bluuebunny/crossref_metadata_2025_split huggingface dataset:
652 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States
Authors: Armstrong April W , Rubin Cory , Jarell Abel , Nguyen Tien , Bagel Jerry , Stinson John , Schneider Shannon , Anastasiadou Dimitra M , Rodriguez Adrian 
Published: August 2024

Abstract

Introduction/Background
Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols.

Objectives
TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice.

Methods
TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients.

Results
Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness.

Conclusions
Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.
655 - Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with chronic hand eczema: results of the phase 3 open-label extension DELTA-3 trial
Authors: Gooderham Melinda , Molin Sonja , Bissonnette Robert , Worm Margitta , Crépy Marie-Noëlle , Stingeni Luca , Warren Richard B , Schliemann Sibylle , Balita-Crisostomo Cherry Lou , Oesterdal Marie Louise , Agner Tove 
Published: August 2024

Abstract

Introduction/Background
In patients with moderate to severe Chronic Hand Eczema (CHE), delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in all efficacy endpoints in DELTA-1 and -2.

Objectives
The objectives of this study were to evaluate the long-term safety and efficacy of twice-daily applications of delgocitinib cream 20 mg/g as needed for up to 36 weeks in adults with CHE in the Phase 3 open-label DELTA-3 trial (NCT04949841), an extension trial of the 16-week DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials.

Methods
In DELTA-3, subjects who completed the 16-week (W) treatment period in DELTA-1 and DELTA-2 were treated on an as-needed basis with twice-daily delgocitinib cream 20 mg/g for 36 weeks (n=801). Subjects with Investigator's Global Assessment for CHE (IGA-CHE) ≥2 received delgocitinib cream until symptoms resolved (i.e., IGA-CHE 0/1 [clear/almost clear]). Primary endpoint was number of treatment-emergent adverse events (TEAEs). Key secondary endpoints were IGA-CHE 0/1 and ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores; Hand Eczema Symptom eDiary captured patient-reported worst severity of itch/pain over the past 24 hours.

Results
No safety concerns were identified during delgocitinib cream treatment in DELTA-1 (n=325; R=305.4; PYO=100.9), DELTA-2 (n=313; R=280.6; PYO=95.9) and DELTA-3 (n=801; R=231.1; PYO=535.7). In DELTA-3, the most frequent TEAEs were COVID-19 and nasopharyngitis. In DELTA-3, IGA-CHE 0/1, HECSI-75, HECSI-90 and ≥4-point itch/pain reduction were maintained from baseline (24.6%, 51.8%, 31.8%, and 50.6%/51.9%, respectively) to W36 (30.0%, 58.6%, 36.6%, and 52.4%/55.4%, respectively) among delgocitinib cream-treated subjects in the parent trials. Among those treated with cream vehicle in parent trials, response rates improved from baseline (9.1%, 23.7%, 12.0%, and 26.3%/32.3%, respectively) to W36 (29.5%, 51.5%, 35.7%, and 41.3%/43.3%, respectively).

Conclusions
Overall, with delgocitinib cream 20 mg/g treatment no safety concerns were identified and efficacy further improved, supporting the benefit of long-term as-needed use of delgocitinib cream in patients with moderate to severe CHE.
679 - Rocatinlimab significantly improves clinical responses in patients with moderate-to-severe atopic dermatitis by week 2 in a randomized double-blind placebo-controlled phase 2b study
Authors: Guttman-Yassky Emma , Esfandiari Ehsanollah , Mano Hirotaka , Arai Takahiro , Kabashima Kenji 
Published: August 2024

Abstract

Introduction/Background
Moderate-to-severe atopic dermatitis (msAD) can cause chronic cycles of pruritus and scratching, impacting quality of life.

