bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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

Abstract

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&lt;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

Abstract
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

Abstract
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

Abstract
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 &gt;2000bp.
popDMS infers mutation effects from deep mutational scanning data
Authors: Hong Zhenchen , Shimagaki Kai S , Barton John P 
Published: August 2024

Abstract

Summary
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

Abstract

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

Abstract

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&lt;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

Abstract

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 &lt;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

Abstract

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 &lt; 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

Abstract

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.