bluuebunny/crossref_metadata_2025_split huggingface dataset:
DECOMICS, a shiny application for unsupervised cell type deconvolution and biological interpretation of bulk omic data
Authors: Karkar Slim , Sharma Ashwini , Herrmann Carl , Blum Yuna , Richard Magali 
Published: September 2024

Abstract

Summary
Unsupervised deconvolution algorithms are often used to estimate cell composition from bulk tissue samples. However, applying cell-type deconvolution and interpreting the results remain a challenge, even more without prior training in bioinformatics. Here, we propose a tool for estimating and identifying cell type composition from bulk transcriptomes or methylomes. DECOMICS is a shiny-web application dedicated to unsupervised deconvolution approaches of bulk omic data. It provides (i) a variety of existing algorithms to perform deconvolution on the gene expression or methylation-level matrix, (ii) an enrichment analysis module to aid biological interpretation of the deconvolved components, based on enrichment analysis, and (iii) some visualization tools. Input data can be downloaded in csv format and preprocessed in the web application (normalization, transformation, and feature selection). The results of the deconvolution, enrichment, and visualization processes can be downloaded.

Availability and implementation
DECOMICS is an R-shiny web application that can be launched (i) directly from a local R session using the R package available here: https://gitlab.in2p3.fr/Magali.Richard/decomics (either by installing it locally or via a virtual machine and a Docker image that we provide); or (ii) in the Biosphere—IFB Clouds Federation for Life Science, a multi-cloud environment scalable for high-performance computing: https://biosphere.france-bioinformatique.fr/catalogue/appliance/193/.
Accurate segmentation of intracellular organelle networks using low-level features and topological self-similarity
Authors: Huang Jiaxing , Luo Yaoru , Guo Yuanhao , Li Wenjing , Wang Zichen , Liu Guole , Yang Ge 
Published: September 2024

Abstract

Motivation
Intracellular organelle networks (IONs) such as the endoplasmic reticulum (ER) network and the mitochondrial (MITO) network serve crucial physiological functions. The morphology of these networks plays a critical role in mediating their functions. Accurate image segmentation is required for analyzing the morphology and topology of these networks for applications such as molecular mechanism analysis and drug target screening. So far, however, progress has been hindered by their structural complexity and density.

Results
In this study, we first establish a rigorous performance baseline for accurate segmentation of these organelle networks from fluorescence microscopy images by optimizing a baseline U-Net model. We then develop the multi-resolution encoder (MRE) and the hierarchical fusion loss (Lhf) based on two inductive components, namely low-level features and topological self-similarity, to assist the model in better adapting to the task of segmenting IONs. Empowered by MRE and Lhf, both U-Net and Pyramid Vision Transformer (PVT) outperform competing state-of-the-art models such as U-Net++, HR-Net, nnU-Net, and TransUNet on custom datasets of the ER network and the MITO network, as well as on public datasets of another biological network, the retinal blood vessel network. In addition, integrating MRE and Lhf with models such as HR-Net and TransUNet also enhances their segmentation performance. These experimental results confirm the generalization capability and potential of our approach. Furthermore, accurate segmentation of the ER network enables analysis that provides novel insights into its dynamic morphological and topological properties.

Availability and implementation
Code and data are openly accessible at https://github.com/cbmi-group/MRE.
Brain network changes after the first seizure: an insight into medication response?
Authors: Pedersen Mangor , Pardoe Heath , Mito Remika , Sethi Moksh , Vaughan David N , Carney Patrick W , Jackson Graeme D 
Published: September 2024

Abstract
After a first epileptic seizure, anti-seizure medications (ASMs) can change the likelihood of having a further event. This prospective study aimed to quantify brain network changes associated with taking ASM monotherapy. We applied graph theoretical network analysis to longitudinal resting-state functional MRI (fMRI) data from 28 participants who had recently experienced their first seizure. Participants were imaged before and during long-term ASM therapy, with a mean inter-scan interval of 6.9 months. After commencing ASM, we observed an increase in the clustering coefficient and a decrease in network path length. Brain changes after ASM treatment were most prominent in the superior frontoparietal and inferior fronto-temporal regions. Participants with recurrent seizures display the most pronounced network changes after ASM treatment. This study shows changes in brain network function after ASM administration, particularly in participants with recurrent seizures. Larger studies that ideally include control cohorts are required to understand further the connection between ASM-related brain network changes and longer-term seizure status.
Impact of the COVID-19 pandemic on telogen effluvium: a nationwide multicentre interrupted time series study
Authors: Choi Jee Woong , Park Hyoung Soo , Kim Sang Seok , Huh Chang-Hun , Kwon Ohsang , Lew Bark-Lynn , Kim Moon Bum 
Published: September 2024

Abstract

Background
There is ongoing debate regarding the association between telogen effluvium (TE) and COVID-19, as well as COVID-19 vaccines.

Objectives
To investigate the impact of the COVID-19 pandemic and vaccination on the development of TE among patients visiting dermatology clinics in South Korea.

Methods
Between 2017 and 2022, data regarding patients with TE and other types of hair loss were collected from 22 hospitals in South Korea. An interrupted time series analysis was conducted, dividing the time into periods before and after the COVID-19 pandemic, as well as before and after the COVID-19 vaccination.

Results
There was a significant slope change in the percentage of cases of TE during the postpandemic period (slope change 0.011, 95% confidence interval 0.005–0.017, P &lt; 0.001), but no significant changes were observed after vaccination. The percentage of patients with other types of hair loss was not associated with COVID-19 or vaccination. The retrospective nature of the study may have limited the ability to establish causation.

Conclusions
This multicentre study provides insights into the epidemiology of TE, showing a significant increase in cases of TE following the COVID-19 pandemic. However, there was no association between the occurrence of TE and COVID-19 vaccines.
Proenkephalin A 119-159 (penKid) and mortality in stable patients at high cardiovascular risk
Authors: Rau Matthias , Kurt Berkan , Hartmann Oliver , Lobo de Sá Fábia Daniela , Schwarz Marvin , Thiele Kirsten , Hartmann Niels-Ulrik Korbinian , Spiesshoefer Jens , Möllmann Julia , Hohl Mathias , Selejan Simina-Ramona , van der Vorst Emiel P C , Dahl Edgar , Marx Nikolaus , Kahles Florian , Lehrke Michael 
Published: September 2024

ABSTRACT

Background
Proenkephalin A 119–159 (penKid) is a novel blood biomarker for real-time assessment of kidney function and was found to be independently associated with worsening kidney function and mortality. A novel penKid-based estimated glomerular filtration rate equation (eGFRPENK-Crea), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance-based measured GFR. In this study, we aimed to evaluate the predictive value of penKid and eGFRPENK-Crea for all-cause mortality in stable patients at high cardiovascular risk.

Methods
Circulating penKid levels were assessed in 615 stable patients hospitalized at the Department of Cardiology at University Hospital Aachen, Germany. The endpoint was all-cause mortality; follow up was 3 years.

Results
penKid levels were higher in 46 non-survivors [58.8 (IQR 47.5–85.0) pmol/l] compared to 569 survivors [43.8 (IQR 34.0–58.0) pmol/l; P &lt; .0001]. Univariable Cox regression analyses found penKid and eGFRPENK-Crea to be associated with all-cause mortality (C index 0.703, χ2 33.27, P &lt; .00001; C index 0.716, χ2 36.51, P &lt; .00001). This association remained significant after adjustment for significant baseline parameters including age, smoking, chronic heart failure, use of diuretics, leucocytes, body mass index, sex, and creatinine (C index 0.799, χ2 72.06, P &lt; .00001). Importantly, penKid provided significant added value on top of eGFRCKD-EPI 2021 (eGFRCKD-EPI 2021: C index 0.716, χ2 34.21; eGFRCKD-EPI 2021 + penKid: C index 0.727, χ2: 40.02; Delta χ2 5.81; all P &lt; .00001) for all-cause mortality prediction in our cohort.

Conclusions
penKid levels and eGFRPENK-Crea is associated with all-cause mortality within a 3-year follow-up period and the addition of penKid on top of eGFRCKD-EPI 2021 provided significant added value in mortality prediction.
Outcomes of Patients With Prior Biologic Intolerance Are Better Than Those With Biologic Failure in Clinical Trials of Inflammatory Bowel Disease
Authors: Samnani Sunil , Wong Emily C L , Hamam Hasan , Dulai Parambir S , Marshall John K , Jairath Vipul , Reinisch Walter , Narula Neeraj 
Published: September 2024

Abstract

Background and Aims
Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance. This study aimed to assess clinical outcomes in IBD patients with prior biologic failure vs intolerance treated with ustekinumab or vedolizumab.

