Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbial Diversity in a North Western Mediterranean Sea Shallow Coastal Lagoon Under Contrasting Water Temperature Conditions

Temperature and light mainly drive seasonal dynamics of microbial planktonic diversity in coastal ecosystems; however, disentangling their effects is challenging because they are always tightly coupled. Shallow coastal lagoons exhibit intense temperature changes throughout the year and high interannual temperature fluctuations, offering the opportunity to study temperature effects on microbial community diversity and succession. Weekly sampling at 16s and 18s rRNA gene OTU diversity associated with high-frequency meteorological and hydrological monitoring was conducted in the northwestern Mediterranean Thau Lagoon (South of France) from winter to spring in 2015 and 2016. While 2015 was a normal climatic year, 2016 had the warmest winter ever recorded in southern France. Water temperature was found to be the main driver of community diversity and succession from winter to spring. During the normal temperature year of 2015, bacterial communities were dominated by Proteobacteria and Bacteroidetes, archaeal community by Thaumarachaeota, and unicellular eukaryotes mainly by picochlorophytes (Bathycoccus prasinos, Micromonas bravo, and Ostreococcus spp.) in winter and diatoms (Chaetoceros spp.) in spring. The unusually warm year 2016 benefited Actinobacteria (ML602J-51), Cyanobacteria (Synechococcus), the picoeukaryote Ostreococcus spp. , and several dinoflagellates. Our results suggest that in a warmer ocean, smaller organisms will dominate microbial communities in shallow coastal waters, potentially affecting ecosystem services.
Maternal Sensitivity Modulates Child’s Parasympathetic Mode and Buffers Sympathetic Activity in a Free Play Situation

Background Behavioral and physiological (self-)regulation in early life is crucial for the understanding of childhood development and adjustment. The autonomic nervous system (ANS) is a main player in the regulative system and should therefore be modulated by the quality of interactive behavior of the caregiver. We experimentally investigated the ANS response of 18–36-month-old children in response to the quality of maternal behavior during a mother–child-interacting paradigm. Method Eighty mothers and their children came to our laboratory and took part in an experimental paradigm, consisting of three episodes: a resting phase (E1), a structured play phase (E2), and a free play situation (E3) between mothers and their child. Children’s and mother’s heart rate (HR), the sympathetic nervous system (SNS) activity via the pre-ejection period (PEP) and the left ventricular ejection time (LVET), and the parasympathetic nervous system (PNS) activity via the respiratory sinus arrhythmia (RSA) were continuously measured by an electrocardiogram. Maternal sensitivity of interactive behavior was assessed by using the Emotional Availability (EA) Scales. Results Children of mothers with insensitive behavior had a significantly lower RSA at baseline, showed a lack of RSA withdrawal during structured and free play, and had shorter LVET across all episodes compared to children of sensitive mothers. Conclusion Our findings depict the influence of low-quality maternal interaction on the child’s ANS regulation, in calm and more stressful play situations. The overall higher SNS mode with impaired PNS reactivity may negatively influence child’s ANS homoeostasis, which may result in a long-term impact on mental and physical wellbeing. Further, the maternal sensitivity may function as a buffer for the stress response of their child. These results could serve as a basis for the development of appropriate psychoeducational programs for mothers of low sensitivity in their interaction with the child.
Arthroscopic Anterior Cruciate Ligament Repair Versus Autograft Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Comparative Studies

Purpose To compare the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) repair and autograft ACL reconstruction for ACL ruptures. Methods PubMed, EMBASE, Scopus, Web of Science and The Cochrane Library were searched for relevant studies from 1 January 1990 to 21 March 2022. Two evaluators independently screened the literature, extracted data and assessed the methodological quality of the enrolled studies. Meta-analysis was conducted using RevMan 5.4 software. Results Ten studies with mean follow-up periods from 12 to 36 months were included. For 638 patients with ACL ruptures, arthroscopic ACL repair showed statistically comparable outcomes of failure (p = 0.18), complications (p = 0.29), reoperation other than revision (p = 0.78), Lysholm score (p = 0.78), Tegner score (p = 0.70), and satisfaction (p = 0.45) when compared with autograft ACL reconstruction. A significantly higher rate of hardware removal (p = 0.0008) but greater International Knee Documentation Committee (IKDC) score (p = 0.009) were found in the ACL repair group. The heterogeneity of the side-to-side difference of anterior tibial translation (ΔATT) was high (I2 = 80%). After the sensitivity analysis, the I2 decreased dramatically (I2 = 32%), and the knees with ACL repair showed significantly greater ΔATT (P = 0.04). Conclusion For proximal ACL ruptures, arthroscopic ACL repair showed similar clinical outcomes, and even better functional performance when compared to autograft ACL reconstruction. ACL repair has a higher rate of hardware removal, and might be related to greater asymptomatic knee laxity. More high-quality prospective trials are needed to confirm our findings.
Single Cell RNA-Seq Analysis of Human Red Cells

Human red blood cells (RBCs), or erythrocytes, are the most abundant blood cells responsible for gas exchange. RBC diseases affect hundreds of millions of people and impose enormous financial and personal burdens. One well-recognized, but poorly understood feature of RBC populations within the same individual are their phenotypic heterogeneity. The granular characterization of phenotypic RBC variation in normative and disease states may allow us to identify the genetic determinants of red cell diseases and reveal novel therapeutic approaches for their treatment. Previously, we discovered diverse RNA transcripts in RBCs that has allowed us to dissect the phenotypic heterogeneity and malaria resistance of sickle red cells. However, these analyses failed to capture the heterogeneity found in RBC sub-populations. To overcome this limitation, we have performed single cell RNA-Seq to analyze the transcriptional heterogeneity of RBCs from three adult healthy donors which have been stored in the blood bank conditions and assayed at day 1 and day 15. The expression pattern clearly separated RBCs into seven distinct clusters that include one RBC cluster that expresses HBG2 and a small population of RBCs that express fetal hemoglobin (HbF) that we annotated as F cells. Almost all HBG2-expessing cells also express HBB, suggesting bi-allelic expression in single RBC from the HBG2/HBB loci, and we annotated another cluster as reticulocytes based on canonical gene expression. Additional RBC clusters were also annotated based on the enriched expression of NIX, ACVR2B and HEMGN, previously shown to be involved in erythropoiesis. Finally, we found the storage of RBC was associated with an increase in the ACVR2B and F-cell clusters. Collectively, these data indicate the power of single RBC RNA-Seq to capture and discover known and unexpected heterogeneity of RBC population.
Lipophilic Constituents in Salvia miltiorrhiza Inhibit Activation of the Hepatic Stellate Cells by Suppressing the JAK1/STAT3 Signaling Pathway: A Network Pharmacology Study and Experimental Validation

Liver fibrosis is currently a global health challenge with no approved therapy, with the activation of hepatic stellate cells being a principal factor. Lipophilic constituents in Salvia miltiorrhiza (LS) have been reported to improve liver function and reduce the indicators of liver fibrosis for patients with chronic hepatitis B induced hepatic fibrosis. However, the pharmacological mechanisms of LS on liver fibrosis have not been clarified. In this study, 71 active compounds, 342 potential target proteins and 22 signaling pathways of LS were identified through a network pharmacology strategy. Through text mining and data analysis, the JAK1/STAT3 signaling pathway was representatively selected for further experimental validation. We firstly confirmed the protective effect of LS on liver fibrosis in vivo by animal experiments. Hepatic stellate cells, which proliferated and displayed a fibroblast-like morphology similar to activated primary stellate cells, were applied to evaluate its underlying mechanisms. The results showed that LS could inhibit the cell viability, promote the cell apoptosis, decrease the expression of liver fibrosis markers, and downregulate the JAK1/STAT3 signaling pathway. These results demonstrated that LS could exert anti-liver-fibrosis effects by inhibiting the activation of HSCs and regulating the JAK1/STAT3 signaling pathway, which is expected to benefit its clinical application.
Aging Alters the Formation and Functionality of Signaling Microdomains Between L-type Calcium Channels and β2-Adrenergic Receptors in Cardiac Pacemaker Cells

Heart rate is accelerated to match physiological demands through the action of noradrenaline on the cardiac pacemaker. Noradrenaline is released from sympathetic terminals and activates β1-and β2-adrenergic receptors (ΑRs) located at the plasma membrane of pacemaker cells. L-type calcium channels are one of the main downstream targets potentiated by the activation of β-ARs. For this signaling to occur, L-type calcium channels need to be located in close proximity to β-ARs inside caveolae. Although it is known that aging causes a slowdown of the pacemaker rate and a reduction in the response of pacemaker cells to noradrenaline, there is a lack of in-depth mechanistic insights into these age-associated changes. Here, we show that aging affects the formation and function of adrenergic signaling microdomains inside caveolae. By evaluating the β1 and β2 components of the adrenergic regulation of the L-type calcium current, we show that aging does not alter the regulation mediated by β1-ARs but drastically impairs that mediated by β2-ARs. We studied the integrity of the signaling microdomains formed between L-type calcium channels and β-ARs by combining high-resolution microscopy and proximity ligation assays. We show that consistent with the electrophysiological data, aging decreases the physical association between β2-ARs and L-type calcium channels. Interestingly, this reduction is associated with a decrease in the association of L-type calcium channels with the scaffolding protein AKAP150. Old pacemaker cells also have a reduction in caveolae density and in the association of L-type calcium channels with caveolin-3. Together the age-dependent alterations in caveolar formation and the nano-organization of β2-ARs and L-type calcium channels result in a reduced sensitivity of the channels to β2 adrenergic modulation. Our results highlight the importance of these signaling microdomains in maintaining the chronotropic modulation of the heart and also pinpoint the direct impact that aging has on their function.
Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology

Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated P. gingivalis peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from P. gingivalis (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined. B cells from inflamed gingival tissue were single-cell sorted, and immunoglobulin (Ig) genes were amplified, sequenced, cloned and expressed (n=63) as recombinant monoclonal antibodies, and assayed for citrulline-reactivities by enzyme-linked immunosorbent assay. Additionally, affinity-purified polyclonal anti-cyclic-citrullinated peptide (CCP2) IgG, and monoclonal antibodies derived from RA blood and synovial fluid B cells (n=175), were screened for CPP3-reactivity. Elevated anti-CPP3 antibody levels were detected in RA (11%), mainly CCP2+ RA, compared to controls (2%), p<0.0001, with a significant association to HLA-DRB1 shared epitope alleles, smoking and baseline pain, but with low correlation to autoimmune ACPA fine-specificities. Monoclonal antibodies derived from gingival B cells showed cross-reactivity between P. gingivalis CPP3 and human citrullinated peptides, and a CPP3+/CCP2+ clone, derived from an RA blood memory B cell, was identified. Our data support the possibility that immunity to P. gingivalis derived citrullinated antigens, triggered in the inflamed gum mucosa, may contribute to the presence of ACPA in RA patients, through mechanisms of molecular mimicry.
Possibility of Enlargement in Left Medial Temporal Areas Against Cerebral Amyloid Deposition Observed During Preclinical Stage

