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Big Data is still gaining attention as a fundamental building block of the Artificial Intelligence and Machine Learning world. Therefore, a lot of effort has been pushed into Big Data research in the last 15 years. The objective of this Systematic Literature Review is to summarize the current state of the art of the previous 15 years of research about Big Data by providing answers to a set of research questions related to the main application domains for Big Data analytics; the significant challenges and limitations researchers have encountered in Big Data analysis, and emerging research trends and future directions in Big Data. The review follows a predefined procedure that automatically searches five well-known digital libraries. After applying the selection criteria to the results, 189 primary studies were identified as relevant, of which 32 were Systematic Literature Reviews. Required information was extracted from the 32 studies and summarized. Our Systematic Literature Review sketched the picture of 15 years of research in Big Data, identifying application domains, challenges, and future directions in this research field. We believe that a substantial amount of work remains to be done to align and seamlessly integrate Big Data into data-driven advanced software solutions of the future. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV), the most common cardiovascular malformation occurs in 0.5–1.2% of the population. Although highly heritable, few causal mutations have been identified in BAV patients. Here, we report the targeted sequencing of HOXA1 in a cohort of BAV patients and the identification of rare indel variants in the homopolymeric histidine tract of HOXA1. In vitro analysis shows that disruption of this motif leads to a significant reduction in protein half-life and defective transcriptional activity of HOXA1. In zebrafish, targeting hoxa1a ortholog results in aortic valve defects. In vivo assays indicates that these variants behave as dominant negatives leading abnormal valve development. In mice, deletion of Hoxa1 leads to BAV with a very small, rudimentary non-coronary leaflet. We also show that 17% of homozygous Hoxa1−1His knock-in mice present similar phenotype. Genetic lineage tracing in Hoxa1−/− mutant mice reveals an abnormal reduction of neural crest-derived cells in the valve leaflet, which is caused by a failure of early migration of these cells. Bicuspid aortic valve (BAV) is the most common cardiac defect and although highly heritable, few causal mutations have been identified. Here, the authors identify variants in the poly-histidine repeat motif of HOXA1 and show that its disruption leads to BAV in mice. [ABSTRACT FROM AUTHOR]

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients. [ABSTRACT FROM AUTHOR]

The objective is to assess the impact of anticoagulant treatment in non-valvular atrial fibrillation (AF) and different categories of renal dysfunction in real world. Electronic Health recordings of patients with diagnosis of AF and renal function collected throughout 5 years and classified according to KDIGO categories. Stroke, transitory ischemic attack (TIA), intracranial hemorrhage and all-cause mortality were identified. Anticoagulant treatments during the study period were classified in untreated (never received therapy), VKA, NOAC and Aspirin. The risk of events was calculated by Cox-proportional hazard models adjusted by confounders. A total of 65,734 patients with AF, mean age 73.3 ± 10.49 years old and 47% females and follow-up of 3.2 years were included. KDIGO classification were: G1 33,903 (51.6%), G2 17,456 (26.6%), G3 8024 (12.2%) and G4 6351 (9.7%). There were 8592 cases of stroke and TIA, 437 intracranial hemorrhage, and 9603 all-cause deaths (incidence 36, 2 and 38 per 103 person/year, respectively). 4.1% of patients with CHA2DS2-VASc Score 2 or higher did not receive anticoagulant therapy. Risk of stroke, TIA, and all-cause mortality increased from G1 to G4 groups. Anticoagulant treatments reduced the risk of events in the four categories, but NOAC seemed to offer significantly better protection. Renal dysfunction increases the risk of events in AF and anticoagulant treatments reduced the risk of stroke and all-cause mortality, although NOAC were better than VKA. Efforts should be done to reduce the variability in the use of anticoagulants even in this high risk group. [ABSTRACT FROM AUTHOR]

The BRCA2 tumor suppressor protects genome integrity by promoting homologous recombination-based repair of DNA breaks, stability of stalled DNA replication forks and DNA damage-induced cell cycle checkpoints. BRCA2 deficient cells display the radio-resistant DNA synthesis (RDS) phenotype, however the mechanism has remained elusive. Here we show that cells without BRCA2 are unable to sufficiently restrain DNA replication fork progression after DNA damage, and the underrestrained fork progression is due primarily to Primase-Polymerase (PRIMPOL)-mediated repriming of DNA synthesis downstream of lesions, leaving behind single-stranded DNA gaps. Moreover, we find that BRCA2 associates with the essential DNA replication factor MCM10 and this association suppresses PRIMPOL-mediated repriming and ssDNA gap formation, while having no impact on the stability of stalled replication forks. Our findings establish an important function for BRCA2, provide insights into replication fork control during the DNA damage response, and may have implications in tumor suppression and therapy response. Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage. [ABSTRACT FROM AUTHOR]

Background: Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH). Methods: This single-center and retrospective study was conducted in a tertiary care specialist headache center in France. Patients were selected between January 2007 and December 2008. We included all patients fulfilling CCH criteria (ICHD-3-beta). Data were collected from medical records. We recorded all the prescriptions of IMC as a prophylactic treatment. Responders were defined by 50% reduction in attack frequency; complete response was defined by disappearance of the attacks. The non-responders must have received at least 100 mg daily during 7 days. Results: The study consisted of 324 CCH, 121 female (37%) and 203 males (63%) with an average age at onset of 33.93 (± 14.71) years. Of the patients, 105 were treated with IMC. Thirty patients (29%) were responders. Thirty-four patients (32%) were non-responders. Responding status was undefined for 41 patients (39%). Twelve patients (11%) had a complete response. Responders were composed by 18 women (60%) and 12 men (40%) and had on average 44.89 (± 12.88) years. The minimal effective dose was 86.11 mg daily (± 48.72). Discussion: This study shows the interest of IMC in CCH patients. We recommend an IMC test as a third-line treatment in CCH. [ABSTRACT FROM AUTHOR]

Organic matter has an important role in biogeochemistry in aquatic environments. This study investigated impact of suspended particulate organic matter (SPOM) on fluorescence signal of mixtures of three water types (river water RW, sea water SW, effluent wastewater WW) using fluorescence (excitation-emission matrix, EEM) spectroscopy and parallel factor analysis (PARAFAC) and multilinear regression. Four irradiation experiments (Expt-1, Expt-2, Expt-3, and Expt-4) were conducted during different times of the year (two in autumn, one in winter, and one in spring season). Samples were exposed to natural sunlight on laboratory rooftop in University of Toulon, France, with another set of samples kept in dark as control samples. Three component (C1, C2, C3) model was validated by split-half and Concordia from the whole EEM dataset of all irradiation experiments. No protein-like fluorophores was found. The study revealed the effect of SPOM presence/absence on fluorescence signal of DOM and on resulting parameters of multilinear regression MLR model and kinetic constant of these MLR parameters. Kinetic constant (k) for all MLR coefficients was in order of greatness as Expt-1 (SPOM of WW only in mixtures) > Expt-3 (SPOM of SW only in mixtures) > Expt-2 (SPOM of RW only in mixtures)> Expt-4 (SPOM of RW + SW + WW in mixtures) indicating that SPOM of WW is the most resistant to photodegradation. For dark control samples, only relative standard deviation RSD could be calculated from dataset. RSD values for C3 were the highest indicating its chaotic variations, and the lowest RSD values were found for both C1 and C2 for all experiments. Statistical differences has been found between control and irradiated experiments. These models developed in this study can be used to predict fluorescence signal of anthropogenic effluent DOM during its transport in river systems to coastal zone. [ABSTRACT FROM AUTHOR]