Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel regulation of PD-1 ligands on mesenchymal stromal cells through MMP-mediated proteolytic cleavage

ABSTRACT Whether fibroblasts regulate immune response is a crucial issue in the modulation of inflammatory responses. Herein, we demonstrate that foreskin fibroblasts (FFs) potently inhibit CD3+ T cell proliferation through a mechanism involving early apoptosis of activated T cells. Using blocking antibodies, we demonstrate that the inhibition of T cell proliferation occurs through cell-to-cell interactions implicating PD-1 receptor expressed on T cells and its ligands, PD-L1 and PD-L2, on fibroblasts. Dual PD-1 ligand neutralization is required to abrogate (i) binding of the PD-1-Fc fusion protein, (ii) early apoptosis of T cells, and (iii) inhibition of T cell proliferation. Of utmost importance, we provide the first evidence that PD-1 ligand expression is regulated through proteolytic cleavage by endogenous matrix metalloproteinases (MMPs) without transcriptional alteration during culture-time. Using (i) different purified enzymatic activities, (ii) MMP-specific inhibitors, and (iii) recombinant human MMP-9 and MMP-13, we demonstrated that in contrast to CD80/CD86, PD-L1 was selectively cleaved by MMP-13, while PD-L2 was sensitive to broader MMP activities. Their cleavage by exogenous MMP-9 and MMP-13 with loss of PD-1 binding domain resulted in the reversion of apoptotic signals on mitogen-activated CD3+ T cells. We suggest that MMP-dependent cleavage of PD-1 ligands on fibroblasts may limit their immunosuppressive capacity and thus contribute to the exacerbation of inflammation in tissues. In contrast, carcinoma-associated fibroblasts appear PD-1 ligand-depleted through MMP activity that may impair physical deletion of exhausted defective memory T cells through apoptosis and facilitate their regulatory functions. These observations should be considered when using the powerful PD-1/PD-L1 blocking immunotherapies.
Grip Width and Forearm Orientation Effects on Muscle Activity During the Lat Pull-Down

Lusk, SJ, Hale, BD, and Russell, DM. Grip width and forearm orientation effects on muscle activity during the lat pull-down. J Strength Cond Res 24(7): 1895-1900, 2010-Based on electromyographic (EMG) studies, an anterior (in front of the face) wide grip with a pronated forearm has been recommended as the optimal lat pull-down (LPD) variation for strengthening the latissimus dorsi (LD) (Signorile, JF, Zink, A, and Szwed, S. J Strength Cond Res 16: 539-546, 2002; Wills, R, Signorile, J, Perry, A, Tremblay, L, and Kwiatkowski, K. Med Sci Sports Exerc 26: S20, 1994). However, it is not clear whether this finding was because of grip width or forearm orientation. This study aimed to resolve this issue by comparing wide-pronated, wide-supinated, narrow-pronated, and narrow-supinated grips of an anterior LPD. Twelve healthy men performed the 4 grip variations using an experimentally determined load of 70% of 1 repetition maximum. Two trials of 5 repetitions were analyzed for each grip type. Participants maintained a cadence of 2-second concentric and 2-second eccentric phases. The grip widths were normalized for each individual by using a wide grip that corresponded to their carrying width and a narrow grip that matched their biacromial diameter. Surface EMG of the LD, middle trapezius (MT), and biceps brachii (BB) was recorded, and the root mean square of the EMG was normalized, using a maximum isometric voluntary contraction. Repeated-measures analysis of variance for each muscle revealed that a pronated grip elicited greater LD activity than a supinated grip (p < 0.05), but had no influence of grip type on the MT and BB muscles. Based on these findings, an anterior LPD with pronated grip is recommended for maximally activating the LD, irrespective of the grip width (carrying width or biacromial diameter).
Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.

BACKGROUND External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. OBJECTIVE To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. DESIGN Randomised, double-blinded, placebo-controlled trial. SETTING UK teaching hospital. POPULATION One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV. METHODS Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat. MAIN OUTCOME MEASURES Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity. RESULTS The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged. CONCLUSIONS The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.
O papel do odontolegista nas perícias criminais

