bluuebunny/crossref_metadata_2025_split huggingface dataset:
An analysis of protein language model embeddings for fold prediction
Authors: Villegas-Morcillo Amelia , Gomez Angel M , Sanchez Victoria 
Published: March 2022

AbstractThe identification of the protein fold class is a challenging problem in structural biology. Recent computational methods for fold prediction leverage deep learning techniques to extract protein fold-representative embeddings mainly using evolutionary information in the form of multiple sequence alignment (MSA) as input source. In contrast, protein language models (LM) have reshaped the field thanks to their ability to learn efficient protein representations (protein-LM embeddings) from purely sequential information in a self-supervised manner. In this paper, we analyze a framework for protein fold prediction using pre-trained protein-LM embeddings as input to several fine-tuning neural network models, which are supervisedly trained with fold labels. In particular, we compare the performance of six protein-LM embeddings: the long short-term memory-based UniRep and SeqVec, and the transformer-based ESM-1b, ESM-MSA, ProtBERT and ProtT5; as well as three neural networks: Multi-Layer Perceptron, ResCNN-BGRU (RBG) and Light-Attention (LAT). We separately evaluated the pairwise fold recognition (PFR) and direct fold classification (DFC) tasks on well-known benchmark datasets. The results indicate that the combination of transformer-based embeddings, particularly those obtained at amino acid level, with the RBG and LAT fine-tuning models performs remarkably well in both tasks. To further increase prediction accuracy, we propose several ensemble strategies for PFR and DFC, which provide a significant performance boost over the current state-of-the-art results. All this suggests that moving from traditional protein representations to protein-LM embeddings is a very promising approach to protein fold-related tasks.
Improving confidence in lipidomic annotations by incorporating empirical ion mobility regression analysis and chemical class prediction
Authors: Rose Bailey S , May Jody C , Picache Jaqueline A , Codreanu Simona G , Sherrod Stacy D , McLean John A 
Published: March 2022

Abstract

Motivation
Mass spectrometry-based untargeted lipidomics aims to globally characterize the lipids and lipid-like molecules in biological systems. Ion mobility increases coverage and confidence by offering an additional dimension of separation and a highly reproducible metric for feature annotation, the collision cross-section (CCS).

Results
We present a data processing workflow to increase confidence in molecular class annotations based on CCS values. This approach uses class-specific regression models built from a standardized CCS repository (the Unified CCS Compendium) in a parallel scheme that combines a new annotation filtering approach with a machine learning class prediction strategy. In a proof-of-concept study using murine brain lipid extracts, 883 lipids were assigned higher confidence identifications using the filtering approach, which reduced the tentative candidate lists by over 50% on average. An additional 192 unannotated compounds were assigned a predicted chemical class.

Availability and implementation
All relevant source code is available at https://github.com/McLeanResearchGroup/CCS-filter.

Supplementary information
Supplementary data are available at Bioinformatics online.
Chemerin effect on transcriptome of the porcine endometrium during implantation determined by RNA-sequencing
Authors: Orzechowska Kinga , Kopij Grzegorz , Paukszto Lukasz , Dobrzyn Kamil , Kiezun Marta , Jastrzebski Jan , Kaminski Tadeusz , Smolinska Nina 
Published: March 2022

