bluuebunny/crossref_metadata_2025_split huggingface dataset:
SeqWho: Reliable, rapid determination of sequence file identity usingk-mer frequencies
Authors: Bennett Christopher , Thornton Micah , Park Chanhee , Henry Gervaise , Zhang Yun , Malladi Venkat S. , Kim Daehwan 
Published: March 2021

AbstractWith the vast improvements in sequencing technologies and increased number of protocols, sequencing is finding more applications to answer complex biological problems. Thus, the amount of publicly available sequencing data has tremendously increased in repositories such as SRA, EGA, and ENCODE. With any large online database, there is a critical need to accurately document study metadata, such as the source protocol and organism. In some cases, this metadata may not be systematically verified by the hosting sites and may result in a negative influence on future studies. Here we present SeqWho, a program designed to heuristically assess the quality of sequencing files and reliably classify the organism and protocol type. This is done in an alignment-free algorithm that leverages a Random Forest classifier to learn from native biases ink-mer frequencies and repeat sequence identities between different sequencing technologies and species. Here, we show that our method can accurately and rapidly distinguish between human and mouse, nine different sequencing technologies, and both together, 98.32%, 97.86%, and 96.38% of the time in high confidence calls respectively. This demonstrates that SeqWho is a powerful method for reliably checking the identity of the sequencing files used in any pipeline and illustrates the program’s ability to leveragek-mer biases.
Single-cell transcriptome reveals a testis-specific expression profile ofTCEAin human spermatogenesis
Authors: Pankaew S. , Pramoj Na Ayutthaya P. 
Published: March 2021

AbstractTranscription elongation factor A (TCEA) is a eukaryotic transcriptional molecule, required for a formation of initiation and elongation of gene transcription-mediated RNA polymerase II (RNAPII) complex, to promote transcription-coupled nucleotide excision repair (TC-NER) after RNAPII backtracking recovery.TCEAshares three isoforms in whichTCEA1is ubiquitously expressed among all eukaryotic cells. We found a spermatogenesisTCEA1andTCEA2expression profile has a unique transcriptional programme, compared with embryogenesis. Moreover, the testis-specificTCEA2profile correlates with gene transcription, whereasTCEA1specifically correlates with genes transcribed for Nuclear excision repair (NER) during human spermatogenesis. We also found that the expression activation ofRNF20, aTCEA1inhibitor, leads to expressionalTCEA1reduction, but having no direct impact onTCEA2expression, implying the potentialRNF20-dependent transcriptional switching ofTCEA2in transcriptional regulation during spermatogenesis. Our analysis defined a transcriptional bursting event where transcription-coupled repair (both Base excision repair and Nuclear excision repair) is a major pathway highly expressed in early spermatogenesis, supporting the transcriptional scanning hypothesis of which mutation of transcribed genes is effectively repaired as proposed by Xia B., et al. (2020).
Forced swim stress dynamically alters neural activity and bi-directionally modulates NMDA receptors in the prefrontal cortex
Authors: Parent Marc-Alexander L.T. , Lockridge Amber , Yuan Li-Lian 
Published: March 2021

AbstractRepeated exposure to stress results in progressively divergent effects on cognitive behaviors that are dependent on the integrity of networks in the medial prefrontal cortex (mPFC). To investigate molecular mechanisms responsive to variable repetition of mild stress, we measured persistent neural activity,in vitro, from mPFC slices in mice that had been repetitively exposed to 10 minutes of forced swim stress for 3-10 days. 3-day short-term stress facilitated persistent neural activity by increasing event duration while 10 days suppressed event duration and amplitude. These dynamic changes were accompanied by a similar bi-directional modulation of the NMDA/AMPA receptor current ratio, an important synaptic mechanism for sustaining the persistency of neural activity. Specifically, short-term stress led to potentiated NMDA currents with slower decay kinetics, and extended stress produced smaller currents with faster decay. The inhibitory action of ifenprodil, a specific blocker of NR2B-containing NMDA receptors, was more effective in NMDA current suppression following light stress and less effective after longer stress compared to naive controls. Persistent activity and glutamate receptor balance in the neocortex have been linked to working memory and impulse control. Therefore, these results could provide insight for generating therapeutic strategies to prevent or reverse stress-induced cognitive deficits.
Normalization and De-noising of Single-cell Hi-C Data with BandNorm and 3DVI
Authors: Zheng Ye , Shen Siqi , Keleş Sündüz 
Published: March 2021