Objectives
To evaluate rocatinlimab for the treatment of msAD To investigate the onset of action of rocatinlimab on pruritis Numerical Rating scale (pNRS) and Eczema Area and Severity Index (EASI) in adults with msAD

Methods
A multicenter, randomized, double-blind, placebo-controlled Phase 2b trial (NCT03703102) evaluated rocatinlimab (anti-OX40 monoclonal antibody) for msAD. Primary endpoint achievement (Percent change from baseline to week 16 in EASI) has been presented. Randomized patients (1:1:1:1:1) received subcutaneous rocatinlimab 150mg/600mg every 4 weeks (Q4W) or 300mg/600mg every 2 weeks (Q2W) for 36 weeks, or placebo (Weeks 0–18) followed by rocatinlimab (600mg Q2W Weeks 18–36). All cohorts had 20-week off-treatment follow-up.

Results
Clinical response onset with rocatinlimab was evaluated post-hoc (N=267; rocatinlimab: n=210; placebo: n=57) by investigating pNRS and EASI between baseline and Week 16. Difference in least squares mean of percent change from baseline between rocatinlimab cohorts and placebo were assessed. Pruritus was significantly improved with rocatinlimab by Week 2 in all cohorts (−18.40% to −21.96%; p≤0.018) except 600mg Q4W (−9.66%; p=0.208), and in all cohorts by Week 4 (−15.70% to −27.19%; p≤0.045); EASI improvements were significant in all rocatinlimab cohorts by Week 6 (−20.50% to −32.13%; p≤0.001) compared with placebo, and the 300mg and 600mg Q2W cohorts by Week 2 (−13.27% and −13.66%; p≤0.028). Further improvements with rocatinlimab continued to Week 16 compared with placebo; improvements from baseline continued in all active cohorts to Week 36 and were maintained for 20 weeks off-treatment, suggesting rocatinlimab may have potential for disease modification in adults with msAD.

Conclusion
Rocatinlimab improved pNRS and EASI by Week 2; improvements continued and were maintained off-treatment until the end of study.
722 - Efficacy of povorcitinib for the treatment of vitiligo by patient demographics and baseline clinical characteristics: week 52 subgroup analysis from a randomized, placebo-controlled, phase 2b clinical trial
Authors: Pandya Amit G , Passeron Thierry , Blauvelt Andrew , van Geel Nanja , Brown Kurt , Erskine Lois , Xue Zhenyi , Ezzedine Khaled 
Published: August 2024

Abstract

Introduction/Background
Povorcitinib—an oral, small-molecule, selective Janus kinase 1 inhibitor—was statistically superior to placebo at Week 24 in patients with nonsegmental vitiligo in a phase 2b clinical trial (NCT04818346).

Objectives
To evaluate the efficacy of povorcitinib in subgroups of patients with nonsegmental vitiligo defined by demographics and baseline clinical characteristics.

Methods
Adults with nonsegmental vitiligo affecting ≥0.5%/≥8% facial/total body surface area (F-BSA/T-BSA) were randomized 1:1:1:1 to once-daily povorcitinib 15/45/75 mg or placebo for 24 weeks; subsequently, patients received povorcitinib 45/75 mg for an additional 28 weeks. The percentage of patients achieving ≥50% reduction from baseline in total Vitiligo Area Scoring Index (T-VASI50) and ≥50% and ≥75% reduction in facial-VASI (F-VASI50 and F-VASI75, respectively) were assessed by demographics and baseline characteristics. Data were analyzed using descriptive statistics; missing values were considered nonresponders.

Results
In total, 171 patients were randomized; at baseline, median (range) age was 50 (23–74) years, mean (SD) disease duration was 19.4 (14.0) years, and mean (SD) T-VASI was 25.5 (19.1). Subgroup analyses were conducted among the 103 patients who received any dose of povorcitinib from Day 1. At Week 52, 35/103 (34.0%) evaluable patients who received povorcitinib 15/45/75 mg achieved T-VASI50, 63/103 (61.2%) achieved F-VASI50, and 47/103 (45.6%) achieved F-VASI75. T-VASI50 responses were consistent within subgroups defined by age (≤40/&gt;40 years, 42.9%/30.7%), sex (male/female, 23.8%/41.0%), race (White/Non-White, 31.6%/41.7%), Fitzpatrick skin type (I–III/IV–VI, 31.4%/39.4%), F-BSA (≤1.5%/&gt;1.5%, 30.4%/41.2%), T-BSA (≤20%/&gt;20%, 35.4%/32.7%), autoimmune comorbidities (Yes/No, 37.9%/32.4%), disease duration (≤10/10–20/&gt;20 years, 41.7%/13.0%/38.6%), and previous therapy (Yes/No, 34.4%/30.0%). Similar findings were observed for F-VASI50 and F-VASI75.

