bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal model of quasi-cyclic behaviour in turbulence driven by Taylor–Green forcing
Authors: Araki Ryo , Bos Wouter J T , Goto Susumu 
Published: June 2023

Abstract
We attempt to formulate the simplest possible model mimicking turbulent dynamics, such as quasi-cyclic behaviour (QCB), using only three variables. To this end, we first conduct direct numerical simulations of three-dimensional flow driven by the steady Taylor–Green forcing to find a similarity between a stable periodic orbit (SPO) at a small Reynolds number (Re) and turbulent QCB at higher Re. A close examination of the SPO allows the heuristic formulation of a three-equation model, representing the evolution of Fourier modes in three distinct scales. The model reproduces the continuous bifurcation from SPO to turbulence with QCB when Re is varied. We also demonstrate that, by changing model parameters, the proposed model exhibits a discontinuous transition from steady to chaotic solutions without going through an SPO.
368 Impact of a digital atopic dermatitis educational intervention on Hispanic patients and family members
Authors: Andrade Luis F , Bekhash MaryJo , Choragudi Siri  , Gonzalez Juan M , Valdes Rodrigo  , Yosipovitch Gil 
Published: June 2023

Abstract
With the increasing incidence of atopic dermatitis (AD) in the USA, the highest prevalence of AD being found in Hispanic countries, and the rising Hispanic-American population, educational resources on eczema focused on Spanish-speaking populations are needed more than ever. As such, the primary goal of this project was to assess the beneficial impact of an educational intervention conducted through a virtual platform for Hispanic individuals living with AD. Utilizing WhatsApp, the study enrolled 55 participants diagnosed with AD and/or parents of children diagnosed with AD. Participants were enrolled in a 7-day educational module with daily topics on AD health knowledge. A health knowledge survey was administered prior to the educational program, upon completion of the program and 1 month after completion. The program found a 14% increase in AD health knowledge upon completion of the program (P &lt; 0.001). Most importantly, there was no significant difference found between the health knowledge survey submitted at program completion and 1 month after completion, signaling that health knowledge taught through the course was successfully retained by participants (P = 0.29). Qualitative themes involving atopic disease were additionally explored through group discussions, including mental health and peer stigma. This study is the first of its kind in dermatology utilizing the WhatsApp format. The success of retained health knowledge regarding AD demonstrates that future virtual endeavors can be effective methods of patient education overall, and be accessible interventions for populations that might not have ease of access to major medical centers, are in rural areas and/or in the international setting.
386 Complete/near-complete itch response observed in adult and adolescent patients with moderate-to-severe atopic dermatitis initiating dupilumab treatment in real-world practice
Authors: Bhatia Neal , Lynde Charles W , Fonacier Luz , Tian Tingting , Bosman Kwinten , Korotzer Andrew  
Published: June 2023

