bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased risk of malignancy and osteoporosis in primary Sjögren’s syndrome with thyroid diseases: potential implication from T cells
Authors: Cui Xiaomeng , Li Jun , Sang Yizhen , Liu Wei , Lu Yikang , Li Wei , Ma Li , Liu Xinying 
Published: December 2024

Abstract

Objectives
To evaluate the impact of thyroid diseases (TDs) on the comorbidities incidence and immune system of patients with primary SS (pSS).

Methods
A total of 329 patients diagnosed with pSS who were admitted between January 2018 and September 2023 were evaluated. The patients were divided into two groups: those with and without TD. Clinical data at the onset of SS were recorded. Kaplan–Meier method and Cox proportional hazards model were utilized for survival analysis. Flow cytometry and immunofluorescence measurements were used to analyse the lymphocyte subtypes.

Results
Of the 329 patients, 109 had TD. The most common types of TD were thyroid nodules (40.4%) and autoimmune thyroid diseases (AITDs) (28.4%). Patients with TD exhibited a significantly elevated incidence risk of malignancy (14.7% vs. 6.4%, P = 0.01) and osteoporosis (OP) (23.9% vs. 14.1%, P = 0.03). TD comorbidity was an independent risk factor of malignancy (HR 4.7, 95% CI 1.1–19.3, P = 0.03) and OP (HR 3.7, 95% CI 1.3–10.2, P = 0.01). Patients with SS and TD exhibited a higher ratio of programmed death-1 (PD1) + subsets of total CD3+ T cells, Th and Tc cells (all P = 0.03), as well as a lower ratio of unswitched memory B cells (P = 0.01) in peripheral blood. The ratio of PD1+ subsets of Th cells in salivary glands also exhibited a significantly increase in these patients compared with those without TD (P = 0.03) and the controls (P &lt; 0.01).

Conclusion
The incidence risk of malignancy and OP was significantly elevated in pSS patients with TD. The significant elevated proportions of PD1+ T cells may influence the occurrence of this process.
Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a phase 2, randomized, placebo-controlled study
Authors: Anders Hans-Joachim , Chan Tak Mao , Sanchez-Guerrero Jorge , Wofsy David , Bensley Karen , Kim Lilianne , Lo Kim Hung , Shu Cathye , Shao Jie , Karyekar Chetan S , Diamond Betty 
Published: December 2024

Abstract

Objective
Evaluate the efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in a phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active LN.

Methods
Adults (18–75 years) with active LN [Class III–IV proliferative nephritis (kidney biopsy) and urine protein-to-creatinine ratio (UPCR) of ≥1 mg/mg despite standard-of-care therapy] were randomized (1:1; planned sample = 60) to receive i.v. infusions of guselkumab 400 mg or placebo at weeks 0, 4 and 8, then s.c. injections (guselkumab 200 mg or placebo) at week 12 and every 4 weeks through week 48 in addition to their background therapy. The primary endpoint was achievement of ≥50% decrease in proteinuria from baseline at week 24. Major secondary endpoints (week 24) were achievement of complete renal response (CRR), sustained reduction in steroid dose (≤10 mg/day prednisone/equivalent) from weeks 16–24, UPCR &lt;0.5 mg/mg; &lt;0.75 mg/mg, time to achieving CRR, and time to treatment failure. Safety was assessed through the end of the study.

Results
Following enrolment challenges (COVID-19 pandemic; Ukraine/Russia crisis), the sponsor terminated the study early; 33 participants were randomized (placebo, n = 16; guselkumab, n = 17). At week 24, 56.3% (9/16) in the placebo group and 35.3% (6/17) in the guselkumab group achieved the primary endpoint. No apparent differences were observed in the secondary endpoints. Through end-of-study, 75% of placebo patients and 71% of guselkumab patients reported ≥1 adverse event; most were of mild-to-moderate severity.