Abstract
It is well known that the body’s metabolism and reproduction are closely related. Chemerin (CHEM) is one of many biologically active proteins secreted by the adipose tissue involved in the regulation of the energy homeostasis of the organism. In the present study, RNA-sequencing was performed to investigate the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and alternatively spliced (AS) transcripts in the cultured porcine endometrium exposed to chemerin for 24 hours (CHEM; 400 ng/mL) collected during the implantation period (15–16 days of gestation). High-throughput sequencing of transcriptomes was performed on the Illumina NovaSeq 6000 platform (Illumina, USA). In the current study, among all 130 DEGs, 58 were upregulated and 72 were downregulated in the CHEM-treated group. DEGs were assigned to 73 functional annotations. Twelve identified lncRNAs indicated a difference in the expression profile after CHEM administration. Additionally, we detected 386 differentially AS events encompassed 274 protein-coding genes and 2 lncRNAs. All AS events were divided into five alternative splicing types: alternative 3′ splice site (A3SS), 5′ splice site (A5SS), mutually exclusive exons (MXE), retention intron (RI), and skipping exon (SE). Within all AS events, we identified 42 A3SS, 43 A5SS, 53 MXE, 9 RI, and 239 SE. In summary, CHEM affects the transcriptomic profile of the porcine endometrium, controlling the expression of numerous genes, including those involved in the cell migration and adhesion, angiogenesis, inflammation, and steroidogenesis. It can be assumed that CHEM may be an important factor for a proper course of gestation and embryo development.
Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait
Authors: Yin Zixiao , Zhu Guanyu , Liu Yuye , Zhao Baotian , Liu Defeng , Bai Yutong , Zhang Quan , Shi Lin , Feng Tao , Yang Anchao , Liu Huanguang , Meng Fangang , Neumann Wolf Julian , Kühn Andrea A , Jiang Yin , Zhang Jianguo 
Published: March 2022

Abstract
Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson’s disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait.
Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson’s disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking.
We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials.
These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel ‘bandwidth model,’ which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.
Mechanisms of induction of regulatory B cells in the tumour microenvironment and their contribution to immunosuppression and pro-tumour responses
Authors: Flores-Borja Fabian , Blair Paul 
Published: March 2022

Abstract
The presence of tumour-infiltrating immune cells was originally associated with the induction of anti-tumour responses and good a prognosis. A more refined characterization of the tumour microenvironment has challenged this original idea and evidence now exists pointing to a critical role for immune cells in the modulation of anti-tumour responses and the induction of a tolerant pro-tumour environment. The coordinated action of diverse immunosuppressive populations, both innate and adaptive, shapes a variety of pro-tumour responses leading to tumour progression and metastasis. Regulatory B cells have emerged as critical modulators and suppressors of anti-tumour responses. As reported in autoimmunity and infection studies, Bregs are a heterogeneous population with diverse phenotypes and different mechanisms of action. Here we review recent studies on Bregs from animal models and patients, covering a variety of types of cancer. We describe the heterogeneity of Bregs, the cellular interactions they make with other immune cells and the tumour itself, and their mechanism of suppression that enables tumour escape. We also discuss the potential therapeutic tools that may inhibit Bregs function and promote anti-tumour responses.
Surgical treatment of tricuspid valve regurgitation in patients with cardiac implantable electronic devices: long-term results
Authors: Carino Davide , Sala Alessandra , Zancanaro Edoardo , Ruggeri Stefania , Lapenna Elisabetta , Del Forno Benedetto , Verzini Alessandro , Schiavi Davide , Castiglioni Alessandro , Alfieri Ottavio , Maisano Francesco , De Bonis Michele 
Published: March 2022

Abstract

OBJECTIVES
With the expanding use of cardiac implantable electronic devices (CIEDs), lead interference with the tricuspid valve (TV) causing significant tricuspid regurgitation (TR) has gained increasing recognition. However, current knowledge about the long-term results of the surgical treatment of TR in this setting is scanty. Therefore, increasing this information was the goal of this study.

METHODS
A retrospective review of our institutional database was carried out to select all patients with previously implanted CIEDs who underwent tricuspid valve repair and replacement from 2000 through 2019. Kaplan–Meier methods were used to analyse long-term survival. To describe the time course of TR, we performed a longitudinal analysis using generalized estimating equations.

RESULTS
A total of 151 patients were identified. Mechanical interference with leaflet mobility and coaptation was detected in 103 patients (68%) (CIED-induced group); in the remaining 48 patients (32%), the lead was associated with TR without being the cause of it (CIED-associated group). A total of 105 patients underwent TV repair; in the remaining 46, a TV replacement was necessary. In patients who underwent TV repair, no significant difference in moderate TR recurrence rate was highlighted between CIED-induced and CIED-associated TR.

CONCLUSIONS
In patients with CIEDs and surgically treated tricuspid regurgitation, TR is CIED-induced in about two-thirds of the cases and CIED-associated in one-third of them. In our experience, TV repair was still possible in 63% of the cases, with good long-term results and no significant durability difference between CIED-induced and CIED-associated TR.
Can Clarity of an Amended Patent Claim Be Challenged Before the UPC (?)
Authors: Hüttermann Aloys 
Published: March 2022

Abstract
This paper assesses whether the clarity of a claim after amendments have been made to it can be challenged in a nullity suit or counterclaim for revocation before the Unified Patent Court (UPC). It argues that, given the uncertainties of Rule 30 of the UPC’s Rules of Procedure, it will be up to the Appeal Court to decide on this matter.
Evaluation of the Vitek Ms system for the identification of filamentous fungi
Authors: Zvezdánova Margarita Estreya , Escribano Pilar , Guinea Jesús , Muñoz Patricia , Rodríguez-Temporal David , Rodríguez-Sánchez Belén 
Published: March 2022

Abstract

The implementation of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of fungal isolates remains challenging and has been limited to experienced laboratories in sample preparation and in-house libraries construction. However, the development of commercial kits for standardized fungal sample preparation and updated reference libraries can fill this gap. This study aimed to evaluate the performance of the commercial VITEK MS Mould Kit (bioMérieux, Marcy l'Etoile, France) and the VITEK MS system (bioMérieux) for identification using a panel of fungal species of clinical interest. Overall, 200 isolates belonging to 13 genera and 43 fungal species were analyzed with the VITEK MS system equipped with the v3.2 IVD database. Overall, 89.0% of the isolates were correctly identified, 41.5 and 43.5% at species and complex level, respectively. For an additional 4.0% of the identifications, correlation at the genus level was reported. The remaining 21 isolates (10.5%) could not be identified among which 85.0% (18/21) were species not claimed in the database. One Syncephalastrum isolate was misidentified as Rhizopus microsporus complex. Specifically, 100% of the Scedosporium/Lomentospora, 97.1% of the Fusarium, 65.7% of the Mucorales and 86.4% of the Aspergillus isolates were correctly identified at the species and complex level. The methodology described allows for an easy implementation of MALDI-TOF MS for routine identification of fungal species in a fast and reliable manner. Although further improvement in the databases is still required, an important number of fungal species can be correctly identified at the species level using this method.

Lay summary
The use of MALDI-TOF for fungal identification remains a challenge. In this study, using a commercial protein extraction kit and updated database, VITEK MS system was able to identify up to 89.0% of a diverse collection of 200 filamentous fungi representing 43 fungal species.
Identifying gravitational wave emission signature in electromagnetic observations of short gamma-ray bursts
Authors: Xie Lang , Wei Da-Ming , Wang Yun , Li Long , Jin Zhi-Ping 
Published: March 2022

