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The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear factor-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin [DHMEQ] treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-κB as a potential target for breast cancer treatment.

Previous studies investigating the effects of transcranial direct current stimulation (tDCS) on muscle strength showed no consensus. Therefore, the purpose of this article was to systematically review the literature on the effects of single dose tDCS to improve muscle strength. A systematic literature search was conducted on PubMeb, ISI Web of Science, SciELO, and Scopus using search terms regarding tDCS and muscle strength. Studies were included in accordance with Population, Intervention, Comparison, Outcomes, and Setting (PICOS) including criteria. Healthy men and women, strength training practitioners or sedentary were selected. The acute effects of single dose anode stimulus of tDCS (a-tDCS) and the placebo stimulus of tDCS (sham) or no interventions were considered as an intervention and comparators, respectively. Measures related to muscle strength were analyzed. To conduct the analyses a weighted mean difference (WMD) and the standardized mean difference (SMD) were applied as appropriate. A total of 15 studies were included in this systematic review and 14 in meta-analysis. Regarding the maximal isometric voluntary contraction (MIVC), a small effect was seen between tDCS and Sham with significant difference between the conditions (SMD = 0.29; CI95% = 0.05 to 0.54; Z = 2.36; p = 0.02). The muscular endurance measured by the seconds sustaining a percentage of MIVC demonstrated a large effect between tDCS and Sham (WMD = 43.66; CI95% = 29.76 to 57.55; Z = 6.16; p < 0.001), showing an improvement in muscular endurance after exposure to tDCS. However, muscular endurance based on total work showed a trivial effect between tDCS and Sham with no significant difference (SMD = 0.22; CI95% = -0.11 to 0.54; Z = 1.32, p = 0.19). This study suggests that the use of tDCS may promote increase in maximal voluntary contraction and muscular endurance through isometric contractions.

It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). In univariate analyses, there were no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85–0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85–0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53–0.79), school closures (RRR 0.63, 95% CI 0.52–0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45–0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis. For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose–response relation, we used preparation-specific covariates assuming linearity on log relative dose. We identified 8973 manuscripts from our search, of which 76 randomised trials with a total of 58 451 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] −0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES −0·57, 95% credibility interval [CrI] −0·69 to −0·45) and etoricoxib 60 mg/day (ES −0·58, −0·74 to −0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0·034). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis. On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients. Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.

There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. Meta-epidemiological study within Cochrane Database of Systematic Reviews. Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis. Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6. The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.

Launched on 12 Aug. 2018, NASA’s Parker Solar Probe had completed 13 of its scheduled 24 orbits around the Sun by Nov. 2022. The mission’s primary science goal is to determine the structure and dynamics of the Sun’s coronal magnetic field, understand how the solar corona and wind are heated and accelerated, and determine what processes accelerate energetic particles. Parker Solar Probe returned a treasure trove of science data that far exceeded quality, significance, and quantity expectations, leading to a significant number of discoveries reported in nearly 700 peer-reviewed publications. The first four years of the 7-year primary mission duration have been mostly during solar minimum conditions with few major solar events. Starting with orbit 8 (i.e., 28 Apr. 2021), Parker flew through the magnetically dominated corona, i.e., sub-Alfvénic solar wind, which is one of the mission’s primary objectives. In this paper, we present an overview of the scientific advances made mainly during the first four years of the Parker Solar Probe mission, which go well beyond the three science objectives that are: (1) Trace the flow of energy that heats and accelerates the solar corona and solar wind; (2) Determine the structure and dynamics of the plasma and magnetic fields at the sources of the solar wind; and (3) Explore mechanisms that accelerate and transport energetic particles.

To compare the psychological responses to continuous (CT) and high-intensity interval training (HIT) sessions. Fifteen men attended one CT session and one HIT session. During the first visit, the maximum heart rate, VO2Peak and respiratory compensation point (RCP) were determined through a maximal cardiopulmonary exercise test. The HIT stimulus intensity corresponded to 100% of VO2Peak, and the average intensity of both sessions was maintained at 15% below the RCP. The order of the sessions was randomized. Psychological and physiological variables were recorded before, during and after each session. There were no significant differences between the average percentages of VO2 during the two exercise sessions (HIT: 73.3% vs. CT: 71.8%; p = 0.779). Lower responses on the feeling scale (p≤0.01) and higher responses on the felt arousal scale (p≤0.001) and the rating of perceived exertion were obtained during the HIT session. Despite the more negative feeling scale responses observed during HIT and a greater feeling of fatigue (measured by Profile of Mood States) afterwards (p<0.01), the physical activity enjoyment scale was not significantly different between the two conditions (p = 0.779). Despite the same average intensity for both conditions, similar psychological responses under HIT and CT conditions were not observed, suggesting that the higher dependence on anaerobic metabolism during HIT negatively influenced the feeling scale responses.

Recent research has shown that criminal networks have complex organizational structures, but whether this can be used to predict static and dynamic properties of criminal networks remains little explored. Here, by combining graph representation learning and machine learning methods, we show that structural properties of political corruption, police intelligence, and money laundering networks can be used to recover missing criminal partnerships, distinguish among different types of criminal and legal associations, as well as predict the total amount of money exchanged among criminal agents, all with outstanding accuracy. We also show that our approach can anticipate future criminal associations during the dynamic growth of corruption networks with significant accuracy. Thus, similar to evidence found at crime scenes, we conclude that structural patterns of criminal networks carry crucial information about illegal activities, which allows machine learning methods to predict missing information and even anticipate future criminal behavior.

This manuscript presents the quantification and correlation of three aspects of Alzheimer’s Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer’s Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer’s Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A β 1-40, A β 1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey’s Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.

In a randomized, controlled trial involving patients with membranous nephropathy, rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission for up to 24 months.