bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroform exposure in air and water in Swedish indoor swimming pools—urine as a biomarker of occupational exposure
Authors: Ragnebro Oskar , Helmersmo Kristin , Fornander Louise , Olsen Raymond , Bryngelsson Ing-Liss , Graff Pål , Westerlund Jessica 
Published: June 2023

Abstract

Introduction
Disinfection by-products are produced in water disinfected with chlorine-based products. One such group is trihalomethanes, and chloroform is the most abundant trihalomethane in swimming pool areas. Chloroform can be absorbed by inhalation, ingestion, and dermal absorption, and is classified as possibly carcinogenic.

Aim
To investigate if chloroform concentrations in air and water affect the chloroform concentration in urine samples of exposed swimming pool workers.

Methods
Workers from 5 adventure indoor swimming pools carried personal chloroform air samplers and provided up to 4 urine samples during one workday. Chloroform concentrations were analyzed with a linear mixed model analysis to investigate a possible correlation between air and urine concentrations.

Results
The geometric mean chloroform concentration was 11 μg/m3 in air and 0.009 µg/g creatinine in urine among individuals with ≤2 h at work, 0.023 µg/g creatinine among those with &gt;2–5 working hours, and 0.026 µg/g creatinine in the group with &gt;5–10 working hours. A risk of higher levels of chloroform in urine was associated with longer hours at work (≤2 h versus &gt;5–10 h, odds ratio [OR] 2.04, 95% confidence interval [CI] 1.25–3.34), personal chloroform concentrations in air (≤17.00 µg/m3 versus &gt;28.00 µg/m3, OR 9.23, 95% CI 3.68–23.13) and working at least half the working day near the swimming pools (OR 3.16, 95% CI 1.33–7.55). Executing work tasks in the swimming pool water was not associated with higher chloroform concentrations in urine compared to only working on land (OR 0.82, 95% CI 0.27–2.45).

Conclusion
There is an accumulation of chloroform concentrations in urine during a workday and a correlation between personal air and urine concentrations of chloroform among workers in Swedish indoor swimming pools.
A novel statistical method for decontaminating T-cell receptor sequencing data
Authors: Li Ruoxing , Altan Mehmet , Reuben Alexandre , Lin Ruitao , Heymach John V , Tran Hai , Chen Runzhe , Little Latasha , Hubert Shawna , Zhang Jianjun , Li Ziyi 
Published: June 2023

Abstract
The T-cell receptor (TCR) repertoire is highly diverse among the population and plays an essential role in initiating multiple immune processes. TCR sequencing (TCR-seq) has been developed to profile the T cell repertoire. Similar to other high-throughput experiments, contamination can happen during several steps of TCR-seq, including sample collection, preparation and sequencing. Such contamination creates artifacts in the data, leading to inaccurate or even biased results. Most existing methods assume ‘clean’ TCR-seq data as the starting point with no ability to handle data contamination. Here, we develop a novel statistical model to systematically detect and remove contamination in TCR-seq data. We summarize the observed contamination into two sources, pairwise and cross-cohort. For both sources, we provide visualizations and summary statistics to help users assess the severity of the contamination. Incorporating prior information from 14 existing TCR-seq datasets with minimum contamination, we develop a straightforward Bayesian model to statistically identify contaminated samples. We further provide strategies for removing the impacted sequences to allow for downstream analysis, thus avoiding any need to repeat experiments. Our proposed model shows robustness in contamination detection compared with a few off-the-shelf detection methods in simulation studies. We illustrate the use of our proposed method on two TCR-seq datasets generated locally.
The spread of infectious diseases from a physics perspective
Authors: Brabers J H V J 
Published: June 2023