Methods
A post-hoc analysis of ulcerative colitis (UC) and Crohn’s disease (CD) clinical trials for ustekinumab (UNITI and UNIFI) and vedolizumab (GEMINI-1 and GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed.

Results
A total of 1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs 38.8%, aOR 1.87 [95% CI, 0.93-3.73]), clinical remission (25.0% vs 11.0%, aOR 2.84 [95% CI, 1.47-5.49]), and endoscopic improvement (40.6% vs 24.8%, aOR 2.76 [95% CI, 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI, 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI, 0.88-2.49).

Conclusions
Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure vs intolerance to mitigate potential bias.
Prenatal exposure to maternal smoking and adult lung cancer risk: a nested case-control study using peripheral blood leukocyte DNA methylation prediction of exposure
Authors: Ru Meng , Michaud Dominique S , Zhao Naisi , Kelsey Karl T , Koestler Devin C , Lu Jiayun , Platz Elizabeth A , Ladd-Acosta Christine M 
Published: September 2024

Abstract
A prior study reported no association between prenatal smoking methylation scores and adult lung cancer risk adjusting for methylation-predicted adult smoking, without considering maternal smoking trends by birth cohort. To address this gap, we examined the association between prenatal smoking methylation scores and adult lung cancer, independent of methylation-predicted adult packyears and by birth cohort, in a study nested in CLUE II. Included were 208 incident lung cancer cases ascertained by cancer registry linkage and 208 controls matched on age, sex, and smoking. DNA methylation was measured in prediagnostic blood. We calculated two prenatal smoking scores, using 19 (Score-19) and 15 (Score-15) previously identified CpGs and a methylation-predicted adult packyears score. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for adult packyears score and batch effects. Score-15 was positively associated with lung cancer (per standard deviation, OR = 1.40, 95% CI = 1.10–1.79, P-trend = .006), especially in the 1930–1938 birth cohort (OR = 3.43, 95% CI = 1.55–7.60, P-trend = .002). Score-19 was associated only in the 1930–1938 birth cohort (OR = 2.12, 95% CI = 1.15–3.91). Participants with both prenatal scores below the median (vs all other combinations) had lower risk (OR = 0.44, 95% CI = 0.27–0.72), especially in the 1930–1938 birth cohort (OR = 0.16, 95% CI = 0.04–0.62). Among ever smokers, participants with higher prenatal smoking scores had higher risk, irrespective of adult packyears (low: OR = 2.81, 95% CI = 1.38–5.72, high: OR = 2.67, 95% CI = 1.03–6.95). This prospective study suggests a positive association between prenatal smoking exposure and adult lung cancer risk, especially in the 1930–1938 birth cohort, independent of active smoking. Future studies with multiple birth cohorts are needed.
Degenerative mitral stenosis by echocardiography: presentation and outcome
Authors: Batista Roberta , Benfari Giovanni , Essayagh Benjamin , Maalouf Joseph , Thapa Prabin , Pellikka Patricia A , Michelena Hector I , Enriquez-Sarano Maurice 
Published: September 2024

Abstract

Aims
Degenerative mitral stenosis (DMS) is due to degenerative mitral annular calcification (MAC) and valvular calcification. However, DMS impacts on the outcome, and therefore, potential treatment needs are poorly known. We aimed at evaluating survival after DMS diagnosis by Doppler echocardiography in routine practice.

