bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal and robust quantum state tomography of star-topology register
Authors: Liu Ran , Hou Yanjun , Wu Ze , Zhou Hui , Chen Jiahui , Li Zhaokai , Peng Xinhua
Published: August 2024

While quantum state tomography plays a vital role in the verification and benchmarking of quantum systems, it is an intractable task if the controllability of the quantum registers is constrained. In this paper, we propose a novel scheme for optimal and robust quantum state tomography for systems with constrained controllability. Based on the specific symmetry, we decompose the Hilbert space to alleviate the complexity of tomography and design a compact strategy with the minimum number of measurements. To switch between these measurement settings, we adopted parameterized quantum circuits consisting of local operations and free evolution, which are easy to implement in most practical systems. Then the parameters of these circuits were optimized to improve the robustness against errors of measurements. We demonstrated the experimental feasibility of our method on a 4-spin star-topology register and numerically studied its ability to characterize large-scale systems on a 10-spin star-topology register, respectively. Our results can help future investigations of quantum systems with constrained ability of quantum control and measurement.
Impact of climate change on major floods flowing into the Georges River estuary, Australia
Authors: Zhu Wenjun , Wang Xiao Hua , Peirson William
Published: August 2024

Coastal flooding induced by storm surges and heavy rainfall is one of the most frequent climate-related natural hazards along the southeast Australian coast, home to more than 55% of the Australian population. Flooding in this densely populated region is a threat to public safety, coastal infrastructure, ecological systems and the economy. Although climate change is expected to cause an increase in major floods, few studies have quantified the potential changes in flood severity. This study quantifies the changes in flood peak discharge flowing to the Georges River estuary in Australia due to climate-change. An event-based hydrological model, Watershed Bounded Network Model (WBNM), was used to predict flood discharge. This hydrological model was forced by rainfall data obtained from the New South Wales and Australian Capital Territory Regional Climate Modelling Project version 1.5 (NARCliM1.5) for both historical and the Representative Concentration Pathway 8.5 (RCP8.5) conditions. Model calibration for the floods of March 1978 and March 2022 achieved a general agreement between the predicted and observed hydrographs, with an overall average 14% error in the peak values, further demonstrating that the modelling approach is generally reliable in projections of flood severity. Using high resolution climate model projections, the present study observed an increase of 22% in the model ensemble average from historical conditions to the RCP8.5 scenario for the 20-year average recurrence interval (ARI) 24 h extreme rainfall. This heightened extreme rainfall consequently resulted in the changes in flood discharge with an average rise of 55%. This study provides specific assessment of climate-generated risks for densely-populated regions, especially those on Australian east coast. Global studies have suggested that extreme precipitation events will increase under climate change. This study supports and enhances these assertions by using high resolution downscaling to quantify the specific changes within a large catchment.
Data-driven sparse modeling of oscillations in plasma space propulsion
Authors: Bayón-Buján Borja , Merino Mario
Published: August 2024

An algorithm to obtain data-driven models of oscillatory phenomena in plasma space propulsion systems is presented, based on sparse regression (SINDy) and Pareto front analysis. The algorithm can incorporate physical constraints, use data bootstrapping for additional robustness, and fine-tuning to different metrics. Standard, weak and integral SINDy formulations are discussed and compared. The scheme is benchmarked for the case of breathing-mode oscillations in Hall effect thrusters, using particle-in-cell/fluid simulation data. Models of varying complexity are obtained for the average plasma properties, and shown to have a clear physical interpretability and agreement with existing 0D models in the literature. Lastly, the algorithm applied is also shown to enable the identification of physical subdomains with qualitatively different plasma dynamics, providing valuable information for more advanced modeling approaches.
Cultural Mismatch Between Early Childhood Teacher–Caregivers and Their Students
Authors: Davidson Kimberly
Published: August 2024

Young children begin to assign meaning to differences they notice in others based on the cultural socialization beliefs and practices of their families, caregivers, and teachers. As differences are explored, cultural learning takes place, making early childhood and elementary classrooms important environments for bridging cultural differences. Young children with diverse cultural heritages bring strong and unique ways of learning and growing to their learning contexts. This chapter highlights mechanisms through which cultural mismatch between teacher–caregivers and their students impacts development during the early childhood years. Review and discussion of extant literature shows elements of mismatch that impede children’s development of positive cultural identity. The saliency of culture in the lives of children must be taken into account in the work with young children around the world who are at critical periods of development.
Implementing Play-Based Pedagogy in Early Childhood Education in Hong Kong
Authors: Chan Stephanie W Y , Rao Nirmala
Published: August 2024

