bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Self-Rated Effects of Alcohol Are Related to Presystemic Metabolism of Alcohol
Authors: Bramness Jørgen G , Skulberg Knut R , Skulberg Andreas , Moe Jenny Skumsnes , Mørland Jørg 
Published: January 2023

AbstractAimsA high number of alcohol units required to feel a subjective effect of alcohol predicts future alcohol use disorders (AUDs). The subjective response to alcohol can be measured using the validated retrospective self-rated effects of alcohol (SRE) questionnaire. Few studies have investigated the specific relationship between SRE and blood alcohol concentration (BAC) in an experimental setting.MethodsTwenty healthy young adult male volunteers who had experience with binge drinking, but did not have AUD, filled out the SRE-questionnaire and were served with a fixed amount of alcohol per body weight. BACs were measured throughout a 12-hour period, reaching a maximum BAC of ~0.13%. Median split of SRE-scores was utilized to compare BACs among participants with relatively high effects (low SRE) and relatively low effects (high SRE) of alcohol.ResultsParticipants reporting a relatively low SRE-score had a statistically significant higher measured BAC at all time points until alcohol was eliminated. This was especially pronounced during the first 2 hours after alcohol (P = 0.015) without a significant difference in the alcohol elimination rate being detected.ConclusionThe study indicates that a self-ated SRE-score is related to BACs after the ingestion of a standardized amount of alcohol per body weight. Reporting a higher number of alcohol units before feeling an effect was related to a lower BAC. As the differences in BAC between relatively high and low self-rated effects appeared rapidly after intake, this could be interpreted as an effect of presystemic metabolism of alcohol.
A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces
Authors: Ceyhan Kubilay , Drawe Patrick , Schupp Thomas 
Published: January 2023

Abstract
Primary aromatic amines (PAAs) are a class of hazardous substances where many compounds are classified as carcinogen, mutagen, and reproduction toxin (CMR). PAAs can be taken up by dermal exposure. In the polyurethane industry, a valid and trustworthy method for the quantification of PAAs in the presence of isocyanates that could interfere is of great interest, especially on workplaces where a regular contact to PAAs cannot be excluded. The aim of this work is the development, validation, and verification of a novel sampling device to quantify selectively the PAA load on work surfaces. We describe the synthesis of Cell-ßALA-PEMSA analytical papers and their characterization by infrared spectroscopy and thermogravimetric analysis. The recovery of TDA and MDA spiked on these filters is satisfactory. An excellent selectivity of Cell-ßALA-PEMSA papers towards PAAs in the presence of isocyanates of almost 100% was found by wipe tests of amine/isocyanate contaminated surfaces. First positive field tests were achieved at certain areas in a Polyurethane Technical Application Department where surface contamination with PAAs was expected, and the Cell-ßALA-PEMSA analytical papers were superior to an established method of surface sampling. However, recovery of these amines from surfaces shows a large variability, and more work is required to address influencing surface properties.
Denoising adaptive deep clustering with self-attention mechanism on single-cell sequencing data
Authors: Su Yansen , Lin Rongxin , Wang Jing , Tan Dayu , Zheng Chunhou 
Published: January 2023

AbstractA large number of works have presented the single-cell RNA sequencing (scRNA-seq) to study the diversity and biological functions of cells at the single-cell level. Clustering identifies unknown cell types, which is essential for downstream analysis of scRNA-seq samples. However, the high dimensionality, high noise and pervasive dropout rate of scRNA-seq samples have a significant challenge to the cluster analysis of scRNA-seq samples. Herein, we propose a new adaptive fuzzy clustering model based on the denoising autoencoder and self-attention mechanism called the scDASFK. It implements the comparative learning to integrate cell similar information into the clustering method and uses a deep denoising network module to denoise the data. scDASFK consists of a self-attention mechanism for further denoising where an adaptive clustering optimization function for iterative clustering is implemented. In order to make the denoised latent features better reflect the cell structure, we introduce a new adaptive feedback mechanism to supervise the denoising process through the clustering results. Experiments on 16 real scRNA-seq datasets show that scDASFK performs well in terms of clustering accuracy, scalability and stability. Overall, scDASFK is an effective clustering model with great potential for scRNA-seq samples analysis. Our scDASFK model codes are freely available at https://github.com/LRX2022/scDASFK.
SCAMPP+FastTree: improving scalability for likelihood-based phylogenetic placement
Authors: Chu Gillian , Warnow Tandy 
Published: January 2023

AbstractSummaryPhylogenetic placement is the problem of placing ‘query’ sequences into an existing tree (called a ‘backbone tree’). One of the most accurate phylogenetic placement methods to date is the maximum likelihood-based method pplacer, using RAxML to estimate numeric parameters on the backbone tree and then adding the given query sequence to the edge that maximizes the probability that the resulting tree generates the query sequence. Unfortunately, this way of running pplacer fails to return valid outputs on many moderately large backbone trees and so is limited to backbone trees with at most ∼10 000 leaves. SCAMPP is a technique to enable pplacer to run on larger backbone trees, which operates by finding a small ‘placement subtree’ specific to each query sequence, within which the query sequence are placed using pplacer. That approach matched the scalability and accuracy of APPLES-2, the previous most scalable method. Here, we explore a different aspect of pplacer’s strategy: the technique used to estimate numeric parameters on the backbone tree. We confirm anecdotal evidence that using FastTree instead of RAxML to estimate numeric parameters on the backbone tree enables pplacer to scale to much larger backbone trees, almost (but not quite) matching the scalability of APPLES-2 and pplacer-SCAMPP. We then evaluate the combination of these two techniques—SCAMPP and the use of FastTree. We show that this combined approach, pplacer-SCAMPP-FastTree, has the same scalability as APPLES-2, improves on the scalability of pplacer-FastTree and achieves better accuracy than the comparably scalable methods.Availability and implementationhttps://github.com/gillichu/PLUSplacer-taxtastic.Supplementary informationSupplementary data are available at Bioinformatics Advances online.
PyGenePlexus: a Python package for gene discovery using network-based machine learning
Authors: Mancuso Christopher A , Liu Renming , Krishnan Arjun 
Published: January 2023

Abstract

Summary
PyGenePlexus is a Python package that enables a user to gain insight into any gene set of interest through a molecular interaction network informed supervised machine learning model. PyGenePlexus provides predictions of how associated every gene in the network is to the input gene set, offers interpretability by comparing the model trained on the input gene set to models trained on thousands of known gene sets, and returns the network connectivity of the top predicted genes.

Availability and implementation
https://pypi.org/project/geneplexus/ and https://github.com/krishnanlab/PyGenePlexus.

Supplementary information
Supplementary data are available at Bioinformatics online.
Postoperative delirium is associated with grey matter brain volume loss
Authors: Kant Ilse M J , de Bresser Jeroen , van Montfort Simone J T , Witkamp Theodoor D , Walraad Bob , Spies Claudia D , Hendrikse Jeroen , van Dellen Edwin , Slooter Arjen J C ,   BioCog consortium, Spies Claudia , Winterer Georg , Pischon Tobias , Boraschi Diana , Schneider Reinhard , Nürnberg Peter , Zacharias Malte Pietzsch Norman , Morgeli Rudolf , Olbert Maria , Lachmann Gunnar , Borchers Friedrich , Ofosu Kwaku , Yurek Fatima , Wolf Alissa , Gallinat Jurgen , Hendrikse Jeroen , Slooter Arjen , van Dellen Edwin , Stamatakis Emmanuel , Preller Jacobus , Menon David , Moreno-Lopez Laura , Winzeck Stefan , Feinkohl Insa , Italiani Paola , Melillo Daniela , Camera Giacomo Della , Krause Roland , Heidtke Karsten , Kuhn Simone , Kronabel Marion , Dscietzig Thomas Bernd , Armbruster Franz Paul , Hafen Bettina , Ruppert Jana , Bocher Axel , Helmschrodt Anja , Weyer Marius , Hartmann Katarina , Diehl Ina , Weber Simon , Fillmer Ariane , Ittermann Bernd 
Published: January 2023

AbstractDelirium is associated with long-term cognitive dysfunction and with increased brain atrophy. However, it is unclear whether these problems result from or predisposes to delirium. We aimed to investigate preoperative to postoperative brain changes, as well as the role of delirium in these changes over time. We investigated the effects of surgery and postoperative delirium with brain MRIs made before and 3 months after major elective surgery in 299 elderly patients, and an MRI with a 3 months follow-up MRI in 48 non-surgical control participants. To study the effects of surgery and delirium, we compared brain volumes, white matter hyperintensities and brain infarcts between baseline and follow-up MRIs, using multiple regression analyses adjusting for possible confounders. Within the patients group, 37 persons (12%) developed postoperative delirium. Surgical patients showed a greater decrease in grey matter volume than non-surgical control participants [linear regression: B (95% confidence interval) = −0.65% of intracranial volume (−1.01 to −0.29, P &lt; 0.005)]. Within the surgery group, delirium was associated with a greater decrease in grey matter volume [B (95% confidence interval): −0.44% of intracranial volume (−0.82 to −0.06, P = 0.02)]. Furthermore, within the patients, delirium was associated with a non-significantly increased risk of a new postoperative brain infarct [logistic regression: odds ratio (95% confidence interval): 2.8 (0.7–11.1), P = 0.14]. Our study was the first to investigate the association between delirium and preoperative to postoperative brain volume changes, suggesting that delirium is associated with increased progression of grey matter volume loss.
Neural suppression in odor recognition memory
Authors: Eek Tom , Lundin Fredrik , Larsson Maria , Hamilton Paul , Georgiopoulos Charalampos 
Published: January 2023

AbstractLittle is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.
Body size dictates physiological and behavioural responses to hypoxia and elevated water temperatures in Murray cod (Maccullochella peelii)
Authors: McPhee Darren , Watson Jabin R , Harding Doug J , Prior Andrea , Fawcett James H , Franklin Craig E , Cramp Rebecca L 
Published: January 2023

Abstract
Increasing drought frequency and duration pose a significant threat to fish species in dryland river systems. As ectotherms, fish thermal and hypoxia tolerances directly determine the capacity of species to persist in these environments during low flow periods when water temperatures are high and waterbodies become highly stratified. Chronic thermal stress can compound the impacts of acute hypoxic events on fish resulting in significant fish mortality; however, it is not known if all size classes are equally susceptible, or if the allometric scaling of physiological processes means some size classes are disproportionately affected. We investigated the physiological responses of Murray cod (Maccullochella peelii) over a four-fold body size range (0.2–3000 g) to acute changes in water temperature and oxygen concentration following 4 weeks of acclimation to representative spring (20°C) and summer (28°C) water temperatures. We recorded maximum thermal tolerance (CTmax), oxygen limited thermal tolerance (PCTmax), lowest tolerable oxygen level (as the oxygen level at which lose equilibrium; O2,LOE), gill ventilation rates and aerial surface respiration threshold, blood oxygen transport capacity and lactate accumulation. Acclimation to elevated water temperatures improved thermal and hypoxia tolerance metrics across all size classes. However, body size significantly affected thermal and hypoxia responses. Small M. peelii were significantly less hypoxia tolerant than larger individuals, while larger fish were significantly less thermal tolerant than smaller fish. Hypoxia constrained thermal tolerance in M. peelii, with both small and large fish disproportionally compromised relative to mid-sized fish. Our findings indicate that both very small/young (larvae, fry, fingerlings) and very large/older M. peelii in dryland rivers are at significant risk from the combined impacts of a warming and drying climate and water extraction. These data will inform policy decisions that serve to balance competing demands on precious freshwater resources.
OP01 Sequencing-based gene network analysis reveals a profound role for ferroptosis key gene GPX4 in post-operative endoscopic recurrence in Crohn’s disease
Authors: Verstockt S , Machiels K , Dehairs J , Rems K , De Greef I , Jans D , Sabino J , Ferrante M , Vermeire S , Verstockt B 
Published: January 2023

Abstract

Background
An ileocolonic resection with ileocolonic anastomosis is often required in patients with Crohn’s disease (CD). Postoperative recurrence (POR) is common, with host-luminal interactions being implicated. However, these interactions are poorly understood. We aimed to obtain insights in the early mechanisms of POR CD focusing on sequencing-based gene networks in the mucosa.