Methods and results
A cohort of 2937 (75 ± 12 years, 67% women) consecutive patients were diagnosed between 2003 and 2014 with DMS (diastolic mean gradient ≥ 5 mmHg), with analysis of short- and long-term survival. All patients had overt mitral annular/valvular degenerative calcification without rheumatic involvement. Mean gradient was 6.5 ± 2.4 mmHg, and DMS was considered mild in 50%, moderate in 44%, and severe in 6%. DMS was associated with left atrial enlargement (52 ± 23 mL/m2) and elevated pulmonary pressure (49 ± 16 mmHg) despite generally normal ejection fraction (61 ± 13%). DMS was associated with frequent comorbid conditions (74% hypertension, 58% coronary disease, and 52% heart failure) and humoural alterations (haemoglobin 11.3 ± 1.8 g/dL and creatinine 1.5 ± 1.4 mg/dL). One-year mortality was 22%, most strongly related to older age, higher comorbidity, and abnormal haemoglobin/creatinine but only weakly to DMS severity (with anaemia 42% irrespective of DMS severity, P = 0.99; without anaemia 18, 23, and 28% with mild, moderate, and severe DMS, respectively, P &lt; 0.0004). Long-term mortality was high (56% at 5 years) also mostly linked to aging and weakly to DMS severity [with anaemia P = 0.90; without anaemia: adjusted-hazard ratio: 1.30 (1.19–1.42), P &lt; 0.0001, for moderate vs. mild DMS and 1.63 (1.34–1.98), P &lt; 0.0001, for severe vs. mild DMS].

Conclusion
DMS is a condition of the elderly potentially resulting in severe mitral obstruction and haemodynamic alterations. However, DMS is frequently associated with severe comorbidities imparting considerable mortality following diagnosis, whereas DMS severity is a weak (albeit independent) determinant of mortality. Hence, patients with DMS should be carefully evaluated and interventional/surgical treatment prudently considered in those with limited comorbidity burden, particularly without anaemia. Keywords: Degenerative Mitral Stenosis; Outcome; Natural history; Ecocardiography; Mitral Stenosis.
Epicardial adipose tissue and muscle distribution affect outcomes in very old patients after transcatheter aortic valve replacement
Authors: Rohrbach Susanne , Uluocak Oezge , Junge Marieke , Knapp Fabienne , Schulz Rainer , Böning Andreas , Nef Holger M , Krombach Gabriele A , Niemann Bernd 
Published: September 2024

Abstract

Aims
To analyse the relevance of body composition and blood markers for long-term outcomes in very old patients after transcatheter aortic valve replacement (TAVR).

Methods and results
A total of 403 very old patients were characterized with regard to subcutaneous, visceral, and epicardial fat, psoas muscle area, plasma growth differentiation factor 15 (GDF-15), and leptin. Cohorts grouped by body mass index (BMI) were analysed for long-term outcomes. Patients underwent transapical and transfemoral TAVR (similar 30-day/1-year survival). Body mass index &gt;35 kg/m2 showed increased 2- and 3-year mortality compared with BMI 25–34.9 kg/m2 but not compared with BMI &lt;25 kg/m2. Fat areas correlated positively to BMI (epicardial: R2 = 0.05, P &lt; 0.01; visceral: R2 = 0.20, P &lt; 0.001; subcutaneous: R2 = 0.13, P &lt; 0.001). Increased epicardial or visceral but not subcutaneous fat area resulted in higher long-term mortality. Patients with high BMI (1781.3 mm2 ± 75.8, P &lt; 0.05) and lean patients (1729.4 ± 52.8, P &lt; 0.01) showed lower psoas muscle area compared with those with mildly elevated BMI (2055.2 ± 91.7). Reduced psoas muscle area and increased visceral fat and epicardial fat areas were independent predictors of long-term mortality. The levels of serum GDF-15 were the highest in BMI &gt;40 kg/m2 (2793.5 pg/mL ± 123.2) vs. BMI &lt;25 kg/m2 (2017.6 pg/mL ±130.8), BMI 25–30 kg/m2 (1881.8 pg/mL ±127.4), or BMI 30–35 kg/m2 (2054.2 pg/mL ±124.1, all P &lt; 0.05). Increased GDF-15 level predicted mortality (2587 pg/mL, area under the receiver operating characteristic curve 0.94). Serum leptin level increased with BMI without predictive value for long-term mortality.

Conclusion
Morbidly visceral and epicardial fat accumulation, reduction in muscle area, and GDF-15 increase are strong predictors of adverse outcomes in very old patients post-TAVR.
Association between exposure to air pollution and increased ischaemic stroke incidence: a retrospective population-based cohort study (EP-PARTICLES study)
Authors: Święczkowski Michał , Lip Gregory Y H , Kurasz Anna , Dąbrowski Emil J , Tomaszuk-Kazberuk Anna , Kamiński Jacek W , Strużewska Joanna , Dobrzycki Sławomir , Kuźma Łukasz 
Published: September 2024

Abstract

Aims
Short-term effects of Polish smog, particularly benzo(alpha)pyrene [B(a)P], are unclear. We aimed to examine the association between short-term exposure to air pollution and ischaemic stroke (IS) incidence.

