bluuebunny/crossref_metadata_2025_split huggingface dataset:
App-SpaM: phylogenetic placement of short reads without sequence alignment
Authors: Blanke Matthias , Morgenstern Burkhard 
Published: October 2021

AbstractMotivationPhylogenetic placement is the task of placing a query sequence of unknown taxonomic origin into a given phylogenetic tree of a set of reference sequences. A major field of application of such methods is, for example, the taxonomic identification of reads in metabarcoding or metagenomic studies. Several approaches to phylogenetic placement have been proposed in recent years. The most accurate of them requires a multiple sequence alignment of the references as input. However, calculating multiple alignments is not only time-consuming but also limits the applicability of these approaches.ResultsHerein, we propose Alignment-free phylogenetic placement algorithm based on Spaced-word Matches (App-SpaM), an efficient algorithm for the phylogenetic placement of short sequencing reads on a tree of a set of reference sequences. App-SpaM produces results of high quality that are on a par with the best available approaches to phylogenetic placement, while our software is two orders of magnitude faster than these existing methods. Our approach neither requires a multiple alignment of the reference sequences nor alignments of the queries to the references. This enables App-SpaM to perform phylogenetic placement on a broad variety of datasets.Availability and implementationThe source code of App-SpaM is freely available on Github at https://github.com/matthiasblanke/App-SpaM together with detailed instructions for installation and settings. App-SpaM is furthermore available as a Conda-package on the Bioconda channel.Contactmatthias.blanke@biologie.uni-goettingen.deSupplementary informationSupplementary data are available at Bioinformatics Advances online.
WikiNetworks: translating manually created biological pathways for topological analysis
Authors: Palshikar Mukta G , Hilchey Shannon P , Zand Martin S , Thakar Juilee 
Published: October 2021

AbstractSummaryWikiPathways is a database of 2979 biological pathways across 31 species created using the drawing software PathVisio. Many of these pathways are not directly usable for network-based topological analyses due to differences in curation styles and drawings. We developed the WikiNetworks package to standardize and construct directed networks by combining geometric information and manual annotations from WikiPathways. WikiNetworks performs significantly better than existing tools. This enables the use of high-quality WikiPathways resource for network-based topological analysis of high-throughput data.Availability and implementationWikiNetworks is written in Python3 and is available on github.com/Thakar-Lab/wikinetworks and on PyPI.Supplementary informationSupplementary data are available at Bioinformatics online.
BERT-Kcr: prediction of lysine crotonylation sites by a transfer learning method with pre-trained BERT models
Authors: Qiao Yanhua , Zhu Xiaolei , Gong Haipeng 
Published: October 2021

AbstractMotivationAs one of the most important post-translational modifications (PTMs), protein lysine crotonylation (Kcr) has attracted wide attention, which involves in important physiological activities, such as cell differentiation and metabolism. However, experimental methods are expensive and time-consuming for Kcr identification. Instead, computational methods can predict Kcr sites in silico with high efficiency and low cost.ResultsIn this study, we proposed a novel predictor, BERT-Kcr, for protein Kcr sites prediction, which was developed by using a transfer learning method with pre-trained bidirectional encoder representations from transformers (BERT) models. These models were originally used for natural language processing (NLP) tasks, such as sentence classification. Here, we transferred each amino acid into a word as the input information to the pre-trained BERT model. The features encoded by BERT were extracted and then fed to a BiLSTM network to build our final model. Compared with the models built by other machine learning and deep learning classifiers, BERT-Kcr achieved the best performance with AUROC of 0.983 for 10-fold cross validation. Further evaluation on the independent test set indicates that BERT-Kcr outperforms the state-of-the-art model Deep-Kcr with an improvement of about 5% for AUROC. The results of our experiment indicate that the direct use of sequence information and advanced pre-trained models of NLP could be an effective way for identifying PTM sites of proteins.Availability and implementationThe BERT-Kcr model is publicly available on http://zhulab.org.cn/BERT-Kcr_models/.Supplementary informationSupplementary data are available at Bioinformatics online.
Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population
Authors: Chen Mo , Xu Wen-Mao , Wang Gui-Yang , Hou Ya-Xuan , Tian Ting-Ting , Li Yu-Qing , Qi Hong-Jiao , Zhou Meng , Kong Wei-Jia , Lu Mei-Xia 
Published: October 2021

