bluuebunny/crossref_metadata_2025_split huggingface dataset:
scRGCL: a cell type annotation method for single-cell RNA-seq data using residual graph convolutional neural network with contrastive learning
Authors: Yuan Lin , Sun Shengguo , Jiang Yufeng , Zhang Qinhu , Ye Lan , Zheng Chun-Hou , Huang De-Shuang 
Published: December 2024

Abstract
Cell type annotation is a critical step in analyzing single-cell RNA sequencing (scRNA-seq) data. A large number of deep learning (DL)–based methods have been proposed to annotate cell types of scRNA-seq data and have achieved impressive results. However, there are several limitations to these methods. First, they do not fully exploit cell-to-cell differential features. Second, they are developed based on shallow features and lack of flexibility in integrating high-order features in the data. Finally, the low-dimensional gene features may lead to overfitting in neural networks. To overcome those limitations, we propose a novel DL-based model, cell type annotation of single-cell RNA-seq data using residual graph convolutional neural network with contrastive learning (scRGCL), based on residual graph convolutional neural network and contrastive learning for cell type annotation of single-cell RNA-seq data. scRGCL mainly consists of a residual graph convolutional neural network, contrastive learning, and weight freezing. A residual graph convolutional neural network is utilized to extract complex high-order features from data. Contrastive learning can help the model learn meaningful cell-to-cell differential features. Weight freezing can avoid overfitting and help the model discover the impact of specific gene expression on cell type annotation. To verify the effectiveness of scRGCL, we compared its performance with six methods (three shallow learning algorithms and three state-of-the-art DL-based methods) on eight single-cell benchmark datasets from two species (seven in human and one in mouse). Experimental results not only show that scRGCL outperforms competing methods but also demonstrate the generalizability of scRGCL for cell type annotation. scRGCL is available at https://github.com/nathanyl/scRGCL.
Pilot study of topical ruxolitinib demonstrates efficacy and blunting of heterogeneous inflammatory processes in mild hidradenitis suppurativa
Authors: Schell Stephanie L , Sennett Mackenzie L , Feehan Robert P , Wallace Tierney E , Meiszberg Elizabeth C , Longenecker Amy L , Helm Matthew F , Kirby Joslyn S , Nelson Amanda M 
Published: December 2024

Abstract

Background
Therapeutic options for mild hidradenitis suppurativa (HS) represent a significant gap in the current treatment landscape, with no U.S. Food and Drug Administration-approved therapies for early-stage HS. Topical Janus kinase (JAK) inhibitors (JAKi) are a compelling option due to the known upregulation of inflammatory JAK signalling in HS lesions and the recent success of systemic JAKi for the treatment of moderate-to-severe HS.

Objectives
To assess the clinical efficacy of ruxolitinib in a pilot cohort and to investigate the underlying biologic mechanisms associated with clinical response.

Methods
This was a pilot single-site open-label prospective 24-week clinical trial of topical ruxolitinib (NCT04414514). Men and women with mild HS (Hurley stage I or II), with active inflammatory nodules, were recruited. All participants were observed for 8 weeks to monitor lesion counts (observational phase); active therapy (treatment phase) was then administered for 16 weeks. Topical ruxolitinib 1.5% cream was applied twice daily, covering the entirety of each HS-affected body site. Clinician- and patient-reported outcome measures were recorded throughout the study. Lesional skin punch biopsies were taken at the start and end of treatment for downstream mechanistic RNA sequencing and histological analyses.

Results
Ten participants were enrolled in the study; four dropped out before the treatment phase of the trial. Six individuals with Hurley stage I (no tunnels) HS completed the study, five of whom successfully achieved Hidradenitis Suppurativa Clinical Response (HiSCR50) through 16 weeks of therapy. In this interim analysis, differential gene expression and gene set enrichment analyses revealed reduced activation of JAK-dependent interferon, interleukin (IL)-6, IL-2 and epidermal growth factor receptor signalling, and antimicrobial and keratinocyte responses. In contrast, signatures of wound healing and lipid metabolism were increased following JAKi treatment, indicating a return to homeostasis. Histological analyses revealed that clinically responsive patients had significantly reduced epidermal and dermal inflammation. Affected inflammatory infiltrate included neutrophils, T cells and plasma cells, with the predominantly affected cell types specific to the patient.