Methods and results
We conducted a retrospective population-based cohort study including an EP-PARTICLES cohort of 8 million inhabitants in the years 2011–20 (80 million person-years of observation). Individual clinical data on emergency hospitalizations due to IS (ICD-10: I63.X) was analysed. We used quasi-Poisson models to examine municipality-specific associations between air pollutants and IS, considering various covariates. We recorded 146 262 cases of IS with a dominance of females (51.8%) and people over 65 years old (77.6%). In the overall population, exposure to PM2.5, NO2, B(a)P, and SO2 increased the risk of IS onset on the day of exposure by 2.4, 1, 0.8, and 0.6%, respectively. Age and sex were modifying variables for PM2.5, NO2, and B(a)P exposure with more pronounced effects in non-elderly individuals and women (all Pinteraction &lt; 0.001). Residents of regions with high tobacco and alcohol consumption were more sensitive to the effects of PM2.5 and SO2. The slopes of response–effect curves were non-linear and steeper at lower concentrations.

Conclusion
Exposure to air pollution may be associated with higher IS incidence, particularly posing a higher risk to non-elderly women. Harmful lifestyle habits might exacerbate its impact. Exposure to even low levels of air pollutants had negative effects.

Registration
The study was registered at ClinicalTrials.gov (NCT05198492).
Female participation, and sex-specific reporting practices, in polypill randomized controlled trials in the prevention of atherosclerotic cardiovascular disease: a secondary analysis of a systematic review
Authors: Peters Sanne A E , Rodgers Anthony , Patel Anushka , Norton Robyn , Huffman Mark D , Agarwal Anubha 
Published: September 2024

Abstract

Aims
The polypill is an emerging strategy for the prevention and management of cardiovascular disease (CVD). We assessed the participation of females in randomized controlled trials evaluating polypills for prevention of CVD and subsequent sex-specific analyses and reporting.

Methods and results
Cardiovascular polypill trials were identified through a systematic review. Data were extracted on the use of sex-specific eligibility criteria, female participation, and the conduct, findings, and interpretation of sex-specific analyses. Of 26 trials included, 12 (46%) excluded groups of females, mainly if pregnant or lactating or of childbearing potential. Female participation ranged from 10% to 73% across trials. Overall, 42% of included participants were female. Of 18 trials conducted in a mostly primary prevention population, females represented 49% of trial participants. In mixed or exclusively secondary prevention trials (n = 8), females represented 26% of trial participants. Females represented 46% of trial participants in trials that excluded groups of females (n = 12). In trials without explicit exclusion criteria (n = 13), females represented 32% of trial participants. Nine out of 26 trials reported sex-stratified analyses (35% of trials; 70% of all participants). Of these, two found some evidence for possible sex differences, both reporting larger blood pressure effects in females than males. Four trials provided sex considerations in the discussion section of the report.

Conclusion
The participation of females in cardiovascular polypill trials is substantially higher in primary prevention trials as compared with trials conducted in mixed or exclusively secondary prevention populations. The use of sex-specific eligibility criteria was not linked to lower female participation. Sex-specific reporting is sparsely conducted, although most frequent in larger trials.
I have a question about evaluative reporting: a comprehensive collection of FAQs
Authors: Ostrum Ronald Brent 
Published: September 2024

Abstract
With various calls in the forensic scientific literature for pattern-matching disciplines to adopt evaluative reporting, which is also known as the likelihood ratio or logical approach, practitioners used to reporting evidence under a more traditional paradigm may have a level of apprehension and face a steep learning curve. There may be doubts about the benefits of evaluative reporting, when it applies and when it does not, what it actually entails, its validity, and how to explain it in court. These questions and more are answered in this comprehensive collection of frequently asked questions on evaluative reporting. While the focus is on providing context for forensic handwriting examiners, many of the questions and answers are general in nature and the concepts can be applied to other disciplines.