Conclusion
Guselkumab+background therapy did not demonstrate superior reduction in proteinuria vs placebo+background therapy in this small cohort of patients with active LN. Safety results were consistent with the known safety profile of guselkumab.

Trial registration
ClinicalTrials.gov: NCT04376827.
Development and internal–external cross-validation of a patient-reported definition for acute calcium pyrophosphate crystal arthritis
Authors: Cipolletta Edoardo , Rozza Davide , Andres Mariano , Ottaviani Sébastien , Pascart Tristan , Calvo-Aranda Enrique , Chiarvetto Peralta Maria Victoria , Muto Pietro , Calabuig Irene , Gómez-Sabater Silvia , Caño Rocío , Léger Bastien , Pacaud Aurore , Moscioni Erica , Bruno Caterina , Caira Virginia , Gómez-González Claudia , Rosa Javier Eduardo , Nakafero Georgina , Filippucci Emilio , Abhishek Abhishek 
Published: December 2024

Abstract

Objective
To develop and validate a patient-reported definition of acute calcium pyrophosphate (CPP) crystal arthritis in people with crystal-proven CPP deposition (CPPD) disease.

Methods
Consecutive patients with crystal-proven CPPD disease from seven centres across four countries were enrolled in a cross-sectional study. In each centre, patient-reported outcomes on the features of acute CPP crystal arthritis were collected. The expert opinion of an independent rheumatologist was the reference standard. We developed definitions based on multivariable logistic regression model with backward selection of predictors and classification and regression tree (CART) approaches.

Results
Two hundred and forty-six patients [mean age 73.2 years (s.d. 10.7), 65.9% female] were enrolled. At the time of the assessment, acute CPP crystal arthritis was diagnosed in 96/246 (39.0%) participants.
Patient-reported joint warmth, patient-reported joint swelling, time from pain onset to peak, and self-reported acute CPP crystal inflammatory arthritis were included in the multivariable logistic model. This model had good discrimination (optimism-adjusted c-index: 0.92; 95% CI: 0.89, 0.95) and calibration (optimism-adjusted calibration slope: 0.95; 95% CI: 0.71, 1.19; optimism-adjusted calibration-in-the-large: 0.005; 95% CI: −0.37, 0.37) in the internal validation. Probability threshold ≥0.53 had sensitivity of 0.83 (95% CI: 0.74, 0.90) and specificity of 0.86 (95% CI: 0.79, 0.91). Performances were similar in the internal–external cross-validation. The CART identified patient-reported acute CPP crystal inflammatory arthritis, followed by joint swelling and joint warmth as the most informative variables for ascertaining acute CPP crystal arthritis [sensitivity 0.83 (95% CI: 0.72, 0.91) and specificity 0.83 (95% CI: 0.74, 0.90)].

Conclusion
We developed and initially validated easy-to-use patient-reported definitions for acute CPP crystal arthritis for use in clinical trials and observational research in CPPD.
Integrating carotid Doppler, greyscale US, and aortic oscillometry to evaluate macroangiopathy in myositides: the MYOCARD cohort
Authors: Triantafyllias Konstantinos , Gauch Svea , Bertsias George , Boumpas Dimitrios , Hasseli Rebecca , Cavagna Lorenzo , Bergner Raoul , Schepers Markus , Schwarting Andreas 
Published: December 2024

Abstract

Objectives
To evaluate the combination of novel colour Doppler US (CDUS), greyscale US (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors.

Methods
We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls. Additionally, we performed GSUS examinations to measure carotid intima-media thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometric assessments determined aortic stiffness using carotid-femoral pulse wave velocity (cfPWV).

Results
We recruited 82 IIM patients and 88 healthy controls. Patients showed significantly higher cIMT (Padj = 0.032), CCA-RI (Padj = 0.015), CCA-PI (Padj = 0.013), ICA-RI (Padj = 0.012), and ICA-PI (Padj = 0.039), compared with controls. RI and PI of CCA and ICA were higher in patients with lower lung function vital capacity, respectively (all Ps &lt; 0.05). cfPWV correlated positively with traditional CV risk factors including age (ρ = 0.546, P &lt; 0.001), mean arterial pressure (ρ = 0.331, P = 0.003), diabetes (P = 0.007), and hyperlipidaemia (P = 0.032), and associated negatively with lung carbon monoxide (CO) diffusion (ρ = −0.329, P = 0.031).