ABSTRACT
Observations of the long-lived X-ray plateau in short gamma-ray burst (SGRB) afterglow suggest that a portion of binary neutron star mergers would leave behind a rapidly spinning, strongly magnetized neutron star (millisecond magnetar). The new-born magnetar may undergo large deformation due to magnetic distortion or unstable oscillation, which would emit the extended gravitational wave (GW) associated with the SGRB X-ray plateau. In this work, we focus on the spin-down luminosity evolution of magnetar by considering the spin energy loss due to the GW and magnetic dipole radiation, and systematically analyse the SGRB light curves of our magnetar sample. The results show that GW emission signatures have existed in the spin-down stage of GRB 090426 and GRB 150424A. We also present constraints on the ellipticity of the new-born magnetar as ε &lt; 1.58 × 10−3(B/1015 G)(P/1 ms). The magnetar can lose significant spin energy via GW radiation if the ellipticity ε ≥ 10−3 and magnetic field strength B ∼ 1015 G. In addition, we derive the evolution of GW strain for magnetars through their spin-down processes. This result shows that the GW signals from these magnetars may be detectable for the Einstein Telescope (ET). For a rapidly spinning magnetar (P ∼ 1 ms), the detection horizons for aLIGO O3, aLIGO O5, and ET detectors are ∼60, ∼210, and ∼900 Mpc, respectively. The detection of the GW emission from new-born millisecond magnetar may reveal the interior composition of magnetar in the near future.
Impact of Janus kinase inhibitors on antibody response to 13-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis
Authors: Mori Shunsuke , Ueki Yukitaka , Ishiwada Naruhiko 
Published: March 2022

ABSTRACTObjectivesTo evaluate the antibody response to 13-valent pneumococcal conjugate vaccine (PCV13) in patients with rheumatoid arthritis receiving Janus kinase inhibitors (JAKIs).MethodsFifty-three patients receiving methotrexate (MTX; n = 10), JAKI (n = 20), or MTX + JAKI (n = 23) were vaccinated with PCV13. Serum concentrations of immunoglobulin G (IgG) antibodies to 13 pneumococcal serotype capsular polysaccharides were quantified before and 4–6 weeks after vaccination. Positive antibody response was defined as a 2-fold or more increase in IgG concentrations from prevaccination levels.ResultsAfter vaccination, IgG concentrations significantly increased in all treatment groups (P &lt;0.001), but fold increases (postvaccination to prevaccination ratios) were different among treatment groups (9.30 for MTX, 6.36 for JAKI, and 3.46 for combination therapy). Positive antibody response rates were comparable between the MTX group (90%) and the JAKI group (95%) but lower in the MTX + JAKI group (52.2%). In a multivariable logistic regression analysis, the combination therapy was the only factor associated with a reduced antibody response to PCV13. No severe adverse events were observed in any treatment group.ConclusionAlthough JAKIs do not impair PCV13 immunogenicity in rheumatoid arthritis patients, the combination of MTX with JAKI can reduce the antibody response in this patient population.
Psoralen mapping reveals a bacterial genome supercoiling landscape dominated by transcription
Authors: Visser Bryan J , Sharma Sonum , Chen Po J , McMullin Anna B , Bates Maia L , Bates David 
Published: March 2022

Abstract
DNA supercoiling is a key regulator of all DNA metabolic processes including replication, transcription, and recombination, yet a reliable genomic assay for supercoiling is lacking. Here, we present a robust and flexible method (Psora-seq) to measure whole-genome supercoiling at high resolution. Using this tool in Escherichia coli, we observe a supercoiling landscape that is well correlated to transcription. Supercoiling twin-domains generated by RNA polymerase complexes span 25 kb in each direction – an order of magnitude farther than previous measurements in any organism. Thus, ribosomal and many other highly expressed genes strongly affect the topology of about 40 neighboring genes each, creating highly integrated gene circuits. Genomic patterns of supercoiling revealed by Psora-seq could be aptly predicted from modeling based on gene expression levels alone, indicating that transcription is the major determinant of chromosome supercoiling. Large-scale supercoiling patterns were highly symmetrical between left and right chromosome arms (replichores), indicating that DNA replication also strongly influences supercoiling. Skew in the axis of symmetry from the natural ori-ter axis supports previous indications that the rightward replication fork is delayed several minutes after initiation. Implications of supercoiling on DNA replication and chromosome domain structure are discussed.
Visualization of ligand-induced c-MYC duplex–quadruplex transition and direct exploration of the altered c-MYC DNA-protein interactions in cells
Authors: Yuan Jia-Hao , Tu Jia-Li , Liu Guo-Cai , Chen Xiu-Cai , Huang Zhi-Shu , Chen Shuo-Bin , Tan Jia-Heng 
Published: March 2022

