STAR: Steiner tree approximation in relationship-graphs

Large-scale graphs and networks are abundant in modern information systems: entity-relationship graphs over relational data or Web-extracted entities, biological networks, social online communities, knowledge bases, and many more. Often such data comes with expressive node and edge labels that allow an interpretation as a semantic graph, and edge weights that reflect the strengths of semantic relations between entities. Finding close relationships between a given set of two, three, or more entities is an important building block for many search, ranking, and analysis tasks. From an algorithmic point of view, this translates into computing the best Steiner trees between the given nodes, a classical NP-hard problem. In this paper, we present a new approximation algorithm, coined STAR, for relationship queries over large graphs that do not fit into memory. We prove that for n query entities, STAR yields an O(log(n))-approximation of the optimal Steiner tree, and show that in practical cases the results returned by STAR are qualitatively better than the results returned by a classical 2-approximation algorithm. We then describe an extension to our algorithm to return the top-k Steiner trees. Finally, we evaluate our algorithm over both main-memory as well as completely disk-resident graphs containing millions of nodes. Our experiments show that STAR outperforms the best state-of-the returns qualitatively better results

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department

Introduction: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians\u2019 decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. Areas covered: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients\u2019 clinical pathways in an ED setting. Expert opinion: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician\u2019s decision making and recognizing the \u2018ill looking well\u2019 and the \u2018well looking ill\u2019 sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally

L-dopa and dopamine-(R)-alpha-lipoic acid conjugates as multifunctional codrugs with antioxidant properties

A series of multifunctional codrugs (1-4), obtained by joining L-Dopa (LD) and dopamine (DA) with (R)-R-lipoic acid (LA), was synthesized and evaluated as potential codrugs with antioxidant and iron-chelating properties. These multifunctional molecules were synthesized to overcome the pro-oxidant effect associated with LD therapy. The physicochemical properties, together with the chemical and enzymatic stabilities of synthesized compounds, were evaluated in order to determine both their stability in aqueous medium and their sensitivity in undergoing enzymatic cleavage by rat and human plasma to regenerate the original drugs. The new compounds were tested for their radical scavenging activities, using a test involving the Fe (II)- H2O2-induced degradation of deoxyribose, and to evaluate peripheral markers of oxidative stress such as plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma. Furthermore, we showed the central effects of compounds 1 and 2 on spontaneous locomotor activity of rats in comparison with LD-treated animals. From the results obtained, compounds 1-4 appeared stable at a pH of 1.3 and in 7.4 buffered solution; in 80% human plasma they were turned into DA and LD. Codrugs 1-4 possess good lipophilicity (log P > 2 for all tested compounds). Compounds 1 and 2 seem to protect partially against the oxidative stress deriving from auto-oxidation and MAO-mediated metabolism of DA. This evidence, together with the “in vivo” dopaminergic activity and a sustained release of the parent drug in human plasma, allowed us to point out the potential advantages of using 1 and 2 rather than LD in treating pathologies such as Parkinson’s disease, characterized by an evident decrease of DA concentration in the brain

Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test

Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n=12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n=12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P<0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted

D-Dimer as Biomarker for Early Prediction of Clinical Outcomes in Patients With Severe Invasive Infections Due to Streptococcus Pneumoniae and Neisseria Meningitidis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; no current clinical measure adequately reflects the concept of dysregulated response. Coagulation plays a pivotal role in the normal response to pathogens (immunothrombosis), thus the evolution toward sepsis-induced coagulopathy could be individuate through coagulation/fibrinolysis-related biomarkers. We focused on the role of D-dimer assessed within 24 h after admission in predicting clinical outcomes in a cohort of 270 patients hospitalized in a 79 months period for meningitis and/or bloodstream infections due to Streptococcus pneumoniae (n = 162) or Neisseria meningitidis (n = 108). Comparisons were performed with unpaired t-test, Mann-Whitney-test or chi-squared-test with continuity correction, as appropriate, and multivariable logistic regression analysis was performed with Bayesian model averaging. In-hospital mortality was 14.8% for the overall population, significantly higher in S. pneumoniae than in N. meningitidis patients: 19.1 vs. 8.3%, respectively (p = 0.014). At univariable logistic regression analysis the following variables were significantly associated with in-hospital mortality: pneumococcal etiology, female sex, age, ICU admission, SOFA score, septic shock, MODS, and D-dimer levels. At multivariable analysis D-dimer showed an effect only in N. meningitidis subgroup: as 500 ng/mL of D-dimer increased, the probability of unfavorable outcome increased on average by 4%. Median D-dimer was significantly higher in N. meningitidis than in S. pneumoniae patients (1,314 vs. 1,055 ng/mL, p = 0.009). For N. meningitidis in-hospital mortality was 0% for D-dimer 7,000 ng/mL. Kaplan-Meier analysis of in-hospital mortality showed for N. meningitidis infections a statistically significant difference for D-dimer >7,000 ng/mL compared to values <500 ng/mL (p = 0.021) and 500\u20133,000 ng/mL (p = 0.002). For S. pneumoniae the mortality risk resulted always high, over 10%, irrespective by D-dimer values. In conclusion, D-dimer is rapid to be obtained, at low cost and available everywhere, and can help stratify the risk of in-hospital mortality and complications in patients with invasive infections due to N. meningitidis: D-dimer <500 ng/mL excludes any further complications, and a cut-off of 7,000 ng/mL seems able to predict a significantly increased mortality risk from much <10% to over 25%

Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine.

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iβ interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care

Codrugs linking L-Dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson’s Disease

A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD