bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared parameter modeling of longitudinal data allowing for possibly informative visiting process and terminal event
Authors: Thomadakis Christos , Meligkotsidou Loukia , Pantazis Nikos , Touloumi Giota 
Published: October 2024

Summary
Joint modeling of longitudinal and time-to-event data, particularly through shared parameter models (SPMs), is a common approach for handling longitudinal marker data with an informative terminal event. A critical but often neglected assumption in this context is that the visiting/observation process is noninformative, depending solely on past marker values and visit times. When this assumption fails, the visiting process becomes informative, resulting potentially to biased SPM estimates. Existing methods generally rely on a conditional independence assumption, positing that the marker model, visiting process, and time-to-event model are independent given shared or correlated random effects. Moreover, they are typically built on an intensity-based visiting process using calendar time. This study introduces a unified approach for jointly modeling a normally distributed marker, the visiting process, and time-to-event data in the form of competing risks. Our model conditions on the history of observed marker values, prior visit times, the marker’s random effects, and possibly a frailty term independent of the random effects. While our approach aligns with the shared-parameter framework, it does not presume conditional independence between the processes. Additionally, the visiting process can be defined on either a gap time scale, via proportional hazard models, or a calendar time scale, via proportional intensity models. Through extensive simulation studies, we assess the performance of our proposed methodology. We demonstrate that disregarding an informative visiting process can yield significantly biased marker estimates. However, misspecification of the visiting process can also lead to biased estimates. The gap time formulation exhibits greater robustness compared to the intensity-based model when the visiting process is misspecified. In general, enriching the visiting process with prior visit history enhances performance. We further apply our methodology to real longitudinal data from HIV, where visit frequency varies substantially among individuals.
The prognostic value of epicardial and pericoronary adipose tissue in heart failure with preserved ejection fraction using coronary computed tomography angiography
Authors: Lin Shuangxiang , Liu Chenjia , Wang Shuyue , Ding Xingfa , Wu Jiaxing , Wang Xinhong , Jianzhong Sun 
Published: October 2024

Abstract

Objectives
To assess the prognostic significance of epicardial adipose tissue volume (EATv) and pericoronary adipose tissue attenuation (PCATa) in patients with heart failure with preserved ejection fraction (HFpEF).

Methods
This retrospective study was based on HFpEF and controls who underwent coronary CT angiography (CCTA) screening to rule out coronary disease. Comparisons of EATv and PCATa were made between HFpEF patients and a control group, using statistical analyses including Kaplan-Meier and Cox regression to assess prognostic significance.

Results
A total of 224 patients were retrospectively analysed. The EATv was 56.1 ± 11.9 cm3 and PCATa in the right coronary artery (PCATa-RCA) was −74.7 HU ± 3.82 in HFpEF patients, which increased significantly compared with controls. Among them, 112 HFpEF patients (mean age: 71.9 ± 8.5 years; 40% male) were followed up for a median of 27 ± 0.6 months (range 2-47 months). EATv and PCATa-RCA were predictive of outcome with an optimal threshold of 56.29 cm3 and −71.17 HU, respectively. In Kaplan-Meier analysis, the high EATv and PCATa-RCA attenuation had significantly higher rates of composite outcomes (log-rank test, all P &lt; .01). EATv and PCATa-RCA were independently predictive of outcome following adjustment for confounding variables (EATv: hazard ratio [HR] 1.03; 95% CI (1.01-1.06); P &lt; .01, PCTAa-RCA: HR 1.44; 95% CI 1.27-1.62; P &lt; .001)).

Conclusions
Increased EATv and PCATa-RCA are associated with worse clinical outcomes in HFpEF patients.

Advances in knowledge
This study highlights the potential of CCTA-derived adipose tissue metrics as novel, non-invasive biomarkers for risk stratification in HFpEF.
Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts
Authors: Binks Sophie N M , Elliott Katherine S , Muñiz-Castrillo Sergio , Gilbert Edmund , Kawasaki de Araujo Tânia , Harper Andrew R , Brown Andrew C , Chong Amanda Y , Band Gavin , Peris Sempere Vicente , Pinto Anne-Laurie , Costantino Felicie , Rayner N William , Mentzer Alexander J , Delanty Norman , Rogemond Veronique , Picard Géraldine , Handel Adam E , Melzer Nico , Titulaer Maarten J , Lee Soon-Tae , Leypoldt Frank , Kuhlenbaeumer Gregor , Honnorat Jérôme , Mignot Emmanuel , Cavelleri Gianpiero L , Knight Julian C , Irani Sarosh R 
Published: October 2024

Abstract
Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leukocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesized the presence of additional genetic predispositions.
In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively.
Outside the known major HLA signal, we found two single nucleotide polymorphisms at genome-wide significance (P &lt; 5 × 10−8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD-mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23.
Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.
Epidemiological, clinical and histological characteristics of melanoma in young adults: a 30-year retrospective study (1993–2022)
Authors: Rodríguez-Sánchez Belén , Rodríguez-Lomba Enrique , Avilés-Izquierdo José Antonio 
Published: October 2024

Abstract

Background
Melanoma in young adults significantly impacts the survival of individuals in this age group. There are few studies that analyse melanoma characteristics in young patients.

Objectives
To describe the epidemiological, clinical and histological characteristics of melanoma in young adults and the temporal trends in these characteristics in recent decades.

Methods
A retrospective observational study was conducted, involving 399 patients with melanoma aged 18–44 years, over a 30-year period (1993–2022). Patients were divided into two groups based on their date of diagnosis (period 1, 1993–2007; period 2, 2008–2022).

Results
Age at diagnosis was higher in period 2 than period 1 (34.3 vs. 36.7 years; P &lt; 0.001). Over time, there was a reduction in median thickness (1.0 vs. 0.68 mm; P = 0.01), a rise in melanomas located on the head and neck [n = 15/230 (6.5%) vs. n = 25/169 (14.8%)] and extremities [n = 97/230 (42.2%) vs. n = 76/169 (45.0%)], and a decrease in melanomas on the trunk [n = 118/230 (51.3%) vs. n = 68/169 (40.2%); P = 0.009]. There was also an increase in lentigo maligna [n = 5/230 (2.3%) vs. n = 5/169 (3.0%)] and superficial spreading melanomas [n = 176/230 (76.5%) vs. n = 142/169 (84.0%)], along with a reduction in nodular types [n = 37/230 (16.1%) vs. n = 10/169 (5.9%); P = 0.01]. In comparison with men, women had a higher prevalence of limb melanoma [n = 125/222 (56.3%) vs. n = 48/177 (27.1%); P &lt; 0.001] and family history of melanoma [n = 26/222 (11.7%) vs. n = 9/177 (5.1%); P = 0.02], thinner melanomas (0.69 vs. 1.10 mm; P = 0.001) and a better prognosis [n = 32/222 (14.4%) vs. n = 37/169 (20.9%) deaths; P = 0.01].

Conclusions
Melanoma diagnoses in young adults are occurring at progressively advanced ages, with a rise in melanomas situated on the head and extremities and in histological types linked to prolonged sun exposure. Strategies such as minimizing sun exposure from a young age and encouraging self-examination could lead to improved survival rates.
3D transoesophageal echocardiographic assessment of acute reverse remodelling of the tricuspid annulus after transcatheter edge-to-edge repair
Authors: Cammalleri Valeria , Antonelli Giorgio , De Luca Valeria Maria , Piscione Mariagrazia , Carpenito Myriam , Gaudio Dario , Nusca Annunziata , Cocco Nino , Mega Simona , Grigioni Francesco , Ussia Gian Paolo 
Published: October 2024

Abstract

Aims
Our study aims to evaluate the acute remodelling of the tricuspid valve annulus immediately after the tricuspid transcatheter edge-to-edge repair (T-TEER) by using intraprocedural transoesophageal 3D echocardiography.

Methods and results
We prospectively enrolled 62 consecutive symptomatic patients with at least severe tricuspid regurgitation (TR), who underwent T-TEER with the TriClip System between March 2021 and June 2024. The following parameters were assessed using a multiplanar reconstruction analysis performed off-line using a 3D data set: septal–lateral (SL) and antero–posterior (AP) annulus diameters; annulus area; annulus perimeter; and eccentricity index. The acute procedural success was achieved in 85.5%. We observed an acute reduction in SL (from a median of 43 to 38 mm, P &lt; 0.0001), AP (from a median of 46 to 45 mm, P &lt; 0.0001), area (from a median of 17.9 to 15.95 cm2, P &lt; 0.0001), perimeter (from a median of 145.5 to 137 mm, P &lt; 0.0001), and eccentricity index (from 0.92 to 0.87, P &lt; 0.0001). The tricuspid valve (TV) annulus was progressively larger in patients with higher residual TR. Analysis of the subgroups according to procedural success showed an acute inverse remodelling of the TV annulus independent of the acute procedural success.