Abstract
Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case–control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend &lt; 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T&gt;C reduced the stability of E2F2 3’-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e−8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02–1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.
Task-relevant representations and cognitive control demands modulate functional connectivity from ventral occipito-temporal cortex during object recognition tasks
Authors: Branzi Francesca M , Martin Clara D , Paz-Alonso Pedro M 
Published: October 2021

AbstractThe left ventral occipito-temporal cortex (vOTC) supports extraction and processing of visual features. However, it has remained unclear whether left vOTC-based functional connectivity (FC) differs according to task-relevant representations (e.g., lexical, visual) and control demands imposed by the task, even when similar visual-semantic processing is required for object identification. Here, neural responses to the same set of pictures of meaningful objects were measured, while the type of task that participants had to perform (picture naming versus size-judgment task), and the level of cognitive control required by the picture naming task (high versus low interference contexts) were manipulated. Explicit retrieval of lexical representations in the picture naming task facilitated activation of lexical/phonological representations, modulating FC between left vOTC and dorsal anterior-cingulate-cortex/pre-supplementary-motor-area. This effect was not observed in the size-judgment task, which did not require explicit word-retrieval of object names. Furthermore, retrieving the very same lexical/phonological representation in the high versus low interference contexts during picture naming increased FC between left vOTC and left caudate. These findings support the proposal that vOTC functional specialization emerges from interactions with task-relevant brain regions.
Ultraviolet-C Light Evaluation as Adjunct Disinfection to Remove Multidrug-Resistant Organisms
Authors: Rock Clare , Hsu Yea Jen , Curless Melanie S , Carroll Karen C , Ross Howard Tracy , Carson Kathryn A , Cummings Stephanie , Anderson Michael , Milstone Aaron M , Maragakis Lisa L 
Published: October 2021

Abstract

Background
Our objective was to determine if the addition of ultraviolet-C (UV-C) light to daily and discharge patient room cleaning reduces healthcare-associated infection rates of vancomycin-resistant enterococci (VRE) and Clostridioides difficile in immunocompromised adults.

Methods
We performed a cluster randomized crossover control trial in 4 cancer and 1 solid organ transplant in-patient units at the Johns Hopkins Hospital, Baltimore, Maryland. For study year 1, each unit was randomized to intervention of UV-C light plus standard environmental cleaning or control of standard environmental cleaning, followed by a 5-week washout period. In study year 2, units switched assignments. The outcomes were healthcare-associated rates of VRE or C. difficile. Statistical inference used a two-stage approach recommended for cluster-randomized trials with &lt;15 clusters/arm.

Results
In total, 302 new VRE infections were observed during 45787 at risk patient-days. The incidence in control and intervention groups was 6.68 and 6.52 per 1000 patient-days respectively; the unadjusted incidence rate ratio (IRR) was 0.98 (95% confidence interval [CI], .78 − 1.22; P = .54). There were 84 new C. difficile infections observed during 26118 at risk patient-days. The incidence in control and intervention periods was 2.64 and 3.78 per 1000 patient-days respectively; the unadjusted IRR was 1.43 (95% CI, .93 − 2.21; P = .98).

