Miracle-dz/UniFAR-FTUs huggingface dataset:
Histone chaperone CAF‐1 promotes HIV‐1 latency by leading the formation of phase‐separated suppressive nuclear bodies

HIV‐1 latency is a major obstacle to achieving a functional cure for AIDS. Reactivation of HIV‐1‐infected cells followed by their elimination via immune surveillance is one proposed strategy for eradicating the viral reservoir. However, current latency‐reversing agents (LRAs) show high toxicity and low efficiency, and new targets are needed to develop more promising LRAs. Here, we found that the histone chaperone CAF‐1 (chromatin assembly factor 1) is enriched on the HIV‐1 long terminal repeat (LTR) and forms nuclear bodies with liquid–liquid phase separation (LLPS) properties. CAF‐1 recruits epigenetic modifiers and histone chaperones to the nuclear bodies to establish and maintain HIV‐1 latency in different latency models and primary CD4+ T cells. Three disordered regions of the CHAF1A subunit are important for phase‐separated CAF‐1 nuclear body formation and play a key role in maintaining HIV‐1 latency. Disruption of phase‐separated CAF‐1 bodies could be a potential strategy to reactivate latent HIV‐1.
Fisheries co-management and legal pluralism: How an analytical problem becomes an institutional one

This paper addresses two issues pertaining to legal pluralism in capture fisheries, particularly with regard to the South. First there is the problem of analysis. If legal pluralism is a common phenomenon, how is it to be discerned and understood? Secondly, there is the matter of institutional design: given the pervasiveness of legal pluralism, which management institutions are better suited to represent and resolve inter-legal system differences? The authors argue the case of co-management. Drawing on examples and insights from a comparative research project in South Asia, four basic types of legal pluralism and co-management are distinguished. The authors conclude that co-management is a process that brings legal systems, and their constituent organizations and groups, together within a single framework. For fisher organizations, which frequently have distinct legal perspectives, co-management is an essential path to legitimacy. For the state, other legal systems are a resource that management can draw upon.
Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed

Abstract Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here, we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).
Female victims of acquaintance rape in college: Incidence and effects of encounters with perpetrators

Abstract Objectives: Acquaintance rape is the most common type of rape perpetrated against college women, but little information exists on later encounters with the perpetrator, lifestyle changes, and symptoms of posttraumatic stress disorder (PTSD). Participants: The sample consisted of 463 college-attending females, 16% of which indicated they were raped since attending college. Methods: The current study examines the incidence and effects of acquaintance rape perpetrated against female college students at a large, public university in the southeastern United States. Results: Eighty-four percent of the women who indicated they had experienced a rape since attending college knew their perpetrator, and 65.5% encountered their perpetrator after the attack. Participants who encountered their perpetrator after the attack reported more lifestyle changes and higher PTSD symptom severity on the PTSD Checklist for DSM-5 (PCL-5). Conclusions: The current research suggests that the effects of acquaintance rape in college is a complicated area needing further research. There is evidence to support negative effects on victims based on interactions with perpetrators.
Modelling the Effect of Biofilm Morphology on Detachment

A biofilm is an assembly of organisms attached to a surface and this feature is utilized in biofilm reactors to retain a high biomass concentration. Biofilm detachment, which is the release of biomass to the surrounding liquid, may significantly alter the performance. It is a local phenomenon which depends on the local shear stress and biofilm morphology. An empirical expression for the effect of morphology on fluid shear stress was constructed based on: (i) deviation of local biofilm thickness from its mean, (ii) from its maximum and (iii) a reference shear stress defined from flow conditions around the biofilm. The expression was calibrated with numerical results in literature obtained from computational fluid dynamics. The expression was integrated with an individual-based model platform where the biofilm morphology was determined by simulation of particles resembling individual bacteria that grow and divide. Biofilm detachment occurred locally where the shear stress exceeded biofilm cohesiveness, after which a new morphology was generated. The model developed was especially useful for predicting the detachment of biofilm when the shear stress suddenly changes. Biofilm detachment and sloughing were more pronounced in pulse shear conditions than biofilms under a constant shear stress.
Increased cardiovascular response to static contraction of larger muscle groups