Conclusions
Collectively, the broad activity of topical ruxolitinib on inflammatory signalling processes resulted in promising efficacy, even with heterogeneity in baseline inflammation, in this pilot cohort. Importantly, topical treatment not only resolved epidermal inflammation, but also cleared deeper inflammatory infiltrate. The observed efficacy provides rationale to further investigate topical JAKi and other novel topical treatments in HS.
Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study
Authors: Prajapati Vimal H , Seyger Marieke M B , Wilsmann-Theis Dagmar , Szakos Erzsebet , Kaszuba Andrzej , van Hartingsveldt Bart , Jett Meg , Jiang Gigi , Li Shu , Sinha Vikash , Crauwels Herta , DeKlotz Cynthia M C , Paller Amy S 
Published: December 2024

Abstract

Background
No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.

Objective
PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.

Methods
This phase 3, randomized, placebo-controlled study enrolled patients ≥6 to &lt;18 years of age with moderate-to-severe plaque psoriasis. In Part 1 (Week [W]0–W16), patients were randomized to receive guselkumab, placebo, or open-label etanercept (active reference arm). At W16, Part 1 patients entered a guselkumab withdrawal/retreatment period or continued/crossed over to receive guselkumab (W16–W52). Co-primary endpoints were Investigator’s Global Assessment (IGA) 0/1 and Psoriasis Area and Severity Index (PASI)75 (or United States Food and Drug Administration-required PASI90 co-primary endpoint) responses at W16 of Part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0–W52).

Results
Of 92 and 28 patients enrolled in Parts 1 and 2, respectively, 86% and 96% continued treatment through W52. In Part 1, at W16, significantly higher proportions of guselkumab-treated than placebo-treated patients achieved IGA 0/1 (66% vs 16%; P&lt;0.001), PASI75 (76% vs 20%; P&lt;0.001), and PASI90 (56% vs 16%; P&lt;0.01). More than one-third of guselkumab-treated patients achieved clear skin (IGA 0: 39% vs 4% placebo; PASI100: 34% vs 0% placebo; both P&lt;0.01). In Part 2, at W52, 86%, 93%, and 82% of guselkumab-treated patients achieved IGA 0/1, PASI75, and PASI90, respectively. Through W16 of Part 1, 42%, 68%, and 58% of guselkumab-, placebo-, and etanercept-treated patients, respectively, had adverse events (AEs). Rates of AEs with guselkumab were similar through W52 in Parts 1 and 2; common AEs included nasopharyngitis, upper respiratory tract infection, and COVID-19. No serious or opportunistic infections occurred.

Conclusions
Guselkumab demonstrated significant and clinically meaningful responses in pediatric patients with moderate-to-severe plaque psoriasis and all co-primary and major secondary endpoints were met. Guselkumab safety outcomes were similar to placebo; no new safety signals were identified. These findings support the use of guselkumab to treat pediatric patients with moderate-to-severe plaque psoriasis.
Complex auditory regularity processing across levels of consciousness in coma: Stage 1 Registered Report
Authors: Pelentritou Andria , Cataldi Jacinthe , Zubler Frederic , Iten Manuela , Haenggi Matthias , Ben-Hamouda Nawfel , Rossetti Andrea O , Tzovara Athina , De Lucia Marzia 
Published: December 2024