The kindergarten education policy in Hong Kong advocates child-centeredness and play-based pedagogy. Meanwhile, Chinese values of diligence, conformity, and obedience are rooted in the community and manifested in early childhood education policy and practice. This chapter examines the interaction among early childhood education policy, Chinese culture, and classroom practices in the context of play-based pedagogy implementation in Hong Kong. First, the chapter discusses policy priorities by examining the evolution of the conceptualization of play across kindergarten education curriculum documents. Second, it explores the dialectic tensions between the expectations of the kindergarten curriculum among stakeholders, including educators and parents. Third, drawing on classroom observations, interviews, and questionnaire studies, it examines how play-based approaches are implemented in classrooms. The interplay of early childhood education policy and cultural forces in shaping the implementation of play-based approaches is discussed.
Addressing the Complexities of Culture in Teaching and Learning in Aotearoa New Zealand
Authors: Ritchie Jenny
Published: August 2024

This chapter offers an overview of the historical and current complexities of education in Aotearoa New Zealand. The historical legacy of colonization by Britain continues to underpin educational inequities for the Indigenous Māori. More recently, immigration policies have resulted in a situation of superdiversity, generating further complexities and tensions, including heightened instances of racism. Some recent educational initiatives which aim to address some of these inequities, particularly in relation to Māori, are outlined. The conclusion calls attention to the urgent need for education policies that prepare teachers to support children and families as the nation faces the onslaught of the climate crisis.
Cultural Relationships and Responsive Contexts for Learning
Authors: Berryman Mere , Eley Elizabeth
Published: August 2024

A historical legacy of assimilation, cultural erasure, and linguicide, predicated on beliefs and practices contained within the 14th-century Doctrine of Discovery, have been imposed through education policies, textbooks, and teaching practices in many colonized countries of the world, including Aotearoa New Zealand. Here, deficit beliefs of Māori, as for many other Indigenous peoples, continue to be reinforced through the ongoing failure to recognize the need to develop “ethical spaces” in the coming together of peoples from disparate worldviews. This chapter proposes that understanding culture, relationships, and responsive contexts for learning means first coming to deeply understand and disrupt historical events that have seen the ongoing, systematic belittlement and redefinition of Māori identities through formal state schooling. It contends that when cultural relationships are respected and prioritized, responsive pedagogy can also flourish.
Global Responses to Increasing Diversity in Schools
Authors: Holmes Robyn M , Kohm Kristen E
Published: August 2024

This chapter discusses both micro- and macro-level variables that connect to school responses and practices to educate children from diverse cultural heritages, including non-native, particularly newly arrived children. It discusses issues that many school systems around the world are now facing as they prepare to educate non-native, culturally diverse children to help them become successful adults. It includes teacher, administrator, and country-level perceptions and practices and explores teacher preparation with an emphasis upon cultural competency and culturally responsive teaching, school policies and practices, and the role of administrators and governments in shaping school policies and building cultural connections between home and school. The review includes diverse geographic regions—Japan, New Zealand, Australia, the European Union, the United States, and Nordic countries. Finally, the chapter presents interviews with present American teachers to highlight the approaches they are using to achieve multicultural inclusion in their classrooms.
The Architects of Dignity
Authors: Pham Kevin D
Published: August 2024

The Architects of Dignity: Vietnamese Visions of Decolonization traces an intergenerational debate among six major political figures in Vietnam who had competing visions for how the Vietnamese should respond to French colonial domination (1858–1954). Each of them—Phan Bội Châu (1867–1940), Phan Chu Trinh (1872–1926), Nguyễn An Ninh (1900–1943), Phạm Quỳnh (1892–1945), Hồ Chí Minh (1890–1969), and Nguyễn Mạnh Tường (1909–1997)—traveled abroad and returned to Vietnam with ideas for how the Vietnamese should generate power among themselves, how they should approach their cultural traditions given the influx of new ideas from the West, and how they should envision a future Vietnam. These thinkers engaged in cross-cultural political thinking, drawing on Indian, Japanese, Chinese, French, and German thinkers, and more, conducting what political theorists would today call an engaged form of “Comparative Political Theory.” Despite their differences, they sought to channel feelings of national shame and inadequacy for constructive, dignifying ends. In contrast to theorists who tend to view shame as a destructive form of false consciousness, these thinkers show how shame can be an emotional engine to generate power for anticolonialism and self-determination. And while dignity is typically understood in the West as something inherent in individuals, as a justification for rights, and as requiring recognition, these Vietnamese thinkers saw dignity as a property of nations, as rooted in the duties a nation’s people embrace, and as something to be asserted by the nation instead of being dependent on recognition by colonizers.
Introduction
Authors: Pham Kevin D
Published: August 2024

This introductory chapter shows how the Vietnamese thinkers profiled in this study eventually realized that appealing to their colonial masters for recognition of Vietnamese dignity and rights was futile and that the Vietnamese had to construct their own dignity. This understanding of dignity has been undertheorized in the existing literature on dignity. Rather than demand that their colonizers recognize Vietnamese dignity, a more effective approach, they believed, was to shame their fellow Vietnamese into asserting national self-worth and self-respect. These thinkers’ political theorizing was informed by their experiences of traveling abroad where they gained insights from other cultures, allowing them to compare traditions to find the right ideas for them. This chapter also describes the structure of the present book.
Phan Chu Trinh’s Democratic Confucianism
Authors: Pham Kevin D
Published: August 2024