Abstract
This article deals with the spread of infectious diseases from a physics perspective. It considers a population as a network of nodes representing the population members, linked by network edges representing the (social) contacts of the individual population members. Infections spread along these edges from one node (member) to another. This article presents a novel, modified version of the SIR compartmental model, able to account for typical network effects and percolation phenomena. The model is successfully tested against the results of simulations based on Monte-Carlo methods. Expressions for the (basic) reproduction numbers in terms of the model parameters are presented, and justify some mild criticisms on the widely spread interpretation of reproduction numbers as being the number of secondary infections due to a single active infection. Throughout the article, special emphasis is laid on understanding, and on the interpretation of phenomena in terms of concepts borrowed from condensed-matter and statistical physics, which reveals some interesting analogies. Percolation effects are of particular interest in this respect and they are the subject of a detailed investigation. The concept of herd immunity (its definition and nature) is intensively dealt with as well, also in the context of large-scale vaccination campaigns and waning immunity. This article elucidates how the onset of herd-immunity can be considered as a second-order phase transition in which percolation effects play a crucial role, thus corroborating, in a more pictorial/intuitive way, earlier viewpoints on this matter. An exact criterium for the most relevant form of herd-immunity to occur can be derived in terms of the model parameters. The analyses presented in this article provide insight in how various measures to prevent an epidemic spread of an infection work, how they can be optimized and what potentially deceptive issues have to be considered when such measures are either implemented or scaled down.
377 Real-world use of OPZELURA™: safety analysis at 1 year
Authors: Hu Wilson , Thornton Michele , Livingston Robert A   
Published: June 2023

Abstract
OPZELURA™ (ruxolitinib cream) became the first approved topical Janus kinase inhibitor (JAKi) in the USA on September 21, 2021, for treatment of mild to moderate atopic dermatitis and on July 18, 2022 for nonsegmental vitiligo. This study aims to review postmarketing safety encompassing nearly 14,000 patient-years of treatment during the first year of market approval through September 20, 2022. The Incyte global safety database and the US Food and Drug Administration (FDA) Adverse Event Reporting System were queried for adverse event (AE) reports received for OPZELURA between September 21, 2021 and September 20, 2022. Search of these databases found 294 postmarketing individual case safety reports (ICSRs) containing 585 nonserious AEs, four serious AEs and no fatal AEs. Of the 294 ICSRs, 220 (75%) were received from spontaneous sources and 74 (25%) were received from noninterventional/solicited sources. Consumers reported 221 ICSRs (75%) and 73 (25%) were medically confirmed by a healthcare professional (i.e. nurse, pharmacist and physician). Gender was reported in 257 ICSRs; of these, 81 (32%) involved male patients and 176 (68%) involved female patients. Age was reported in 64 ICSRs (22%), with a median age of 39 years. The AEs (any unfavorable sign, symptom or disease) with frequency &gt;2% out of all events included application site pain (16 events), dermatitis atopic, skin irritation (15 events each), scratch (14 events) and condition aggravated (13 events). Application site pain, skin irritation and scratch were mostly related to an initial issue with cream texture that was rapidly addressed. ‘Dermatitis atopic’ and ‘condition aggravated’ reflected worsening of the underlying condition or lack of improvement. The four serious AEs were skin cancer (two events), pericarditis and thrombocytopenia (one event each), all of which had insufficient information for assessment of relatedness to OPZELURA. Because indications for OPZELURA are inflammatory conditions, OPZELURA has been subject to the same class warnings as oral JAKi that include the risk of serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis, imposed by FDA subsequent to the ORAL Surveillance trial of tofacitinib in rheumatoid arthritis (Kragstrup et al., RMD Open, 2022; 8:e002236). Topical application of OPZELURA results in low systemic bioavailability of ruxolitinib, and serious AEs associated with oral JAKi were not reported with OPZELURA. Safety data from the first year of marketing confirm that OPZELURA is well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.
388 Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial: assessment of pruritus
Authors: Blauvelt Andrew , Draelos Zoe D , Gooderham Melinda  , Lain Edward , Moore Angela Y , Papp Kim A , Zirwas Matthew , Krupa David , Burnett Patrick , Berk David R , Chu David H 
Published: June 2023

