Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery and Further Studies on Giant Viruses at the IHU Mediterranee Infection That Modified the Perception of the Virosphere

The history of giant viruses began in 2003 with the identification of Acanthamoeba polyphaga mimivirus. Since then, giant viruses of amoeba enlightened an unknown part of the viral world, and every discovery and characterization of a new giant virus modifies our perception of the virosphere. This notably includes their exceptional virion sizes from 200 nm to 2 µm and their genomic complexity with length, number of genes, and functions such as translational components never seen before. Even more surprising, Mimivirus possesses a unique mobilome composed of virophages, transpovirons, and a defense system against virophages named Mimivirus virophage resistance element (MIMIVIRE). From the discovery and isolation of new giant viruses to their possible roles in humans, this review shows the active contribution of the University Hospital Institute (IHU) Mediterranee Infection to the growing knowledge of the giant viruses’ field.
Family businesses restrict accrual and real earnings management: Case study in Saudi Arabia

Abstract This paper investigates accrual earnings management (AEM) and real earnings management (REM) in family businesses (FB) in Saudi Arabia. Current literature indicates that minority rights are confiscated by the controlling shareholders in a business environment weak to protect investors. Based on this argument, considering the various implications of AEM and REM on family businesses, the results show evidence that family businesses in Saudi Arabia engaged in both types of earnings management during the period 2014–2018, with a positive and signiﬁcant effect on both AEM and REM. This evidence supports the entrenchment hypothesis that FB have lower earnings quality due to manipulation in accruals and real activities. The results therefore indicate that earnings announced in Saudi family businesses’ financial statements are less reliable. These findings, that family-controlled firms are able to manipulate earnings, should be considered by regulators and policy makers.
Saline Environments as a Source of Potential Quorum Sensing Disruptors to Control Bacterial Infections: A Review

Saline environments, such as marine and hypersaline habitats, are widely distributed around the world. They include sea waters, saline lakes, solar salterns, or hypersaline soils. The bacteria that live in these habitats produce and develop unique bioactive molecules and physiological pathways to cope with the stress conditions generated by these environments. They have been described to produce compounds with properties that differ from those found in non-saline habitats. In the last decades, the ability to disrupt quorum-sensing (QS) intercellular communication systems has been identified in many marine organisms, including bacteria. The two main mechanisms of QS interference, i.e., quorum sensing inhibition (QSI) and quorum quenching (QQ), appear to be a more frequent phenomenon in marine aquatic environments than in soils. However, data concerning bacteria from hypersaline habitats is scarce. Salt-tolerant QSI compounds and QQ enzymes may be of interest to interfere with QS-regulated bacterial functions, including virulence, in sectors such as aquaculture or agriculture where salinity is a serious environmental issue. This review provides a global overview of the main works related to QS interruption in saline environments as well as the derived biotechnological applications.
Hydrothermal Carbonization as a Valuable Tool for Energy and Environmental Applications: A Review

Hydrothermal carbonization (HTC) represents an efficient and valuable pre-treatment technology to convert waste biomass into highly dense carbonaceous materials that could be used in a wide range of applications between energy, environment, soil improvement and nutrients recovery fields. HTC converts residual organic materials into a solid high energy dense material (hydrochar) and a liquid residue where the most volatile and oxygenated compounds (mainly furans and organic acids) concentrate during reaction. Pristine hydrochar is mainly used for direct combustion, to generate heat or electricity, but highly porous carbonaceous media for energy storage or for adsorption of pollutants applications can be also obtained through a further activation stage. HTC process can be used to enhance recovery of nutrients as nitrogen and phosphorous in particular and can be used as soil conditioner, to favor plant growth and mitigate desertification of soils. The present review proposes an outlook of the several possible applications of hydrochar produced from any sort of waste biomass sources. For each of the applications proposed, the main operative parameters that mostly affect the hydrochar properties and characteristics are highlighted, in order to match the needs for the specific application.
Apoptotic resistance in chronic lymphocytic leukemia and therapeutic perspectives

Abstract Increased resistance to apoptosis represents a key oncogenic mechanism in chronic lymphocytic leukemia (CLL) that has been attributed to the upregulation of the anti-apoptotic B cell lymphoma 2 (Bcl-2) family members. Such an observation was associated with the development of molecules inhibiting Bcl-2 activity, and among them, BH3-mimetics represent a novel class of therapeutic compounds. In 2016, venetoclax became the first approved oral inhibitor of Bcl-2, and it has been used with success in patients with CLL who present with a 17p deletion or TP53 mutations and in those who have received at least one prior therapy. However, its mechanism for controlling relapses, and its optimal use in terms of duration and combinations with other drugs, remain unknown. Therefore, this review focuses on the mechanisms controlling apoptosis, CLL B cell strategies to prevent apoptosis including in response to BH3-mimetics, and arguments supporting the use of BH3-mimetics in association with other therapies in order to limit compensatory mechanisms.
Assessing Support for Advantaged and Disadvantaged Groups: A Comparison of Urban Food Environments

