Miracle-dz/UniFAR-FTUs huggingface dataset:
Customizable Ligand Exchange for Tailored Surface Property of Noble Metal Nanocrystals

It is highly desirable, while still challenging, to obtain noble metal nanocrystals with custom capping ligands, because their colloidal synthesis relies on specific capping ligands for the shape control while conventional ligand exchange processes suffer from “the strong replaces the weak” limitation, which greatly hinders their applications. Herein, we report a general and effective ligand exchange approach that can replace the native capping ligands of noble metal nanocrystals with virtually any type of ligands, producing flexibly tailored surface properties. The key is to use diethylamine with conveniently switchable binding affinity to the metal surface as an intermediate ligand. As a strong ligand, it in its original form can effectively remove the native ligands; while protonated, it loses its binding affinity and facilitates the adsorption of new ligands, especially weak ones, onto the metal surface. By this means, the irreversible order in the conventional ligand exchange processes could be overcome. The efficacy of the strategy is demonstrated by mutual exchange of the capping ligands among cetyltrimethylammonium, citrate, polyvinylpyrrolidone, and oleylamine. This novel strategy significantly expands our ability to manipulate the surface property of noble metal nanocrystals and extends their applicability to a wide range of fields, particularly biomedical applications.
Nutrition interventions implemented in hospital to lower risk of sarcopenia in older adults: A systematic review of randomised controlled trials

Abstract Aim There is no standardised interventional approach to preventing or treating sarcopenia in older adults in hospital. The aim of this review was to systematically identify and synthesise the effects of nutritional interventions on markers of sarcopenia in hospitalised patients aged 65 years and older. Methods Four databases were searched using terms for intervention, population and setting. Eligibility screening of title and abstract and then full‐text papers was competed in duplicate, independently. The final included papers were assessed for quality, and outcome data extracted independently and in duplicate. Outcome data were synthesised by meta‐analysis, where possible, or narratively. Results Seven hundred and thirty‐two articles were screened for eligibility yielding six studies for inclusion. All studies provided oral nutritional support that aimed to increase protein intake ranging from an additional 10 to 40 g/d, each with a unique formulation of amino acids and/or micronutrients; three studies combined nutritional intervention with an enhanced physical activity program. Five studies measured hand grip strength, the mean difference was 1.97 kg (95% CI 0.55‐3.39, P = .006) greater in the intervention group (n = 166) compared with control group (n = 165). Assessment of muscle mass and activities of daily living were heterogeneous and the changes inconsistent between studies. Conclusions Few studies inform nutritional management of inpatients with sarcopenia or at risk of sarcopenia. High quality, large intervention trials are needed urgently to identify the optimal nutrition and physical activity intervention combinations to manage sarcopenia in older hospitalised adults. These studies need to include outcome measures of physical function and muscle quality.
Role of the hippocampus in the spacing effect during memory retrieval

It is well known that distributed learning (DL) leads to improved memory performance compared with massed learning (ML) (i.e., spacing effect). However, the extent to which the hippocampus is involved in the spacing effect at shorter and longer retention intervals remains unclear. To address this issue, two groups of participants were asked to encode face–scene pairs at 20‐min, 1‐day, and 1‐month intervals before they were scanned using fMRI during an associative recognition task. The pairs were repeated six times in either a massed (i.e., six times in 1 day) or a distributed (i.e., six times over 3 days, twice per day) manner. The results showed that compared with that in the ML group, the activation of the left hippocampus was stronger in the DL group when the participants retrieved old pairs correctly and rejected new pairs correctly at different retention intervals. In addition, the posterior hippocampus was more strongly activated when the new associations were rejected correctly after DL than ML, especially at the 1‐month interval. Hence, our results provide evidence that the hippocampus is involved in better memory performance after DL compared to ML at both shorter and longer retention intervals.
Bayesian Spatial Survival Models for Hospitalisation of Dengue: A Case Study of Wahidin Hospital in Makassar, Indonesia

Spatial models are becoming more popular in time-to-event data analysis. Commonly, the intrinsic conditional autoregressive prior is placed on an area level frailty term to allow for correlation between areas. We considered a range of Bayesian Weibull and Cox semiparametric spatial models to describe a dataset on hospitalisation of dengue. This paper aimed to extend these two models, to evaluate the suitability of these models for estimation and prediction of the length of stay, compare different spatial priors, and determine factors that significantly affect the duration of hospital stay for dengue fever patients in the case study location, namely Wahidin hospital in Makassar, Indonesia. We compared two different models with three different spatial priors with respect to goodness of fit and generalisability. For all models considered, the Leroux prior was preferred over the intrinsic conditional autoregressive and independent priors, but Cox and Weibull versions had similar predictive performance, model fit, and results. Age and platelet count were negatively associated with the length of stay, while red blood cell count was positively associated with the length of stay of dengue patients at this hospital. Using appropriate Bayesian spatial survival models enables identification of factors that substantively affect the length of stay.
Cyclin F is involved in response to cisplatin treatment in melanoma cell lines