Abstract
Itch is a major complaint among patients with seborrheic dermatitis (SD). Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor under investigation as a once-daily foam for treatment of SD. This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial (NCT04973228) was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or nonscalp areas. Patients were randomized 2 : 1 to apply once-daily roflumilast foam 0.3% (n = 304) or vehicle (n = 153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included Worst Itch Numeric Rating Scale (WI-NRS), which was completed daily by patients. Safety and local tolerability were also evaluated. Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA success (79.5% vs. 58.0%; P &lt; 0.0001) and IGA status of Clear (50.6% vs. 27.7%; P &lt; 0.0001) at Week 8. Significantly greater percentages of roflumilast- than vehicle-treated patients had ≥4-point improvement on WI-NRS at Weeks 2 (32.7% vs. 15.5%; P = 0.0016), 4 (47.6% vs. 29.1%; P = 0.0007) and 8 (62.8% vs. 40.6%; P = 0.0001). Greater improvement in itch was observed among roflumilast-treated patients as early as 48 h after the first application (mean percent change from baseline: −27.87% vs. −13.11%; nominal P = 0.0024). Local tolerability and safety were favorable. Once-daily roflumilast foam provided improvement across multiple efficacy endpoints including rapid itch improvement, while demonstrating favorable safety and tolerability.
392 Safety of amlitelimab in a Phase 2a clinical trial of patients with moderate-to-severe atopic dermatitis
Authors: Weidinger Stephan , Cork Michael , Reich Adam , Bieber Thomas , Gilbert Sally , Quaratino Sonia , Wilson Rosamund , Porter-Brown Ben 
Published: June 2023

Abstract
Amlitelimab (SAR445229), a fully human, nondepleting, noncytotoxic, monoclonal antibody, binds to OX40Ligand (OX40L) on antigen-presenting cells to block OX40-OX40L interactions. Outcomes from a 36-week, double-blind, Phase 2a trial (NCT03754309) in patients with moderate-to-severe atopic dermatitis are described. This study aims to assess the safety of OX40-OX40L signaling blockade with amlitelimab in patients with moderate-to-severe atopic dermatitis. Eighty-nine patients were randomized to amlitelimab low-dose (LD; 200-mg loading/100-mg maintenance Q4W), high-dose (HD; 500 mg/250 mg Q4W) or placebo. The coprimary safety endpoint was treatment-emergent adverse event (TEAE) incidence to W16. Safety was assessed to W36. Amlitelimab was well tolerated. Related TEAE incidence was similar between amlitelimab [LD 35% (10/29); HD 20% (6/30)] and placebo [31% (9/29)] to W16 and W36 [LD 10% (2/20); HD 0 (0/22); placebo 0 (0/17)]. The TEAEs more common with amlitelimab vs. placebo (≥5% difference) to W16 included headache [LD 0; HD 3 (10%); placebo 1 (3.4%)], upper respiratory tract infection [3 (10.3%); 0; 1 (3.4%)], hyperhidrosis [0; 2 (6.7%); 0], pyrexia [2 (6.9%); 0; 0], aspartate aminotransferase increased [0; 2 (6.7%); 0] and iron-deficiency anemia [2 (6.9%); 0; 0]; and to W36, Herpes simplex [0; 2 (9.1%); 0]. Before W16, one severe adverse event (SAE) of infected dermal cyst was reported as possibly related; it resolved, and the patient completed the study. Post-W16, one unrelated SAE of sudden death occurred 87 days following the final amlitelimab dose. No hypersensitivity or tolerability events, or clinically meaningful changes in laboratory values, vital signs or electrocardiogram recordings were reported. Amlitelimab was well tolerated in a Phase 2a trial of patients with moderate-to-severe atopic dermatitis, confirming the unremarkable safety profile observed in Phase 1.
411 Long term laboratory safety of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis
Authors: Siegfried Elaine , Cork Michael J , Lockshin Benjamin  , Boguniewicz Mark , Uppal Sumeet  , Khokhar Faisal A , Bansal Ashish , Sierka Debra , Cyr Sonya 
Published: June 2023

Abstract
Systemic treatments often require laboratory monitoring. Here we report 52-week laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe AD. LIBERTY AD PED-OLE (NCT02612454) is an open-label extension study of children aged 6 months to &lt;18 years with moderate-to-severe AD. This analysis includes hematologic and chemistry laboratory parameters in children aged 6 months to 5 years treated with dupilumab every 4 weeks (q4w; 200 mg: ≥5 to &lt;15 kg; 300 mg: ≥15 to &lt;30 kg). Of the 180 patients enrolled, 122 (67.8%) completed up to 16 weeks and 30 (16.7%) completed up to 52 weeks. Mean (SD) eosinophil counts increased slightly from baseline [1.15 × 109/L (1.18) ] to Week 16 [1.5 × 109/L (1.91)], but then decreased below baseline by Week 52 [0.80 × 109/L (0.64)]. Mean (SD) platelet counts were relatively stable with a modest decrease from baseline [388.7 × 109/L (102.51)] to Week 52 [356.1 × 109/L (107.48)]. Chemistry parameters remained within the normal reference ranges. One patient (0.6%) reported a mild case of anemia, and one patient (0.6%) reported a mild case of thrombocytopenia, which were resolving and resolved at the time of this interim analysis, respectively. Overall safety was consistent with the known dupilumab safety profile. No clinically meaningful changes in hematologic and chemistry parameters were observed during 52 weeks of dupilumab treatment. As with adults, adolescents and older children, routine laboratory monitoring is unnecessary in children aged 6 months to 5 years with moderate-to-severe AD.
414 Baseline serum biomarkers do not predict dupilumab treatment response in adults with moderate-to-severe atopic dermatitis
Authors: Weidinger Stephan , Beck Lisa A , de Bruin-Weller Marjolein S   , Thyssen Jacob P , Kabashima Kenji  , Guttman-Yassky Emma , Akdis Cezmi A , Chen Zhen , Levit Noah A , Bastian Mike 
Published: June 2023