This chapter focuses on Vietnam’s first democrat, Phan Chu Trinh (1872–1926). The lack of genuine Confucian morality in Vietnam, he argued, was the reason that the Vietnamese were sick and vulnerable to foreign conquest. The solution was for the Vietnamese to adopt European liberalism and the form of government that he thought came from liberalism (democracy) to revive Confucianism in Vietnam. His claim was puzzling, considering that contemporary political theorists agree that liberalism and Confucianism are opposed. Trinh ignored liberalism’s individualism while celebrating other aspects of liberalism and Western civilization. His interpretation of Western ideas, though naive, is a creative one that offers us a lesson: it may be useful to view foreign ideas as foreign, to interpret them generously, and to import the creative distortion to revive our own cherished, yet faltering, traditions.
Phạm Quỳnh’s Cultural Resistance
Authors: Pham Kevin D
Published: August 2024

This chapter provides a new interpretation of the infamous Phạm Quỳnh (1892–1945). Historians and nationalists often typecast Quỳnh as an “arch-collaborator” with the French colonial regime, but closer attention to his writings reveals how he uses his colonial privilege as editor of a French-commissioned journal, Nam Phong (The Southern Wind), to resist colonial discourse. His writings seek to conserve, develop, and assert the Vietnamese national language and culture. For Quỳnh, Vietnam’s Confucian tradition embodied “Eastern wisdom” which the Vietnamese should revive to resist the domination of the “Western ideal” of “power,” while also adapting the ‘best’ ideas from the West. For him, this synthesis of East and West could provide a basis for Vietnamese national dignity. Ultimately, Quỳnh is today best understood not as a collaborator or a resistor but as an architect of a modern Vietnamese national identity.
Phan Bội Châu’s Nationalist Groundwork
Authors: Pham Kevin D
Published: August 2024

This chapter surveys early Vietnamese reactions to French colonialism through the lens of Phan Bội Châu (1867–1940), Vietnam’s first modern nationalist. His writings seek to persuade his compatriots to see themselves as citizens of a country rather than mere subjects of a ruler, thus shifting Vietnamese political thought from royalism to notions of popular sovereignty. His writings about French cruelty were aimed at inducing indignation in his readers so that they could channel these feelings into national consciousness and political action. Châu also sought to induce pleasure and joy by writing utopian descriptions of what Vietnam could be in the future to motivate his readers to fulfill their national duty of improving their nation. Among his other contributions, he helped to inspire the Tonkin Free School. Châu’s fledgling resistance against colonialism provided a nationalist framework that the rest of the thinkers covered in this book would work from and develop in new directions.
Revisiting unstable disability and the fluctuations of frailty: a measurement burst approach
Authors: Stolz Erwin , Schultz Anna , Mayerl Hannes , Roller-Wirnsberger Regina , Clegg Andrew
Published: August 2024

Background

It has been hypothesised that frailty is the root cause of clinically observed but rarely systematically measured unstable disability among older adults. In this study, we measure the extent of short-term disability fluctuations and estimate their association with frailty using intensive longitudinal data.

Methods

Repeated measurements of disability were collected under a measurement burst design in the FRequent health Assessment In Later life (FRAIL70+) study. A total of 426 community-dwelling older adults (70+) in Austria were interviewed about difficulties with basic, instrumental and mobility-related activities of daily living biweekly up to a total of 14 times in two measurement bursts (2891 and 2192 observations). Baseline frailty was assessed with both physical frailty (FP) and the frailty index (FI). Disability fluctuations were measured with the intra-individual interquartile range (iIQR) and estimated with a two-step generalised mixed regression procedure.

Results

Fewer participants were frail at baseline according to FP (11%) than FI (32%). Frail study participants reported not only more severe disability but also had more short-term disability fluctuations (iIQR = 1.0–1.5) compared with their robust counterparts (iIQR = 0). Regression models indicated that baseline frailty was associated with 2–3 times larger short-term disability fluctuations, which were also more prevalent among women, and increased with age and disability severity.