Conclusion
In one of the largest CV surrogate marker studies in IIM, patients exhibited increased carotid pulsatility, resistance, and atherosclerosis compared with controls. Lower lung function parameters predicted aortic stiffness and Doppler indices, suggesting a possible link between lung involvement and increased CV risk. Angiopathy markers may reveal significant vascular abnormalities in IIM patients, enhancing CV screening and risk classification.
Drug-induced liver injury related to avacopan therapy
Authors: Mori Kentaro , Shirai Tsuyoshi , Mutoh Tomoyuki , Inoue Jun , Fujishima Fumiyoshi , Kubo Satsuki , Watanabe Hirofumi , Sato Satoko , Narita Mamoru , Hoshi Yosuke , Sato Hiroko , Fujii Hiroshi 
Published: December 2024

Abstract

Objectives
The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment.

Methods
This study included 22 patients with AAV who were treated with avacopan at multiple centres in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023).

Results
Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index and early onset DILI following the initiation of avacopan treatment.

Conclusion
Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.
Enhancing 3D-printed chocolate drug delivery: the role of soy lecithin in improving formulation printability and consistency
Authors: Lesutan Vlad-Nicolae , Milliken Rachel Louise , Browne Amber , Ferguson Tommy , Lamprou Dimitrios A 
Published: December 2024

Abstract

Objectives
This study explores the potential of extrusion-based 3D printing to improve medication adherence by developing chocolate-based oral dosage forms incorporating active pharmaceutical ingredients such as paracetamol and ibuprofen while using soy lecithin as an emulsifier to enhance the flow properties of the chocolate formulation, enabling consistent and reliable 3D printing of the dosage forms.

Methods
Extrusion-based 3D printing was used to obtain drug-loaded solid oral dosage forms. The formulation components as well as the printing design and conditions were optimized, to enhance the appearance and patient acceptability of the final products. Techniques such as spectroscopy, thermal analysis, rheology, mechanical analysis, and in-vitro dissolution were employed to assess the physicochemical properties of these formulations.

Key findings
Soy lecithin was essential in obtaining robust and consistent dosage forms. The formulations showed good physicochemical stability of the components and demonstrated consistent drug release.

Conclusions
The findings suggest that extrusion-based 3D printing, with the aid of emulsifiers such as soy lecithin, is a viable method for producing personalized, chocolate-based drug delivery systems, potentially improving adherence through customizable dosage forms. Further research could enhance understanding of factors such as particle size, crystallinity, and the impact of chewing on drug release to optimize therapeutic outcomes.
Association Between Peptide Antigen-Related Antibody Levels and the Short- and Long-Term Efficacy of Antipsychotic Treatment in Drug-Naïve First-Episode Schizophrenia Patients
Authors: Zheng Yue , Du Jian , Wang Mingqia , Zhou Enpeng , Zhou Qi , Ji Yunfei , Huang Bingjie , Guo Xiaodong , Gao Tianqi , Hu Wanheng , Yin Xiaolin , Wang Xianghe , Pu Chengcheng , Yu Xin 
Published: December 2024

Abstract

Objective
This study investigated the relationships between baseline peptide antigen-related IgG levels and 8-week antipsychotic drug (APD) treatment response rates and one-year treatment outcomes, as well as the relationships between changes in peptide antigen-related IgG levels and one-year treatment outcomes, in first-episode schizophrenia (FES) patients.

Methods
Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genome-wide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155) and in plasma samples from 60 healthy controls (HCs). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear regression analysis, linear mixed-effects models, and simple slope analysis.

