Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Multiscale multifactorial approaches for engineering tendon substitutes

The physiology of tendons and the continuous strains experienced daily make tendons very prone to injury. Excessive and prolonged loading forces and aging also contribute to the onset and progression of tendon injuries, and conventional treatments have limited efficacy in restoring tendon biomechanics. Tissue engineering and regenerative medicine (TERM) approaches hold the promise to provide therapeutic solutions for injured or damaged tendons despite the challenging cues of tendon niche and the lack of tendon-specific factors to guide cellular responses and tackle regeneration. The roots of engineering tendon substitutes lay in multifactorial approaches from adequate stem cells sources and environmental stimuli to the construction of multiscale 3D scaffolding systems. To achieve such advanced tendon substitutes, incremental strategies have been pursued to more closely recreate the native tendon requirements providing structural as well as physical and chemical cues combined with biochemical and mechanical stimuli to instruct cell behavior in 3D architectures, pursuing mechanically competent constructs with adequate maturation before implantation.Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marinederived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Authors acknowledge the H2020 Achilles Twinning Project No. 810850, and also the European Research Council CoG MagTendon No. 772817, and the FCT Project MagTT PTDC/CTM-CTM/ 29930/2017 (POCI-01-0145-FEDER-29930

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Therapeutic potential of thymoquinone in regulating p63, claudin, and periostin in chronic rhinosinusitis with nasal polyps: An animal model study

High recurrence rate and the necessity for repeated surgical interventions contribute to the chronicity and treatment-resistant nature of chronic rhinosinusitis with nasal polyps (CRSwNP). Thymoquinone, known for its protective effects on epithelial integrity, has not been previously explored in CRSwNP. The aim of this study was to investigate the therapeutic potential of thymoquinone to restore epithelial integrity by assessing p63 transcription factor and claudin protein expressions, as well as periostin mRNA expression in an animal model. An in vivo study using post-test-only control group design was conducted in which male Wistar rats were randomly assigned to three groups, each consisting of 10 animals: healthy group, CRSwNP group, and thymoquinone-treated group for three weeks. Immunohistochemistry was used to analyze the p63 and claudin protein expressions, while periostin mRNA expression was quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). This study found that thymoquinone significantly reduced p63 transcription factor expression compared to the untreated CRSwNP group (p=0.009). Claudin protein expression was significantly higher in thymoquinone-treated group compared to CRSwNP group (p=0.007), indicating improved epithelial barrier function. Periostin mRNA expression showed no significant difference between healthy and thymoquinone-treated groups (p=0.564), but a significant decrease was observed in CRSwNP group compared to thymoquinone-treated group (p=0.000) and between the healthy and CRSwNP groups (p=0.002), suggesting attenuation of tissue remodeling and inflammation. In conclusion, thymoquinone could enhance sinonasal epithelial barrier integrity in CRSwNP by downregulating p63 transcription factor, upregulating claudin protein expression, and reducing periostin mRNA expression. These findings emphasize the potential of thymoquinone as a therapeutic agent to mitigate inflammation and tissue remodeling in CRSwNP, warranting further investigation as a novel treatment option