Conclusion

Compared with those who were robust, frail older adults were characterised by not only more severe but also more unstable disability. Short-term disability fluctuations are closely tied to disability severity. Future studies should assess both stressors that may cause disability fluctuations among frail older adults as well as their potential consequences to inform frailty-centred care.
Abuse-deterrent formulations and opioid-related harms in North Carolina, 2010-2018
Authors: DiPrete Bethany L , Dasgupta Nabarun , Oh G Yeon , Moga Daniela C , Slavova Svetla , Slade Emily , Delcher Chris , Pence Brian W , Ranapurwala Shabbar I
Published: August 2024

Abuse-deterrent formulations of opioid analgesics (ADFs) were introduced to reduce opioid-related harms among pain patients, but postmarketing study results have been mixed. However, these studies may be subject to bias from selection criteria, comparator choice, and potential confounding by “indication,” highlighting the need for thorough study design considerations. In a sample of privately insured patients prescribed ADF or non-ADF extended-release/long-acting (ER/LA) opioids in North Carolina, we implemented a version of the prevalent new-user design to evaluate the relationship between ADFs and opioid use disorder (OUD, n = 235) and opioid overdose (n = 18) through 6 months of follow-up using inverse probability-weighted cumulative incidence functions and Fine-Gray models. The weighted hazard ratio (HRw) of opioid overdose among patients initiating ADFs was 0.87 (95% CI, 0.23-3.24) times as high as among patients who initiated, restarted, or continued non-ADF ER/LA opioids. We observed a short-term benefit of ADFs for incident OUD (HRw = 0.58; 95% CI, 0.35-0.93) compared to non-ADF ER/LA opioids in the first 6 weeks of follow-up, but this benefit disappeared later in follow-up (HRw = 1.30; 95% CI, 0.86-1.95). In summary, our findings add to the expanding body of evidence that there is no clear long-term reduction in harm from ADF opioids among patients in outpatient use.

This article is part of a Special Collection on Pharmacoepidemiology.
Ambulatory Blood Pressure Phenotypes, Arterial Stiffness, and Cardiac Remodeling
Authors: Cuspidi Cesare , Facchetti Rita , Gherbesi Elisa , Quarti-Trevano Fosca , Vanoli Jennifer , Mancia Giuseppe , Grassi Guido
Published: August 2024

BACKGROUND

Evidence on the association of arterial stiffness and left ventricular (LV) concentric remodelling/LVH assessed by echocardiography, with abnormal blood pressure (BP) phenotypes, defined by office and ambulatory BP monitoring (ABPM) in the community is scanty. Thus, we investigated this issue in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study.

METHODS

The present study included 491 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, blood examinations, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements.

RESULTS

In the whole study sample (age 66+10 years, 50% males), the prevalence rates of sustained normotension (NT), white coat hypertension (WCH), masked hypertension (MH), sustained hypertension (SH) and non-dipping (ND) were 31.2, 10.0, 24.2, 34.6, and 35.8% and respectively. The likelihood of having SH, the BP phenotype carrying the greatest CV risk, was four times higher (OR= 4.31, CI:2.39-7.76, p<0.0001) in participants with increased CAVI and LV remodelling/LVH compared to their counterparts without organ damage. This association showed an incremental value in discriminating SH compared to both isolated markers of organ damage (OR=1.92,p=0.03 for increased CAVI and OR= 2.02, p=0.02 for LV remodelling/LVH). The presence of isolated but also combined organ damage was unrelated to ND.

CONCLUSIONS

Our study provides new evidence of the incremental value of looking for both vascular and cardiac target organ damage to optimize the identification and clinical management of SH in the general population.
Pressing Buttons: Kodak, Advertising Psychotechnics, and the Politics of Graphic Design, c. 1915
Authors: Greenhill Jennifer A
Published: August 2024

This essay focuses on a print advertising campaign that the Eastman Kodak Company launched in 1912 to promote the services of studio photographers. Examining period conceptions of mental picturing, the social and racial dimensions of design, and print media as an extension of the scientific laboratory, I argue that the open layouts of the series establish consumer imagination as the fundamental advertising apparatus. By reconceiving what the print advert could do, and sacrificing illustration in the layout so that a more personal and powerful impression could emerge, Kodak’s advertising department made the advert a thought machine every bit as complex as the company’s most advanced imaging technologies.
The scent of offspring: chemical profiles of larvae change during development and affect parental behavior in a burying beetle
Authors: Sahm Jacqueline , Brobeil Beatrice , Grubmüller Eric , Conrad Taina , Schott Matthias , Stökl Johannes , Steiger Sandra
Published: August 2024

Chemical cues and signals, especially in insects, play a pivotal role in mediating interactions between individuals. Past studies have largely focused on adult semiochemicals and have neglected those of juvenile stages. Especially in the context of parental care, the larval odor might have a profound impact on parenting behavior, guiding parents in how much resources they should allocate to the different developmental stages. However, whether ontogenetic changes occur in subsocial species and whether larval-emitted scents influence parent–offspring interactions is largely unknown. Using 3 different sampling techniques, we analyzed the cuticular and VOC profile of the 3 larval instars of the burying beetle Nicrophorus vespilloides, which is known for its elaborate parental care. We found distinct differences in the cuticular and VOC profiles across the 3 larval stages. Second-instar larvae, which receive more frequent feedings from parents than the other larval stages, released greater amounts of acetophenone, methyl geranate, and octanoic acid isopropyl ester than the first and third instar. Additionally, using a newly developed bioassay with automated video tracking, we found that adding the odor of second-instar larvae to first-instar larvae increased the number of maternal feeding trips. Our results suggest that the odor produced by larvae plays an important role in mediating parent–offspring interactions. Given these findings, burying beetles might emerge as a promising candidate for identifying a potential begging pheromone.
DeePhafier: a phage lifestyle classifier using a multilayer self-attention neural network combining protein information
Authors: Miao Yan , Sun Zhenyuan , Lin Chen , Gu Haoran , Ma Chenjing , Liang Yingjian , Wang Guohua
Published: August 2024