Abstract
Chronic itch (pruritus) is a defining characteristic of atopic dermatitis (AD) and is a significant contributor to poor quality of life in patients. A Pruritus/Peak Pruritus Numerical Rating Scale (NRS) score of 0/1 could be considered a complete or near-complete itch response. This study aims to report Pruritus NRS and Overall Disease Severity (ODS) score of 0/1 over time in patients older than 12 years with moderate-to-severe AD initiating dupilumab treatment in real-world practice. Patients aged ≥12 years with moderate-to-severe AD, initiating real-world dupilumab treatment for AD per approved prescribing information in the USA and Canada, were eligible for entry into PROSE (NCT03428646). Enrolled patients received their first dose of dupilumab at the baseline visit; there were no restrictions on post-baseline dupilumab dosing changes, or concomitant medication use; patients were encouraged to stay in the study if they discontinued dupilumab. Data presented are from an interim analysis (data cut taken as of November 2022); only ≥36 months of patient experience in PROSE at the time of interim analysis is reported. No formal hypothesis testing was performed; descriptive statistics are presented. Among 857 patients [mean (SD) age 40.1 (17.9) years and 42% male], mean (SD) duration of dupilumab treatment was 23.1 (13.7) months. At Month 36, 185 patients (21.6%) had discontinued from the study; the main reason was withdrawal of consent by the patient (76 patients, 8.9%). The proportion of patients with available observations reporting a Pruritus NRS score of 0/1 increased from baseline (2.7%) to Month 3 (28.1%) and continued to increase up to Month 36 (56.3%). Similarly, the proportion of patients with a clinician-reported ODS score of 0/1 also increased from baseline (2.2%) to Month 3 (39.8%) and up to Month 36 (65.1%). Safety was consistent with the known dupilumab safety profile. In this interim analysis of PROSE, a majority of patients reported a complete/near-complete pruritus response and overall disease severity response over a 36-month period.
405 Understanding patient experience and factors influencing patient preference in the treatment of moderate-to-severe atopic dermatitis through in-depth qualitative patient interviews
Authors: Feldman Steven R , Guerin Annie , Gauthier-Loiselle Marjolaine  , Claxton Ami J , Meng Yan  , Hazra Nisha C , Balu Sanjeev 
Published: June 2023

Abstract
Atopic dermatitis (AD) can enormously affect the lives of patients and their caregivers. Treatments for moderate-to-severe AD include phototherapy, topical and systemic corticosteroids, other immunosuppressive agents and biologic therapies. These treatments offer varied levels of efficacy, safety, response times and modes of administration. Patient preferences for these treatment options and attributes influencing their treatment choice are not well characterized. This qualitative interview-based study evaluated treatment attributes important to adult patients with moderate-to-severe AD providing a basis for a future quantitative discrete choice experiment (DCE). Semi-structured interviews were conducted in adults (≥18 years) recruited via a panel of geographically and demographically diverse patients with AD in the USA. Inclusion required (i) diagnosis of AD for at least one year, (ii) inadequate response to prior topical therapy and (iii) self-reported moderate-to-severe AD or experience with systemic therapy. One-on-one, in-depth 60-min phone interviews were conducted by a trained interviewer in AD real-word evidence studies. Subjects with experience with systemic therapy for AD were queried concerning their involvement in initiating, logistics of and general experience with their most recent systemic treatment. Finally, participants were asked to rate the importance (on a 1–5 scale with 5 being the most important) of 17 attributes that could play a role in their treatment decision-making; these attributes were identified from a targeted literature review and expert dermatologist clinical input. Attributes included treatment efficacy, adverse events and treatment logistics. Interviews are ongoing, and results will be ready and presented in the poster upon acceptance. Findings from the interviews will shed light on recent patient experience with treatments for moderate-to-severe AD and elucidate the treatment attributes that most impact patient treatment preferences. These results will guide the design of a subsequent DCE survey, which will help quantify the relative importance of the treatment attributes identified herein.
408 Dupilumab treatment in patients with atopic hand and foot dermatitis: results from a phase 3, randomized, double-blind, placebo-controlled trial
Authors: Simpson Eric L , Silverberg Jonathan I , Worm Margitta  , Honari Golara , Masuda Koji , Sygula Ewa , Maloney Jennifer , Mannent Leda P   , Xiao Jing , Dubost-Brama Ariane , Bansal Ashish  
Published: June 2023

Abstract
Atopic dermatitis (AD) of the hands and/or feet is often chronic, difficult to treat and substantially impacts patient quality of life. This study aims to report the effect of dupilumab treatment on signs, symptoms and quality of life in patients with atopic hand and foot dermatitis using dedicated clinical and patient reported instruments. The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients ≥12 years with moderate-to-severe [Investigator’s Global Assessment (IGA) 3/4] atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg q2w in adults; 200/300 mg every 2 weeks in adolescents, or placebo for 16 weeks. The primary endpoint was hand and foot IGA 0/1 score at Week 16. Safety/tolerability was assessed. The 133 patients enrolled were randomized to dupilumab (n = 67) or placebo (n = 66). At Week 16, the primary and all secondary endpoints were met. Significantly more patients in the dupilumab vs. placebo group achieved hand and foot IGA 0/1 (40.3% vs. 16.7%; P = 0.003; primary endpoint) and ≥4-point improvement in the hand and foot Peak Pruritus Numerical Rating Scale (52.2% vs. 13.6%; P &lt; 0.0001; a key secondary endpoint). Dupilumab-treated patients experienced significant improvement in percent change from baseline in the modified Total Lesion Sign Score for hand and foot lesions vs. placebo [LS mean (SE) −69.4 (5.8) vs. −31.0 (5.9); P &lt; 0.0001] and Hand Eczema Severity Index [HECSI; LS mean (SE) −74.8 (6.3) vs. −39.9 (6.2); P &lt; 0.0001]. At Week 16, treatment with dupilumab also significantly increased the proportion of patients achieving a 75% improvement in HECSI (46.9% vs. 21.5%; P = 0.0028) and improved Quality of Life in Hand Eczema Questionnaire scores [LS mean (SE) −40.3 (4.0) vs. −16.2 (4.2); P &lt; 0.0001]. The most common TEAEs (≥10%) were nasopharyngitis (16% vs. 11%) and dermatitis atopic (5% vs. 18%). Dupilumab significantly improved signs, symptoms and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis and had an acceptable safety profile.
413 Improvement in itch, symptoms and quality of life with upadacitinib through week 16 in adults and adolescents with atopic dermatitis: results from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up)
Authors: Lio Peter , Eichenfield Lawrence F , Marcoux Danielle  , Lee Wan-Ju , Teixeira Henrique D   , Raymundo Eliza M , Gamelli Amy E  , Grada Ayman , Hu Xiaofei , Irvine Alan D 
Published: June 2023

Abstract
Atopic dermatitis (AD) is characterized by intense itch and symptoms that adversely impact quality of life (QoL). Upadacitinib is a selective Janus kinase-1 inhibitor approved for moderate-to-severe AD. We assessed the effect of once daily oral upadacitinib (15 or 30 mg), with or without concurrent topical corticosteroid treatment, on patient-reported outcomes for adults and adolescents with moderate-to-severe atopic dermatitis during the double-blind, placebo-controlled phase 3 clinical trials, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422) and AD Up (NCT03568318). Assessments included itch (Worst Pruritus Numerical Rating Scale), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient Oriented Eczema Measure) and sleep, daily activities and emotional state (AD Impact Scale). Post hoc analysis of 2240 adults and 344 adolescents randomized patients was performed. By Week 2, more patients receiving upadacitinib achieved a clinically relevant response in itch, skin pain, symptom severity, symptom frequency, sleep, daily activities and emotional state vs. placebo across studies among adults (upadacitinib 15 mg: 30.8–87.3%; upadacitinib 30 mg: 38.0–89.9%; placebo: 2.1–43.1%; nominal P &lt; 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 19.4–82.9%; upadacitinib 30 mg: 35.3–97.6%; placebo: 0–41.0%; nominal P &lt; 0.05 for 37/42 comparisons). These trends continued through week 16 where response rates for all outcomes improved with upadacitinib vs. placebo in adults (upadacitinib 15 mg: 42.9–80.4%; upadacitinib 30 mg: 60.9–84.6%; placebo: 10.1–38.1%; nominal P &lt; 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 33.3–78.0%; upadacitinib 30 mg: 50.0–85.7%; placebo: 2.8–43.6%; nominal P &lt; 0.05 for 41/42 comparisons). These findings highlight the rapid, sustained efficacy of once daily oral upadacitinib in improving symptom burden and QoL in adults and adolescents with moderate-to-severe AD.
426 Efficacy and safety of abrocitinib in adolescents with moderate-to-severe atopic dermatitis from the JADE clinical trial program
Authors: Eichenfield Lawrence F , Flohr Carsten , Bangert Christine  , Irvine Alan D , Weidinger Stephan  , Nesnas John , Koppensteiner Herwig  , Zhang Fan , Rojo Ricardo , Chan Gary 
Published: June 2023

