Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data.

BACKGROUND Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. METHODS To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. RESULTS Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. CONCLUSIONS Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.
The 24 hour savings of adaptation to novel movement dynamics initially reflects the recall of previous performance.

Humans rapidly adapt reaching movements in response to perturbations (e.g., manipulations of movement dynamics or visual feedback). Following a break, when re-exposed to the same perturbation, subjects demonstrate savings-a faster learning rate compared to the timecourse of initial training. Although well studied, there are open questions on the extent early savings reflects the rapid recall of previous performance. To address this question we examined how the properties of initial training (duration and final adaptive state) influence initial single-trial adaptation to force-field perturbations when training sessions were separated by 24 hours. There were two main groups that were distinct based on the presence or absence of a washout period at the end of Day 1 (with washout versus without washout). We also varied the training duration on Day 1 (15, 30, 90 or 160 training trials) resulting in eight subgroups of subjects. We show that single-trial adaptation on Day 2 scales with training duration, even for similar asymptotic levels of learning on Day 1 of training. Interestingly, the temporal force profile following the first perturbation on Day 2 matched that at the end of Day 1 for the longest training duration group that did not complete the washout. This correspondence persisted, but was significantly lower for shorter training durations and the washout subject groups. Collectively, the results suggest that the adaptation observed very early in re-exposure results from the rapid recall of the previously learned motor recalibration, but is highly dependent on the initial training duration and final adaptive state.
Data Mining for a student database

Educational data mining is an emerging research area that produces useful, previously unknown issues from educational database for better understanding and improving the performance and assessment of the student learning process (see [2] and the included references, for a detailed description of the state of the art in this context). This paper presents some data mining models to analyze the careers of University students and extends the research illustrated in [1], introducing a new approach to this research area. The career of a student can be analyzed from various points of view, among which the following two are particularly important: i) the perspective of the student, who evaluates how difficult and important an exam is, in order to decide to take it immediately at the end of the course, or delay it as much as possible; this aspect is studied in Section 2 with cluster and classification algorithms by introducing a notion of distance between careers; and ii) the perspective of each course, by analyzing the distribution of students with respect to the delay with which they take an examination, to discover common characteristics between two or more courses; this is done in Section 3 in terms of Poisson distributions.
Experimental Evidence for Adaptation to Species-Specific Gut Microbiota in House Mice

The communities of bacteria that reside within mammalian guts are deeply integrated with their hosts, but the impact of this gut microbiota on mammalian evolution remains poorly understood. Experimental transplantation of the gut microbiota between mouse species revealed that foreign gut microbiotas lowered the host growth rate and upregulated the expression of an immunomodulating cytokine. In addition, foreign gut microbiotas increased host liver sizes and attenuated sex-specific differences in host muscle and fat content. These results suggest that the house mouse has adapted to its species-specific gut microbiota. ABSTRACT The gut microbial communities of mammals have codiversified with host species, and changes in the gut microbiota can have profound effects on host fitness. Therefore, the gut microbiota may drive adaptation in mammalian species, but this possibility is underexplored. Here, we show that the gut microbiota has codiversified with mice in the genus Mus over the past ∼6 million years, and we present experimental evidence that the gut microbiota has driven adaptive evolution of the house mouse, Mus musculus domesticus. Phylogenetic analyses of metagenome-assembled bacterial genomic sequences revealed that gut bacterial lineages have been retained within and diversified alongside Mus species over evolutionary time. Transplantation of gut microbiotas from various Mus species into germfree M. m. domesticus showed that foreign gut microbiotas slowed growth rate and upregulated macrophage inflammatory protein in hosts. These results suggest adaptation by M. m. domesticus to its gut microbiota since it diverged from other Mus species. IMPORTANCE The communities of bacteria that reside within mammalian guts are deeply integrated with their hosts, but the impact of this gut microbiota on mammalian evolution remains poorly understood. Experimental transplantation of the gut microbiota between mouse species revealed that foreign gut microbiotas lowered the host growth rate and upregulated the expression of an immunomodulating cytokine. In addition, foreign gut microbiotas increased host liver sizes and attenuated sex-specific differences in host muscle and fat content. These results suggest that the house mouse has adapted to its species-specific gut microbiota.
Hydroxylated long-chain acylcarnitines are biomarkers of mitochondrial myopathy.

CONTEXT Plasma acylcarnitines are biomarkers of beta-oxidation and are useful in diagnosing several inborn errors of metabolism but has never been systematically investigated in patients with mitochondrial myopathy. OBJECTIVE We hypothesized that acylcarnitines can also be biomarkers of mitochondrial myopathy and sought to investigate the prevalence and pattern of elevated acylcarnitines. DESIGN The study was a prospective cohort study of patients with confirmed mitochondrial myopathy followed at Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen, Denmark. PATIENTS We included 35 patients (44±15 years, 15 women) with mitochondrial myopathy caused by single, large-scale deletions of mt-DNA (n=17), pathogenic variants in mt-tRNA (n=13) or in proteins of the respiratory chain complexes (n=5). Concentrations of 35 acylcarnitines were measured using ultra-high-performance liquid-chromatography and tandem mass-spectrometry. Findings were compared to muscle mutation load in all patients, and to respiratory chain activity in 26 patients. MAIN OUTCOME MEASURES Prevalence of elevated concentrations of acylcarnitines related to acyl-CoA dehydrogenases in patients with mitochondrial myopathy and relation to geno-/phenotypes. RESULTS In total, 27 (77%) patients had elevated concentrations of acylcarnitines related to acyl-CoA dehydrogenases. Elevated concentrations of seven acylcarnitine species were significantly more common in patients compared to a control cohort of> 900 individuals, and a specific pattern involving hydroxylated long-chain acylcarnitines occurred in 22 (63%) patients. Severity of derangements was correlated with muscle mutation load and geno-/phenotypes. CONCLUSION In conclusion, elevated concentrations of acylcarnitines is common in patients with mitochondrial myopathy and shows a specific pattern affecting hydroxylated long-chain acylcarnitines, which can have implications for future diagnostic work-up of patients.
Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory

Background: Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. Methods: Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). Results: Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being (r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases. Conclusions: Here we validate a six-item ‘Emotional Breakthrough Inventory’. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.
Efficient anti-tumor nano-lipoplexes with unsaturated or saturated lipid induce differential genotoxic effects in mice

Abstract Cationic lipids are well-known excipients for nanometric liposomal gene delivery systems. However, because of the suspected, collateral toxicity in normal cells, the use of cationic lipids for the treatment of human tumor is largely limited. Recently, we developed a glucocorticoid receptor (GR)-targeted liposomal, anticancer delivery system (DXE nano-lipoplex), which carried cationic lipid of saturated twin aliphatic chains. It exhibited efficient anti-tumor effect in aggressive and drug-resistant tumor models. Toward exploring lipoplex’s human clinical use, we incorporated another nano-lipoplex (D1XE) group that carried cationic lipid with one of its aliphatic chain carrying unsaturation and compared in vivo genotoxicological profiling-based safety assessment and the respective anti-tumor efficacy of the lipoplexes. Thus, both the lipoplexes differ only by the chemical identity of one of their constituent cationic lipid. Unsaturated aliphatic chains in lipid generally impart efficient cell surface fusogenic property in lipid formulations. Herein, we report that nanoplex with unsaturated cationic lipid (D1XE) exhibited better physical appearance with less flocculent behavior than nanoplex with saturated lipid (DXE). Upon multiple injections, D1XE nanoplex imparted better tumor regression but most importantly, exhibited much lower overall toxicity (e.g. genotoxicity, weight loss, etc.) than DXE nanoplex. With a higher antitumor effect but a lower genotoxic effect, D1XE is proved to be a better nanoplex than DXE for the potential clinical trial. Thus, this study clearly delineates the importance of incorporating a constituent lipid that carries a single unsaturated aliphatic chain toward developing efficient anti-tumor nano-lipoplexes with reduced genotoxicity.
Impaired microvascular reactivity after eccentric muscle contractions is not restored by acute ingestion of antioxidants or dietary nitrate

Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg serving as nonexercising control (CON). Participants were randomized into three groups ingesting an antioxidant cocktail (AO), beetroot juice (BR) or placebo 46 h postexercise. At baseline and 48 h postexercise, hyperemic responses to brief muscle contractions and 5 min of cuff occlusion were assessed bilaterally in the TA muscles using blood oxygen level dependent (BOLD) magnetic resonance imaging. Eccentric contractions resulted in delayed time‐to‐peak (~22%; P < 0.001), blunted peak (~21%; P < 0.001) and prolonged time‐to‐half relaxation (~12%, P < 0.001) in the BOLD response to brief contractions, with no effects of AO or BR, and no changes in CON. Postocclusive time‐to‐peak was also delayed (~54%; P < 0.001) in ECC, with no effects of AO or BR, and no changes in CON. Impaired microvascular reactivity after eccentric contractions is confined to the exercised tissue, and is not restored with acute ingestion of AO or BR. Impairments in microvascular reactivity after unaccustomed eccentric contractions may result from structural changes within the microvasculature that can diminish muscle blood flow regulation during intermittent activities requiring prompt adjustments in oxygen delivery.
Full-Squat as a Determinant of Performance in CrossFit

Abstract This study analyzed the relationship between CrossFit performance and power and strength variables measured in the full-squat exercise. Twenty male trained subjects (33±7 years) performed an incremental load full-squat test for assessment of the 1-repetition maximum (1RM) and the mean (Pmean) and peak (Ppeak) power. Performance in 5 different Workouts of the Day (WODs) was measured on different days, and overall CrossFit performance was determined as the sum of the scores obtained in these WODs. Athletes were then assigned to a high (HP) or low (LP) performance group based on the median score for overall performance. Correlation analysis between squat variables and performance was performed and between-group differences were assessed. Moderate to strong (r=0.47–0.69, p<0.05) positive correlations were found between squat variables and performance in the different WODs. Overall CrossFit performance was strongly and positively associated with absolute (r=0.62, p=0.01) and relative 1RM (r=0.65, p=0.07), and relative Pmean (r=0.56, p=0.02) and Ppeak (r=0.53, p=0.03). Large differences (effect sizes ranging 1.1–1.7, all p<0.05) were observed between HP and LP for absolute and relative 1RM, relative Pmean, and absolute and relative Ppeak. In summary, strength and power indexes measured in a squat test are positively associated with CrossFit performance.
Edge Capping of 2D-MXene Sheets with Polyanionic Salts to Mitigate Oxidation in Aqueous Colloidal Suspensions.

MXenes have shown promise in many applications such as energy storage, catalysis, EMI shielding, among many others. However, MXene oxidation in aqueous colloidal suspensions when stored in water at ambient conditions remains a challenge. Herein we show that by simply capping the edges of individual MXene flakes - Ti3C2Tz and V2CTz - by polyanions such as polyphosphates, polysilicates and polyborates it is possible to quite significantly reduce their propensity for oxidation even in aerated water for weeks. This breakthrough resulted from the realization that the edges of MXene sheets were positively charged. It is thus the first example of selectively functionalizing the edges differently from the MXene sheet surfaces.
Microtubule depletion domain 1 localizes at the boundary between female gametes in Arabidopsis thaliana

To support their skeleton-less bodies, plants have rigid cell walls that consist mainly of cellulose. During fertilization, however, a thick gamete cell wall blocks plasmogamy. In several plant species, the central cell and the egg apparatus (egg cell and synergid cell) lack a cell wall at their boundary (Huang & Russell, 1992). This cell wall boundary is also discontinuous in Brassicaceae species, such as Capsella bursa-pastoris and Arabidopsis thaliana (Schulz & Jensen, 1968; Tekleyohans, Mao, Kägi, Stierhof, & Groß-Hardt, 2017), which provides space for successful fertilization. However, little is known about the underlying molecular mechanism.
Polyvinyl alcohol-poly acrylic acid bilayer oral drug delivery systems: A comparison between thin films and inverse double network bilayers