Objetivo: o presente trabalho foi realizado com o objetivo de discutir a atuacao do odontolegista no âmbito criminal, com intuito de trazer a comunidade academica informacoes relevantes sobre o assunto. Revisao de literatura: a atuacao do profissional especialista em Odontologia Legal restringe-se a analise, pericia e avaliacao de eventos relacionados com a area de competencia do cirurgiao-dentista e e regulada pelos artigos 63 e 64 da Resolucao CFO – 63/2005. O odontolegista pode atuar, no âmbito criminal, na identificacao no vivo, no cadaver e em pericias antropologicas. A cavidade oral apresenta um grande potencial para a identificacao, e a atuacao do especialista em Odontologia Legal e de extrema importância, na medida em que o exame de um corpo por meio da boca e das arcadas dentarias pode ser fundamental em uma pericia criminal, sendo a analise odontologica um meio muito utilizado. Consideracoes finais: o cirurgiao-dentista deve ser cuidadoso ao guardar o prontuario, as radiografias e os modelos em gesso dos pacientes, alem de anotar todas as informacoes, pois podem servir futuramente para a identificacao positiva de vitimas.
Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease has been implicated in virus maturation, dysregulation of host inflammation and antiviral immune responses. We showed that PLpro preferably cleaves the K48-ubiquitin linkage while also being capable of cleaving ISG15 modification. The multiple functions of PLpro render it a promising drug target. Therefore, we screened an FDA-approved drug library and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising IC50 of 2.1 μM. The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. NMR data indicate that GRL0617 blocks the binding of ISG15 to PLpro. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. One Sentence Summary Co-crystal structure of PLpro in complex with GRL0617 reveals the druggability of PLpro for SARS-CoV-2 treatment.
Metabolic syndrome, CKD progression, and death: the good, the bad, and the ugly.

Previous studies have reported an association between metabolic syndrome, proteinuria, incidence and progression of CKD, and ESRD among different ethnic groups ([1][1]–[6][2]). With an increasing sedentary lifestyle and high rates of obesity, the prevalence of metabolic syndrome stands at 34% ([7
Email thread identification using latent Dirichlet allocation and non-negative matrix factorization based clustering techniques

Emails are the most popular and effective way of communicating over the internet. A number of applications are available today for computers and mobile devices for email messaging. Email messaging is constantly getting more popular and, as a result, numbers of sent and received emails are also increasing. It is very difficult for a user to remember emails and relate newer incoming emails to previous communications made on similar topics. Email threads provide a mechanism using which a user can obtain sequences of emails for a particular set of communication in a time frame and provides a number of benefits to users. In this work two email thread identification algorithms based on a nested textual clustering approach are presented. The work is planned in two stages; in the first stage two popular text clustering approaches, latent Dirichlet allocation and non-negative matrix factorization, are applied over the email messages to form the email clusters. Then in the second stage, clustering is again performed over the created email clusters to identify the email threads using threading features. Performance parameters like accuracy, precision, recall and F-measure are evaluated for the presented thread identification algorithms.
Macrophage Migration Inhibitory Factor in Normal Human Skeletal Muscle and Inflammatory Myopathies

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine secreted by activated T cells and macrophages that has antiapoptotic, proproliferative, and chemotactic effects. Because these cells are major components of many muscle disorders with different etiologies, we investigated the amount and distribution of MIF in inflammatory myopathies. Concentrations of MIF in protein lysates from dermatomyositis (n = 6), polymyositis (n = 7), sporadic inclusion body myositis (n = 9) muscle samples and control biopsies without specific changes (n = 10) were determined by ELISA. In polymyositis, MIF concentrations were higher than in controls (p<0.05), whereas they were not significantly different in other inflammatory myopathies. By immunohistochemistry, MIF was detected not only in inflammatory cells, but also at muscle fiber membranes where they were invaded or bordered infiltrates or necrotic fibers; focal sarcoplasmic reactivity was also observed. A similar distribution was found in areas of infiltration, necrosis, myophagocytosis, degeneration, and regeneration in 8 muscular dystrophy samples. The expression of MIF was verified in human myogenic tissue cultures; MIF immunoreactivity decreased with progressive differentiation, and its distribution changed. These data suggest that MIF is a skeletal muscle cytokine with probable functions beyond inflammatory pathology in the complex regenerative response to muscle fiber damage.
Increasing heart vascularisation after myocardial infarction using brain natriuretic peptide stimulation of endothelial and WT1+ epicardium-derived cells

Brain natriuretic peptide (BNP) treatment increases heart function and decreases heart dilation after myocardial infarction. Here, we investigated whether part of the cardioprotective effect of BNP in infarcted hearts related to improved neovascularisation. Infarcted mice were treated with saline or BNP for 10 days. BNP treatment increased vascularisation and the number of endothelial cells in the infarct border and remote zones of infarcted hearts. Endothelial cell lineage tracing showed that BNP directly stimulated the proliferation of resident mature endothelial cells in both areas of the infarcted hearts, via NPR-A binding and p38 MAP kinase activation. BNP also stimulated the proliferation of WT1+ epicardium-derived cells but only in the hypoxic area of infarcted hearts. Our results demonstrated that these immature cells have a natural capacity to differentiate into endothelial cells in infarcted hearts. BNP treatment increased their proliferation but not their differentiation capacity. We identified new roles for BNP and new therapeutic strategies to improve heart recovery in infarcted hearts.
Novel Mechanisms of Efflux-Mediated Levofloxacin Resistance and Reduced Amikacin Susceptibility in Stenotrophomonas maltophilia