Bacteriophages are the viruses that infect bacterial cells. They are the most diverse biological entities on earth and play important roles in microbiome. According to the phage lifestyle, phages can be divided into the virulent phages and the temperate phages. Classifying virulent and temperate phages is crucial for further understanding of the phage–host interactions. Although there are several methods designed for phage lifestyle classification, they merely either consider sequence features or gene features, leading to low accuracy. A new computational method, DeePhafier, is proposed to improve classification performance on phage lifestyle. Built by several multilayer self-attention neural networks, a global self-attention neural network, and being combined by protein features of the Position Specific Scoring Matrix matrix, DeePhafier improves the classification accuracy and outperforms two benchmark methods. The accuracy of DeePhafier on five-fold cross-validation is as high as 87.54% for sequences with length >2000bp.
popDMS infers mutation effects from deep mutational scanning data
Authors: Hong Zhenchen , Shimagaki Kai S , Barton John P
Published: August 2024

Deep mutational scanning (DMS) experiments provide a powerful method to measure the functional effects of genetic mutations at massive scales. However, the data generated from these experiments can be difficult to analyze, with significant variation between experimental replicates. To overcome this challenge, we developed popDMS, a computational method based on population genetics theory, to infer the functional effects of mutations from DMS data. Through extensive tests, we found that the functional effects of single mutations and epistasis inferred by popDMS are highly consistent across replicates, comparing favorably with existing methods. Our approach is flexible and can be widely applied to DMS data that includes multiple time points, multiple replicates, and different experimental conditions.

Availability and Implementation

PopDMS is implemented in Python and Julia, and is freely available on GitHub at https://github.com/bartonlab/popDMS.

Supplementary information

Supplementary data are available at Bioinformatics online.
623 - Topical steroid withdrawal is a targetable overproduction of nicotinic acid from mitochondrial complex I overexpression
Authors: Shobnam Nadia , Ratley Grace , Saksena Sarini , Yadav Manoj , Chaudhary Prem Prashant , Sun Ashleigh A , Howe Katherine N , Gadkari Manasi , Franco Luis M , Ganesan Sundar , McCann Katelyn J , Hsu Amy P , Kanakabandi Kishore , Ricklefs Stacy , Lack Justin , Yu Weiming , Similuk Morgan , Walkiewicz Magdalena A ,   for the NIAID Centralized Sequencing Program, Gardner Donna D , Barta Kelly , Tullos Kathryn , Myles Ian A
Published: August 2024

Background

Topical glucocorticoids (more commonly termed topical corticosteroids; TCS) are first line therapy for management of numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. Although the disease may be confused for eczematous disorders or dismissed outright, there have been no systematic clinical or mechanistic studies to either refute or support TSW as molecularly distinct from other dermatopathies. This study aimed to clinically differentiate TSW symptomatology, delineate abnormal molecular pathways, and investigate potential therapeutic agents.

Methods

A re-analysis of a previous survey encompassing 1,889 patients with eczematous skin disease who either did or did not self-report TSW was performed to evaluate potential TSW distinguishing symptoms. We then conducted a pilot study of 16 patients who fit the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines.

Results

Clinically distinct TSW symptoms included thermodysregulation, burning, and flushing. Metabolomic and transcriptomic assessments both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure both in vitro and in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW.

Conclusion

Taken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.
657 - Impact of pruritus on patient fatigue: a case-control study
Authors: Andrade Luis F , Haq Zaim , Abdi Parsa , Diaz Michael J , Yosipovitch Gil
Published: August 2024

Background

Pruritus, either as a chronic standalone disease or secondary to inflammatory skin disease, can have a very detrimental effect on the overall quality of life for patients suffering from intense itch, particularly on patients suffering from atopic dermatitis. Symptoms of itching have a reported association with worsened quality of life across various psychological and social domains, including fewer periods of rest and reduced sleep quality. While prior studies have been made to determine the relationship between both fatigue and pruritus combined on systematic disease severity, there is limited data on how the prevalence of pruritus directly correlates with the prevalence of fatigue.

Objective

We utilized the AoU database to perform a nested case-control study to determine the impact of pruritus on patient-reported fatigue.