Results
Anti-MOB4 IgG and anti-PDIA3 IgG levels were significantly lower in drug-naïve FES patients compared to HCs and showed a negative correlation with baseline excitement factor scores. Baseline anti-EMB IgG levels were associated with the 8-week treatment response, whereas anti-MAD1L1 IgG levels were correlated with one-year outcomes in drug-naïve FES patients. The one-year trajectory of changes in anti-FURIN IgG, anti-MAPK3 IgG, and anti-ACTR1B IgG levels was related to remission.

Conclusion
This study revealed that patients with schizophrenia had autoimmune abnormalities, with different peptide antigen-related IgG being associated with short-term or long-term treatment efficacy, and that these antibody levels were regulated by APDs.
Revisiting the Defeatist Performance Belief Scale in Adults With Schizophrenia and Youth at Clinical High-Risk for Psychosis: A Comprehensive Psychometric Analysis
Authors: Luther Lauren , Ahmed Anthony O , Grant Paul M , Granholm Eric , Gold James M , Williams Trevor F , Pratt Danielle , Holden Jason , Walker Elaine F , Arnold Lauren , Ellman Lauren M , Mittal Vijay A , Zinbarg Richard , Silverstein Steve M , Corlett Philip R , Powers Albert R , Woods Scott W , Waltz James A , Schiffman Jason , Strauss Gregory P 
Published: December 2024

Abstract

Background and Hypothesis
In accordance with the Cognitive Model of Negative Symptoms, defeatist performance beliefs (DPBs) are an important psychosocial mechanism of negative symptoms in schizophrenia-spectrum groups. DPBs are also mediators of negative symptom improvement in clinical trials. Despite the clinical significance of DPBs and their inclusion as a mechanism of change measure in clinical trials, the psychometric properties of the DPB scale have not been examined in any schizophrenia-spectrum group.

Study Design
This study evaluated the factor structure, reliability, and validity of the DPB scale in 943 schizophrenia and 250 clinical high-risk for psychosis (CHR) participants from multiple US sites. Confirmatory factor analyses tested competing factor structures: a unidimensional model—consistent with how DPBs are currently assessed—and multifactorial models with up to 4 factors identified with exploratory factor analyses.

Study Results
Models with 3 and 4 factors provided superior fit compared to the unidimensional model, with an advantage for the 3-factor model. The 3-factor model, consisting of Overvaluing Success, Overvaluing Failure, and Overvaluing Social Evaluation factors, demonstrated good replicability, temporal stability, and measurement invariance in schizophrenia and CHR samples. Convergent validity was demonstrated via significant correlations with negative symptoms and functioning, but limited associations were present with neurocognition. Discriminant validity was supported by low correlations with positive symptoms.

Conclusions
Findings support the validity and reliability of the 3-factor structure of the DPB scale across phases of psychosis. Use of a 3-factor structure may clarify the most critical DPB targets for negative symptom treatment and early prevention and intervention.
O002 Sleepy teens and the use of screens: A repeated measures analysis examining the relationship between pre-bedtime screen use and sleep
Authors: Wickham S , Brosnan B , Haszard J , Meredith-Jones K , Galland B , Taylor R 
Published: December 2024

Abstract

Aims
Pre-bedtime screen use among adolescents is highly prevalent and fast-paced, often involving multiple devices, and frequent switching between activities, which is presumed to be harmful to sleep. The aim of this study was to determine how objectively-measured evening screen time influenced sleep in young adolescents.

Methods
BED was a repeated-measures observational study in 85 healthy adolescents (11-14.9 years). Objective screen time data were captured over four non-consecutive nights using video cameras from two hours before bedtime until the adolescent attempted sleep (shuteye time) and coded using a reliable protocol (κ ≥ 0.8). Sleep outcomes (sleep timing, total sleep time, and WASO) were measured objectively via wrist-worn AX3 accelerometers. Screen use was related to sleep on a night-by-night basis using a mixed-effects regression model, which considered participant as a random effect and adjusted for weekends.