Neurodegenerative changes in the preclinical stage of Alzheimer’s disease (AD) have recently been the focus of attention because they may present a range of treatment opportunities. A total of 134 elderly volunteers who lived in a local community were investigated and grouped into preclinical and mild cognitive impairment stages according to the Clinical Dementia Rating test; we also estimated amyloid deposition in the brain using positron emission tomography (PET). A significant interaction between clinical stage and amyloid PET positivity on cerebral atrophy was observed in the bilateral parietal lobe, parahippocampal gyri, hippocampus, fusiform gyrus, and right superior and middle temporal gyri, as previously reported. Early AD-specific voxel of interest (VOI) analysis was also applied and averaged Z-scores in the right, left, bilateral, and right minus left medial temporal early AD specific area were computed. We defined these averaged Z-scores in the right, left, bilateral, and right minus left early AD specific VOI in medial temporal area as R-MedT-Atrophy-score, L-MedT-Atrophy-score, Bil-MedT-Atrophy-score, and R_L-MedT-Atrophy-score, respectively. It revealed that the R_L-MedT-Atrophy-scores were significantly larger in the amyloid-positive than in the amyloid-negative cognitively normal (CN) elderly group, that is, the right medial temporal areas were smaller than left in amyloid positive CN group and these left-right differences were significantly larger in amyloid positive than amyloid negative CN elderly group. The L-MedT-Atrophy-score was slightly larger (p = 0.073), that is, the left medial temporal area was smaller in the amyloid-negative CN group than in the amyloid-positive CN group. Conclusively, the left medial temporal area could be larger in CN participants with amyloid deposition than in those without amyloid deposition. The area under the receiver operating characteristic curve for differentiating amyloid positivity among CN participants using the R_L-MedT-Atrophy-scores was 0.73; the sensitivity and specificity were 0.828 and 0.606, respectively. Although not significant, a negative correlation was observed between the composite cerebral standardized uptake value ratio in amyloid PET images and L-MedT-Atrophy-score in CN group. The left medial temporal volume might become enlarged because of compensatory effects against AD pathology occurring at the beginning of the amyloid deposition.
The Expanding Arsenal of Cytotoxic T Cells

Cytotoxic T cells (CTLs) are the main cellular mediators of the adaptive immune defenses against intracellular pathogens and malignant cells. Upon recognition of specific antigen on their cellular target, CTLs assemble an immunological synapse where they mobilise their killing machinery that is released into the synaptic cleft to orchestrate the demise of their cell target. The arsenal of CTLs is stored in lysosome-like organelles that undergo exocytosis in response to signals triggered by the T cell antigen receptor following antigen recognition. These organelles include lytic granules carrying a cargo of cytotoxic proteins packed on a proteoglycan scaffold, multivesicular bodies carrying the death receptor ligand FasL, and the recently discovered supramolecular attack particles that carry a core of cytotoxic proteins encased in a non-membranous glycoprotein shell. Here we will briefly review the main features of these killing entities and discuss their interrelationship and interplay in CTL-mediated killing.
Dehydroquinate Synthase Directly Binds to Streptomycin and Regulates Susceptibility of Mycobacterium bovis to Streptomycin in a Non-canonical Mode

Antimicrobial resistance (AMR) represents one of the main challenges in Tuberculosis (TB) treatment. Investigating the genes involved in AMR and the underlying mechanisms holds promise for developing alternative treatment strategies. The results indicate that dehydroquinate synthase (DHQS) regulates the susceptibility of Mycobacterium bovis BCG to first-line anti-TB drug streptomycin. Perturbation of the expression of aroB encoding DHQS affects the susceptibility of M. bovis BCG to streptomycin. Purified DHQS impairs in vitro antibacterial activity of streptomycin, but did not hydrolyze or modify streptomycin. DHQS directly binds to streptomycin while retaining its own catalytic activity. Computationally modeled structure analysis of DHQS–streptomycin complex reveals that DHQS binds to streptomycin without disturbing native substrate binding. In addition, streptomycin treatment significantly induces the expression of DHQS, thus resulting in DHQS-mediated susceptibility. Our findings uncover the additional function of DHQS in AMR and provide an insight into a non-canonical resistance mechanism by which protein hijacks antibiotic to reduce the interaction between antibiotic and its target with normal protein function retained.
Aplicação de uma Estratégia Incremental para o Teste de Linha de Produto de Software

, e contribuiu para reduzir tempo e esforço da atividade de teste, quando comparada a uma estratégia tradicional. Abstract. In the test of Software Product Line (SPL), incremental strategies enable the systematic reuse of test cases. However, SPL testing is an emergent research area, and in the literature, works that report results from the use of test strategies for SPL are scarce. Considering this fact, this work describes a case study using an incremental test strategy to test a SPL in the domain of games for mobile devices. A methodology is proposed to allow the application of the strategy and its integration with a test case generation method based on use cases, since this is a model largely used in the development of SPL. In the study, it was observed that the strategy allows test cases reuse and reduction of time and effort of the test activity, compared with a traditional strategy.
A Case Study on Improving Maintainability and Evolvability using Architectural Constraints