Methods
We included 36 CD patients who underwent ileocolonic resection with ileocolonic anastomosis, and collected mucosal biopsies from the neoterminal ileum 6 months after surgery (Table 1). We defined POR by a Rutgeerts score ≥i2b at month 6, and compared this to complete absence of endoscopic activity (i0). All biopsies underwent single-end RNA sequencing (Illumina TruSeq Stranded mRNA). Gene co-expression network clusters were identified using weighted gene co-expression network analysis (R\WGCNA), were tested for correlation with the primary outcome POR and clinical factors, and multiple testing correction was applied (FDR&lt;0.05). Cellular deconvolution was performed using xCell; and top enriched pathways and upstream regulators were analysed using IPA (p&lt;0.05).

Results
WGCNA analysis identified 25 co-expression clusters, of which five correlated with the postoperative outcome (clusters V, VI, IX, XV, XXV) (Fig.1). All but cluster XXV were upregulated in POR, with a profound immune-related enrichment in cluster V and VI (eg. (a)granulocyte adhesion and diapedesis, and IL17 signalling); microRNA biogenesis (cluster IX) and wound healing and fibrosis signalling (cluster XV). Interestingly, one cluster (XXV) was inversely correlated with POR, and genes within this cluster were mainly involved in autophagy, ferroptosis and oxidative stress response. The main hub gene (r=0.95, FDR=8.17E-19) within this cluster XXV was GPX4 (Glutathione peroxidase 4), a negative regulator of ferroptosis. Moreover, after cellular deconvolution, we found a positive correlation between the epithelial gene enrichment signature and the expression of GPX4 (r=0.52, p=0.0011). Finally, the main upstream regulator of the genes within this cluster XXV was HNF4A, a transcription factor known to regulate ferroptotic response.

Conclusion
We identified a mucosal transcriptomic signature associated with postoperative CD recurrence. Both autophagy and ferroptosis were found to be key protective pathways for recurrence with GPX4 as central hub. Our results complement recent findings of impaired epithelial GPX4 activity in ileal CD lesions evoking an inflammatory response to dietary lipids (Mayr et al Nat Comm 2020).
OP05 High-dimensional single-cell analysis identifies cellular signatures associated with response to vedolizumab therapy in ulcerative colitis
Authors: Pibiri P , Sun S , Karmi N , Oelen R , de Jong S , Bangma A , Teunis J , Hermoso M A , Paraskevopoulou M D , Farahmand S , Bleck B , Xia G , Weersma R K , Bigaeva E , Festen E A 
Published: January 2023

Abstract

Background
The unpredictability of response to biological therapy in ulcerative colitis (UC) patients, including vedolizumab (VDZ), an anti-α4β7 integrin antibody, poses a serious challenge for medical care. This study aims to identify the relevant cellular and molecular signatures that mark response to VDZ by combining single-cell transcriptomics (scRNAseq) and high-dimensional flow cytometry (Cytek).

Methods
Gut biopsies and peripheral blood mononuclear cells (PBMCs) from patients with active UC were collected 2 weeks prior and 14 weeks after starting VDZ therapy. Response was evaluated at week 14 based on endoscopy and Physician Global Assessment. Transcriptome profiles of 159.188 and 95.057 high-quality single cells were generated from biopsies and PBMCs, respectively. Additional 797.670 CD45+ mucosal cells and 900.000 PBMCs were processed for validating scRNAseq results by Cytek.