Conclusion
The TV geometry necessitates the use of 3D echocardiography for accurate assessment of annular remodelling post T-TEER. The reduction in TR grade and TV annulus dimensions begins immediately after TriClip implantation. Concurrently, the baseline TV geometry influences the procedural results.
Comparison between invasive cardiac output and left ventricular assist device flow parameter
Authors: Segev Amitai , Copeland Viana , Sokolski Mateusz , Azaria Sivan , Morgan Avi , Maor Elad , Jura Maksym , Wilk Mateusz , Przybylski Roman , Freimark Dov , Tal-Ben Ishay Rotem , Regev Udi , Fardman Alexander , Grupper Avishay 
Published: October 2024

Abstract

OBJECTIVES
To evaluate the correlation between left ventricular assist device flow parameter and invasive cardiac output measurements.

METHODS
We retrospectively evaluated right heart catheterization examinations performed in left ventricular assist device patients from 2 tertiary medical centres. We evaluated the correlation between cardiac output measurement methods (indirect Fick and thermodilution) and pump flow parameter using linear regression, and the agreement was graphically displayed using Bland–Altman plot technique. Clinical, echocardiographic, pump and haemodynamic parameters were compared between patients with and without discordance, defined as at least a 20% difference between measurements.

RESULTS
The study population consisted of 102 patients [median age 58 (51–64), 86% males, 17 ± 12 months post left ventricular assist device implantation] with a total of 544 measurements compared. Discordance between measurements was present in 102 of 226 (45%) comparisons between indirect Fick and pump flow and in 72 of 161 (48%) between thermodilution and pump flow. A comparison of indirect Fick and left ventricular assist device exhibited a statistical correlation of R = 0.751, and that of thermodilution and left ventricular assist device of R = 0.789. Parameters associated with the presence of discordance between cardiac output measurements included a higher rate of aortic valve opening, lower indirect Fick and higher thermodilution cardiac output. After excluding the lowest tertile of indirect Fick cardiac output values, the correlation between measurements improved (thermodilution: R = 0.879 and indirect Fick: R = 0.843, P &lt; 0.001).

CONCLUSIONS
The current left ventricular assist device flow parameter provides an estimation of cardiac output that correlates well with indirect Fick and exhibits the strongest correlation with thermodilution. This correlation was stronger after excluding lower cardiac output values.
Clinical risk prediction, coronary computed tomography angiography, and cardiovascular events in new-onset chest pain: the PROMISE and SCOT-HEART trials
Authors: Rasmussen Laust Dupont , Schmidt Samuel Emil , Knuuti Juhani , Vrints Christiaan , Bøttcher Morten , Foldyna Borek , Williams Michelle C , Newby David E , Douglas Pamela S , Winther Simon 
Published: October 2024

Abstract

Background and Aims
Whether index testing using coronary computed tomography angiography (CTA) improves outcomes in stable chest pain is debated. The risk factor weighted clinical likelihood (RF-CL) model provides likelihood estimation of obstructive coronary artery disease. This study investigated the prognostic effect of coronary CTA vs. usual care by RF-CL estimates.

Methods
Large-scale studies randomized patients (N = 13 748) with stable chest pain to coronary CTA as part of the initial work-up in addition to or instead of usual care including functional testing. Patients were stratified according to RF-CL estimates [RF-CL: very-low (≤5%), low (&gt;5%–15%), and moderate/high (&gt;15%)]. The primary endpoint was myocardial infarction or death at 3 years.

