bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alignment-free estimation of sequence conservation for identifying functional sites using protein sequence embeddings
Authors: Yeung Wayland , Zhou Zhongliang , Li Sheng , Kannan Natarajan 
Published: January 2023

AbstractProtein language modeling is a fast-emerging deep learning method in bioinformatics with diverse applications such as structure prediction and protein design. However, application toward estimating sequence conservation for functional site prediction has not been systematically explored. Here, we present a method for the alignment-free estimation of sequence conservation using sequence embeddings generated from protein language models. Comprehensive benchmarks across publicly available protein language models reveal that ESM2 models provide the best performance to computational cost ratio for conservation estimation. Applying our method to full-length protein sequences, we demonstrate that embedding-based methods are not sensitive to the order of conserved elements—conservation scores can be calculated for multidomain proteins in a single run, without the need to separate individual domains. Our method can also identify conserved functional sites within fast-evolving sequence regions (such as domain inserts), which we demonstrate through the identification of conserved phosphorylation motifs in variable insert segments in protein kinases. Overall, embedding-based conservation analysis is a broadly applicable method for identifying potential functional sites in any full-length protein sequence and estimating conservation in an alignment-free manner. To run this on your protein sequence of interest, try our scripts at https://github.com/esbgkannan/kibby.
scDCCA: deep contrastive clustering for single-cell RNA-seq data based on auto-encoder network
Authors: Wang Jing , Xia Junfeng , Wang Haiyun , Su Yansen , Zheng Chun-Hou 
Published: January 2023

Abstract
The advances in single-cell ribonucleic acid sequencing (scRNA-seq) allow researchers to explore cellular heterogeneity and human diseases at cell resolution. Cell clustering is a prerequisite in scRNA-seq analysis since it can recognize cell identities. However, the high dimensionality, noises and significant sparsity of scRNA-seq data have made it a big challenge. Although many methods have emerged, they still fail to fully explore the intrinsic properties of cells and the relationship among cells, which seriously affects the downstream clustering performance. Here, we propose a new deep contrastive clustering algorithm called scDCCA. It integrates a denoising auto-encoder and a dual contrastive learning module into a deep clustering framework to extract valuable features and realize cell clustering. Specifically, to better characterize and learn data representations robustly, scDCCA utilizes a denoising Zero-Inflated Negative Binomial model-based auto-encoder to extract low-dimensional features. Meanwhile, scDCCA incorporates a dual contrastive learning module to capture the pairwise proximity of cells. By increasing the similarities between positive pairs and the differences between negative ones, the contrasts at both the instance and the cluster level help the model learn more discriminative features and achieve better cell segregation. Furthermore, scDCCA joins feature learning with clustering, which realizes representation learning and cell clustering in an end-to-end manner. Experimental results of 14 real datasets validate that scDCCA outperforms eight state-of-the-art methods in terms of accuracy, generalizability, scalability and efficiency. Cell visualization and biological analysis demonstrate that scDCCA significantly improves clustering and facilitates downstream analysis for scRNA-seq data. The code is available at https://github.com/WJ319/scDCCA.
Capturing variation in metagenomic assembly graphs with MetaCortex
Authors: Martin Samuel , Ayling Martin , Patrono Livia , Caccamo Mario , Murcia Pablo , Leggett Richard M 
Published: January 2023

Abstract

Motivation
The assembly of contiguous sequence from metagenomic samples presents a particular challenge, due to the presence of multiple species, often closely related, at varying levels of abundance. Capturing diversity within species, for example, viral haplotypes, or bacterial strain-level diversity, is even more challenging.

Results
We present MetaCortex, a metagenome assembler that captures intra-species diversity by searching for signatures of local variation along assembled sequences in the underlying assembly graph and outputting these sequences in sequence graph format. We show that MetaCortex produces accurate assemblies with higher genome coverage and contiguity than other popular metagenomic assemblers on mock viral communities with high levels of strain-level diversity and on simulated communities containing simulated strains.

Availability and implementation
Source code is freely available to download from https://github.com/SR-Martin/metacortex, is implemented in C and supported on MacOS and Linux. The version used for the results presented in this article is available at doi.org/10.5281/zenodo.7273627.