Abstract
Previous analyses based on short-term, phase 2 studies reported that baseline biomarkers do not correlate with clinical outcomes following dupilumab treatment in patients with atopic dermatitis (AD). This new analysis based on 16-week, phase 3 studies reports whether pretreatment levels of common serum biomarkers can predict treatment response to dupilumab in adults with moderate-to-severe AD. LIBERTY AD SOLO 1 and 2 (NCT02277743 and NCT02277769), two randomized, double-blind studies, included patients ≥18 years-old with moderate-to-severe AD treated with dupilumab 300 mg every 2 weeks or placebo for 16 weeks. Correlation between change in Eczema Area and Severity Index (EASI) and log of baseline IgE, CC chemokine ligand 17 [CCL17; previously referred to as thymus and activation-regulated chemokine (TARC)] and lactate dehydrogenase (LDH) at baseline was assessed using Spearman’s correlation coefficient (ρ). At Week 16, change in EASI showed little correlation with baseline total IgE [Spearman’s correlation coefficient (ρ) = –0.14, n = 370 for dupilumab; ρ = –0.03, n = 202 for placebo], baseline CCL17 (ρ = –0.28, n = 369 for dupilumab; ρ = –0.05, n = 201 for placebo) or baseline LDH (ρ = –0.30, n = 370 for dupilumab; ρ = –0.08, n = 202 for placebo). Overall safety was consistent with the known dupilumab safety profile. Baseline levels of total IgE, CCL17 and LDH do not predict treatment response to dupilumab, as measured by EASI, in adults with moderate-to-severe AD.
437 Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial
Authors: Paller Amy S , Siegfried Elaine C , Sidbury Robert  , Lockshin Benjamin , Cork Michael  , Pinter Andreas , Xiao Jing , Khokhar Faisal A , Bansal Ashish , Prescilla Randy  
Published: June 2023

Abstract
Atopic dermatitis (AD) is a chronic systemic inflammatory disease requiring long-term management. However, availability of long-term AD treatments with an acceptable risk-benefit profile is limited in pediatric patients. This ongoing phase 3 open-label extension (OLE; NCT02612454) enrolled patients aged 6 months to 17 years with moderate-to-severe AD. Patients were treated with dupilumab (weight-based dosing): 200 mg every 4 weeks (q4w; 5–14 kg), 300 mg q4w (15–29 kg) and 200 mg q2w (30–59 kg). Here we report safety data (cutoff date July 31, 2021) for 180 patients aged 6 months to 5 years who enrolled in the OLE. Of the 180 patients reported, 122 (67.8%) completed up to 16 weeks of the study, 30 (16.7%) up to Week 52 and 15 (8.3%) up to Week 156. A total of 167 (92.8%) patients were continuing treatment at the time of data cutoff. At baseline, the mean (SD) age was 3.9 (1.3) years. One hundred and nine (60.6%) patients reported treatment-emergent adverse events (TEAEs); the most common were nasopharyngitis (12.8%), upper respiratory tract infection (11.7%) and pyrexia (11.7%). One (0.6%) patient had a treatment-related severe TEAE (urticaria) that led to study drug discontinuation. Two (1.1%) patients had serious TEAEs (anaphylactic reaction and pneumonia mycoplasmal) of severe and moderate intensity, respectively. Both serious TEAEs were unrelated to treatment. Long-term safety of dupilumab in this pediatric population was generally consistent with the known dupilumab safety profile in adults and older pediatric patients.
440 Prevalence and burden of rhinoconjunctivitis in atopic dermatitis patients: a cross-sectional study
Authors: Betaharon Isaac , Silverberg Jonathan I 
Published: June 2023

