Miracle-dz/UniFAR-FTUs huggingface dataset:
A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia.

BACKGROUND Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is inconclusive. METHODS We conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (non-invasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7(death) at 14 days, and primary analysis was performed in the intention-to-treat population. RESULTS Between April 4, 2020 and February 5, 2021, 350 patients were randomly assigned to either CP (n=179) or SOC (n=171). At 14 days, proportion of patients on categories 5, 6 or 7 was 11.7% in CP group versus 16.4% in control group (p=0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in CP group versus 17.0% in control group (p=0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95%CI 0.19-1.14, log-rank p=0.087). CONCLUSION CP showed a significant benefit in preventing progression to non-invasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant. TRIAL REGISTRATION clinicaltrials.gov, NCT04345523FUNDING. Government of Spain, Instituto de Salud Carlos III.
Acute cerebral microbleeds at the edge of lacunar strokes: cause or result

We investigated the pathogenic relationship between cerebral microbleeds and lacunar strokes. Two cases of lacunar strokes in the region of the basal ganglia, a 72-year-old man and a 67-year-old man, were studied; both cases showed cerebral microbleeds in the stroke areas. The cerebral microbleeds were surrounded by oedema, and the oedema faded out over time, suggesting the cerebral microbleeds had developed acutely. The cerebral microbleeds were located at the ventrolateral edge of the lacunar infarctions, and the locations appeared to be at or near the sites of occlusion of the lenticulostriatal branches. Although a cerebral microbleed and a lacunar infarction may be two unrelated events on juxtapositioned vessels, or a cerebral microbleed may be haemorrhagic conversion of an infarction, a cerebral microbleed could cause an occlusion of the arterial branch, leading to lacunar infarction of its supplying territories.
Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy

Cancer is known as a second major cause of death globally. Nowadays, several modalities have been developed for the treatment of cancer. Radiotherapy and chemotherapy are the most common modalities in most countries. However, newer modalities such as immunotherapy and targeted therapy drugs can kill cancer cells with minimal side effects. All anticancer agents work based on the killing of cancer cells. Numerous studies are ongoing to kill cancer cells more effectively without increasing side effects to normal tissues. The combination modalities with low toxic agents are interesting for this aim. Curcumin is one of the most common herbal agents that has shown several anticancer properties. It can regulate immune system responses against cancer. Furthermore, curcumin has been shown to potentiate cell death signalling pathways and attenuate survival signalling pathways in cancer cells. The knowledge of how curcumin induces cell death in cancers can improve therapeutic efficiency. In this review, the regulatory effects of curcumin on different cell death mechanisms and their signalling pathways will be discussed. Furthermore, we explain how curcumin may potentiate the anticancer effects of other drugs or radiotherapy through modulation of apoptosis, mitotic catastrophe, senescence, autophagy and ferroptosis.
European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment

The optimal management of post-stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment and prognosis. These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post-stroke cognitive impairment and most acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on acute MRI brain may help predict cognitive outcomes. These guidelines have highlighted fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research.
Western lowland gorillas (Gorilla gorilla gorilla) do not show an aversion to inequity in a token exchange task

Although individuals in some species refuse foods they normally accept if their partner receives a more preferred one, this is not true across all species. The cooperation hypothesis proposes that this species‐level variability evolved because inequity aversion is a mechanism to identify situations in which cooperation is not paying off, and that species regularly observed cooperating should be more likely to be averse to inequity. To rule out other potential explanations of inequity aversion, we need to test the converse as well: species rarely observed cooperating, especially those phylogenetically close to more cooperative species, should be less likely to be inequity averse. To this end, we tested eight zoo‐housed Western lowland gorillas (Gorilla gorilla gorilla) on a token exchange task in which subjects received either the same food reward or a less‐preferred reward for the same or more effort than their partner, recording both refusals to participate in the exchange and refusals to accept the reward. Supporting the cooperation hypothesis, even with procedural differences across sessions, gorillas were significantly more likely to refuse in all conditions in which they received a low‐value food reward after completing an exchange, regardless of what their partner received, suggesting that gorillas were not inequity averse, but instead would not work for a low‐value reward. Additionally, gorillas were more likely to refuse later in the session; while the pattern of refusals remained unchanged after accounting for this, this suggests that species should be tested on as many trials as is practical.
The nature of the self: Neural analyses and heritability estimates of self‐evaluations in middle childhood