Supplementary information
Supplementary data are available at Bioinformatics online.
CAMR: cross-aligned multimodal representation learning for cancer survival prediction
Authors: Wu Xingqi , Shi Yi , Wang Minghui , Li Ao 
Published: January 2023

Abstract

Motivation
Accurately predicting cancer survival is crucial for helping clinicians to plan appropriate treatments, which largely improves the life quality of cancer patients and spares the related medical costs. Recent advances in survival prediction methods suggest that integrating complementary information from different modalities, e.g. histopathological images and genomic data, plays a key role in enhancing predictive performance. Despite promising results obtained by existing multimodal methods, the disparate and heterogeneous characteristics of multimodal data cause the so-called modality gap problem, which brings in dramatically diverse modality representations in feature space. Consequently, detrimental modality gaps make it difficult for comprehensive integration of multimodal information via representation learning and therefore pose a great challenge to further improvements of cancer survival prediction.

Results
To solve the above problems, we propose a novel method called cross-aligned multimodal representation learning (CAMR), which generates both modality-invariant and -specific representations for more accurate cancer survival prediction. Specifically, a cross-modality representation alignment learning network is introduced to reduce modality gaps by effectively learning modality-invariant representations in a common subspace, which is achieved by aligning the distributions of different modality representations through adversarial training. Besides, we adopt a cross-modality fusion module to fuse modality-invariant representations into a unified cross-modality representation for each patient. Meanwhile, CAMR learns modality-specific representations which complement modality-invariant representations and therefore provides a holistic view of the multimodal data for cancer survival prediction. Comprehensive experiment results demonstrate that CAMR can successfully narrow modality gaps and consistently yields better performance than other survival prediction methods using multimodal data.

Availability and implementation
CAMR is freely available at https://github.com/wxq-ustc/CAMR.

Supplementary information
Supplementary data are available at Bioinformatics online.
Estimation of high-dimensional vector autoregression via sparse precision matrix
Authors: Poignard Benjamin , Asai Manabu 
Published: January 2023

SummaryWe consider the problem of estimating sparse vector autoregression (VAR) via penalized precision matrices. This matrix is the output of the underlying directed acyclic graph of the VAR process, whose zero components correspond to the zero coefficients of the graphical representation of the VAR. The sparsity-based precision matrix estimator is deduced from the D-trace loss with convex and nonconvex penalty functions. We establish the consistency of the penalized estimator and provide the conditions for which all true zero entries of the precision matrix are actually estimated as zero with probability tending to one. The relevance of the method is supported by simulated experiments and a real data application.
ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis
Authors: Lee Grace , Chikwe Joanna , Milojevic Milan , Wijeysundera Harindra C , Biondi-Zoccai Giuseppe , Flather Marcus , Gaudino Mario F L , Fremes Stephen E , Tam Derrick Y 
Published: January 2023

AbstractAortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria.
Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality
Authors: Wadström Benjamin N , Pedersen Kasper M , Wulff Anders B , Nordestgaard Børge G 
Published: January 2023

Abstract

Aims
Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. The association with cause-specific mortality is, however, unclear. The aim of this study was to test the hypothesis that elevated remnant cholesterol and plasma triglycerides are associated with increased mortality from cardiovascular disease, cancer, and other causes.

Methods and results
Using a contemporary population-based cohort, 87 192 individuals from the Copenhagen General Population Study aged 20–69 years at baseline in 2003–2015 were included. During up to 13 years of follow-up, 687 individuals died from cardiovascular disease, 1594 from cancer, and 856 from other causes, according to the National Danish Causes of Death Registry. In individuals with remnant cholesterol ≥1.0 mmol/L (≥39 mg/dL; 22% of the population) compared with those with levels &lt;0.5 mmol/L (&lt;19 mg/dL), multivariable-adjusted mortality hazard ratios were 2.2 (95% confidence interval 1.3–3.5) for cardiovascular disease, 1.0 (0.7–1.3) for cancer, and 2.1 (1.4–3.3) for other causes. Exploratory analysis of the cause of death subcategories showed corresponding hazard ratios of 4.4 (1.6–11) for ischemic heart disease, 8.4 (2.0–34) for infectious diseases, and 9.1 (1.9–43) for endocrinological diseases. Results for plasma triglycerides &gt;2 vs. &lt;1 mmol/L (&gt;177 vs. &lt;89 mg/dL) were similar.