Abstract
A key question for the scientific study of consciousness is whether it is possible to identify specific features in brain activity that are uniquely linked to conscious experience. This question has important implications for the development of markers to detect covert consciousness in unresponsive patients. In this regard, many studies have focused on investigating the neural response to complex auditory regularities. One noteworthy example is the local global paradigm, which allows for the investigation of auditory regularity encoding at the ‘global’ level, based on the repetition of groups of sounds. The inference of global regularities is thought to depend on conscious access to such complex auditory stimuli as mostly shown in chronic stages of disorders of consciousness patients. However, whether global regularity encoding can identify covert consciousness along the consciousness spectrum including earlier stages of these disorders remains controversial. Here, we aim to fill this gap by investigating whether the inference of global auditory regularities can occur in acute coma, in the absence of consciousness, and how this may be modulated by the severity of the patients’ clinical condition and consciousness level measured using the Full Outline of UnResponsiveness (FOUR) score. We will acquire 63-channel continuous electroencephalography to measure the neural response to global auditory regularity in comatose patients (N = 30) during the first day after cardiac arrest, when patients are unconscious, sedated and under normothermia, and during the second day (with reduced or absent sedation and body temperature control). We hypothesize that global regularity encoding will persist in the absence of consciousness independent of patient outcome, observed as above chance decoding of the neural response to global regularities using multivariate decoding analyses. We further hypothesize that decoding performance will positively correlate with the FOUR score, which indexes consciousness level, and typically improves between the first and second day after coma onset following cardiac arrest in patients with favourable outcome. In an exploratory analysis, we will also evaluate whether global regularity encoding may be influenced by the patients’ clinical management, specifically sedation, also shown to affect global deviance detection. Our results will shed light on the neurophysiological correlates of complex auditory regularity processing in unconscious patients and on the link to residual levels of consciousness during the underexplored state of coma upon the first days after cardiac arrest.
Low-dose ionizing radiation exposure and its impact on skin ageing among healthcare workers
Authors: Koç Huriye Aybüke , Altınöz Güney Cansu 
Published: December 2024

Abstract

Background
Exposure to ionizing radiation (IR) is an occupational risk for healthcare professionals and can result in a range of health issues.

Objectives
To assess the relationship between chronic low-dose IR exposure and the development of early ageing-related facial skin wrinkles in healthcare workers.

Methods
Facial skin wrinkles present in 70 healthcare workers who had been exposed to low-dose IR for at least 5 years were compared with those of 70 nonexposed healthcare workers. Skin wrinkles were assessed using the Lemperle wrinkle assessment scale and the scores of the IR-exposed healthcare workers were compared with those of the nonexposed controls.

Results
There were no statistically significant differences in sociodemographic factors and Fitzpatrick skin types between the IR-exposed healthcare workers and the control group. Analysis of the Lemperle wrinkle assessment scale scores revealed significant differences, with IR-exposed workers showing higher scores for all facial wrinkle categories evaluated (all P &lt; 0.001) and for horizontal neck folds (P = 0.002).

Conclusions
To our knowledge, this is the first study to assess healthcare workers with long-term exposure to low-dose IR for facial skin wrinkles, a visible consequence of skin ageing. Chronic low-dose IR exposure can lead to increased skin wrinkles, representative of advanced skin ageing in healthcare workers. These findings underscore the need for enhanced protective measures and regular monitoring for individuals exposed to occupational radiation.
Structure of subcortico-cortical tracts in middle-aged and older adults with autism spectrum disorder
Authors: Cordova Michaela , Hau Janice , Schadler Adam , Wilkinson Molly , Alemu Kalekirstos , Shryock Ian , Baker Ashley , Chaaban Chantal , Churchill Emma , Fishman Inna , Müller Ralph-Axel , Carper Ruth A 
Published: December 2024

Abstract
Middle-aged and older adults with autism spectrum disorder may be susceptible to accelerated neurobiological changes in striato- and thalamo-cortical tracts due to combined effects of typical aging and existing disparities present from early neurodevelopment. Using magnetic resonance imaging, we employed diffusion-weighted imaging and automated tract-segmentation to explore striato- and thalamo-cortical tract microstructure and volume differences between autistic (n = 29) and typical comparison (n = 33) adults (40 to 70 years old). Fractional anisotropy, mean diffusivity, and tract volumes were measured for 14 striato-cortical and 12 thalamo-cortical tract bundles. Data were examined using linear regressions for group by age effects and group plus age effects, and false discovery rate correction was applied. Following false discovery rate correction, volumes of thalamocortical tracts to premotor, pericentral, and parietal regions were significantly reduced in autism spectrum disorder compared to thalamo-cortical groups, but no group by age interactions were found. Uncorrected results suggested additional main effects of group and age might be present for both tract volume and mean diffusivity across multiple subcortico-cortical tracts. Results indicate parallel rather than accelerated changes during adulthood in striato-cortical and thalamo-cortical tract volume and microstructure in those with autism spectrum disorder relative to thalamo-cortical peers though thalamo-cortical tract volume effects are the most reliable.
Crucial rhythms and subnetworks for emotion processing extracted by an interpretable deep learning framework from EEG networks
Authors: Li Peiyang , Lin Ruiting , Huang Weijie , Tang Hao , Liu Ke , Qiu Nan , Xu Peng , Tian Yin , Li Cunbo 
Published: December 2024