Conclusions
Patients receiving povorcitinib achieved T-VASI50, F-VASI50, and F-VASI75 responses regardless of demographics or baseline clinical characteristics. Results should be confirmed in larger populations.
725 - The TCS/TCI-free rate remains high and stable while on lebrikizumab for treatment of moderate-to-severe atopic dermatitis over 1 year
Authors: Del Rosso James , Nosbaum Audrey , Golant Alexandra , Nakahara Takeshi , Murase Jenny E , Pink Andrew , Montmayeur Sonia , Qiao Meihua , Chen Sherry , Pau-Charles Ignasi , Bieber Thomas 
Published: August 2024

Abstract

Background
The ADvocate1 and ADvocate2 phase 3 trials investigated lebrikizumab (LEB), a monoclonal antibody selectively targeting interleukin-13, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are commonly used as concomitant treatment for AD. However, long term use can result in side effects. Thus, remaining free of TCS/TCI usage is important for evaluating the benefit of systemic AD therapies.

Objectives
To summarize and assess the proportion of patients without TCS or TCI usage over the course of the maintenance period based on pooled ADvocate1 and ADvocate2 studies.

Methods
This study consisted of pooled ADvocate1 and ADvocate2 data for patients responding to LEB at week 16 (induction period). Responders (N = 291) were re-randomized in a 2:2:1 ratio to receive 250 mg LEB every 2 weeks (Q2W; N = 113), 250 mg LEB every 4 weeks (Q4W; N = 118), or placebo every 2 weeks (LEB withdrawal/PBO; N = 60) for 36 weeks (maintenance period). Lack of TCS/TCI use was interpreted as an advantageous outcome of LEB treatment. Data are presented as observed data.

Results
Across the maintenance period, high proportions of patients in all groups (Q2W – 90.3%; Q4W – 88.1%; PBO – 86.7%) did not use TCS. Higher proportions (Q2W – 96.5%; Q4W – 98.3%; PBO – 95%) did not use TCI. Importantly, 88.5% of Q2W, 86.4% of Q4W, and 81.7% of PBO, did not use either TCS or TCI. This high TCS/TCI free rate remained stable over the course of the maintenance period.

Conclusions
Most patients with moderate-to-severe AD responding to LEB remained free of TCS, TCI, and TCS/TCI use throughout the first year of treatment.
Total mesorectal excision quality in rectal cancer surgery affects local recurrence rate but not distant recurrence and survival: population-based cohort study
Authors: Collin Åsa , Dahlbäck Cecilia , Folkesson Joakim , Buchwald Pamela 
Published: August 2024

Abstract

Background
The quality of the total mesorectal excision specimen in rectal cancer surgery is assessed with a three-tier grade (mesorectal, intramesorectal and muscularis propria). This study aimed to analyse the prognostic impact of the total mesorectal excision grade on survival, and to identify risk factors for intramesorectal and muscularis propria resection in a population-based setting.

Methods
All patients in the Swedish Colorectal Cancer Registry with rectal cancer stage I–III ≤ 10 cm from the anal verge, diagnosed 2015–2019, undergoing total mesorectal excision were analysed. Clinical, surgical and pathological data were retrieved and analysed for the following primary outcomes: local and distant recurrence and overall and relative survival; secondary outcomes were risk factors for total mesorectal excision grading (intramesorectal or muscularis propria resection). Of note, postoperative death &lt; 30 days or recurrence within 90 days were exclusion criteria for survival and recurrence analysis. Recurrence-free patients with less than 3 years follow-up, and patients lacking data regarding recurrence, were also excluded from recurrence analyses.