AbstractSingle-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling long-range genomic interactions at the single-cell resolution; however, data from these technologies are prone to technical noise and bias that, when unaccounted for, hinder downstream analysis. Here we developed a fast band normalization approach, BandNorm, and a deep generative modeling framework, 3DVI, to explicitly account for scHi-C specific technical biases. We present robust performances of BandNorm and 3DVI compared to existing state-of-the-art methods. BandNorm is effective in separating cell types, identification of interaction features, and recovery of cell-cell relationship, whereas de-noising by 3DVI successfully enables 3D compartments and domains recovery, especially for rare cell types.
Use of digital technology tools to examine patient adherence to a prescription omega-3 polyunsaturated acids therapy intended to mitigate cardiovascular risk: protocol and preliminary demographic data from the DIAPAsOn prospective observational study
Authors: Arutyunov Gregory P. , Arutyunov Alexander G. , Ageev Fail T. , Fofanova Tatiana V. 
Published: March 2021

AbstractSustained adherence and persistence with prescription medications is considered essential to achieve maximal treatment benefit for patients with major chronic non-communicable diseases such as hyperlipidemia and lipid-associated cardiovascular disease. It is widely documented, however, that a large percentage of patients with these conditions have poor longer-term compliance with their treatments. The population of Russia is affected by poor compliance in the same ways as populations elsewhere and continues to have high rates of cardiovascular disease.Hypertriglyceridemia is suspected of contributing to residual cardiovascular risk in patients whose low-density lipoprotein cholesterol (LDL-C) is well controlled. A preparation of highly purified omega-3 polyunsaturated fatty acids (EPA/DHA=1.2/1-90%, marketed as OMACOR), is indicated for the control of high triglyceride levels and also for secondary prevention of myocardial infarction (MI).DIAPAsON is a prospective observational program designed to evaluate the impact of digital technologies on patient compliance and adherence in a large sample of patients whose treatment scheme includes EPA/DHA=1.2/1-90%. A bespoke electronic data capture system has been developed for this purpose that enables information obtained during clinic visits to be supplemented by remote patient self-reporting. Other objectives of the program include raising patients’ awareness about their condition via educational materials available in patient personal accounts in the electronic system.This report outlines the rationale and methodology of DIAPAsOn and the primary demographics of the study population.
A novel whole-blood stimulation assay to detect and quantify memory T-cells in COVID-19 patients
Authors: Mouton William , Compagnon Christelle , Saker Kahina , Daniel Soizic , Lacoux Xavier , Pozzetto Bruno , Oriol Guy , Djebali Sophia , Berthier Franck , Marvel Jacqueline , Walzer Thierry , Brengel-Pesce Karen , Trouiller-Assant Sophie 
Published: March 2021

AbstractSARS-CoV-2 specific T-cells responses are essential for virus clearance. We present a novel and simple whole-blood assay allowing the detection of interferon-gamma-producing antiviral T-cells following peptide stimulation. We show that unlike neutralizing antibodies, antiviral memory T-cells persist at least 6 months in convalescent Covid-19 individuals.
Population based mean Vitamin D levels in 19 European Countries & COVID-19 Mortality
Authors: Ahmad Amar , Heumann Christian , Ali Raghib , Oliver Tim 
Published: March 2021

ABSTRACTObjectivesReports early in the epidemic linking low mean national Vitamin D level with increased COVID-19 death, and until recently little research on the impact of Vitamin D deficiency on severity of COVID-19, led to this update of the initial report studying mortality up to the end of January 2021.Design and SettingCoronavirus pandemic data for 19 European countries were downloaded from Our World in Data, which was last updated on January 24, 2021. Data from March 21, 2020 to January 22, 2021 were included in the statistical analysis. Vitamin-D (25)-HD mean data were collected by literature review. Poisson mixed-effect model was used to model the data.ResultsEuropean countries with Vitamin-D (25)-HD mean less than or equal to 50 have higher COVID-19 death rates as compared with European countries with Vitamin-D (25)-HD mean greater than 50, relative risk of 2.155 (95% CI: 1.068 – 4.347, p-value = 0.032). A statistically significant negative moderate Spearman rank correlation was observed between Vitamin-D (25)-HD mean and the number of COVID-19 deaths for each 14-day period during the COVID-19 pandemic time period.ConclusionsThe observation of the significantly lower COVID-19 mortality rates in countries with lowest annual sun exposure but highest mean Vitamin-D (25)-HD levels provides support for the use of food fortification. The need to consider re-configuring vaccine strategy due to emergence of large number of COVID-19 variants provides an opportunity to undertake such therapeutic randomized control trials.
Rationale and design of the Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) Trial and LIGHT-ACD Trial
Authors: Song Jiali , Wang Xiu-Ling , Wang Bin , Gao Yan , Liu Jia-Min , Zhang Hai-Bo , Li Xi , Li Jing , Wang Ji-Guang , Cai Jun , Herrin Jeph , Armitage Jane , Krumholz Harlan M. , Zheng Xin 
Published: March 2021

ABSTRACTBackgroundComputerized clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs testing in pragmatic trials.MethodsThe Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care practices in China. For each city-based stage, practices are randomly assigned to either implementation of the CDSS for hypertension management (which guides physicians treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided.In a separate sub-study conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual- antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the change in blood pressure from the first visit after site randomization to 9 months.DiscussionThe LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The sub-study, LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.Trial registrationClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.
Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers
Authors: Theocharidis Georgios , Thomas Beena E. , Sarkar Debasree , Pilcher William JR , Dwivedi Bhakti , Sandoval-Schaefer Teresa , Sîrbulescu Ruxandra F. , Kafanas Antonios , Mezghani Ikram , Wang Peng , Lobao Antonio , Vlachos Ioannis , Dash Biraja , Hsia Henry C. , Horsley Valerie , Bhasin Swati S. , Veves Aristidis , Bhasin Manoj 
Published: March 2021

AbstractTo understand the diabetic wound healing microenvironment, we profiled 174,962 single cells from foot, forearm, and PBMCs using single-cell RNA sequencing (scRNASeq) approach. Our analysis shows enrichment of a unique population of fibroblasts overexpressingMMP1, MMP3, MMP11, HIF1A, CHI3L1, andTNFAIP6genes and M1 macrophage polarization in the DFU patients with healing wounds. Further, scRNASeq of spatially separated samples from same patient and spatial transcriptomics (ST) revealed preferential localization of these healing associated fibroblasts toward deep wound/ulcer bed as compared to wound edge or non-wounded skin. ST also validated our findings of higher enrichment of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.
Behavioral read out of population value signals in primate orbitofrontal cortex
Authors: McGinty Vincent B. , Lupkin Shira M. 
Published: March 2021

ABSTRACTThe primate orbitofrontal cortex (OFC) has long been recognized for its role in value-based decisions; however, the exact mechanism linking OFC value representations to decision outcomes has remained elusive. To address this question we show for the first time that trial-wise variability in choices can be explained by variability in value signals decoded from many simultaneously recorded OFC neurons. Mechanistically, this relationship is consistent with the projection of activity within a low-dimensional value-encoding subspace onto a potentially higher-dimensional, behaviorally-potent output subspace.
Neural Correlates of Reactivation and Vividness Reveal Separable Contributions to Objective and Subjective Measures of Episodic Memory
Authors: Barker Ryan M. , St-Laurent Marie , Buchsbaum Bradley R. 
Published: March 2021

AbstractEpisodic recollections vary in fidelity, sharpness, and strength—qualities that can be examined using both introspective judgements of mental states and objective measures of brain activity. Subjective and objective measures are both valid ways of “reading out” the content of someone’s internal mnemonic states, each with different strengths and weaknesses. St-Laurent and colleagues (2015) investigated the neural correlates of memory vividness ratings and neural reactivation during memory recall and found considerable overlap, suggesting common neural basis underlying these different markers of successful recollection. Here we extended this work with a much more extensive examination in which we used meta-analytic methods to pool four neuroimaging datasets in order to compare and contrast the neural substrates of neural reactivation and vividness judgements. While reactivation and vividness judgements correlated positively with one another and were associated with common univariate activity in the dorsal attention network and anterior hippocampus, some differences were also observed. Vividness judgments were tied to stronger activation in the striatum and dorsal attention network, together with suppression of default mode network nodes, and we also observed a trend for reactivation to be more closely associated with early visual cortex activity. A mediation analysis found support for the hypothesis that neural reactivation is necessary for vivid recollection, with activity in the anterior hippocampus associated with greater reactivation. Our results suggest that neural reactivation and vividness judgements reflect common recollective processing but differ in the extent to which they engage effortful, attentional processing. Additionally, the similarity between reactivation and vividness appears to arise, partly, through hippocampal processing during recollection.
3D soft hydrogels induce human mesenchymal stem cells “deep” quiescence
Authors: Gomes David Boaventura , Henriques Lourenço Ana Filipa , Tomasina Clarissa , Chömpff Bryan , Liu Hong , Bouvy Nicole , Camarero-Espinosa Sandra , Moroni Lorenzo 
Published: March 2021