The purpose of this study was to investigate the influence of the size of the active muscle mass on the cardiovascular response to static contraction. Twelve male subjects performed one-arm handgrip (HG), two-leg extension (LE), and a “dead-lift” maneuver (DL) in a randomly assigned order for 3 min at 30% of maximal voluntary contraction. O2 uptake (VO2), heart rate (HR), and mean intra-arterial blood pressure (MABP) were measured at rest and, in addition to absolute tension exerted, throughout contraction. There was a direct relationship between the size of the active muscle mass and the magnitude of the increases in VO2, HR, and MABP, even though all contractions were performed at the same relative intensity. Tension, VO2, HR, and MABP increased progressively from HG to LE to DL. It was concluded that at the same percentage of maximal voluntary contraction, the magnitude of the cardiovascular response to isometric exercise is directly influenced by the size of the contracting muscle mass.
Evaluating the state-of-the-art in mapping research spaces: A Brazilian case study

Scientific knowledge cannot be seen as a set of isolated fields, but as a highly connected network. Understanding how research areas are connected is of paramount importance for adequately allocating funding and human resources (e.g., assembling teams to tackle multidisciplinary problems). The relationship between disciplines can be drawn from data on the trajectory of individual scientists, as researchers often make contributions in a small set of interrelated areas. Two recent works propose methods for creating research maps from scientists’ publication records: by using a frequentist approach to create a transition probability matrix; and by learning embeddings (vector representations). Surprisingly, these models were evaluated on different datasets and have never been compared in the literature. In this work, we compare both models in a systematic way, using a large dataset of publication records from Brazilian researchers. We evaluate these models’ ability to predict whether a given entity (scientist, institution or region) will enter a new field w.r. t. the area under the ROC curve. Moreover, we analyze how sensitive each method is to the number of publications and the number of fields associated to one entity. Last, we conduct a case study to showcase how these models can be used to characterize science dynamics in the context of Brazil.
Inhibition of Matrix Metalloproteinase 9 Activity Promotes Synaptogenesis in the Hippocampus

Abstract Information coding in the hippocampus relies on the interplay between various neuronal ensembles. We discovered that the application of a cholinergic agonist, carbachol (Cch), which triggers oscillatory activity in the gamma range, induces the activity of matrix metalloproteinase 9 (MMP-9)—an enzyme necessary for the maintenance of synaptic plasticity. Using electrophysiological recordings in hippocampal organotypic slices, we show that Cch potentiates the frequency of miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs, respectively) in CA1 neurons and this effect is MMP-9 dependent. Interestingly, though MMP-9 inhibition prevents the potentiation of inhibitory events, it further boosts the frequency of excitatory mEPSCs. Such enhancement of the frequency of excitatory events is a result of increased synaptogenesis onto CA1 neurons. Thus, the function of MMP-9 in cholinergically induced plasticity in the hippocampus is to maintain the fine-tuned balance between the excitatory and the inhibitory synaptic transmission.
Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study)

Abstract Objective To investigate the efficacy and safety of rituximab + LEF in patients with RA. Methods In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators’ control. Results Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders. Conclusion The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring. Trial registration EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958.
5-methoxytryptophan alleviates liver fibrosis by modulating FOXO3a/miR-21/ATG5 signaling pathway mediated autophagy