Conclusions
When used daily and at post discharge in addition to standard environmental cleaning, UV-C disinfection did not reduce VRE or C. difficile infection rates in cancer and solid organ transplant units.
Resistance in Enterobacterales Is Higher Among People Living With Human Immunodeficiency Virus
Authors: Henderson Heather I , Napravnik Sonia , Gower Emily W , Aiello Allison E , Kinlaw Alan C , Williams Billy , Wohl David A , van Duin David 
Published: October 2021

AbstractBackgroundMultidrug-resistant Enterobacterales (MDR-E) are important pathogens. People living with human immunodeficiency virus (HIV; PLWH) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities.MethodsWe analyzed data from 36 521 patients in a healthcare system in North Carolina who had a clinical culture with growth of an Enterobacterales species from 2000 to 2018; 440 were PLWH. We used generalized linear models to estimate prevalence ratios and differences, contrasting PLWH and people not living with HIV (PNLWH) for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models.ResultsThe overall prevalence of MDR-E was higher among PLWH (21.5%; 95% confidence interval [CI], 18.2%–25.1%) vs PNLWH (16.5%; 95% CI, 16.2%–16.9%), with an adjusted prevalence ratio of 1.38 (95% CI, 1.14–1.65). PLWH had higher rates of antimicrobial resistance than PNLWH for all antibiotic classes analyzed, including penicillins, penicillin/beta lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PLWH than PNLWH throughout the study period based on the 5-year moving average.ConclusionsIn a large clinical study population in the southeastern United States from 2000 to 2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PLWH than PNLWH. These data highlight the importance of identifying and mitigating the factors that contribute to antimicrobial resistance in PLWH, given the potential clinical consequences of these resistant pathogens.
Point-of-care Intestinal Ultrasound in IBD Patients: Disease Management and Diagnostic Yield in a Real-world Cohort and Proposal of a Point-of-care Algorithm
Authors: Bots S , De Voogd F , De Jong M , Ligtvoet V , Löwenberg M , Duijvestein M , Ponsioen C Y , D’Haens G , Gecse K B 
Published: October 2021

Abstract

Introduction
Intestinal ultrasound [IUS] is useful for assessment of inflammation, complications, and treatment follow-up in inflammatory bowel disease [IBD] patients. We aimed to study outcomes and impact on disease management for point-of-care [POC] IUS in IBD patients.

Methods
Two patient cohorts undergoing POC IUS [January 2016–July 2018 and October 2019–December 2019] were included retrospectively. Disease management after IUS was analysed and IUS outcomes were compared with symptoms, biomarkers, and additional imaging within 8 weeks from IUS. To study differences in use of IUS over time, cohorts were compared.

Results
In total, 345 examinations (280 in Crohn’s disease [CD]/65 in ulcerative colitis [UC]) were performed. Present inflammation on IUS was comparable between symptomatic and asymptomatic CD [67.6% vs 60.5%; p = 0.291]. In 60%, IUS had impact on disease management with change in medication in 47.8%. Additional endoscopy/magnetic resonance imaging [MRI] was planned after 32.8% examinations, showing good correlation with IUS in 86.3% [ρ = 0.70, p &lt;0.0001] and 80.0% [ρ = 0.75, p &lt;0.0001] of cases, respectively. Faecal calprotectin was higher in active versus inactive disease on IUS [664 µg/g vs 79 µg/g; p &lt;0.001]. Over the years, IUS was performed more frequently to monitor treatment response and the use of MRI was reduced within the cohort.

Conclusions
POC IUS affects clinical decision making and could detect preclinical relapse in CD patients, with potential to reduce additional endoscopy or MRI. In addition, the paradigm expands towards monitoring treatment and close follow-up for IUS. Based on our results, we propose a POC IUS algorithm for follow-up of IBD patients.
Speckle-tracking-based global longitudinal and circumferential strain detect early signs of antibody-mediated rejection in heart transplant patients
Authors: Ciarka Agnieszka , Cordeiro Filipa , Droogne Walter , Van Cleemput Johan , Voigt Jens-Uwe 
Published: October 2021

Abstract

Aims
Acute rejection is an important cause of mortality after heart transplant (HTx), but symptoms develop only when myocardial damage is already extensive. We sought to investigate if echocardiographic parameters can detect and predict an acute cellular rejection (ACR) or antibody-mediated rejection (AMR) episode in HTx patients.