Methods

Within this database, patients experiencing pruritus (chronic pruritus, chronic pruritus of unknown origin (CPUO), prurigo nodularis, psoriasis, and atopic dermatitis) were identified and matched to four controls using nearest neighbor propensity-score matching, with sex, age, and race/ethnicity. Comparative analyses between pruritus cases and controls were performed utilizing the Fisher's exact test for categorical variables and the unpaired t-test for continuous variables. Logistic regression models were developed to calculate the odds ratio (OR) of having pruritus (SNOMED: 279333002, ICD10CM-L29), and developing fatigue (SNOMED: 84229001, ICD10CM-R53.83), with covariates including age, race/ethnicity, sex, income, education, anxiety, and depression. A significance level was set at P<0.05, and 95% confidence intervals were developed using the Wald method.

Results

From the cohort with accessible electronic health records (EHR) in 91,212 controls and 22,803 cases of pruritus were identified (mean age 59.91 [standard deviation: 15.95], 63.57% female). Patients afflicted with pruritus demonstrated a noticeably elevated prevalence of fatigue (40.81%) compared to the control group (22.06%). After adjusting for demographics and other covariates in multivariable analysis, chronic pruritus remained significantly associated with fatigue, with a multivariable adjusted odds ratio (aOR) of 1.56 (95% CI 1.16-2.07. In-depth analysis revealed that specific pruritic conditions exhibited strong associations with fatigue, namely, CPOU (aOR 2.27, 95% CI 1.35-3.82), prurigo nodularis (aOR 2.21, 95% CI 1.87-2.61), and atopic dermatitis (Aor 2.05, 95% CI 1.97-2.13).

Conclusion

Our study provides a quantitative measure of pruritus’ impact on the prevalence of patient-reported fatigue across many pruritic conditions, including atopic dermatitis. This two-fold increase in fatigue in patients with itch further emphasizes the clinical importance of understanding the impact of pruritus on patient quality of life.
658 - IMG-007, a novel nondepleting anti-OX40 monoclonal antibody with Fc bioengineering, exhibited reduced safety risks: evidence from nonclinical studies
Authors: Guo Chongtian , Wu Xiaotong , Lin Zi , Lu Yufang
Published: August 2024

Introduction/Background

Inflammatory T cell response is promoted by OX40, whose expression is increased in atopic dermatitis (AD). Targeting OX40 is a rational therapeutic strategy in treating AD. We hypothesized that an anti-OX40 monoclonal antibody (mAb) with a silenced antibody-dependent cell-mediated cytotoxicity (ADCC) function would have minimal T cell toxicities, thereby minimizing safety risks. IMG-007 is a novel nondepleting anti-OX40 mAb, bioengineered in its Fc region with a N297A mutation to abolish the ADCC function.

Objectives

To characterize the effects of a N297A mutation on the pharmacodynamic effect of IMG-007 in non-clinical studies.

Methods

The kinetics of IMG-007’s binding to recombinant human Fcg receptors was measured using surface plasmon resonance (SPR) Biacore 8K. The ADCC function was evaluated by measuring cytotoxicity to HEK293-OX40-Luc cells cocultured with primary human NK cells and antibody and quantified by flow cytometry. The cytokine release potential was assessed by incubating human peripheral blood mononuclear cells (PBMCs) with antibody under both solid and solution phases from 10 donors, followed with measurement of 10 cytokines in the culture supernatant using the Meso Scale Discovery (MSD) Proinflammatory Panel 1.

Results

IMG-007 exhibited a minimal binding affinity to Fcg receptors, including FcgRs I, IIA, IIIA (V176), IIIA (F176), IIB and IIIB. At up to the highest concentration tested, IMG-007 did not induce any antibody induced cytotoxicity to the OX40+ HEK293-Luc cells. Furthermore, it did not induce the release of all 10 proinflammatory cytokines tested in human PBMCs under both solid and solution testing formats.

Conclusions

Silencing ADCC function in IMG-007 via bioengineering resulted in minimal binding to the Fcg receptors and diminished cytotoxicity to OX40+ cells. IMG-007 represents a promising drug candidate for potentially treating AD.
692 - Dupilumab reduces atopic dermatitis lesion severity and extent in children <12 years of age with moderate-to-severe AD: interim results from the PEDISTAD real-world registry
Authors: Lee Lara Wine , Irvine Alan D , Ramien Michele , Marcoux Danielle , Baselga Eulalia , de Graaf Marlies , Antila Martti , Rosario Filho Nelson A , Lara-Corrales Irene , Joyce Joel C , Gupta Rajan , Redman Patrick , Zhang Annie
Published: August 2024

Introduction/Background

In clinical trials, dupilumab has consistently improved disease severity in children with moderate-to-severe atopic dermatitis (AD).

Objectives

To investigate the impact of systemic treatments on the individual anatomical regions that comprise the Eczema Area and Severity Index (EASI).