ABSTRACT Liver fibrosis is a critical health issue in the world due to its rapidly increasing prevalence. It is of great demand to develop effective drugs for the treatment of liver fibrosis. 5-methoxytryptophan (5-MTP) has been reported to play an important role in anti-inﬂammatory, anti-cancer, myocardial-protective eﬀects. However, the anti-fibrotic eﬀect of 5-MTP is never covered in liver. Here, we investigated anti-fibrotic effects of 5-MTP on liver fibrosis and its underlying mechanism. In vitro, 5-MTP treatment could inhibit TGF-β1-induced elevated levels of collagen I, collagen III, fibronectin and α-smooth muscle actin (SMA) by stimulating autophagy process. Mechanically, the expression of FOXO3a was enhanced by 5-MTP and then repressed the level of miR-21, eventually leading to a restoration of autophagy-related gene ATG5. Furthermore, rescue experiments showed 5-MTP could activate autophagy process and suppress the activation of LX-2 cells by regulating FOXO3a/miR-21/ATG5 pathway. Consistently, 5-MTP significantly attenuated CCl4-induced hepatic fibrosis in rat model. In conclusion, our research discovered that 5-MTP effectively alleviated liver fibrosis in vitro and in vivo, which provided new insights into the application of 5-MTP for liver fibrosis.
Prediction of LncRNA-encoded small peptides in glioma and oligomer channel functional analysis using in silico approaches

Glioma is a lethal malignant brain cancer, and many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small peptides and form oligomers for water or ion regulation. However, because the peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and evaluate lncRNAs, which may encode small transmembrane peptides in gliomas. Combining ab initio homology modeling, molecular dynamics simulations, and free energy calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs. We found that one key hub lncRNA, namely, DLEU1, which contains two smORFs (ORF1 and ORF8), encodes small peptides that form pentameric channels. The mechanics of water and ion (Na+ and Cl-) transport through this pentameric channel were simulated. The potential mean force of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 permeated neither ions nor water. This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, this study provides a theoretical basis for drug development.
Congo red removal using oxidized multiwalled carbon nanotubes: kinetic and isotherm study

AbstractIn this study, Congo red (CR) was removed from aqueous solution by multiwalled carbon nanotube (MWCNT) oxidized and treated with HNO3. In this regard, the influence of variables such as size and amount of MWCNT, pH, stirring time, and initial dye concentration on the procedure efficiency was examined and optimized. At optimum value of all variables, high adsorption capacity (357.14 mg g−1) indicates the efficiency and suitability of MWCNT for achievement a safe and clean environment. The initial pH has significant role on the chemistry of dye molecules and adsorbent, and the best pH was 1.0. The removal rates follow the pseudo-second order in cooperate with interparticle diffusion models. The correlation coefficients were in the range of 0.9987–0.9998. The high adsorption capacities make MWCNT superior to activated carbon and admit to design safe, economic, and non-toxic wastewater treatment technology. The pH of zero charge of MWCNT was around 1.0. The higher the fraction of mesopores with size b.
Clinical and Analytical Evaluation of the Alinity m HR HPV Assay within the VALGENT-3 Framework

Only clinically validated human papillomavirus (HPV) tests should be used in cervical cancer screening. VALGENT provides a framework to validate new HPV tests. ABSTRACT Only clinically validated human papillomavirus (HPV) tests should be used in cervical cancer screening. VALGENT provides a framework to validate new HPV tests. In the VALGENT-3 study, the clinical accuracy of the recently launched Abbott Alinity m HR HPV assay (Alinity m) to detect cervical precancerous lesions was assessed against the standard comparator test (Hybrid Capture 2; HC2) and against two previously validated alternative comparator tests (Abbott RealTime HR HPV and Roche cobas 4800 assays). Validation was conducted using 1,300 consecutive cervical samples from women attending an organized population-based cervical screening program enriched with 300 cytologically abnormal samples. Overall high-risk HPV test concordance was assessed by kappa values; the concordance for HPV-16 and HPV-18 was assessed for Alinity m, RealTime, and cobas, and the Linear Array (Roche) was used for more detailed genotyping concordance. In the total study population, the relative sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ of Alinity m compared to HC2 was 1.02 (95% confidence interval [CI], 0.99 to 1.06) and 1.03 (95% CI, 0.99 to 1.06), respectively. The relative specificity for nondiseased subjects (≤CIN1) was 1.01 (95% CI, 1.00 to 1.02) (all pnon-inferiority ≤ 0.001). Alinity m showed noninferior clinical accuracy among women 30 years or older when cobas or RealTime was used as a comparator. HPV genotype-specific concordance between Alinity m and the three comparator tests showed excellent agreement, with kappa values ranging from 0.82 to 1.00. In conclusion, Alinity m fulfills the international accuracy requirements for use in cervical cancer screening and shows excellent HPV genotype-specific concordance with three clinically validated HPV tests.
Development and Implementation of a Brief Healthcare Professional Support Program Based in Gratitude, Mindfulness, Self-compassion, and Empathy