Abstract
Electroencephalogram (EEG) brain networks describe the driving and synchronous relationships among multiple brain regions and can be used to identify different emotional states. However, methods for extracting interpretable structural features from brain networks are still lacking. In the current study, a novel deep learning structure comprising both an attention mechanism and a domain adversarial strategy is proposed to extract discriminant and interpretable features from brain networks. Specifically, the attention mechanism enhances the contribution of crucial rhythms and subnetworks for emotion recognition, whereas the domain-adversarial module improves the generalization performance of our proposed model for cross-subject tasks. We validated the effectiveness of the proposed method for subject-independent emotion recognition tasks with the SJTU Emotion EEG Dataset (SEED) and the EEGs recorded in our laboratory. The experimental results showed that the proposed method can effectively improve the classification accuracy of different emotions compared with commonly used methods such as domain adversarial neural networks. On the basis of the extracted network features, we also revealed crucial rhythms and subnetwork structures for emotion processing, which are consistent with those found in previous studies. Our proposed method not only improves the classification performance of brain networks but also provides a novel tool for revealing emotion processing mechanisms.
Time to Staphylococcus aureus Blood Culture Positivity as a Risk Marker of Infective Endocarditis: A Retrospective Cohort Study
Authors: Strömdahl Martin , Hagman Karl , Hedman Karolina , Westman Anna , Hedenstierna Magnus , Ursing Johan 
Published: December 2024

Abstract

Background
Endocarditis occurs in approximately 10%–15% of patients with Staphylococcus aureus bacteremia (SAB). Short time to positivity (TTP) in blood culture flasks has been linked to endocarditis in smaller studies. This study evaluated the association between TTP and endocarditis in SAB in a large cohort.

Methods
Adult patients with ≥1 S. aureus positive blood culture treated at a tertiary-level, 500-bed hospital in Stockholm, Sweden between 2011–2021 were retrospectively identified. The primary outcome was the presence of infective endocarditis.

Results
A total of 1703 episodes of SAB (23/1703 methicillin-resistant) in 1610 patients were included. Median age was 75 (interquartile range [IQR], 63–84) years and median Charlson comorbidity index score was 2 (IQR, 1–3). Echocardiography was performed in 1102/1703 (65%). Thirty-day mortality was 406/1703 (24%) and endocarditis was found in 154/1703 (9%). Median TTP was shorter in patients with endocarditis (9 [IQR, 7–12] hours) compared to patients without endocarditis (13 [interquartile range, 10–18] hours; P &lt; .001). The risk of endocarditis decreased with 11% per hour (odds ratio [OR], 0.89 [95% confidence interval {CI}, .54–.92]; P &lt; .001) in a univariate analysis using TTP as a continuous variable. In multivariate analysis, TTP &lt;13 hours (the median) was independently associated with endocarditis (OR, 3.59 [95% CI, 2.35–5.3]; P &lt; .001). The negative predictive value of TTP &gt;13 hours for endocarditis was 96% (95% CI, 95%–97%).