Individuals from lower-socio-economic status (SES) communities have increased risk of developing obesity in developed countries such as Australia. Given the influence of the environment on dietary behaviour, this paper seeks to examine food environments in areas of differing social advantage. An established measurement tool (the NEMS—Nutrition Environment Measurement Survey), that captures aspects of support for healthy eating within restaurants (NEMS-R) and grocery/convenience stores (NEMS-S), was applied to both a high-SES and a low-SES suburb within Brisbane, Australia. The study found a significantly more supportive restaurant food environment in the high-SES suburb, with greater access to and availability of healthful foods, as well as facilitators for, reduced barriers to, and substantially more nutrition information for healthful eating. A higher number of outlets were found in the high-SES suburb, and later opening times were also observed. Overall, the results from stores (NEMS-S) suggest poor support for healthful eating across both suburbs. This study highlights how food environments in low-SES regions continue to be less supportive of healthful eating. Public health strategies must move beyond individual-focused strategies to ensure that our most disadvantaged, low-SES communities have an equal opportunity to access healthful foods.
Implementation of antibiotic stewardship programmes in French ICUs in 2018: a nationwide cross-sectional survey.

BACKGROUND Antibiotic stewardship programmes have a pivotal role in ICUs, but the level of implementation of these programmes at the regional or national level is not well known. OBJECTIVES The aim of our study was to assess the level of implementation of antibiotic stewardship programmes in French ICUs. METHODS We conducted a nationwide cross-sectional survey from January to March 2018 using an online questionnaire sent as an E-mail link to ICU specialists (one questionnaire per ICU). RESULTS Overall, 113 out of 206 (55%) ICUs participated. Access to local epidemiology regarding bacterial resistance and antibiotic consumption data was reported in 84% and 65% of ICUs, respectively. Local guidelines for antibiotic use were available in 54% of ICUs. The duration of empirical antibiotic therapy was limited in 46% of cases, following the recommendation of an external expert in 33%. An antibiotic stewardship programme leader was reported at the hospital level by 94% of respondents, being an infectious disease physician in 80%. His/her role in the ICU was mostly to discuss specific cases (50%) and to provide advice on antibiotic prescriptions (26%). Regarding microbiological diagnosis, blood cultures were not processed at night or during weekends in 57%. Molecular biology and MS techniques were available in 62% and 59% of cases, respectively. Therapeutic drug monitoring of β-lactams was available in 46% of cases. Forty-three percent of respondents knew the expression 'antimicrobial/antibiotic stewardship'. CONCLUSIONS Antibiotic stewardship programmes are not optimally implemented in French ICUs. Improvement efforts and regular monitoring of the level of implementation are needed.
THE EFFECT OF GIVING DELTAMETHRIN AND CYPERMETHRIN INSECTICIDES ON THE LEVEL OF INTRATESTICULAR TESTOSTERONE IN MALE WISTAR STRAIN RATS

Email: ika.puspitasari@gmail.com The use of deltamethrin and cypermethrin insecticides to control pests has been implemented in Indonesia. Irregular and excessive use of insecticides can have toxic effects on the male reproductive system. Deltamethrin and cypermethrin insecticides can inhibit androgen biosynthesis and disrupt the growth of sperm. Therefore, this research was conducted to determine the effect of deltamethrin and cypermethrin insecticides toward the level of intratesticular testosterone in male Wistar strain rats. This research was conducted in vivo using male Wistar strain rats. Nine rats were divided into three groups of treatment, namely control group, deltamethrin group with 0.26mg/kg of weight, and cypermethrin group with 0.26mg/kg of weight. Treatment was conducted every day for 15 days orally, and then the rats were dissected to take their testicles. Testicles were chopped and their intratesticular homogenates were taken by adding the medium of DMEM and collagenase (0.25mg/mL). The measurement of the level of testosterone was conducted by using the Electrochemiluminescence immunoassay (ECLIA) method. Data on the change of the increase of bodyweight, organ weight, and the level of testosterone was analyzed statistically using the one-way ANOVA test. The research result shows that giving 0.26mg/kg of weight of deltamethrin and 0.26mg/kg of weight of cypermethrin does not affect the increase in bodyweight, relative weight of the reproductive organ, and the level of intratesticular testosterone of male Wistar strain rats.
What’s the rate of knee osteoarthritis 10 years after anterior cruciate ligament injury? An updated systematic review