Fluoroquinolone resistance in Stenotrophomonas maltophilia is multifactorial, but the most significant factor is overproduction of efflux pumps, particularly SmeDEF, following mutation. Here, we report that mutations in the glycosyl transferase gene smlt0622 in S. maltophilia K279a mutant K M6 cause constitutive activation of SmeDEF production, leading to elevated levofloxacin MIC. Selection of a levofloxacin-resistant K M6 derivative, K M6 LEVr, allowed identification of a novel two-component regulatory system, Smlt2645/6 (renamed SmaRS). ABSTRACT Fluoroquinolone resistance in Stenotrophomonas maltophilia is multifactorial, but the most significant factor is overproduction of efflux pumps, particularly SmeDEF, following mutation. Here, we report that mutations in the glycosyl transferase gene smlt0622 in S. maltophilia K279a mutant K M6 cause constitutive activation of SmeDEF production, leading to elevated levofloxacin MIC. Selection of a levofloxacin-resistant K M6 derivative, K M6 LEVr, allowed identification of a novel two-component regulatory system, Smlt2645/6 (renamed SmaRS). The sensor kinase Smlt2646 (SmaS) is activated by mutation in K M6 LEVr causing overproduction of two novel ABC transporters and the known aminoglycoside efflux pump SmeYZ. Overproduction of one ABC transporter, Smlt1651-4 (renamed SmaCDEF), causes levofloxacin resistance in K M6 LEVr. Overproduction of the other ABC transporter, Smlt2642/3 (renamed SmaAB), and SmeYZ both contribute to the elevated amikacin MIC against K M6 LEVr. Accordingly, we have identified two novel ABC transporters associated with antimicrobial drug resistance in S. maltophilia and two novel regulatory systems whose mutation causes resistance to levofloxacin, clinically important as a promising drug for monotherapy against this highly resistant pathogen.
Identification of cephalic vein in the deltopectoral groove and its surgical

Introduction: Identification and recognition of the of critical importance when considering emergency procedures. Therefore, the present cadaveric study was undertaken to identify the CV in the deltopectoral groove and its termination in the axillary vein with respect to th e relevant anatomical landmarks. Material and methods: The length of the CV was taken from the lowest limit of the deltopect groove to its draining point into the axillary vein. The coracoid process (CP), first costo junction (CCJ) and the mid clavicular point (MCP) were used as the landmarks and their distances from the drainage point of CV into the axillary vein were measured. Results: In all cadavers, the CV traversed the deltopectoral groove and terminated into the axillary vein. The mean le ngth of the CV was 15.46 sternoclavicular joint, midclavicular point, first costo were 8.26 ± 0.99 cm, 3.51 ± 0.8 cm, 5.66 Conclusion: The present anatomical study describes the location of cephalic vein in relation to the anatomical landmarks which would be commonly used in the intervention procedures in this region.
Automatic 3d Prostate Surface Detection From Trus With Level Sets

Prostate boundary detection from ultrasound images plays an important role in prostate disease diagnoses and treatments. However, due to the low contrast, speckle noise and shadowing in ultrasound images, this still remains a difficult task. Currently, prostate boundary detection is performed manually, which is arduous and heavily user dependent. A possible solution is to improve the efficiency by automating the boundary detection process with minimal manual involvement. This paper presents a new approach based on the level set method to automatically detect the prostate surface from 3D transrectal ultrasound images. The user interaction in the initialization procedure is relieved by automatically putting the centroid of the initial zero level sets close to the image center. Region information, instead of the image gradient, is integrated into the level set method to remedy the "boundary leaking" problem caused by gaps or weak boundaries. Moreover, to increase the accuracy and robustness, knowledge-based features, such as expected shape (kidney-like) and ultrasound appearance of the prostate (looking from within the gland, the intensities are transitions from dark to light), are also incorporated into the model. The proposed method is applied to eight 3D TRUS images and the results have shown its effectiveness.
Digital Training in the Aeronautical Industry: Measuring the Usability of Two Mobile Applications