Results
Overall, of 7979 patients treated during the study interval, 1499 patients were eligible for recurrence, 2441 patients for survival and 2476 patients for risk-factor analyses, of which 75% were graded mesorectal, 17% intramesorectal and 8% muscularis propria. Median follow-up for survival was 42 (1–77) months. The worst total mesorectal excision grading (muscularis propria resection) was an independent risk factor for local recurrence in multivariable analysis (HR 2.73, 95% c.i. 1.07 to 7.0, P = 0.036). Total mesorectal excision grade had no impact on distant recurrence or survival. Female sex, tumour level &lt;5 cm, abdominoperineal resection, minimally invasive surgery (laparoscopic and robotic), high blood loss, long duration of surgery and intraoperative perforation were independent risk factors for worse total mesorectal excision grading (intramesorectal and/or muscularis propria resection) in multivariable analyses.

Conclusion
Muscularis propria resection increases the risk of local recurrence but does not seem to affect distant recurrence or survival.
Examining cognition and brain networks using magnetoencephalography in paediatric autoimmune encephalitis and acute disseminated encephalomyelitis: a preliminary study
Authors: Billaud Charly H A , Wood Amanda G , Griffiths-King Daniel , Kessler Klaus , Wassmer Evangeline , Foley Elaine , Wright Sukhvir K 
Published: August 2024

Abstract
Paediatric autoimmune encephalitis, including acute disseminated encephalomyelitis, are inflammatory brain diseases presenting with cognitive deficits, psychiatric symptoms, seizures, MRI and EEG abnormalities. Despite improvements in disease recognition and early immunotherapy, long-term outcomes in paediatric autoimmune encephalitis remain poor. Our aim was to understand functional connectivity changes that could be associated with negative developmental outcomes across different types of paediatric autoimmune encephalitis using magnetoencephalography. Participants were children diagnosed with paediatric autoimmune encephalitis at least 18 months before testing and typically developing children. All completed magnetoencephalography recording at rest, T1 MRI scans and neuropsychology testing. Brain connectivity (specifically in delta and theta) was estimated with amplitude envelope correlation, and network efficiency was measured using graph measures (global efficiency, local efficiency and modularity). Twelve children with paediatric autoimmune encephalitis (11.2 ± 3.5 years, interquartile range 9 years; 5M:7F) and 12 typically developing controls (10.6 ± 3.2 years, interquartile range 7 years; 8M:4F) participated. Children with paediatric autoimmune encephalitis did not differ from controls in working memory (t(21) = 1.449; P = 0.162; d = 0.605) but had significantly lower processing speed (t(21) = 2.463; P = 0.023; Cohen’s d = 1.028). Groups did not differ in theta network topology measures. The paediatric autoimmune encephalitis group had a significantly lower delta local efficiency across all thresholds tested (d = −1.60 at network threshold 14%). Theta modularity was associated with lower working memory (β = −0.781; t(8) = −2.588, P = 0.032); this effect did not survive correction for multiple comparisons (P(corr) = 0.224). Magnetoencephalography was able to capture specific network alterations in paediatric autoimmune encephalitis patients. This preliminary study demonstrates that magnetoencephalography is an appropriate tool for assessing children with paediatric autoimmune encephalitis and could be associated with cognitive outcomes.
Interaction of the dorsolateral prefrontal cortex with the precuneal medial parietal cortex for the monitoring of information in working memory in the macaque monkey
Authors: Petrides Michael , Lefebvre Sarah , Novek Jennifer , Zlatkina Veronika 
Published: August 2024