Results
From a total of 25 UC patients (mean age 41±12.7 years, 52% female, 36% anti-TNFα naive), 15 patients (60%) reached response at week 14. Patients with no prior use of anti-TNFα were more likely to achieve remission with VDZ compared to anti-TNFα exposed patients (89% vs 44% response rate, respectively). Analysis of cell abundances revealed a partial recovery of the epithelial and stromal cell mucosal compartments in responders at week 14. Both scRNAseq and Cytek show that in responders VDZ prevented T cells (CD8+IL17+ and CD4+PD1+ subsets) and innate immune cells (NKs, DCs and inflammatory monocytes) from entering mucosa, resulting in their enrichment in PBMCs. In contrast, non-response to VDZ was marked by an expansion of inflammatory fibroblasts and activated endothelial cells, and depletion of most epithelial subsets. VDZ retained CD4 T cells in PBMCs in non-responders, but failed to halt active mucosal inflammation at week 14. Strikingly, involvement of the innate immune cells in UC inflammation prior to VDZ treatment was much more prominent in non-responders who showed higher baseline abundance of NKs, ILCs, γδ-T cells, DCs and inflammatory monocytes in their peripheral blood and mucosa compared to responders. While VDZ inhibited integrin β7 expression on circulating T cells in all patients, only in responders it coincided with the lower mucosal abundance of lymphocytes, suggesting that T cells in non-responders might employ alternative, β7-independent trafficking routes.

Conclusion
This is the largest prospective scRNAseq study addressing the response to biological therapy in UC. We showed that active, innate immune cell-mediated inflammation marks the primary non-response to VDZ that persists prior to and throughout the treatment, accompanied by β7-independent lymphocyte migration.
OP07 Absolute and relative risks of kidney and urological complications in patients with Inflammatory Bowel Disease
Authors: Yang Y , Ludviggson J F , Olén O , Sjölander A , Carrero J J 
Published: January 2023

Abstract

Background
Kidney-related complications are considered relatively common extraintestinal manifestations of inflammatory bowel disease (IBD), but absolute risks are not well characterized. We aimed at providing a comprehensive characterization of the burden of kidney-related complications in people with incident IBD by analysing issued clinical diagnoses and trajectories of estimated glomerular filtration rate (eGFR) in the complete population of Stockholm, Sweden.

Methods
We included 1,682,795 participants aged 11 or older, free from IBD or chronic kidney disease (CKD) diagnosis and who had a measurement of eGFR during 2006-2018. We analysed the association between developing IBD (time-varying exposure) and the risk of receiving a CKD diagnosis, acute kidney injury (AKI), kidney stones, or secondary amyloidosis, and experiencing the composite of declining their eGFR at least 30% from baseline or kidney failure (collectively termed as CKD progression). Absolute risks were calculated at 5- and 10-year of follow-up, and relative risks were calculated with Cox regression. We compared kidney-related risks overall and for Crohn’s disease (CD) and ulcerative colitis (UC) separately.

Results
After median 9 years, 10,117 participants newly developed IBD. Their mean age was 45 years. Compared with non-IBD periods, developing IBD associated with higher relative risks: the HR (95% CI) for the risk of receiving a CKD diagnosis was 1.24 (1.10-1.40), 1.11 (1.00-1.24) for the risk of CKD progression, and 1.25 (1.14-1.36) for the composite outcome of these two events. Within 10 years from IBD diagnosis, 6.4% (5.8-7.0%) of participants received a diagnosis of CKD, but 11.4% (10.4-12.4%) had a clinically relevant reduction in eGFR. The risks of AKI (HR 1.97 [1.70-2.29]; 10-y absolute risk 3.6%), kidney stones (HR 1.69 [1.48-1.93]; 10-y risk 5.6%) and secondary amyloidosis (HR 2.77 [1.44-5.35]; 10-y risk 0.2%) were also higher in persons developing IBD compared to non-IBD periods. In general, CD patients exhibited higher absolute and relative kidney risks than UC patients.

Conclusion
One in ten persons with IBD develop chronic kidney disease within 10 years from diagnosis, with many of these events not being identified through diagnostic codes. This, together with higher risks of AKI and kidney stones emphasizes the need for monitoring of kidney function and established protocols for referral to nephrological/urological care.