Background This updated systematic review reports data from 2009 on the prevalence, and risk factors, for knee osteoarthritis (OA) more than 10 years after anterior cruciate ligament (ACL) tear. Methods We systematically searched five databases (PubMed, EMBASE, AMED, Cinahl and SPORTDiscus) for prospective and retrospective studies published after 1 August 2008. Studies were included if they investigated participants with ACL tear (isolated or in combination with medial collateral ligament and/or meniscal injuries) and reported symptomatic and/or radiographic OA at a minimum of 10 years postinjury. We used a modified version of the Downs and Black checklist for methodological quality assessment and narrative synthesis to report results. The study protocol was registered in PROSPERO. Results Forty-one studies were included. Low methodological quality was revealed in over half of the studies. At inclusion, age ranged from 23 to 38 years, and at follow-up from 31 to 51 years. Sample sizes ranged from 18 to 780 participants. The reported radiographic OA prevalence varied between 0% and 100% >10 years after injury, regardless of follow-up time. The studies with low and high methodological quality reported a prevalence of radiographic OA between 0%–100% and 1%–80%, respectively. One study reported symptomatic knee OA for the tibiofemoral (TF) joint (35%), and one study reported symptomatic knee OA for the patellofemoral (PF) joint (15%). Meniscectomy was the only consistent risk factor determined from the data synthesis. Conclusion Radiographic knee OA varied between 0% and 100% in line with our previous systematic review from 2009. Symptomatic and radiographic knee OA was differentiated in two studies only, with a reported symptomatic OA prevalence of 35% for the TF joint and 15% for PF joint. Future cohort studies need to include measurement of symptomatic knee OA in this patient group. PROSPERO registration number CRD42016042693.
Chemical synthesis rewriting of a bacterial genome to achieve design flexibility and biological functionality

Significance The fundamental biological functions of a living cell are stored within the DNA sequence of its genome. Classical genetic approaches dissect the functioning of biological systems by analyzing individual genes, yet uncovering the essential gene set of an organism has remained very challenging. It is argued that the rewriting of entire genomes through the process of chemical synthesis provides a powerful and complementary research concept to understand how essential functions are programed into genomes. Understanding how to program biological functions into artificial DNA sequences remains a key challenge in synthetic genomics. Here, we report the chemical synthesis and testing of Caulobacter ethensis-2.0 (C. eth-2.0), a rewritten bacterial genome composed of the most fundamental functions of a bacterial cell. We rebuilt the essential genome of Caulobacter crescentus through the process of chemical synthesis rewriting and studied the genetic information content at the level of its essential genes. Within the 785,701-bp genome, we used sequence rewriting to reduce the number of encoded genetic features from 6,290 to 799. Overall, we introduced 133,313 base substitutions, resulting in the rewriting of 123,562 codons. We tested the biological functionality of the genome design in C. crescentus by transposon mutagenesis. Our analysis revealed that 432 essential genes of C. eth-2.0, corresponding to 81.5% of the design, are equal in functionality to natural genes. These findings suggest that neither changing mRNA structure nor changing the codon context have significant influence on biological functionality of synthetic genomes. Discovery of 98 genes that lost their function identified essential genes with incorrect annotation, including a limited set of 27 genes where we uncovered noncoding control features embedded within protein-coding sequences. In sum, our results highlight the promise of chemical synthesis rewriting to decode fundamental genome functions and its utility toward the design of improved organisms for industrial purposes and health benefits.
Another Look at the Relationship between Portfolio Returns and Market Multiples

Equity investors are always interested in identifying profitable trading strategies. The price-to-earnings ratio (P/E) and price-to-sales ratio (P/S) are two simple metrics that researchers have reported may meet this objective under particular market conditions. During our study period, which is longer in duration than most of the previous works, the performance of portfolios based on P/S dominated those based on P/E. However, portfolios based upon the combination of low P/E and net profit momentum outperformed all other strategies tested. Another way the predictive power of P/E may be improved is by dividing it by a measure of the firm’s earnings growth, yielding a composite metric known as the price-to-earnings-to-earnings growth ratio (PEG). This metric has gained the attention of professional investors and researchers. Because many investors prefer P/S over P/E, it is surprising that a counterpart to PEG has not gained similar traction. Our results provide evidence that helps explain why the price-to-sales-to-sales growth ratio (PSG) has failed to gain attention. Our results also indicate that none of these market multiples alone can be employed to provide consistently profitable investment performance.
Association Between Enthesitis and Health-related Quality of Life in Psoriatic Arthritis in Biologic-naive Patients from 2 Phase III Ustekinumab Trials