Results
The primary endpoint occurred in 313 (2.3%) patients. Event rates were similar in patients allocated to coronary CTA vs. usual care [risk difference (RD) 0.3%, hazard ratio (HR) 0.84 (95% CI 0.67–1.05)]. Overall, 33%, 44%, and 23% patients had very-low, low, and moderate/high RF-CL. Risk was similar in patients with very low and moderate/high RF-CL allocated to coronary CTA vs. usual care [very low: RD 0.3%, HR 1.27 (0.74–2.16); moderate/high: RD 0.5%, HR 0.88 (0.63–1.23)]. Conversely, patients with low RF-CL undergoing coronary CTA had lower event rates [RD 0.7%, HR 0.67 (95% CI 0.47–0.97)]. The number needed to test using coronary CTA to prevent one event within 3 years was 143.

Conclusions
Despite an overall good prognosis, low RF-CL patients have reduced risk of myocardial infarction or death when allocated to coronary CTA vs. usual care. Risk is similar in patients with very-low and moderate/high likelihood.
Spatiotemporal evolution of post-seismic deformation caused by large earthquakes around the Pacific and its impact on plate movement
Authors: Fu Guangyu , Zhao Junzhe , Liu Tai , Gao Shanghua , Wang Zhenyu 
Published: October 2024

SUMMARY
The fully relaxed deformation caused by an earthquake refers to the total deformation of the earth caused by the earthquake, including the coseismic deformation and the total effect of post-seismic stress relaxation in the mantle on crustal deformation. An in-depth investigation into post-seismic and fully relaxed deformation resulting from large earthquakes is conducive to comprehending the feedback effect of earthquakes on plate motion. In this paper, we first calculated theoretically the coseimic, post-seicmic and fully relaxed deformations caused by the Tohoku-Oki Mw9.0 earthquake using the spherical dislocation theory. The post-seismic displacement caused by the great earthquake leads to the continuous convergence of plates on both sides of the seismogenic fault, which will certainly facilitate the downward insertion of the subduction plate. As time goes by the influence range of seismic deformations becomes larger and larger. The Tohoku-Oki Mw9.0 earthquake can produce &gt;5 cm of cumulative post-seismic horizontal displacement at a far place like the East Pacific Rise over 100 millenniums. Then, we built slip models of 375 earthquakes with Mw7.0 and above in the circum-Pacific seismic belt, calculated the cumulative post-seismic deformations of them, and found that significant post-seismic horizontal displacements covered the entire Pacific Ocean. The post-seismic deformation field caused by the 2011 Tohoku-Oki Mw9.0 earthquake, the 2010 Chile Mw8.8 earthquake, the 1964 Prince William Sound Mw9.1 earthquake and the 1960 Chile Mw(9.3–9.4) earthquake determines the overall distribution pattern of the deformation field in the Pacific region. Those large earthquakes around the Pacific make the total Pacific Plate present a tension strain in the northwest–southeast direction. The one at the East Pacific Rise reaches 300–400 nstr, with orientation of principle strain approximately perpendicular to the Rise. This tensile strain is bound to encourage transverse expansion of the mid-ocean ridge. By a logical extension, the post-seismic stress relaxation in the mantle caused by past earthquakes should be an important driving force for the current plate movement, in addition to the classic driving force like negative buoyancy and plate material phase transition. This study proves theoretically that there is a two-way relationship between great earthquakes and plate movement, and the viscous structure of mantle plays a key role in the relationship.
No accelerated progression of subclinical atherosclerosis with integrase strand transfer inhibitors compared to non-nucleoside reverse transcriptase inhibitors
Authors: García-Abellán Javier , García José A , Padilla Sergio , Fernández-González Marta , Agulló Vanesa , Mascarell Paula , Botella Ángela , Gutiérrez Félix , Masiá Mar 
Published: October 2024

Abstract

Background
The role of integrase strand transfer inhibitors (INSTI) in the cardiovascular risk of people with HIV is controversial.

Objectives
To assess the association of INSTI to subclinical atherosclerosis progression measured with the carotid intima-media thickness (cIMT).

Methods
Prospective study in virologically suppressed people with HIV receiving INSTI- or NNRTI-based regimens. cIMT was measured at baseline, 48 and 96 weeks. cIMT progression was analysed both as a continuous and categorical variable, defined as cIMT increase ≥ 10% and/or new carotid plaque. Adjustments through Cox proportional hazard regression and linear mixed models, and propensity score matching were conducted.

