bluuebunny/crossref_metadata_2025_split huggingface dataset:
P23 The influence of maternal inflammatory status on the risk of atopic eczema in offspring during infancy
Authors: El-Heis Sarah , Crozier Sarah , Tham Elizabeth , Inskip Hazel , Harvey Nick , Godfrey Keith 
Published: May 2024

Abstract

Introduction and aims
Maternal influences on infantile atopic eczema are complex, with emerging evidence for a protective role for maternal T helper (Th)1 inflammation during pregnancy. Substantial literature on characterization of a proinflammatory dietary pattern, led us to hypothesize that analyses of maternal diet and markers of inflammation might help identify mechanisms influencing the risk of infantile atopic eczema. The aim of this study was to examine the associations between energy-adjusted dietary inflammatory index (eDII) scores indicative of a proinflammatory diet pattern, maternal serum neopterin levels (a biomarker elevated in Th1 immune activation which counteracts Th2 inflammation seen in atopic eczema), and infantile risk of atopic eczema.

Methods
Within the UK Southampton Women’s Survey, scores for the eDII were derived from mothers’ diets (questionnaires at preconception, early and late pregnancy). Atopic eczema was ascertained at age 6 and 12 months using the UK Working Party Diagnostic Criteria (n = 262 and 270, respectively). Late pregnancy maternal serum neopterin levels were measured in a subsample (n = 497). Directed acyclic graphs were used to determine covariates to be included in linear regression analyses.

Results
A higher eDII score in late pregnancy was associated with a reduced risk of atopic eczema at age 6 months [odd ratios (OR) 0.89, 95% CI confidence interval (CI) 0.81–0.98; P = 0.02], with a similar trend at age 12 months (OR 0.91, 95% CI 0.83–1.00; P = 0.06). Consistent with this, and adjusting for maternal body mass index, education, smoking during pregnancy, and recent eczema, and infant filaggrin single-nucleotide polymorphism rs7512552, breastfeeding duration and sex, higher maternal serum concentrations of neopterin were associated with lower risks of infant eczema at age 6 months (OR 0.72, 95% CI 0.51–1.01; P = 0.05) and 12 months (OR 0.71, 95% CI 0.53–0.96; P = 0.03).

Conclusions
These findings suggest that a proinflammatory maternal diet that promotes a Th1 predominant environment protects the developing infant from Th2 inflammation and reduces the risk of atopic eczema.
P39 Using single-cell transcriptomics to investigate the potential role of the human hair follicle dermal papilla in controlling hair fibre pigmentation
Authors: Redmond Leah C , Limbu Summik , Jiménez Francisco , D’Souza Chris , Williams Greg , Higgins Claire 
Published: May 2024

Abstract

Introduction and aims
The human dermal papilla (DP) is a population of cells located at the base of the hair follicle, which signals to surrounding matrix cells facilitating their incorporation into the layers of the hair fibre and the hair follicle. The DP controls the process of hair follicle induction, reflecting its critical role in orchestrating processes integral in hair growth. We hypothesize that distinct functional subgroups exist within the structure, which would mean that there are different types of DP cells within each follicle.

Methods
To begin testing this, we reanalysed the single-cell RNA sequencing (RNA-Seq) dataset of the human anagen hair follicle used in the 2022 study by Shim et al. To expand on this, we are now generating single-cell RNA-Seq datasets of patient-matched pigmented and nonpigmented hair follicles (n = 4 patients). These datasets will be used to explore heterogeneity in the human DP, and to investigate which subpopulations are potentially changed in the case of pigmentation loss. This will allow us to explore a potentially undiscovered role of the DP in controlling hair fibre pigmentation.

Results
We found four distinct subpopulations in the DP with statistically significant marker genes in the Shim dataset. This confirms transcriptional heterogeneity in the human DP, hinting at clusters of DP cells with specialized functions within each hair follicle. One subcluster, which expressed S100B, endothelin-3 and bone morphogenetic protein (BMP)4, was of particular interest and gene ontology analysis of the genes in this cluster revealed terms associated with skeletal development and BMP signalling. We hypothesize that this DP cluster regulates melanin transfer from bulbar melanocytes to neighbouring keratinocytes, owing to the known involvement of the mentioned genes in both melanogenesis and melanin transfer.

Conclusions
The human DP is a heterogeneic structure, with a potentially unexplored role in controlling hair fibre pigmentation.
National epidemiology of digital papillary adenocarcinoma in England 2013–2020: a population-based registry study
Authors: Andrew Kashini , van Bodegraven Birgitta , Vernon Sally , Balogun Mariam , Craig Paul , Rajan Neil , Venables Zoe C , Tso Simon 
Published: May 2024

Abstract

Background
Digital papillary adenocarcinoma (DPA), formerly known as aggressive DPA, is a rare adnexal cancer of sweat gland differentiation with metastatic potential. DPA epidemiology and patient outcome data are prerequisites for developing diagnostic and therapeutic guidance, which are lacking for this rare cancer.

Objectives
To report the incidence, patient demographics and treatment of patients with DPA in England from 1 January 2013 to 31 December 2020 using national cancer registry data.

Methods
DPA diagnoses in England during 2013–2020 were identified from the National Cancer Registration and Analysis Service dataset using morphology and behaviour codes. These were registered from routinely collected pathology reports, along with cancer outcomes and services datasets. The 2013 European age-standardized incidence rates (EASRs) were calculated.

Results
In total, 36 cases of DPA (7 in women and 29 in men) were diagnosed. The median age at diagnosis for the cohort was 54 years (interquartile range 46–64). The most frequently affected sites were the upper limbs (81%). All patients in the cohort received surgical excisions. The EASR was 0.10 (95% confidence interval 0.07–0.14) per 1 000 000 person-years.

Conclusions
This study reports the incidence and variation of DPA in England between 2013 and 2020. DPA was more common in older men and predominantly affected the upper limbs. This finding supports the need to develop a national policy for the reporting and management of DPA as well as development of a clinical guideline.
Association Between Infectious Diseases Consultation and Mortality in Hospitalized Patients With Gram-negative Bloodstream Infection: A Retrospective Population-wide Cohort Study
Authors: Ong Sean W X , Luo Jin , Fridman Daniel J , Lee Samantha M , Johnstone Jennie , Schwartz Kevin L , Diong Christina , Patel Samir N , MacFadden Derek R , Langford Bradley J , Tong Steven Y C , Brown Kevin A , Daneman Nick 
Published: May 2024

Abstract

Objectives
Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases.

Methods
Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1–10 days after the first positive blood culture was treated as a time-varying exposure.

Results
Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%–76.1%, interquartile range 19.6%–41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77–.88, P &lt; .0001; translating to absolute risk reduction of −3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source).

Conclusions
Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.
Using artificial intelligence to predict mortality in AKI patients: a systematic review/meta-analysis
Authors: Raina Rupesh , Shah Raghav , Nemer Paul , Fehlmen Jared , Nemer Lena , Murra Ali , Tibrewal Abhishek , Sethi Sidharth Kumar , Neyra Javier A , Koyner Jay 
Published: May 2024

ABSTRACT

Background
Acute kidney injury (AKI) is associated with increased morbidity/mortality. With artificial intelligence (AI), more dynamic models for mortality prediction in AKI patients have been developed using machine learning (ML) algorithms. The performance of various ML models was reviewed in terms of their ability to predict in-hospital mortality for AKI patients.

Methods
A literature search was conducted through PubMed, Embase and Web of Science databases. Included studies contained variables regarding the efficacy of the AI model [the AUC, accuracy, sensitivity, specificity, negative predictive value and positive predictive value]. Only original studies that consisted of cross-sectional studies, prospective and retrospective studies were included, while reviews and self-reported outcomes were excluded. There was no restriction on time and geographic location.

Results
Eight studies with 37 032 AKI patients were included, with a mean age of 65.1 years. The in-hospital mortality was observed to be 19.8%. The pooled [95% confidence interval (CI)] AUC was observed to be highest for the broad learning system (BLS) model [0.852 (0.820–0.883)] and elastic net final (ENF) model [0.852 (0.813–0.891)], and lowest for proposed clinical model (PCM) [0.765 (0.716–0.814)]. The pooled (95% CI) AUC of BLS and ENF did not differ significantly from other models except PCM [Delong's test P = 0.013]. PCM exhibited the highest negative predictive value, which supports this model's use as a possible rule-out tool.

Conclusion
Our results show that BLS and ENF models are equally effective as other ML models in predicting in-hospital mortality, with variability across all models. Additional studies are needed.
Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease
Authors: Koba Shinji , Satoh Noriyuki , Ito Yasuki , Yokota Yuya , Tsunoda Fumiyoshi , Sakai Koshiro , Nakamura Yuya , Shoji Makoto , Hirano Tsutomu , Shinke Toshiro 
Published: May 2024

Abstract

Background
This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD.

Methods
D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves.

Results
CAD events were observed in 238 male and 67 female patients. The Kaplan–Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15–1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27–2.37).

Conclusions
Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not.
UMIN-CTR Clinical Trial Number: UMIN000027504
Cyclophosphamide-free Mobilisation Increases Safety While Preserving the Efficacy of Autologous Haematopoietic Stem Cell Transplantation in Refractory Crohn’s Disease Patients
Authors: Giordano Antonio , Rovira Montserrat , Veny Marisol , Barastegui Rebeca , Marín Pedro , Martínez Carmen , Fernández-Avilés Francesc , Suárez-Lledó María , Domènech Ariadna , Serrahima Anna , Lozano Miquel , Cid Joan , Ordás Ingrid , Fernández-Clotet Agnés , Caballol Berta , Gallego Marta , Vara Alejandro , Masamunt Maria Carme , Giner Àngel , Teubel Iris , Esteller Miriam , Corraliza Anna María , Panés Julian , Salas Azucena , Ricart Elena 
Published: May 2024

Abstract

Background and Aim
Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn’s disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT’s safety and efficacy using a cyclophosphamide [Cy]-free mobilisation regimen.