Objective. Evaluate enthesitis, physical function, and health-related quality of life (HRQOL) among patients with psoriatic arthritis (PsA) who are naive to anti–tumor necrosis factor agents. Methods. In PSUMMIT 1 and 2, patients with PsA were randomized to placebo or ustekinumab 45 mg or 90 mg. Enthesitis was assessed at weeks 0 and 24 (Maastricht Ankylosing Spondylitis Enthesitis Score). Assessments included Health Assessment Questionnaire–Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 (SF-36) physical component summary/mental component summary (PCS/MCS), and American College of Rheumatology 20 (ACR20). Results. At Week 24, 21 had worsened enthesitis, 158 had improved enthesitis, and 412 had unchanged enthesitis. Improved enthesitis was associated with improvements in HAQ-DI and SF-36 MCS. Results were similar for ACR20 responders and nonresponders. Conclusion. Improvement in enthesitis at Week 24 was associated with improvements in physical function/HRQOL regardless of ACR20 response.
Accuracy and Prognostic Significance of Oncologists' Estimates and Scenarios for Survival Time in Advanced Gastric Cancer.

BACKGROUND Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists' estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. MATERIALS AND METHODS Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists' estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise (<33% within 0.67-1.33 times the OST); independently predictive of overall survival (OS); and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario). RESULTS Oncologists' estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67-1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists' estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. CONCLUSION Oncologists' estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. IMPLICATIONS FOR PRACTICE Results of this study demonstrate that oncologists' estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.
A Comprehensive Review of Bioactive Glass Coatings: State of the Art, Challenges and Future Perspectives

Bioactive glasses are promising biomaterials for bone and tissue repair and reconstruction, as they were shown to bond to both hard and soft tissues stimulating cells towards a path of regeneration and self-repair. Unfortunately, due to their relatively poor mechanical properties, such as brittleness, low bending strength and fracture toughness, their applications are limited to non-load-bearing implants. However, bioactive glasses can be successfully applied as coatings on the surface of metallic implants to combine the appropriate mechanical properties of metal alloys to bioactivity and biocompatibility of bioactive glasses. In this review, several available coating techniques to coat metal alloys using bioactive glasses are described, with a special focus on thermal spraying, which nowadays is the most used to deposit coatings on metallic implants.
An Acid Up-Regulated Surface Protein of Lactobacillus paracasei Strain GCRL 46 is Phylogenetically Related to the Secreted Glucan- (GpbB) and Immunoglobulin-Binding (SibA) Protein of Pathogenic Streptococci

Bacterial cell wall hydrolases, including amidases and peptidases, play a critical role in peptidoglycan turnover during growth, impacting daughter cell separation, and cell death, through autolysis. When exploring the regulation of protein expression across the growth cycle of an acid-resistant strain of Lactobacillus paracasei, GCRL 46, we observed temporal up-regulation of proteins in the 40–45 kDa molecular weight range for whole-cell extracts when culturing in fermenters at a controlled pH of 4.0 versus optimum growth pH of 6.3. Up-regulation of proteins in this size range was not detected in SDS-PAGE gels of the cytosolic fraction, but was routinely detected following growth at low pH in whole cells and cell debris obtained after bead beating and centrifugation, indicating a cell surface location. N-terminal sequencing and in silico analyses showed sequence similarity with proteins in the L. casei group (L. casei, L. paracasei and L. rhamnosus) which were variously annotated as uncharacterized proteins, surface antigens, possible TrsG proteins, CHAP (cysteine, histidine-dependent amidohydrolases/peptidases)-domain proteins or putative peptidoglycan d,l-endopeptidase due to the presence of a CwlO domain. This protein is a homologue of the p40 (Msp2) secreted protein of L. rhamnosus LGG, which is linked to probiotic functionality in this species, and is phylogenetically related to structurally-similar proteins found in Enterococcus, Streptococcus and Bifidobacterium species, including the glucan-binding (GbpB), surface antigen (SagA) proteins detected in pathogenic group A streptococci species as secreted, immunoglobulin-binding (SibA) proteins (also named PcsB). Three-dimensional (3D) modelling predicted structural similarities in the CHAP proteins from the L. casei group and streptococcal species, indicating retention of overall architecture despite sequence divergence, and an implied retention of function during evolution. A phylogenetically-related hydrolase also contained the CwlO domain with a NLPC_P60 domain, and showed similar overall but distinct architecture to the CHAP proteins. We concluded that the surface-located, CHAP protein in L. casei is up-regulated during long-term exposure to acidic conditions during growth but not during acid shock.