Methods

PEDISTAD (NCT03687359) is an international, longitudinal, observational 10-year registry study of patients aged < 12 years with moderate-to-severe AD. This interim analysis reports mean Eczema Area and Severity Index (EASI) scores of the head and neck and upper limbs at therapy start and last observation.

Results

A total of 207 patients received dupilumab, 127 received methotrexate and 139 received cyclosporine. The mean observation period was 17.0 months, 18.7 months, and 14.3 months for dupilumab, methotrexate and cyclosporine respectively. Mean (SD) EASI scores for the head and neck area of dupilumab patients improved from 2.0 (0.2) at therapy start to 0.7 (0.1) at last observation. Improvement was also seen in patients receiving methotrexate (therapy start: 2.0 [0.2]; last observation: 1.0 [0.2]) and cyclosporine (therapy start: 2.2 [0.2]; last observation: 1.6 [0.2]. A numerically greater improvement in mean (SD) EASI scores of the upper limbs was observed in patients receiving dupilumab (therapy start: 4.5 [0.2]; last observation: 1.5 [0.2]) than methotrexate (therapy start: 3.8 [0.2]; last observation: 2.1 [0.2]) and cyclosporine (therapy start: 4.1 [0.2]; last observation: 2.9 [0.3]). Adverse events were experienced by 23.7%, 30.5% and 32.6% of patients receiving dupilumab, methotrexate and cyclosporine, respectively.

Conclusion

Children with moderate-to-severe AD receiving dupilumab, methotrexate, or cyclosporine had improvement in AD lesion severity and extent in individual anatomical regions, with the greatest numerical improvement observed in those receiving dupilumab.
710 - Improving pediatric atopic dermatitis care: online intervention in the Deep South
Authors: Huynh Thy N , Sharma Manoj , Morrissette Summer V , Brodell Robert T , Nahar Vinayak K
Published: August 2024

Introduction/Background

Atopic dermatitis (AD) affects about 9.6 million children in the United States (US) under the age of 18. Most of these young people have moderate-to-severe AD symptoms, which have a significant negative impact on their own and their families' quality of life. Preventing triggers, repairing the skin's protective layer, and reducing inflammation are the main goals of effective AD treatment. Even though medical experts play a crucial role in teaching parents about managing AD, many caregivers struggle to follow treatment plans, which results in preventable flare-ups.

Objectives

The purpose of this study was twofold: firstly, to assess the efficacy of an intervention aimed at enhancing healthcare professionals' confidence and practices in managing AD; and secondly, to pinpoint areas for improvement to better assist parents in navigating their children's chronic illness.

Methods

The study involved the recruitment of 37 healthcare workers from a large university medical center located in the deep South of the United States using email and word-of-mouth. The medical professionals watched a 20-minute YouTube movie, conducted an online pre-test survey, and then completed an online post-test survey.

Results

The majority of participants (68.6%) identified as female, and the largest racial group was White (59.4%). The participant pool encompassed residents, fellows, or trainees (40.5%), physicians (37.8%), and advanced practice providers (10.8%), with an average age of 39.74 years. The findings indicated an improvement in participants' confidence to prescribe new therapies and educate patients about self-management behaviors for AD. Additionally, more respondents felt capable of offering resources to aid their patients' self-management and mobilizing social support for this purpose.

Conclusions

In the era of new targeted therapies, this online intervention presents an opportunity to bolster healthcare professionals' confidence and refine their practices in managing AD, potentially yielding enhanced outcomes for children and their families.
719 - Modulating Nav1.8-expressing neurons offers promising direction to address symptoms of atopic dermatitis
Authors: Scoles Madeline C , Wang Jacqueline C , Sung Winnie , Olivarez Mason , Liu Ellen , Lev Emmy , Shah Rishi B , Kim Seongmin , Kaplan Nihal , Paller Amy S
Published: August 2024

Introduction/Background

Atopic dermatitis (AD) is an inflammatory skin condition characterized by eczematous lesions, itch and pain. The inflammation and itch associated with AD are caused in part by dysregulation of neuroimmune circuits. Understanding these circuits is crucial for comprehending the pathophysiology of AD. Nav1.8 is a sodium channel expressed on C afferent fibers in the dorsal root ganglia (DRG). Knockdown of signaling pathways in Nav1.8+ nerves has been previously shown to reduce severity of AD in mice.

Objectives

We hypothesized that ablating Nav1.8 receptor-expressing neurons would lead to reduced severity of AD symptoms including itch and pain, and decreased expression of AD-related genes in a mouse model for AD.

Methods

Mice expressing iDTR (diphtheria toxin receptor) under the control of Nav1.8-Cre were used. Diphtheria toxin (DTX) was injected to ablate Nav1.8+ nerves and phosphate-buffered saline (PBS) was injected as a control. We achieved AD-like symptoms in both Nav1.8-ablated mice and control mice using topically-applied MC903 to mouse shaved nape skin.