Abstract
Allergic rhinoconjuncitivitis can be highly symptomatic and burdensome and complicates the management of eyelid and facial dermatitis in persons with atopic dermatitis (AD). However, little is known about the prevalence, burden and predictors of allergic rhinoconjunctivitis symptoms in patients with AD, particularly among adults. This study aims to determine the prevalence and predictors of allergic rhinoconjunctivitis severity in patients with AD. A cross-sectional, dermatology practice-based study was performed at an urban academic medical center (n = 507). Atopic dermatitis severity was assessed by investigator-assessed Eczema Area and Severity Index (EASI), body surface area (BSA), investigator’s global assessment (IGA), objective-SCORing AD and patient-reported Global Assessment (PtGA). Impact of allergic rhinoconjunctivitis symptoms was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. The cohort included children (&lt;18 years; n = 36, 7.1%), young adults (18–49 years; n = 281, 55.4%) and older adults (≥50 years; n = 190, 37.5%), males (n = 219, 43.2%) and females (n = 288, 56.8%), Hispanics (n = 43, 8.5%), Blacks (n = 50, 9.9%), White non-Hispanics (n = 349, 68.8%), Asians (n = 51, 10.1%) and multiracial/other race (n = 14, 2.8%); 413 (81.5%) had private insurance. Overall, 246 (48.5%) reported a history of hay fever, and 15 (3.0%) and 416 (82.1%) of patients with AD reported having trouble with one or multiple rhinoconjunctivitis symptoms in the past 2 weeks; 30 (5.9%) and 365 (72.0%) of patients with AD had quite a bit or extreme trouble with one or multiple rhinoconjunctivitis symptoms, respectively. More severe AD overall (EASI, BSA, IGA and PtGA), as well as more severe facial dermatitis, flexural eczema and xerosis were associated with worse rhinoconjunctivitis symptoms, whereas, race, gender and presence of nummular dermatitis were generally not associated with rhinoconjunctivitis symptom severity. Quite a bit or extreme trouble from one or more rhinoconjunctivitis symptoms was reported in 39 (56.5%) patients with clear/almost clear, 85 (74.6%) mild, 135 (82.8%) moderate and 106 (84.8%) severe PtGA scores. In multivariable ordinal logistic regression models that controlled for demographics, AD severity was significantly associated with higher odds of a wide range of nasal and ocular symptoms, as well as rhinoconjunctivitis symptoms negatively impacting daily activities, causing sleep and practical problems, and negative emotions. Allergic rhinoconjunctivitis symptoms occurred in more than 4 out of 5 patients with AD overall, and almost 90% of patients with severe AD. Allergic rhinoconjunctivitis was more common in those with more severe AD, and particularly those with more severe facial dermatitis, flexural eczema and xerosis. Rhinconjunctivitis symptoms negatively impact the lives of patients with AD and warrant appropriate screening and management in clinical practice.
Report on Sino–Indian Border Disputes: International Law and International Relations Perspectives
Authors: Lone Fozia Nazir 
Published: June 2023

Abstract
This article is based on remarks and presentations made at two symposiums—namely, the International Online Symposium on Sino–Indian Border Disputes: A Dialogue between International Law and International Relations, and the Second International Online Symposium on The Peaceful Settlement of the Sino–Indian Boundary Dispute: A Pragmatic Multidisciplinary Framework (中國法與比較法研究中心第二次國際在線研討會—[和平解決中印邊界爭端：務實的多學科框架]). These were hosted by the City University of Hong Kong’s School of Law: Centre for Chinese and Comparative Law, in collaboration with the Public Law and Human Rights Forum, on 4 March 2021 and 9 December 2021 respectively. The article reflects on the nature of the Sino–Indian Border Dispute (SIBD) and provides transitory remarks on concepts that promote either its settlement or the mitigation/maintenance of its status quo. Based on the range of issues and variables raised by discussants regarding challenges and opportunities of the SIBD, articulated from the perspectives of international law and international relations, history, political science, geography, and more, this article emphasizes a multidisciplinary approach to SIBD settlement with a context-specific assessment of each sector.