Abstract
The executive control process of monitoring information in working memory depends on the mid-dorsolateral prefrontal cortical region (cytoarchitectonic areas 46 and 9/46) in interaction with the hippocampal memory system. Anatomical studies demonstrated strong connectivity between the mid-dorsolateral prefrontal cortex and the medial parietal area PGm that lies on the precuneus. Area PGm is also strongly connected with the attentional system on the lateral inferior parietal lobule (area PG) and the limbic retrosplenial/posterior cingulate region that interacts with the hippocampal memory system. Thus, in terms of anatomical connectivity, area PGm appears to be a critical node for the integration of executive control processing from the prefrontal cortex with the online attentional and memory related processing. This hypothesis was tested in macaque monkeys with the crossed unilateral lesion methodology. A unilateral lesion in the mid-dorsolateral prefrontal cortex was combined with a unilateral lesion in area PGm in the opposite hemisphere. The results demonstrated an impairment on the externally ordered working memory task that assesses the monitoring of information in working memory. Thus, the medial parietal area PGm is a critical node in mediating the functional interaction between the prefrontal region for the executive control process of monitoring information and the memory system.
Spatiotemporal whole-brain activity and functional connectivity of melodies recognition
Authors: Bonetti Leonardo , Brattico Elvira , Carlomagno Francesco , Cabral Joana , Stevner Angus , Deco Gustavo , Whybrow Peter C , Pearce Marcus , Pantazis Dimitrios , Vuust Peter , Kringelbach Morten L 
Published: August 2024

Abstract
Music is a non-verbal human language, built on logical, hierarchical structures, that offers excellent opportunities to explore how the brain processes complex spatiotemporal auditory sequences. Using the high temporal resolution of magnetoencephalography, we investigated the unfolding brain dynamics of 70 participants during the recognition of previously memorized musical sequences compared to novel sequences matched in terms of entropy and information content. Measures of both whole-brain activity and functional connectivity revealed a widespread brain network underlying the recognition of the memorized auditory sequences, which comprised primary auditory cortex, superior temporal gyrus, insula, frontal operculum, cingulate gyrus, orbitofrontal cortex, basal ganglia, thalamus, and hippocampus. Furthermore, while the auditory cortex responded mainly to the first tones of the sequences, the activity of higher-order brain areas such as the cingulate gyrus, frontal operculum, hippocampus, and orbitofrontal cortex largely increased over time during the recognition of the memorized versus novel musical sequences. In conclusion, using a wide range of analytical techniques spanning from decoding to functional connectivity and building on previous works, our study provided new insights into the spatiotemporal whole-brain mechanisms for conscious recognition of auditory sequences.
Goal-directed learning is multidimensional and accompanied by diverse and widespread changes in neocortical signaling
Authors: Marrero Krista , Aruljothi Krithiga , Delgadillo Christian , Kabbara Sarah , Swatch Lovleen , Zagha Edward 
Published: August 2024

Abstract
New tasks are often learned in stages with each stage reflecting a different learning challenge. Accordingly, each learning stage is likely mediated by distinct neuronal processes. And yet, most rodent studies of the neuronal correlates of goal-directed learning focus on individual outcome measures and individual brain regions. Here, we longitudinally studied mice from naïve to expert performance in a head-fixed, operant conditioning whisker discrimination task. In addition to tracking the primary behavioral outcome of stimulus discrimination, we tracked and compared an array of object-based and temporal-based behavioral measures. These behavioral analyses identify multiple, partially overlapping learning stages in this task, consistent with initial response implementation, early stimulus–response generalization, and late response inhibition. To begin to understand the neuronal foundations of these learning processes, we performed widefield Ca2+ imaging of dorsal neocortex throughout learning and correlated behavioral measures with neuronal activity. We found distinct and widespread correlations between neocortical activation patterns and various behavioral measures. For example, improvements in sensory discrimination correlated with target stimulus evoked activations of response-related cortices along with distractor stimulus evoked global cortical suppression. Our study reveals multidimensional learning for a simple goal-directed learning task and generates hypotheses for the neuronal modulations underlying these various learning processes.