Results

We noted no obvious clinical differences between Nav1.8-ablated mice and control mice skin. We found that Nav1.8+ ablation resulted in a ∼70% (p<0.05) reduction in scratching behavior and ∼40% (p=0.05) reduction in pain-related behaviors compared to control mice with intact Nav1.8. Nav1.8-nerve ablation similarly resulted in reduced expression of Tac1 (substance P – a neuropeptide known to mediate itch signaling) (p<0.05) and Il31ra (an itch-related cytokine receptor) (p<0.05) in Nav1.8-ablated mouse DRG tissue. However, we see no changes in expression of AD-related cytokines in Nav1.8-ablated nape skin tissue compared to control skin, including Il4, Il13, Il31, and Tslp.

Conclusions

These results suggest that Nav1.8-expressing neurons play a key role in the itch and pain associated with AD, but may have no effect on AD-induced cutaneous inflammation. These findings could offer a promising new direction for further research into treatments targeting the itch and pain caused by AD.
Adrenal gland haemangioma, a rare entity difficult to differentiate from malignancy
Authors: López Gómez Paola , Paniagua Gonzalez Miguel , García Pérez Angela , Mullor Delgado Luis Alberto
Published: August 2024

Adrenal haemangioma is a rare benign vascular lesion, which is usually asymptomatic and it is typically discovered incidentally on radiographic imaging. Differential diagnosis from other benign or malignant adrenal neoplasms may be challenging, and in many cases, the diagnosis is only possible after surgical resection. We present a case of a 39-year-old female with abdominal pain in the upper right quadrant, who was referred to our hospital after incidentally discovering a mass above the right kidney on abdominal ultrasonography. MRI revealed an adrenal mass, with features not indicative of adenoma and suggestive of adrenal haemangioma, without ruling out other possible diagnoses such us phaeochromocytoma and adrenal cortical carcinoma. Biochemical tests did not reveal any endocrine dysfunction. The patient underwent adrenalectomy, and histopathological analysis confirmed a venous haemangioma. Adrenal gland haemangioma is an unusual vascular lesion, typically diagnosed incidentally during abdominal imaging. Certain radiologic features may raise suspicion for malignancy, making it difficult to distinguish them from a primary adrenal cortical carcinoma. They may also grow large, compressing surrounding structures and causing abdominal pain, or may rupture, leading to retroperitoneal haemorrhage. For these reasons, some authors recommend excision of all suspected adrenal haemangiomas, and in many cases, the final diagnosis is made only after surgical removal.
The migration history of the Kamchatka rhododendron (Therorhodion camtschaticum s.l.) indicates two distinct dispersal routes towards Eastern Beringia
Authors: Polezhaeva Maria A , Modorov Makar V , Mochalova Olga A , Ickert-Bond Stefanie M
Published: August 2024

The Kamchatka rhododendron (Therorhodion camtschaticum s.l.) is a small, cold-resistant arcto-alpine shrub species with a controversial taxonomy and a wide Beringian distribution, from northern Eurasia to Arctic North America. Some authors regard T. camtschaticum and the closely related Therorhodion glandulosum as separate species while others suggest that they represent regionally differentiated subspecies. In order to resolve this relationship, we sampled 33 populations within the native species ranges, using three fragments of plastid DNA (ptDNA) and ten nuclear microsatellites (nSSR). We recovered two genetic lineages consistent with species rather than subspecies. The distribution of these genetic lineages are consistent with two different migration pathways of species from western Beringia to eastern Beringia: (i) for T. glandulosum a northern pathway from northern East Asia to the Seward Peninsula in northern Alaska; and (ii) for T. camtschaticum a southern pathway from the southern part of western Beringia to the Aleutian Islands and the seashore of south-east Alaska. The northern route extends from the Okhotsk seashore through the Kolyma region, Chukotka, and central and northern Kamchatka. The southern route begins at the Sikhote-Alin ridge, and goes through Sakhalin Island, the Kuril Islands, and southern Kamchatka. Demographic analysis using nSSR data inferred a divergence time between T. camtschaticum and T. glandulosum long before the Last Glacial Maximum.
An alternative therapeutic approach to haematopoetic stem cell transplantation in early cerebral adrenoleukodystrophy
Authors: Chataway Jeremy , Wade Charles , Murphy Elaine , Lynch David S
Published: August 2024

This scientific commentary refers to ‘Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy’ by Golse et al. (https://doi.org/10.1093/brain/awae169).
Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1
Authors: Sun Yixuan , Peng Qihua , Wang Ruiwen , Yin Yifan , Mutailifu Musitaba , Hu Lipeng , Teng Yincheng , Zhou Yang
Published: August 2024

As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma—CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared with normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced the nuclear factor-kappaB (NF-κB) pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TANK binding kinase 1 (TBK1), modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cell infiltration, suggesting its potential role in the tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us with a new approach to CESC target therapy.