Conclusion
Remnant cholesterol of ≥1 mmol/L (39 mg/dL), present in 22% of the population, and plasma triglycerides of ≥2 mmol/L (177 mg/dL), present in 28% of the population, were associated with two-fold mortality from cardiovascular and other causes, but not from cancer. This novel finding should be confirmed in other cohorts.
Audit and feedback interventions involving pharmacists to influence prescribing behaviour in general practice: a systematic review and meta-analysis
Authors: Carter Mary , Abutheraa Nouf , Ivers Noah , Grimshaw Jeremy , Chapman Sarah , Rogers Philip , Simeoni Michelle , Antony Jesmin , Watson Margaret C 
Published: January 2023

Abstract

Introduction
Pharmacists, as experts in medicines, are increasingly employed in general practices and undertake a range of responsibilities. Audit and feedback (A&F) interventions are effective in achieving behaviour change, including prescribing. The extent of pharmacist involvement in A&F interventions to influence prescribing is unknown. This review aimed to assess the effectiveness of A&F interventions involving pharmacists on prescribing in general practice compared with no A&F/usual care and to describe features of A&F interventions and pharmacist characteristics.

Methods
Electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, (Social) Science Citation Indexes, ISI Web of Science) were searched (2012, 2019, 2020). Cochrane systematic review methods were applied to trial identification, selection, and risk of bias. Results were summarized descriptively and heterogeneity was assessed. A random-effects meta-analysis was conducted where studies were sufficiently homogenous in design and outcome.

Results
Eleven cluster-randomized studies from 9 countries were included. Risk of bias across most domains was low. Interventions focussed on older patients, specific clinical area(s), or specific medications. Meta-analysis of 6 studies showed improved prescribing outcomes (pooled risk ratio: 0.78, 95% confidence interval: 0.64–0.94). Interventions including both verbal and written feedback or computerized decision support for prescribers were more effective. Pharmacists who received study-specific training, provided ongoing support to prescribers or reviewed prescribing for individual patients, contributed to more effective interventions.

Conclusions
A&F interventions involving pharmacists can lead to small improvements in evidence-based prescribing in general practice settings. Future implementation of A&F within general practice should compare different ways of involving pharmacists to determine how to optimize effectiveness.
PRISMA-compliant abstract included in Supplementary Material 1.
The synthesis, biological activities and applications of protein–polysaccharide conjugates in food system: a review
Authors: Zhang Shixuan , Wang Kai , Qin Yongtao , Zhu Shunyi , Gao Qikuan , Liu Diru 
Published: January 2023

AbstractProteins are important ingredients in the food industry for their excellent nutritional, functional and biological properties, while the application is limited by their sensitivity to environmental stresses such as high temperature, pH changes and ionic strength. The Maillard reaction and transglutaminase-catalyzed glycosylation are the two main effective glycosylation ways to improve the stability and biological properties of proteins by mainly attaching monosaccharides or disaccharides to proteins, while protein–polysaccharide conjugates with superior functional properties are rarely discussed. Therefore, the present study reviews current state of the synthesis, biological activities and applications in the food system of protein–polysaccharide conjugates formed via the Maillard reaction and transglutaminase-catalyzed glycosylation. The biological activities including antioxidant, antimicrobial and immunomodulatory activities of proteins are improved after glycosylation, and the formed protein–polysaccharide conjugates can be applied to stabilize emulsions or deliver bioactive compounds in foods. The bioactivities produced under precisely controlled glycosylation conditions would make protein–polysaccharide conjugates a promising application in foods with healthy properties.
Metagenomics Shines Light on the Evolution of “Sunscreen” Pigment Metabolism in theTeloschistales(Lichen-Forming Ascomycota)
Authors: Llewellyn Theo , Nowell Reuben W , Aptroot Andre , Temina Marina , Prescott Thomas A K , Barraclough Timothy G , Gaya Ester 
Published: January 2023

AbstractFungi produce a vast number of secondary metabolites that shape their interactions with other organisms and the environment. Characterizing the genes underpinning metabolite synthesis is therefore key to understanding fungal evolution and adaptation. Lichenized fungi represent almost one-third of Ascomycota diversity and boast impressive secondary metabolites repertoires. However, most lichen biosynthetic genes have not been linked to their metabolite products. Here we used metagenomic sequencing to survey gene families associated with production of anthraquinones, UV-protectant secondary metabolites present in various fungi, but especially abundant in a diverse order of lichens, the Teloschistales (class Lecanoromycetes, phylum Ascomycota). We successfully assembled 24 new, high-quality lichenized-fungal genomes de novo and combined them with publicly available Lecanoromycetes genomes from taxa with diverse secondary chemistry to produce a whole-genome tree. Secondary metabolite biosynthetic gene cluster (BGC) analysis showed that whilst lichen BGCs are numerous and highly dissimilar, core enzyme genes are generally conserved across taxa. This suggests metabolite diversification occurs via re-shuffling existing enzyme genes with novel accessory genes rather than BGC gains/losses or de novo gene evolution. We identified putative anthraquinone BGCs in our lichen dataset that appear homologous to anthraquinone clusters from non-lichenized fungi, suggesting these genes were present in the common ancestor of the subphylum Pezizomycotina. Finally, we identified unique transporter genes in Teloschistales anthraquinone BGCs that may explain why these metabolites are so abundant and ubiquitous in these lichens. Our results support the importance of metagenomics for understanding the secondary metabolism of non-model fungi such as lichens.
Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a US cohort
Authors: Jones Rena R , Fisher Jared A , Medgyesi Danielle N , Buller Ian D , Liao Linda M , Gierach Gretchen , Ward Mary H , Silverman Debra T 
Published: January 2023

AbstractBackgroundEthylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers.MethodsUsing the US Environmental Protection Agency’s Toxics Release Inventory, we estimated historical exposures for National Institutes of Health–AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction–adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945).ResultsWe observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs&gt;10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs&gt;10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs&gt;10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk.ConclusionsA novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.
Paul Hirst, liberal education and the postcolonial project
Authors: Daniels Stephen , Enslin Penny 
Published: January 2023

Abstract
Paul Hirst’s defence of liberal education and his forms of knowledge thesis are likely to seem out of step with contemporary calls to decolonize knowledge by ‘delinking’ it from ‘Western’ Enlightenment traditions. In view of the decolonial challenge, and emphasizing too that Hirst’s work should be located in its time, we consider the extent to which his account of liberal education still has a place in the postcolonial era. We outline Hirst’s defence of liberal education and how it changed over time, and show how philosophy of education in the tradition in which he has been so influential departed from Hirst’s account of liberal education, with some of these trends anticipating postcolonial imperatives. While there is a pressing need for attention to the significance of colonialism in philosophy of education, the discipline has moved on and diversified considerably over the last half century, including by developing more expansive conceptions of liberal education with the potential to contribute to the postcolonial project. Some elements of Hirst’s defence of liberal education are compatible with the postcolonial project, but it would need adjustment to make it relevant to the postcolonial era. After addressing the postcolonial critique of liberal thought in general as complicit in colonialism, we conclude by assessing what contribution Hirst’s conception of liberal education could make to the postcolonial project, noting a degree of openness to aspects of the decolonial project.
Effect of curcumin on γ–ray-induced cell response
Authors: Kostova Nora , Staynova Albena , Popova-Hadjiiska Ljubomira , Georgieva Dimka , Ivanova Ilonka , Aneva Nevena , Atanasova Margarita , Hristova Rositsa 
Published: January 2023

AbstractThe purpose of the present study is to evaluate the effect of curcumin as a natural compound against radiation induced γ-foci and stable chromosome aberrations. Whole blood samples form three human volunteers were pretreated with curcumin at different concentrations (0.5, 10, 20 and 100 μg/ml). After 1-hour incubation, the lymphocytes were exposed to γ-rays (0.05, 0.5, 1 and 2 Gy). Radiation induced changes in cells were quantified using γ-H2AX/53BP1 assay and FISH analysis. Our results have shown that curcumin significantly reduced the frequency of both γ-foci and translocations. We found concentration-dependent increase of curcumin protective effect on γ-H2AX/53BP1 foci formation at all radiation doses. Concerning the translocations, after 0.05 and 0.5 Gy γ-rays the values of genomic frequencies are comparable within each dose and we did not observe any impact of curcumin. The most protective effect after 1 Gy exposure was found at 100 μg/ml curcumin. At 2 Gy irradiation, the maximum protection was achieved at 0.5 and 10 μg/ml of curcumin. Concentrations of 20 and 100 μg/ml also prevent lymphocytes but to less extent. Our in vitro study indicates radioprotective efficacy of curcumin against γ-ray induced damages in human lymphocytes. This observation suggests that curcumin may play a role to protect patients undergoing radiological procedures.