How neural correlates of self‐concept are influenced by environmental versus genetic factors is currently not fully understood. We investigated heritability estimates of behavioral and neural correlates of self‐concept in middle childhood since this phase is an important time window for taking on new social roles in academic and social contexts. To do so, a validated self‐concept fMRI task was applied in a twin sample of 345 participants aged between 7 and 9 years. In the self‐concept condition, participants were asked to indicate whether academic and social traits applied to them whereas the control condition required trait categorization. The self‐processing activation analyses (n = 234) revealed stronger medial prefrontal cortex (mPFC) activation for self than for control conditions. This effect was more pronounced for social‐self than academic self‐traits, whereas stronger dorsolateral prefrontal cortex (DLPFC) activation was observed for academic versus social self‐evaluations. Behavioral genetic modeling (166 complete twin pairs) revealed that 25–52% of the variation in academic self‐evaluations was explained by genetic factors, whereas 16–49% of the variation in social self‐evaluations was explained by shared environmental factors. Neural genetic modeling (91 complete twin pairs) for variation in mPFC and anterior prefrontal cortex (PFC) activation for academic self‐evaluations confirmed genetic and unique environmental influences, whereas anterior PFC activation for social self‐evaluations was additionally influenced by shared environmental influences. This indicates that environmental context possibly has a larger impact on the behavioral and neural correlates of social self‐concept at a young age. This is the first study demonstrating in a young twin sample that self‐concept depends on both genetic and environmental factors, depending on the specific domain.
Dietary sodium intake and sodium load is associated with arterial stiffness in children and young adults

Objective: The aim of this study was to examine the association of sodium intake (g/day) and sodium load (Na-L; mg/kcal/day) on arterial stiffness in youth. Methods: A cross-sectional analysis of 723 youth enrolled in a study evaluating the cardiovascular effects of obesity and type 2 diabetes mellitus (T2DM). Three measures of arterial stiffness were evaluated: brachial distensibility (BrachD), carotid-femoral pulse wave velocity (PWVcf) and augmentation index (AIx). Three-day diet histories yielded mean daily sodium and calorie intake. Youth were divided into Na-L tertiles: Low (≤1.67 mg/kcal per day); Medium (1.68--1.98 mg/kcal per day) and High (>1.98 mg/kcal per day). General linear models adjusting for demographics, % body fat, T2DM and SBP z-score evaluated the independent association of Na-L with arterial stiffness Results: Mean age was 17.9 years (10–24 years), 35% male, 59% nonwhite and 31% T2DM. Mean (±standard deviation) dietary intake was calories = 2074 (±797) kcal/day; Na = 3.793 (±1567) g/day; Na- = 1.86 (±0.753) mg/kcal per day. With higher levels of dietary Na intake and Na-L, measures of arterial stiffness worsened: BrachD decreased (Na intake: beta = −0.09, P = 0.003; Na-L: beta = −0.28, P < 0.0001), PWVcf increased (Na intake: beta = 0.07, P = 0.007; Na-L: beta = 0.21, P < 0.0001) but AIx did not change (Na intake: beta = −0.4, P = 0.2; Na-L: beta = 0.89, P = 0.11). In multivariable analysis, High Na-L was independently associated with BrachD, PWVcf and AIx (P < 0.05 for all), with age modifying the association of High Na-L with PWVcf and AIx. Conclusion: Sodium intake and load are associated with arterial stiffness, a preclinical measure of CVD, among a paediatric population. Paediatricians should stress healthy dietary choices to reduce accelerated vascular ageing.
Increased Serum Levels of soluble ST2 as a Predictor of Disease Progression in Systemic Sclerosis

Objective Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. Method Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. Results Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017–1.126, p < 0.009). Conclusion In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.
Functional characterization of naturally-occurring constitutively activating/inactivating mutations in equine follicle-stimulating hormone receptor

Objective Follicle-stimulating hormone (FSH) is the central hormone involved in mammalian reproduction, maturation at puberty, and gamete production that mediates its function by control of follicle growth and function. The present study investigated the mutations involved in the regulation of FSH receptor (FSHR) activation. Methods We analyzed seven naturally-occurring mutations that were previously reported in human FSHR (hFSHR), in the context of equine FSHR (eFSHR); these include one constitutively activation variant, one allelic variant, and five inactivating variants. These mutations were introduced into wild-type eFSHR (eFSHR-wt) sequence to generate mutants that were designated as eFSHR-D566G, -A306T, -A189V, -N191I, -R572C, -A574V, and -R633H. Mutants were transfected into PathHunter EA-parental CHO-K1 cells expressing β-arrestin. The biological function of mutants was analyzed by quantitating cAMP accumulation in cells incubated with increasing concentrations of FSH. Results Cells expressing eFSHR-D566G exhibited an 8.6-fold increase in basal cAMP response, as compared to that in eFSHR-wt. The allelic variation mutant eFSHR-A306T was not found to affect the basal cAMP response or half maximal effective concentration (EC50) levels. On the other hand, eFSHR-D566G and eFSHR-A306T displayed a 1.5- and 1.4-fold increase in the maximal response, respectively. Signal transduction was found to be completely impaired in case of the inactivating mutants eFSHR-A189V, -R572C, and -A574V. When compared with eFSHR-wt, eFSHR-N191I displayed a 5.4-fold decrease in the EC50 levels (3,910 ng/mL) and a 2.3-fold decrease in the maximal response. In contrast, cells expressing eFSHR-R633H displayed in a similar manner to that of the cells expressing the eFSHR-wt on signal transduction and maximal response. Conclusion The activating mutant eFSHR-D566G greatly enhanced the signal transduction in response to FSH, in the absence of agonist treatment. We suggest that the state of activation of the eFSHR can modulate its basal cAMP accumulation.
Clinical Outcome Data of First Cohort of Chronic Pain Patients Treated With Cannabis‐Based Sublingual Oils in the United Kingdom: Analysis From the UK Medical Cannabis Registry

Cannabis‐based medicinal products (CBMPs) are an emerging therapeutic option in the management of primary chronic pain, using the role of the endocannabinoid system in modulating central and peripheral pain processes. Despite promising preclinical data, there is a paucity of high‐quality evidence to support the use of CBMPs for chronic pain. This study aimed to investigate the health‐related quality‐of‐life outcomes of patients with chronic pain who were prescribed CBMP oil preparations (Adven, Curaleaf International, Guernsey, UK).
Prevalence and predictors of medication non-adherence among people living with multimorbidity: a systematic review and meta-analysis

Objectives This systematic review aimed to describe medication non-adherence among people living with multimorbidity according to the current literature, and synthesise predictors of non-adherence in this population. Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. PubMed, EMBASE, CINAHL and PsycINFO were searched for relevant articles published in English language between January 2009 and April 2019. Quantitative studies reporting medication non-adherence and/or predictors of non-adherence among people with two or more chronic conditions were included in the review. A meta-analysis was conducted with a subgroup of studies that used an inclusive definition of multimorbidity to recruit participants, rather than seeking people with specific conditions. Remaining studies reporting prevalence and predictors of non-adherence were narratively synthesised. Results The database search produced 10 998 records and a further 75 were identified through other sources. Following full-text screening, 178 studies were included in the review. The range of reported non-adherence differed by measurement method, at 76.5% for self-report, 69.4% for pharmacy data, and 44.1% for electronic monitoring. A meta-analysis was conducted with eight studies (n=8949) that used an inclusive definition of multimorbidity to recruit participants. The pooled prevalence of non-adherence was 42.6% (95% CI: 34.0 - 51.3%, k=8, I 2=97%, p<0.01). The overall range of non-adherence was 7.0%–83.5%. Frequently reported correlates of non-adherence included previous non-adherence and treatment-related beliefs. Conclusions The review identified a heterogeneous literature in terms of conditions studied, and definitions and measures of non-adherence used. Results suggest that future attempts to improve adherence among people with multimorbidity should determine for which conditions individuals require most support. The variable levels of medication non-adherence highlight the need for more attention to be paid by healthcare providers to the impact of multimorbidity on chronic disease self-management. PROSPERO registration number CRD42019133849.
Peak exercise SBP and future risk of cardiovascular disease and mortality

Supplemental Digital Content is available in the text Objectives: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing. Methods: Data from 10 096 clinical exercise tests (54% men, age 18—85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations. Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile. Results: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59–2.52) in men and 2.60 (1.97–3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28–1.89, men) and 1.34 (1.05–1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22–0.54) and 0.72 (0.57–0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted. Conclusion: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity.
Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant

Abstract The role of allogeneic hematopoietic cell transplant (allo-HCT) as consolidation after initial venetoclax therapy and the efficacy of venetoclax salvage therapy for relapse after allo-HCT in patients with acute myeloid leukemia (AML) are unclear. We conducted a retrospective study of patients with AML or myelodysplastic syndrome (MDS) who received venetoclax either before or after allo-HCT at Memorial Sloan Kettering Cancer Center and Yale University from 11 August 2016 to 16 November 2020. Among 39 heavily pretreated patients who received venetoclax before allo-HCT, median OS from allo-HCT was not reached after a median follow up of 12.5 months resulting in a 12-month OS estimate of 79.0%. In 37 patients who had received venetoclax-based combinations as salvage therapy after allo-HCT, the overall response rate was 32% with a median OS of 4.7 months (12-month OS estimate: 43.4%). Four patients underwent a second allo-HCT following venetoclax-based salvage therapy suggesting it as a potential salvage treatment option.
Efficient Deterministic Search With Robust Loss Functions for Geometric Model Fitting

Geometric model fitting is a fundamental task in computer vision, which serves as the pre-requisite of many downstream applications. While the problem has a simple intrinsic structure where the solution can be parameterized within a few degrees of freedom, the ubiquitously existing outliers are the main challenge. In previous studies, random sampling techniques have been established as the practical choice, since optimization-based methods are usually too time-demanding. This prospective study is intended to design efficient algorithms that benefit from a general optimization-based view. In particular, two important types of loss functions are discussed, i.e., truncated and <inline-formula><tex-math notation="LaTeX">$l_1$</tex-math><alternatives><mml:math><mml:msub><mml:mi>l</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:math><inline-graphic xlink:href="ma-ieq1-3109784.gif"/></alternatives></inline-formula> losses, and efficient solvers have been derived for both upon specific approximations. Based on this philosophy, a class of algorithms are introduced to perform deterministic search for the inliers or geometric model. Recommendations are made based on theoretical and experimental analyses. Compared with the existing solutions, the proposed methods are both simple in computation and robust to outliers. Extensive experiments are conducted on publicly available datasets for geometric estimation, which demonstrate the superiority of our methods compared with the state-of-the-art ones. Additionally, we apply our method to the recent benchmark for wide-baseline stereo evaluation, leading to a significant improvement of performance. Our code is publicly available at <uri>https://github.com/AoxiangFan/EifficientDeterministicSearch</uri>.