Methods and results
Data of 403 consecutive HTx recipients between 2003 and 2020 from our centre were reviewed. Patients with severe ACR (n = 10) and AMR (n = 7) were identified. Each HTx patient presenting with rejection was matched to a control HTx patient. Echocardiographic variables from the moment of rejection and 3, 6, and 12 months before were analysed and compared among groups. At acute rejection episode, patients with rejection had lower values of global longitudinal strain (GLS), global circumferential strain (GCS), and left ventricular ejection fraction (LVEF) compared to controls. HTx patients with AMR showed a progressive decline of GLS and GCS in the months preceding acute rejection, while controls and ACR patients had stable strain values except for the moment of rejection. In our cohort, a GLS cut-off lower than 15.5% and a GCS cut-off lower than 15.2% could distinguish with a sensitivity and specificity of 100.0% AMR from controls 3 months before rejection. LVEF and other conventional echo parameters could not differentiate among groups.

Conclusion
GLS and GCS show a progressive decrease months before AMR becomes clinically apparent. Our data suggest that global strain assessment by echocardiography allows an early detection of a developing AMR, which could improve the clinical management of HTx patients.
CAD-RADS may underestimate coronary plaque progression as detected by serial CT angiography
Authors: Szilveszter Bálint , Vattay Borbála , Bossoussou Melinda , Vecsey-Nagy Milán , Simon Judit , Merkely Béla , Maurovich-Horvat Pál , Kolossváry Márton 
Published: October 2021

Abstract

Aims
We wished to assess whether different clinical definitions of coronary artery disease (CAD) [segment stenosis and involvement score (SSS, SIS), Coronary Artery Disease—Reporting and Data System (CAD-RADS)] affect which patients are considered to progress and which risk factors affect progression.

Methods and results
We enrolled 115 subsequent patients (60.1 ± 9.6 years, 27% female) who underwent serial coronary computed tomography angiography (CTA) imaging with &gt;1year between the two examinations. CAD was described using SSS, SIS, and CAD-RADS. Linear mixed models were used to investigate the effects of risk factors on the overall amount of CAD and the effect on annual progression rate of different definitions. Coronary plaque burdens were SSS 4.63 ± 4.06 vs. 5.67 ± 5.10, P &lt; 0.001; SIS 3.43 ± 2.53 vs. 3.89 ± 2.65, P &lt; 0.001; CAD-RADS 0:8.7% vs. 0.0% 1:44.3% vs. 40.9%, 2:34.8% vs. 40.9%, 3:7.0% vs. 9.6% 4:3.5% vs. 6.1% 5:1.7% vs. 2.6%, P &lt; 0.001, at baseline and follow-up, respectively. Overall, 53.0%, 29.6%, and 28.7% of patients progressed over time based on SSS, SIS, and CAD-RADS, respectively. Of the patients who progressed based on SSS, only 54% showed changes in CAD-RADS. Smoking and diabetes increased the annual progression rate of SSS by 0.37/year and 0.38/year, respectively (both P &lt; 0.05). Furthermore, each year increase in age raised SSS by 0.12 [confidence interval (CI) 0.05–0.20, P = 0.001] and SIS 0.10 (CI 0.06–0.15, P &lt; 0.001), while female sex was associated with 2.86 lower SSS (CI −4.52 to −1.20, P &lt; 0.001) and 1.68 SIS values (CI −2.65 to −0.77, P = 0.001).