Developers usually rely on patterns and best practices to increase the quality of their projects. However, as projects evolve, it is usual to observe deviations in the use of the patterns and best practices deﬁned during the initial design of a system. This article aims to illustrate the application of a static, domain-speciﬁc, and declarative dependency constraint language, called DCL, to express architectural patterns and design principles that contribute to the maintainability and evolvability – and therefore to the internal quality – of a software system. We present in the paper several architectural constraints that demonstrate the beneﬁts achieved by DCL in one motivating system and in ﬁve real-world, open-source object-oriented applications.
METACOM: Um Método para Análise de Correlação entre Métricas de Produto de Software e Propensão a Manutenção

Considering that software quality technical characteristics influence its maintenance, this paper presents a Method for Correlation Analysis between Software Product Metrics and Maintenance Proneness named METACOM. The proposed method defines an Extract, Transform, and Load (ETL) process for metrics of object-oriented software and volume of software maintenance. The METACOM involves a correlation analysis model between obtained product measures to identify the most predictive metrics. Besides, this paper describes the METACOM application on the analysis of some software industry real projects. At the end, some remarks are presented about the main analysis results obtained from specialists.
Improving the foundation and practice of reliability engineering

Reliability engineering is today a well-established field, accounting for many scientific journals and conferences, educational programmes and courses, academic positions and societies. There are also many standards which guide the practice of reliability engineering, and every year a number of scientific papers are published which address reliability engineering issues. Yet the area faces many challenges, in particular when addressing systems characterised by large uncertainties, and accurate prediction models are not easily established. We see alternative analysis perspectives being advocated, with varying degrees of theoretical justification. This article argues that there is potential for improvements to be made in terms of both theoretical frameworks and the practice of reliability engineering to meet these challenges and guide reliability engineers and decision-makers. Examples relate to the understanding and treatment of uncertainties, and the use of ideas and methods from risk management. Clear recommendations are provided on how to obtain such improvements.
R-Net Prime

Building upon the Bidirectional Attention Flow model (BiDAF) and inspired by R-NET we implemented R-NET Prime. Featuring character level embeddings and a pointer network for an output layer, R-NET Prime improves the performance of the baseline model by using self attention in addition to the bidirectional attention layer in BiDAF. Our version of self attention is more easily parallelizable as opposed to R-NET’s, allowing for faster training. This faster training allowed us to perform an ablation study to isolate the performance contribution of each R-NET Prime component, as well as thorough hyper-parameter tuning. In the end our best model improved upon the baseline F1 and EM scores by almost 6% in both categories
Commercial Driver Medical Examinations: Prevalence of Obesity, Comorbidities, and Certification Outcomes

Objective: The objective of this study was to assess relationships between body mass index (BMI) and comorbid conditions within a large sample of truck drivers. Methods: Commercial driver medical examination data from 88,246 commercial drivers between 2005 and 2012 were analyzed for associations between BMI, medical disorders, and driver certiﬁcation. Results: Most drivers were obese (53.3%, BMI > 30.0 kg/m 2 ) and morbidly obese (26.6%, BMI > 35.0 kg/m 2 ), higher than prior reports. Obese drivers were less likely to be certiﬁed for 2 years and more likely to report heart dis- ease, hypertension, diabetes mellitus, nervous disorders, sleep disorders, and chronic low back pain (all P < 0.0001). There are relationships between multiple potentially disqualifying conditions and increasing obesity (P < 0.0001). Morbid obesity prevalence increased 8.9% and prevalence of three or more multiple conditions increased fourfold between 2005 and 2012. Conclusions: Obesity is related to multiple medical factors as well as in- creasing numbers of conditions that limit driving certiﬁcation.