Results
Screen time in the two hours before bed had little effect on sleep that night. However, once in bed, screen time delayed sleep onset by 35 (95% CI: 20, 50) minutes compared to nights without screen use. Interactive screen use reduced TST more than passive screen use (9 compared with 4 minutes for every 10 minutes of use, but time since last screen use did not impact any measure of sleep health examined.

Conclusion
Improved methodology shows that screen time may impair sleep once in bed, especially if interactive. Current sleep hygiene recommendations to restrict all screen time before bed seem neither achievable nor appropriate within this age group.
O016 Characterizing K-Complexes in PTSD Patients
Authors: Coussens S , Chatburn A , Malagutti N , Denson T 
Published: December 2024

Abstract

Introduction
K-complexes play a crucial role in sleep maintenance. Disturbances in these processes are linked to sleep disorders such as insomnia. Post-traumatic stress disorder (PTSD) features substantial disruption of sleep patterns. This study aims to retrospectively analyze sleep studies of PTSD patients to identify changes in the amplitude of K-complexes which help understanding PTSD-related sleep disruption.

Methods
150 sleep recordings of individuals diagnosed with PTSD from the BigSleep data repository will be examined. These recordings will be compared to those of 150 age- and sex-matched controls from the same source. By measuring the characteristics of K-complexes in both clinical and healthy populations, we hope to uncover distinctive patterns associated with PTSD-related sleep disturbances.

Results
Preliminary analysis of a small subset of data suggests a reduced amplitude of K-complexes in PTSD patients. This finding may suggest impaired stimulus gating during sleep, which may contribute to disrupted sleep in PTSD. If these results are corroborated in the larger dataset, it could provide valuable insights into neural mechanisms underlying sleep disturbances in PTSD.

Conclusion
By identifying specific EEG markers, such as altered K-complex characteristics, we may be better able to understand the neurobiological underpinnings of sleep disturbances associated with PTSD. Our ongoing analysis seeks to confirm preliminary findings and potentially pave the way for an evidence-based, mechanistic understanding of sleep disruption in trauma.
O033 Identifying risk factors for probable insomnia development during late pregnancy: Preliminary findings from an Australian cohort study
Authors: Crowther M , Hughes* J , Clayton* K , Bennett C , Davey M , Drummond S , Manber R , Mol B , Mortimer D , O’Connor D , Rolnik D , Ryan J , Wiley J , Bei B 
Published: December 2024

Abstract
Pregnancy insomnia symptoms are prevalent and associated with adverse parent and infant outcomes. Psychosocial and cognitive factors may contribute to the development and persistence of insomnia symptoms. To date, there is little evidence exploring these risk factors before the onset of probable insomnia disorder.
To investigate the development of probable insomnia (Insomnia Severity Index: ISI ≥10 with sufficient sleep opportunity) at late pregnancy, we examined a cohort of parents without existing probable insomnia (≤7 ISI) at 26-32 weeks of gestation. We then surveyed this cohort again later in pregnancy (five weeks postbaseline) and conducted multiple logistic regression to calculate the odds of probable insomnia at later pregnancy, based on baseline risk factors. Risk factors included: other children, mental health history, sleep reactivity (Ford Insomnia Response to Stress Test), beliefs about sleep (Dysfunction Beliefs and Attitudes about Sleep Scale), and emotional support (PROMIS Emotional support).
A total of 159 (mean age: 32.9 ±3.7 years) parents were included in the present analysis with 12.4% of these meeting the criteria for probable insomnia at later pregnancy. When considering all risk factors for probable insomnia (other children, mental health history, sleep reactivity, beliefs about sleep, and emotional support), only emotional support showed significantly increased odds of insomnia development (OR: 0.90, p=0.027).
Lower perceived emotional support is associated with increased odds of new onset probable insomnia during late pregnancy. Future research should further explore potential mechanisms underlying these associations, and whether targeting emotional support may lower the risk of insomnia development.