, and on how SDoH inequalities should be addressed.
US practice adoption of patient-engagement strategies and spending for adults with diabetes and cardiovascular disease
Authors: Rodriguez Hector P , Rubio Karl , Miller-Rosales Chris , Wood Andrew J 
Published: June 2023

Abstract
Patient-engagement strategies are being encouraged by payers and governments, but with limited evidence about whether practice adoption of these strategies impacts utilization and spending. We examine the association of physician practice adoption of patient-engagement strategies (low vs moderate vs high) with potentially preventable utilization and total spending for patients with type 2 diabetes and/or cardiovascular disease using US physician practice survey (n = 2086) and Medicare fee-for-service (n = 736 269) data. In adjusted analyses, there were no differences in potentially preventable utilization associated with practice adoption of patient-engagement strategies. Compared with patients attributed to practices with moderate adoption, patients attributed to practices with high adoption had higher total spending ($26 364 vs $25 991; P &lt; .05) driven by spending for long-term services and supports, including home health agency, long-term care, skilled nursing facilities, and hospice payments. In contrast, patients attributed to practices with low adoption had higher total spending ($26 481 vs $25 991; P &lt; .01) driven by spending for tests and acute care and clinical access spending. The results highlight that stakeholders that encourage the use of patient-engagement strategies should not necessarily expect reduced spending.