The air traffic control industry is highly regulated, with stringent processes and procedures to ensure that IP (Intellectual Property) and workplaces are kept secure. The training of air traffic controllers (ATCs) and other roles relating to air traffic services is a lengthy and expensive process. The rate in which trainees can be trained is projected to fall significantly short of the demand for staff to work in the air traffic industry. This paper focuses on two prototype mobile training applications—Location Indicators (LI) and the Aircraft Control Positions Operator (ACPO) Starter Pack. LI and the ACPO Starter Pack have been produced to explore how air traffic control training could be improved and supported using digital applications. Each application explores a key learning area for trainees in the air traffic control industry and presents an alternative to the equivalent training that is currently in use. The two prototypes that have been designed focus on producing a succinct user experience alongside gamified elements to improve engagement. As part of this paper, usability testing has been undertaken with LI and the ACPO Starter Pack. A total of nine usability tests have been undertaken at four different locations. These usability tests consisted of participants from differing demographics, varying experience with the current training and differing amounts of time with both applications. The System Usability Scale (SUS) was adapted and used to quantify participant's reactions to the usability of each application. Usability scores for both applications were collected and then averaged to produce an overall score for each application. We can conclude from both usability scores and qualitative feedback that digital applications have the potential to engage future trainees in the air traffic services industry.
System design considerations for risk perception

The perception of risk is a driver for security analysts' decision making. However, security analysts may have conflicting views of a risk based on personal, system and environmental factors. This difference in perception and opinion, may impact effective decision making. In this paper, we propose a model that highlights areas contributing to the perception of risk in a socio-technical environment and their implication to system design. We validate the model through the use of a hypothetical scenario, which is grounded in both the literature and empirical data.
An investigation into learning effective speaker subspaces for robust unsupervised DNN adaptation

Subspace methods are used for deep neural network (DNN)-based acoustic model adaptation. These methods first construct a subspace and then perform the speaker adaptation as a point in the subspace. This paper aims to investigate the effectiveness of subspace methods for robust unsupervised adaptation. For the analysis, we compare two state-of-the-art subspace methods, namely, the singular value decomposition (SVD)-based bottleneck adaptation and the factorized hidden layer (FHL) adaptation. Both of these methods perform speaker adaptation as a linear combination of rank-1 bases. The main difference between the subspace construction is that FHL adaptation constructs a speaker subspace separate from the phoneme classification space while SVD-based bottleneck adaptation shares the same subspace for both the phoneme classification and the speaker adaptation. So far, no direct comparisons between these two methods are reported. In this work, we compare these two methods for their robustness to unsupervised adaptation on Aurora 4, AMI IHM and AMI SDM tasks. Our findings show that the FHL adaptation outperforms the SVD-based bottleneck adaptation especially in challenging conditions where the adaptation data is limited, or the quality of the adaptation alignments are low.
A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit

Transcription factor NF-kappaB is generally considered to be a heterodimer with two subunits, p50 and p65. The p50 subunit has been suggested to be generated from its precursor, p105, via the ubiquitin-proteasome pathway. During processing, the C-terminal portion of p105 is rapidly degraded whereas the N-terminal portion (p50) is left intact. We report here that a 23-amino-acid, glycine-rich region (GRR) in p105 functions as a processing signal for the generation of p50. A GRR-dependent endoproteolytic cleavage downstream of the GRR releases p50 from p105, and this cleavage does not require any specific downstream sequences. p50 can be generated from chimeric precursor p105N-GRR-IkappaBalpha, while the C-terminal portion (IkappaBalpha) can also be recovered, suggesting that p105 processing includes two steps: a GRR-dependent endoproteolytic cleavage and the subsequent degradation of the C-terminal portion. We have also demonstrated that the GRR can direct a similar processing event when it is inserted into a protein unrelated to the NF-kappaB family and that it is therefore an independent signal for processing.
Modélisation computationnelle du rôle de la dopamine dans les boucles cortico-striatales dans l'apprentissage et la régulation de la sélection de l'action

Dans ce travail de these, nous avons modelise le role de la dopamine dans l'apprentissage et dans les processus de selection de l'action en lien avec les ganglions de la base. L'activite des neurones dopaminergiques presente de nombreuses similarites avec l'erreur de prediction de la recompense utilisee par les algorithmes d'apprentissage par renforcement. Ainsi, ces neurones sont supposes guider le processus de selection de l'action.Dans une premiere partie, nous avons analyse l'information encodee par les neurones dopaminergiques dans une tâche a choix multiples en la comparant a differentes informations utilisees par les modeles d'apprentissage par renforcement. Nos resultats suggerent que l'information encodee par les neurones dopaminergiques enregistrer dans la tâche n'est que partiellement compatible avec une erreur de prediction et semble en partie dissociee du comportement.Dans une deuxieme partie, nous avons simule l'effet de la dopamine sur un modele des ganglions de la base prenant en compte des connections existant chez le primate, souvent negligees dans la litterature. La plupart des modeles actuels font en effet l'hypothese d'une separation stricte de deux chemins dans les ganglions de la base : le chemin direct lie a la recompense et le chemin indirect lie a la punition. Cependant des etudes anatomiques remettent en question cette dissociation, en particulier chez le primate. Nous proposons ainsi d'etudier comment differents niveaux de dopamine, dans le contexte de la maladie de Parkinson, affectent l'apprentissage et la selection de l'action dans ce modele