Abstract
Once-daily oral abrocitinib, a Janus kinase 1-selective inhibitor, was effective and well tolerated as a monotherapy in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), as well as in combination with medicated topical therapy in adolescents with moderate-to-severe AD. This study aims to investigate efficacy and safety of abrocitinib in adolescents with moderate-to-severe AD from the JADE clinical trial program. Patients aged 12–17 years with moderate-to-severe AD and an inadequate response to ≥4 consecutive weeks of topical medication or treatment with systemic therapy for AD, both within the past 6 months, were randomly assigned [2:2:1 JADE MONO-1/MONO-2 (NCT03349060/NCT03575871); 1:1:1 JADE TEEN (NCT03796676)] to receive once-daily oral abrocitinib (200 or 100 mg) or placebo as monotherapy (JADE MONO-1 and JADE MONO-2) or in combination with medicated topical therapy (JADE TEEN) for 12 weeks. Coprimary endpoints were proportion of patients achieving Investigator’s Global Assessment (IGA) response [clear (0) or almost clear (1) with ≥2-grade improvement from baseline] and proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index score (EASI-75) at Week 12. A key secondary endpoint was the proportion of patients achieving ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi) at Week 12. Drug safety was also assessed. Overall, 285 and 124 adolescents in JADE TEEN and JADE MONO-1/MONO-2, respectively, were treated. In JADE TEEN, more abrocitinib-treated (200 mg, 100 mg) than placebo-treated patients achieved IGA (46.2%, 41.6% vs. 24.5%; P &lt; 0.05 for both doses), EASI-75 (72.0%, 68.5% vs. 41.5%; P &lt; 0.05 for both doses) and PP-NRS4 (55.4%, 52.6% vs. 29.8%; P &lt; 0.01 for 200 mg vs. placebo) responses at Week 12. Adverse events (AEs) were reported for 62.8%, 56.8% and 52.1% of patients in 200 mg, 100 mg and placebo groups, respectively; 1 (1.1%), 0 and 2 patients (2.1%) had serious AEs. JADE MONO-1/MONO-2 safety results were similar, but efficacy results were lower, as expected for monotherapies. Results from JADE clinical trials suggest that abrocitinib was effective in adolescents with moderate-to-severe AD, with an acceptable safety profile.
432 Comparative treatment persistence of different advanced-therapies in patients with atopic dermatitis
Authors: Sanfilippo Eric , Iyer Sneha , Silverberg Jonathan I 
Published: June 2023