Conclusions
Short TTP was associated with endocarditis. The negative predictive value of &gt;95% suggests that TTP &gt;13 hours can be used to risk-stratify patients with SAB.
Derivation and Validation of an Electronic Health Record Penicillin Allergy De-Labeling Prevalence Measure
Authors: Blumenthal Kimberly G , Jiang Bohang , King Andrew J , Mann Jushin T , Zhang Yuqing , Wurcel Alysse G 
Published: December 2024

Abstract
With no standard method to capture penicillin allergy de-labeling prevalence across populations, we developed and validated a simple penicillin allergy de-labeling prevalence measure from electronic health records that achieved perfect sensitivity (100.0%), high specificity (99.4%), and strong agreement with a comprehensive algorithm that included free-text manual review (kappa = .997).
Validation of a high bleeding risk definition in cancer patients undergoing percutaneous coronary intervention
Authors: Gitto Mauro , Gilhooley Sean , Smith Kenneth , Vogel Birgit , Sartori Samantha , Bay Benjamin , Krishnan Prakash , Sweeny Joseph , Oliva Angelo , Moreno Pedro , Di Muro Francesca Maria , Krishnamoorthy Parasuram Melarcode , Kini Annapoorna , Dangas George , Mehran Roxana , Sharma Samin 
Published: December 2024

Abstract

Aims
Due to the absence of validated bleeding risk tools in cancer patients undergoing percutaneous coronary intervention (PCI), we aimed to validate an adapted version of the Academic Research Consortium (ARC) High Bleeding Risk (HBR) criteria.

Methods and results
Consecutive patients with active or remission cancer undergoing PCI between 2012 and 2022 at Mount Sinai Hospital (New York, USA) were included. Patients were considered at HBR if they met at least one of the major ARC-HBR criteria, other than cancer, or two minor criteria. The primary endpoint was a composite of periprocedural in-hospital or post-discharge bleeding at 1 year. The key secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), including death, myocardial infarction, or stroke. Of the 2007 cancer patients included in this study, 1142 (56.9%) were classified as HBR. Moderate to severe anaemia was the most prevalent major HBR criterion (35%). At 1 year, the incidence of bleeding was significantly higher in HBR compared with non-HBR patients [10.9 vs. 3.9%, adjusted hazard ratio (HR): 2.36, 95% confidence interval (CI): 1.57–3.53, P &lt; 0.001], mainly driven by higher periprocedural bleeding. Similarly, HBR patients were at higher risk of MACCE (11.0% vs. 3.2%, adjusted HR: 2.78, 95% CI: 1.72–4.47, P &lt; 0.001) and death (8.8% vs. 2.2%, adjusted HR: 3.28, 95% CI: 1.87–5.77, P &lt; 0.001) than non-HBR patients.

Conclusion
An adapted version of the ARC-HBR criteria, in which cancer is not a major criterion, effectively delineates cancer patients undergoing PCI who are at HBR. Cancer patients at HBR according to this definition also exhibited a higher mortality risk.
Impact and Heterogeneity of Self-reported Hearing on Trajectories of Cognitive Function in Middle-Aged and Older Couples
Authors: Wang Xinfeng , Ye Xin 
Published: December 2024

Abstract

Objectives
Hearing status is identified as a significant predictor of cognitive function. The life course principle of linked lives posits that the lives of couples often become increasingly interconnected or embedded over time, thereby cumulatively intensifying their influence on spouse’s health and well-being. We aim to examine the impact of self-reported hearing on cognitive function among married couples across adulthood and whether there is heterogeneity in the associations.

Methods
Utilizing data from the 2011, 2013, 2015, to 2018 waves of the China Health and Retirement Longitudinal Study (n = 2,847 middle-aged and older couples, totaling 5,694 observations across all waves), we employ the growth curve model to examine the impact of self-reported hearing, both individually and from spouses, on the age-related trajectories of cognitive function.

Results
This study demonstrates that poor self-reported hearing is significantly associated with worse cognitive function compared with those with good hearing. Additionally, there is a significant temporal association between poor spousal hearing and cognitive decline, compared with individuals whose spouses have good hearing. Heterogeneity analysis shows that the association between poor spousal hearing and increasing cognitive disadvantage across time is particularly significant among men and rural residents.

Discussion
This research provides new evidence of the longitudinal association between hearing and cognitive function among married couples, thus contributing to a growing body of literature documenting the importance of understanding how spousal health conditions affect health trajectories.