Conclusion
CAD-RADS could not capture the progression of CAD in almost half of patients with serial CTA. Differences in CAD definitions may lead to significant differences in patients who are considered to progress, and which risk factors are considered to influence progression.
Late primary angioplasty (beyond 12 h): are we sure it should be avoided?
Authors: Bolognese Leonardo 
Published: October 2021

Abstract
Optimal management for patients with ST-segment elevation myocardial infarction (STEMI) who arrive at a hospital late remains uncertain since evidence and real-world data are limited. Patients who present late with a STEMI are a heterogeneous population, and the clinical decision regarding percutaneous coronary intervention (PCI) should not be the same for all. One randomized clinical trial, multiple mechanistic studies, and contemporary registries suggest a presumed benefit for a prompt restoration of coronary flow even in late presenting STEMI. Crucial elements in decision-making are the presence of haemodynamic or electrical instability, and ongoing ischaemic signs or symptoms to tip the scales toward PCI. Among clinically stable, late-presenting patients, myocardial viability assessment and functional testing can identify yet another subgroup that may benefit from late PCI
New prevention scenarios: polygenic risk
Authors: Boccanelli Alessandro , Bottà Giordano 
Published: October 2021

Abstract
Although coronary heart disease is a highly preventable disease, it is still the leading cause of morbidity and mortality in developed countries. This is also due to the fact that the risk models used in clinical practice have proved ineffective in identifying people at risk: up to 30% of cases of myocardial infarction do not have traditional risk factors used in risk estimation models. Although the genetic component of myocardial infarction has been known for many years, with an inheritance rate of between 40% and 60%, it is not yet used as a risk factor in primary prevention models such as the Heart Card or the European SCORE. Recent advances in genomics and the use of clinical big data have allowed the development of genetic risk scores called Polygenic Risk Score (PRS), capable of identifying populations with average LDL-C levels, but with the same risk of heart attack of carriers of hypercholesterolaemia. The clinical usefulness of the PRS lies precisely in identifying high-risk individuals who are invisible to traditional models. The clinical applications of PRS for coronary artery disease are discussed in this report.
Mitral valve prolapse with ventricular arrhythmias: does it carries a worse prognosis?
Authors: Coutsoumbas Gloria Vassilikì , Di Pasquale Giuseppe 
Published: October 2021

Abstract
The association of mitral valve prolapse (MVP) with ventricular arrhythmias has long been known and has generally been considered a benign condition. In recent years, however, a small but not negligible risk of malignant ventricular arrhythmias and sudden cardiac death has been documented in the large population of subjects with MVP. The main predictors of major arrhythmic risk identified so far include history of syncope, ventricular repolarization abnormalities in the inferior-lateral electrocardiogram leads, right bundle branch block morphology of ventricular ectopic beats, finding of areas of myocardial fibrosis on cardiac magnetic resonance, and mitral annular disjunction (MAD) on echocardiogram, as well as a possible pro-arrhythmic genetic substrate. The stratification of arrhythmic risk, with the active search for red flags and in particular of MAD, is important to identify patients with the malignant arrhythmic variant of MVP in whom to implement closer surveillance and possible therapeutic interventions.
Recurrent pericarditis is less scary: the new therapeutic solutions
Authors: Del Pinto Rita , Ferri Claudio 
Published: October 2021

Abstract
Pericarditis is a common inflammatory disease affecting the pericardial sac, resulting from a variety of stimuli that trigger a stereotyped immune response. Generally self-limiting, this condition can be burdened by a significant risk of acute complications and relapses, with recurrence rates affecting up to 30% of patients, especially in the case of diagnostic and therapeutic delay. Therapeutic options in recurrent forms, initially based only on the use of traditional drugs such as colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids, have recently been enriched with new molecules, such as interleukin 1 blockers anakinra and rilonacept, particularly indicated in refractory forms dependent on corticosteroids. Other medically relevant therapeutic possibilities in refractory disease include azathioprine, methotrexate, and intravenous immunoglobulins. This brief review aims to summarize the treatment strategies of recurrent pericarditis in light of the most up-to-date evidence and recommendations.