Abstract
Multiple advanced therapies are used to treat atopic dermatitis (AD), each with different efficacy, safety, tolerability, accessibility and treatment success that can affect treatment persistence. Little is known about how treatment persistence rates compare between different therapies. We compared treatment persistence for subcutaneous dupilumab, oral cyclosporine, mycophenolate, and upadacitinib, and narrowband ultraviolet B (NB-UVB) treatment of AD. A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015 to 10/1/2021. The AD cases were identified using Hanifin–Rajka criteria. Drug persistence was assessed using proportion of patients who discontinued therapy and median time to discontinuation. Chi-square tests were used to assess if there were differences in drug discontinuation rates by advanced therapy. Overall, 766 patients with AD were identified, including 139 (18.1%) prescribed dupilumab, 10 (1.3%) cyclosporine, 21 (2.7%) mycophenolate, 5 (0.7%) upadacitinib and 64 (8.4%) NB-UVB; no patients were treated with methotrexate. Drug persistence was highest for upadacitinib (100%), followed by dupilumab (86.3%), mycophenolate (38.1%), cyclosporine (30.0%) and NB-UVB (12.5%) (Chi-square, P &lt; 0.0001). Highest median (days) time to discontinuation was observed with dupilumab (638), followed by cyclosporine (539), mycophenolate (274) and NB-UVB (167). Lack of efficacy was the most common reason for discontinuation of dupilumab, cyclosporine, mycophenolate and NB-UVB alike. Discontinuation due to adverse-events was highest for cyclosporine (42.9%), followed by dupilumab (31.6%), mycophenolate (30.8%) and NB-UVB (16.1%). Dupilumab had the most patients who discontinued due to disease improvement and no longer requiring advanced-therapy (21.1%). Our data suggest that drug persistence varies substantially across different advanced therapies for AD. Recently approved advanced therapies, including dupilumab and upadacitinib, showed the highest proportion of drug persistence.
A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM)
Authors: Wilck Marissa , Cornely Oliver A , Cordonnier Catherine , Velez Juan Diego , Ljungman Per , Maertens Johan , Selleslag Dominik , Mullane Kathleen M , Nabhan Samir , Chen Qiuxu , Dagan Ron , Richmond Peter , Daus Caroline , Geddie Kateasha , Tamms Gretchen , Sterling Tina , Patel Shrita M , Shekar Tulin , Musey Luwy , Buchwald Ulrike K ,   for the V114-022 (PNEU-STEM) Study Group
Published: June 2023

Abstract

Background
Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE; Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients.

Methods
Participants received 3 doses of V114 or PCV13 (Prevnar 13; Wyeth LLC) in 1-month intervals starting 3–6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAX 23 or a fourth dose of PCV (if they experienced chronic graft vs host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group.

Results
A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at day 90.

Conclusions
V114 was well tolerated in allo-HCT recipients, with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and was higher for V114 serotypes 22F and 33F. Study results support the use of V114 in allo-HCT recipients.
Clinical Trials Registration. clinicaltrials.gov (NCT03565900) and European Union at EudraCT 2018-000066-11.
Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial
Authors: West Emily , Zeeb Marius , Grube Christina , Kuster Herbert , Wanner Katrin , Scheier Thomas , Neumann Kathrin , Jörimann Lisa , Hampel Benjamin , Metzner Karin J , Kouyos Roger D , Braun Dominique L , Günthard Huldrych F 
Published: June 2023

Abstract

Background
Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy.

Methods
EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART &lt;180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired.

Results
Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively.

Conclusions
This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy.
Workplace Sexual Harassment in China: A Comparative Inquiry into the Personality-Based Paradigm
Authors: Duan Jiahui 
Published: June 2023

Abstract
Western researchers have produced significant insight into sexual harassment in Western contexts, but sexual harassment in Chinese society remains largely unexplored. To address this comparative inquiry, this article explores the development of an understanding of workplace sexual harassment and the legal regulation thereof in China—a State with a socialist legal system that has characteristics specific to its context. Through a thorough review of the historical foundations, legislative change over time, and judicial practice, I explore two questions: (i) how do Chinese laws define sexual harassment and (ii) how do Chinese lawmakers perceive the wrong done by sexual harassment? This article reveals that, over two decades of legislation, a sexual harassment legal system has gradually taken shape in China. This system is based on a paradigm distinct from the two major paradigms in the Western world: the American-style discrimination approach and the Continental employee dignity approach. Notwithstanding some attempts to use the American approach, the Chinese legal authorities are developing an alternative personality paradigm where sexual harassment is framed as a tortious infringement on an individual’s right to personality. I argue that the personality paradigm, though strategic and advantageous in terms of expanding the scope of protection to victims, is inadequate in addressing workplace sexual harassment as well as protecting women as the most vulnerable class of victims, which calls for further legal reform to rectify the deviation. In light of this, I offer concrete proposals for China’s sexual harassment legal reform in the future.