AbstractHuman mesenchymal stem/stromal cells (hMSCs) present a great opportunity for tissue regeneration due to their multipotent capacity. However, when cultured on 2D tissue culture polystyrene (TCPS) plates, hMSCs lose their differentiation capacity and clinical potential. It has been reported that cells need a more physiologically relevant micro-environment that allows them to maintain their phenotype. Here, we have developed a 3D alginate hydrogel functionalized with the Arg-Gly-Asp (RGD) sequence and having low mechanical stiffness that mimics the mechanical properties (>5 KPa) of bone marrow. hMSCs cultured in these hydrogels appeared to be halted in G1phase of the cell cycle and to be non-proliferative, as shown by flow cytometry and 5-Ethynyl-2’-deoxyuridine (EdU) staining, respectively. Their quiescent state was characterized by an upregulation of enhancer of zeste homolog 1 (EZH1) at the gene level, forkhead box O3 (FoxO3) and cyclin-dependent kinase inhibitor 1B (p27) at the gene and protein levels compared to hMSCs grown in 2D TCPS. Comparative studies in 3D hydrogels of alginate-RGD presenting higher concentration of the peptide or in collagen hydrogels revealed that independently of the concentration of RGD or the chemistry of the adhesion motives, hMSCs cultured in 3D presented a similar phenotype.This quiescent phenotype was exclusive of 3D cultures. In 2D, even when cells were starved of fetal bovine serum (FBS) and became also non-proliferative, the expression of these markers was not observed. We propose that this difference may be the result of mammalian target of rapamycin complex 1 (mTORC1) being downregulated in hMSCs cultured in 3D hydrogels, which induces cells to be in “deep” quiescence and be kept aliveex vivofor a long period of time. Our results represent a step forward towards understanding hMSCs quiescence and its molecular pathways, providing more insight for hMSCs cell therapies.
A dynamic equilibrium between TTP and CPEB4 controls mRNA stability and inflammation resolution
Authors: Suñer Clara , Sibilio Annarita , Martín Judit , Castellazzi Chiara Lara , Reina Oscar , Dotu Ivan , Caballé Adrià , Rivas Elisa , Calderone Vittorio , Díez Juana , Nebreda Angel R. , Méndez Raúl 
Published: March 2021

SUMMARYTemporal control of inflammation is critical to avoid pathological developments, and is largely defined through the differential stabilities of mRNAs. While TTP-directed mRNA deadenylation is known to destabilize ARE-containing mRNAs, this mechanism alone cannot explain the variety of mRNA expression kinetics observed during inflammation resolution. Here we show that inflammation resolution requires CPEB4 expression,in vitroandin vivo. Our results identify that CPEB4-directed polyadenylation and TTP-mediated deadenylation compete during the resolutive phase of the LPS response to uncouple the degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. The outcome of this equilibrium is quantitatively defined by the relative number of CPEs and AREs in each mRNA, and further shaped by the coordinated regulation by the MAPK signalling pathway of the levels and activities of their trans-acting factors, CPEB4 and TTP. Altogether, we describe a temporal- and transcript-specific regulatory network controlling the extent of the inflammatory response.
Seronegative MSM at high-risk of HIV-1 acquisition show Immune quiescent profile with normal immune response against common antigens
Authors: Ossa-Giraldo Ana C. , Blanquiceth Yurany , Flórez-Álvarez Lizdany , Contreras-Ramírez Katherin , Rojas Mauricio , Hernandez Juan C. , Zapata Wildeman 
Published: March 2021

AbstractHIV infection still represents a major public health problem worldwide, and a vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection and opens doors for new preventive and therapeutic strategies. Among HESN groups there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for the study of HESN because of their major exposure to HIV in the absence of infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. Sixty MSM at high-risk (n=16) and low-risk (n=44) of HIV-1 acquisition were included. No sex worker nor homozygous delta 32 mutation subjects were included. All the participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. The high-risk MSM presented a higher frequency of sexual partners in the last 3 months previous to the study’s enrollment (Median 30 vs. 2), lifetime sexual partners (Median 1708 vs. 26), and unprotected anal intercourse (Median 12.5 vs. 2) than low-risk MSM. This group also showed a quiescent profile of T cells and NK cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38- and a tendency to show a higher percentage of CD8+HLADR+CD38-T cells, than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this cohort of MSM could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells, and increased expression of Serpin A1. It is necessary to continue the study of MSM at high-risk of exposure to HIV-1 to better understand the natural resistance to HIV.