Abstract
Ligand-Induced duplex-quadruplex transition within the c-MYC promoter region is one of the most studied and advanced ideas for c-MYC regulation. Despite its importance, there is a lack of methods for monitoring such process in cells, hindering a better understanding of the essence of c-MYC G-quadruplex as a drug target. Here we developed a new fluorescent probe ISCH-MYC for specific c-MYC G-quadruplex recognition based on GTFH (G-quadruplex-Triggered Fluorogenic Hybridization) strategy. We validated that ISCH-MYC displayed distinct fluorescence enhancement upon binding to c-MYC G-quadruplex, which allowed the duplex-quadruplex transition detection of c-MYC G-rich DNA in cells. Using ISCH-MYC, we successfully characterized the induction of duplex to G-quadruplex transition in the presence of G-quadruplex stabilizing ligand PDS and further monitored and evaluated the altered interactions of relevant transcription factors Sp1 and CNBP with c-MYC G-rich DNA. Thus, our study provides a visualization strategy to explore the mechanism of G-quadruplex stabilizing ligand action on c-MYC G-rich DNA and relevant proteins, thereby empowering future drug discovery efforts targeting G-quadruplexes.
E-Cigarette Provision to Promote Switching in Cigarette Smokers With Serious Mental Illness—A Randomized Trial
Authors: Pratt Sarah I , Ferron Joelle C , Brunette Mary F , Santos Meghan , Sargent James , Xie Haiyi 
Published: March 2022

Abstract

Background
High cigarette smoking prevalence and low quit rates in people with serious mental illness (SMI) contribute to disparate rates of chronic disease and premature death. This prospective trial tested the impact of switching to a potentially lower-harm nicotine-containing product on smoking in this population.

Aims and Methods
A total of 240 cigarette smokers with SMI who tried but were currently unwilling to quit were randomly assigned to receive disposable e-cigarettes for 8 weeks or not, with assessments at baseline, 2, 4, 6, 8, 13, and 26 weeks. Generalized linear mixed models examined the effects of e-cigarette provision on e-cigarette appeal, cigarettes per day (CPD), breath carbon monoxide (CO), nicotine dependence, and side effects. Clinical Trial registration: NCT03050853.

Results
Self-reported smoking was similar between groups at baseline (mean = 18.7 CPD). By week 2, 79% of the e-cigarette group were using e-cigarettes daily. During weeks 2–8, CPD and CO decreased in the e-cigarette versus assessment-only group (eg, 7.5 CPD [95% CI = 5.9, 9.2] vs. 18.1 CPD [CI = 16.4, 19.8] and 16.4 ppm [CI = 13.4, 19.5] vs. 25.4 ppm [CI = 22.4, 28.9], respectively, at week 2). Additionally, 19%–22% in the e-cigarette group reported smoking no cigarettes in weeks 2–8 compared to 0% in the assessment-only group. By 13 and 26 weeks, group differences in CPD, but not CO, remained significant. Nicotine dependence did not increase and side effects were minor.

Conclusions
Providing e-cigarettes for 8 weeks to smokers with SMI resulted in substantial reductions in CPD and CO. Enhancing and maintaining switching from cigarettes to e-cigarettes warrant further study.

Implications
This was the first prospective study to compare e-cigarette provision with assessments only to evaluate the appeal and impact of e-cigarettes on smoking behavior, carbon monoxide exposure, and nicotine dependence among smokers with SMI who had tried but were unable to quit and were not currently interested in cessation treatment. The finding that e-cigarette provision led to significant reductions in smoking and carbon monoxide without increasing nicotine dependence has implications for reducing harm not only among the millions of smokers with SMI who struggle to quit, but also for other vulnerable smokers who cannot achieve cessation.