Polymer network structures in the design of bilayer hydrogels for oral drug delivery systems contribute to the mechanical stability as well as the stimulus responsive drug release. We report a strategy to improve the stability of polyelectrolyte layer interfaces in bilayer hydrogels by employing concepts from tough interpenetrating hydrogel network design. Polyvinyl alcohol as the neutral substrate and Polyacrylic acid as the pH-sensitive layer were used to prepare bilayers capable of pH-sensitive bending behavior, and inverse double network structures were compared to conventional thin film coated bilayers in this study. The morphology of the bilayers observed after exposure to stimulus revealed that the polyacrylic acid layer was fragmented in conventional thin films. The delamination of the coating also had an adverse impact on bending behavior. Additionally, bilayers with inverse double network structure had a better pH-sensitive swelling behavior which was lacking in regular thin films. Controllable, pH-specific drug release behavior was a direct benefit of using the inverse double network structure, and was demonstrated by controlled vancomycin release under different pHs chosen to simulate the physiological milieu of exposure corresponding to hydrogel passage along the gastrointestinal tract. Additionally, the inverse double networks showed improved mucoadhesive properties and mechanical stability compared to the thin film bilayers. The use of inverse double network structured hydrogels has many potential applications in improving bilayer hydrogel stability; specifically, for drug delivery systems, designing hydrogel origamis, and to prepare soft material actuators.
The contemporary view of intellectual and developmental disabilities: Implications for psychologists.

BACKGROUND The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially regarding shared aspects such as a focus on the human and legal rights, the eligibility for services and supports, and an emphasis on individualized supports provided within inclusive community-based environments. Accompanying this transformation is the increased need of precision in both the operational definitions of IDD-related constructs, and the terminology used to describe the respective construct. METHOD the specialized literature was revised, and previous works on the subject by the authors were updated. RESULTS This article provides psychologists with the current definition of intellectual disability, operational definitions of intellectual disability and developmental disabilities constructs and associated terminology, and the parameters of an integrated approach to disability. CONCLUSIONS Implications for psychologists who are involved in diagnosis, classification, and planning supports for persons with intellectual or developmental disability are discussed.
K+ and the renin–angiotensin–aldosterone system: new insights into their role in blood pressure control and hypertension treatment

Approximately 25% of the adult population is diagnosed with hypertension and it is therefore one of the biggest challenges for the health sector. The renin–angiotensin–aldosterone system (RAAS) adjusts effective circulating volume and ultimately blood pressure (BP). Accordingly, antihypertensive drugs targeting the RAAS have been a major focus in modern medical treatment. Low and high dietary K+ intakes are associated with increased or decreased BP and risk of cardiac failure, respectively, suggesting that dietary K+ augmentation has the potential to supplement or replace conventional anti‐hypertensive drugs. Animal studies have indicated that the beneficial effects of high dietary K+ may be linked to a dominant regulatory role of plasma K+ on key renal transport proteins controlled by the RAAS. However, only a limited number of studies have investigated whether the reported mechanisms in animal models apply to humans. Furthermore, hypertension is often treated with so‐called ‘K+ sparing’ drugs, thus complicating co‐treatment with K+ supplementation. In this review, we revisit old concepts of RAAS effects in the kidney, relate them to effects of dietary K+ manipulation, and finally consider the clinical potential of treating hypertension with K+ supplementation alone or in combination with RAAS inhibitors. Collectively, a wealth of data suggest that increased dietary K+ intake may have beneficial effects on BP in the general population, but underlying medical conditions or current treatment regimens need to be carefully considered before implementing K+ supplementation in patients.