Results
190 participants were recruited and 173 completed the 96 week follow-up. 107 (56.3%) were receiving an INSTI-containing, 128 (67.4%) a NNRTI-containing and 45 (23.7%) a NNRTI plus an INSTI-containing regimen. The overall median (IQR) 2-year change of cIMT was 0.029 (−0.041 to 0.124) mm; 87 (45.8%) participants experienced a cIMT increase ≥ 10%, of whom 54 (28.4%) developed a new carotid plaque. Adjusted Cox regression showed no differences between INSTI and NNRTI groups in the categorical 2-year progression of cIMT, both including or excluding participants receiving INSTI + NNRTI. Similar results were observed for the continuous cIMT increase through adjusted linear mixed models. Propensity score matching showed no significant differences in the 2 year cIMT change between treatment groups [0.049 mm (−0.031–0.103) in the INSTI group versus 0.047 mm (−0.023–0.115) in the NNRTI group; P = 0.647]. cIMT progression was associated with traditional cardiovascular risk factors.

Conclusions
INSTI-based regimens are not associated with increased progression of subclinical atherosclerosis when compared to NNRTI.
Monitoring community antibiotic consumption in Belgium: reimbursement versus retail data (2013–22)
Authors: Damian Elena , Bonacini Laura , Kelly Moira , Allaoui El Maati , Maertens De Noordhout Charline , Coenen Samuel , Deckers Ivo , De Clercq Sarah , De Falleur Marc , Versporten Ann , Catry Boudewijn , Catteau Lucy 
Published: October 2024

Abstract

Background and objectives
In Belgium, monitoring antibiotic consumption relies on reimbursement data, which is obtained with a time delay and does not account for over-the-counter or nonreimbursed products. This study aims to bridge this gap by comparing reimbursement and retail data for primary care to understand variations and assess the accuracy of current surveillance methods.

Method
Reimbursement data were obtained from the National Institute for Health and Disability Insurance, and retail data were obtained from IQVIA for the period 2013–22. The community consumption of systemic antibiotics was expressed in defined daily doses (DDD—WHO ATC/DDD Index 2023) per inhabitants per day (DID). Relative differences in DID (RDs) based on the two data sets were computed and validated through Bland–Altman plots and correlation analysis.

Results
The sales of antibiotics declined from 22.89 DID (2013) to 20.50 (2022), with a steep drop during the COVID-19 pandemic—from 21.31 DID in 2019 to 16.55 DID in 2020—and a subsequent rebound. Reimbursement data slightly underestimated consumption compared to retail data, with RDs ranging from 2% (2013) to 9% (2022) when including quinolones and from 2% to 4% when excluding them. Bland–Altman plots showed high agreement between reimbursement and retail estimates, identifying quinolones as outliers.

Conclusion
Our findings suggest that reimbursement data are generally reliable for monitoring antibiotic consumption, but incorporating retail data is crucial for accurate assessments. The use of retail data can facilitate timely interventions and inform public health strategies to effectively address antimicrobial resistance.
Long-term estrogen-deprived estrogen receptor α-positive breast cancer cell migration assisted by fatty acid 2-hydroxylase
Authors: Kanamaeda Koki , Hirao-Suzuki Masayo , Kobayashi Takanobu , Sato Yuhki , Ohara Masahiro , Takeda Shuso 
Published: October 2024

Abstract
The risk of breast cancer (BC) recurrence is high in postmenopausal women, though the underlying molecular mechanisms are not yet fully understood. We developed a long-term estrogen-deprived (LTED) cell line from MCF-7 cells, which we used as an in vitro model for aromatase inhibitor (AI)-resistant estrogen receptor α (ERα)-positive postmenopausal BC. We also describe the involvement of fatty acid 2-hydroxylase (FA2H) in the modulation of LTED cell migration. Small interfering RNA specific to FA2H (siFA2H) could reduce cell migration, whereas the introduction of plasmid expressing FA2H, but not its inactive mutant, resulted in enhanced migration. Moreover, proliferation of the LTED cells was not affected by modulation of FA2H expression. Fulvestrant (FUL), a selective estrogen receptor degrader used to treat AI-resistant ERα-positive postmenopausal BC, was found to induce degradation of ERα together with a decrease in ER-mediated transcription; however, FA2H protein expression and migration remained unchanged. Overall, the findings of this study suggest that FA2H is one of the drivers of LTED cell migration, and that LTED cells resistant to FUL therapy may be involved in malignancy and metastatic mechanisms.