Supplemental digital content is available in the text. OBJECTIVE To highlight the development, implementation, and initial findings of a brief healthcare professional support program called “GRACE. ” BACKGROUND Healthcare professionals face significant work-related stressors that when left unmanaged can negatively affect their overall well-being and contribute to burnout. METHODS Over a 2-year period, the GRACE program was delivered to 8 clinical units at a midsized southwestern hospital. Questionnaires were administered at baseline and 1 month. RESULTS Program participants were 36 years old on average, female (81%), and White (68%) and mostly employed as nurses (66%). Attendees reported increased knowledge, understanding, and confidence and found the program to be acceptable. One month after training, participants demonstrated significant improvements in self-compassion. Medical units that received GRACE training saw significantly greater increases in patient satisfaction scores compared with units that did not receive training. CONCLUSIONS The GRACE program was feasible and acceptable to deliver, and initial proof-of-concept evidence was supported.
Tip of the iceberg: Measuring racial discrimination in studies of health.

There is compelling evidence that racial discrimination is a risk factor for illness and disease. But what are health scientists measuring-and what do they think they are measuring-when they include measures of racial discrimination in health research? We synthesize theoretical conceptualizations of racial discrimination in health research and critically assess whether and how these concepts correspond (or not) to widely used measures of racial discrimination. In doing so, we show that while researchers often use terms such as "self-reported discrimination," "perceptions of discrimination," and "exposure to discrimination" interchangeably, these concepts are indeed unique, with each holding a distinct epistemological position and theoretical and methodological capacity to uncover the impact of racial discrimination on health and health disparities. Importantly, we argue that commonly used measures of self-reported or perceived racial discrimination are just the "tip of the iceberg" in terms of revealing the ways in which discrimination shapes health inequities. Scientists and practitioners must be cognizant of and intentional in their measurement choices and language, as the framing of these processes will inform policy and intervention efforts aimed at eliminating discrimination. This article is protected by copyright. All rights reserved.
Complete chloroplast genome sequence of Adenophora racemosa (Campanulaceae): Comparative analysis with congeneric species

Adenophora racemosa, belonging to the Campanulaceae, is an important species because it is endemic to Korea. The goal of this study was to assemble and annotate the chloroplast genome of A. racemosa and compare it with published chloroplast genomes of congeneric species. The chloroplast genome was reconstructed using de novo assembly of paired-end reads generated by the Illumina MiSeq platform. The chloroplast genome size of A. racemosa was 169,344 bp. In total, 112 unique genes (78 protein-coding genes, 30 tRNAs, and 4 rRNAs) were identified. A Maximum likelihood (ML) tree based on 76 protein-coding genes divided the five Adenophora species into two clades, showing that A. racemosa is more closely related to Adenophora stricta than to Adenophora divaricata. The gene order and contents of the LSC region of A. racemosa were identical to those of A. divaricata and A. stricta, but the structure of the SSC and IRs was unique due to IR contraction. Nucleotide diversity (Pi) >0.05 was found in eleven regions among the three Adenophora species not included in sect. Remotiflorae and in six regions between two species (A. racemosa and A. stricta).
Targeted next-generation sequencing: a Swiss army knife for mycobacterial diagnostics?

The genus Mycobacterium encompasses almost 200 species that fall into four main groups [1]. Specifically, the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB) and leading cause of death by a single infectious agent, is distinguished from mycobacteria causing Buruli ulcer and leprosy [2, 3]. The remaining species are referred to as nontuberculous mycobacteria (NTM), which mainly cause lung disease and have become more frequent in many parts of the world, particularly amongst older patients [4]. Like a multifunctional Swiss army knife, Deeplex offers unprecedented versatility directly from the clinical sample and represents a welcome addition to the diagnostic and epidemiological toolbox https://bit.ly/38s6ukF