Methods
A prospective, observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12–16 μg/kg/daily for 5 days, and optional Plerixafor 240 μg/d [1–2 doses] if the CD34 + cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up.

Results
All patients achieved successful outpatient mobilisation [seven patients needed Plerixafor] and underwent transplantation. Median follow-up was 106 weeks (interquartile range [IQR] 52–348). No mobilisation-related serious adverse events [SAEs] or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up, respectively. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up, respectively. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation.

Conclusions
Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction.
Serum Extracellular Matrix Molecules and Their Fragments as Biomarkers of Inflammation and Fibrosis in Inflammatory Bowel Diseases: A Systematic Review
Authors: Poulsen Anja , Ovesen Pernille Dige , Lu Cathy , Bettenworth Dominik , Jairath Vipul , Feagan Brian G , Seidelin Jakob Benedict , Rieder Florian 
Published: May 2024

Abstract

Background and Aim
Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease [IBD], such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix [ECM] biomarkers and their relevance in IBD.

Methods
We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining to ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use.

Results
Thirty-one ECM markers were identified, 28 of which demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated [1212 IBD patients], with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curve of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers.

Conclusions
Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a ‘window’ into transmural tissue remodelling and fibrosis burden, warranting further investigation.
Tractable Bayesian estimation of smooth transition vector autoregressive models
Authors: Bruns Martin , Piffer Michele 
Published: May 2024

Summary
We develop a tractable way of estimating the parameters ruling the nonlinearity in the popular smooth transition VAR model, and identify structural shocks using external instruments. This jointly offers an alternative to the option of identifying shocks recursively and calibrating key parameters. In an illustration, we show that monetary policy shocks generate larger effects on economic activity during economic expansions compared to economic recessions. We then document that calibrating rather than estimating the parameters ruling the nonlinearity of the model can lead to values for which the key results are lost. This suggests caution in the calibration of these parameters.
Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification
Authors: Dubin Ruth F , Deo Rajat , Ren Yue , Wang Jianqiao , Pico Alexander R , Mychaleckyj Josyf C , Kozlitina Julia , Arthur Victoria , Lee Hongzhe , Shah Amil , Feldman Harold , Bansal Nisha , Zelnick Leila , Rao Panduranga , Sukul Nidhi , Raj Dominic S , Mehta Rupal , Rosas Sylvia E , Bhat Zeenat , Weir Matthew R , He Jiang , Chen Jing , Kansal Mayank , Kimmel Paul L , Ramachandran Vasan S , Waikar Sushrut S , Segal Mark R , Ganz Peter ,   CRIC Study Investigators, Appel Lawrence J , Cohen Debbie L , Lash James P , Nelson Robert G , Shah Vallabh O , Unruh Mark L 
Published: May 2024

Abstract

Background and Aims
Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed.

Methods
In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score.

Results
Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P &lt; 1 × 10−5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P &lt; 1 × 10−5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787).

Conclusions
Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.
Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilization
Authors: Crowley Rose , Chieng David , Sugumar Hariharan , Ling Liang-Han , Segan Louise , William Jeremy , Prabhu Sandeep , Voskoboinik Aleksandr , Wong Geoffrey , Morton Joseph B , Lee Geoffrey , McLellan Alex J , Wong Michael , Pathak Rajeev K , Sterns Laurence , Ginks Matthew , Sanders Prashanthan , Kalman Jonathan M , Kistler Peter M 
Published: May 2024

Abstract

Background and Aims
Patterns of atrial fibrillation (AF) recurrence post-catheter ablation for persistent AF (PsAF) are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for PsAF and the implications for healthcare utilization and quality of life (QoL).

Methods
This was a post-hoc analysis of the CAPLA study, an international, multicentre study that randomized patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring.

Results
154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomization groups (P = .508). Median AF burden was 27.4% in PsAF recurrence and .9% in paroxysmal AF (PAF) recurrence (P &lt; .001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs. PAF 60%, P &lt; .001) and larger left atrial volume (PsAF 54.2 ± 19.3 mL/m² vs. PAF 44.8 ± 11.6 mL/m², P = .008). Healthcare utilization was significantly higher in PsAF (45 patients [78.9%]) vs. PAF recurrence (45 patients [46.4%], P &lt; .001) and lowest in those without recurrence (17 patients [9.5%], P &lt; .001). Patients without AF recurrence had greater improvements in QoL as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3 ± 25.2 points) compared to those with PAF (Δ24.0 ± 25.0 points, P = .012) or PsAF (Δ13.4 ± 22.9 points, P &lt; .001) recurrence.

Conclusions
AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilization and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.