Cyclin F is a non-canonical cyclin which is a part of the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin-protein ligase complex. Cyclin F is responsible for target recognition, ubiquitination, and degradation of various molecular targets. This protein also controls genome stability through the degradation of ribonucleotide reductase subunit M2 (RRM2). In the present study, the difference between cyclin F expression in cell lines derived from primary and metastatic melanoma, A375 and RPMI-7951, respectively, were investigated using a western blot analysis and flow cytometry assays. A decrease in cyclin F expression in the A375 cells and an increase in RPMI-7951 cells after cisplatin treatment were observed. These changes may be related to a mutation in p53 in the RPMI-7951 cell line. Flow cytometry was conducted to observe that the RPMI-7951 cell line exhibited greater susceptibility to cisplatin, associated with lack of proper cell cycle control. Therefore, it is possible that cyclin F may modulate drug response in melanoma. The presented data describe cyclin F as a new potential factor that contributes to drug resistance in melanoma patients.
Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment—most likely via a cyclooxygenase-dependent mechanism.
miRNA‐mediated macrophage behaviors responding to matrix stiffness and ox‐LDL

Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low‐density lipoproteins (ox‐LDL) play important roles in atherosclerosis through modulating cellular behaviors. However, whether there is a synergistic effect for ox‐LDL and matrix stiffness on macrophages behavior has not been explored yet. In this study, we developed a model system to investigate the synergistic role of ox‐LDL and matrix stiffness on macrophage behaviors, such as migration, inflammatory and apoptosis. We found that there was a matrix stiffness‐dependent behavior of monocyte‐derived macrophages stimulated with ox‐LDL. What's more, macrophages were more sensitive to ox‐LDL on the stiff matrices compared to cells cultured on the soft matrices. Through next‐generation sequencing, we identified miRNAs in response to matrix stiffness and ox‐LDL and predicted pathways that showed the capability of miRNAs in directing macrophages fates. Our study provides a novel understanding of the important synergistic role of ox‐LDL and matrix stiffness in modulating macrophages behaviors, especially through miRNAs signaling pathways, which could be potential key regulators in atherosclerosis and immune‐targeted therapies.
Initial psychometric testing of the coach-adapted version of the empowering and disempowering motivational climate questionnaire: A Bayesian approach

ABSTRACT The present study examined the psychometric properties of the coach-adapted version of the Empowering and Disempowering Motivational Climate Questionnaire (EDMCQ) using Bayesian structural equation modelling (BSEM). The sample included 780 (M age = 36.4; SD = 10.8; males n = 698; females n = 54; 28 participants did not report sex) youth sport coaches representing five European countries (i.e., England, France, Greece, Norway, and Spain). The results did not support a 34-item five-factor, hierarchical, a two-factor BSEM, or a bifactor BSEM model across the participating countries. However, the results supported a reduced 19-item first-order, two-factor BSEM model that largely showed approximate metric invariance, but not approximate scalar invariance across the five countries. The pool of items constituting empowering and disempowering motivational climates should be refined to further enhance the empirical operationalisation of the coach-adapted version of the EDMCQ. Advancing the quality of translation-back-translation procedures across cultures and conducting multi-national pilot testing seems warranted as well. These recommendations may help to identify the distinctive aspects of each underlying sub-dimension of the EDMCQ, where coaches are the respondents, and pave the way for further examination of the proposed hierarchical multidimensional factor structure and the cross-cultural equivalence of the EDMCQ for this population.
Dlx1/2 mice have abnormal enteric nervous system function.

Decades ago, investigators reported that mice lacking DLX1 and DLX2, transcription factors expressed in the enteric nervous system (ENS), die with possible bowel motility problems. These problems were never fully elucidated. We found that mice lacking DLX1 and DLX2 (Dlx1/2-/- mice) had slower small bowel transit and reduced or absent neurally-mediated contraction complexes. In contrast, small bowel motility seemed normal in adult mice lacking DLX1 (Dlx1-/-). Even with detailed anatomic studies, we found no defects in ENS precursor migration, or neuron and glia density, in Dlx1/2-/- or Dlx1-/- mice. However, RNA sequencing of Dlx1/2-/- ENS revealed dysregulation of many genes, including vasoactive intestinal peptide (Vip). Our study reveals a novel connection between Dlx genes and Vip and highlights the observation that dangerous bowel motility problems can occur in the absence of easily identifiable ENS structural defects. These findings may be relevant for disorders like chronic intestinal pseudo-obstruction (CIPO) syndrome.
α-Globin Genotypes Associated with Hb H Disease: A Report from Oman and a Review of the Literature from the Eastern Mediterranean Region

Abstract α-Thalassemia (α-thal) is the most common autosomal recessive hemoglobinopathy. There is a vast diversity and geographical variability in underlying genotypes in Hb H (β4) patients. Herein, we describe the genotypes found in the largest report of Omani Hb H patients. Moreover, we reviewed and summarized the literature published from the Eastern Mediterranean region. A retrospective review of all genetically confirmed Hb H disease patients diagnosed between 2007 and 2017 at Sultan Qaboos University Hospital, Muscat, Oman, was performed. Hematological parameters and clinical presentations were assessed. Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. A total of 52 patients (27 females and 25 males) with a mean age of 20.6 years (range 0.23–80.0) were molecularly confirmed to carry Hb H disease. The patients had a hemoglobin (Hb) level of 9.3 g/dL (range 5.7–13.0) and mean corpuscular volume (MCV) of 58.4 fL (range 48.2–82.1). A total of eight genotype combinations were identified, with α2 polyadenylation signal mutation (polyA1) (AATAAA>AATAAG (αPA1α/αPA1α), often cited as αT-Saudiα/αT-Saudiα, being the most common (53.8%) followed by –α3. 7/– –MED I (28.8%). Our cohort also included patients with combinations of αPA1 with other Hb variants: αPA1α/αPA1α with Hb S (HBB: c.20A>T) trait (n = 2), –α3. 7/αPA1α (n = 2) and αcodon 19α (HBA2: c.56delG)/αPA1α (n = 1). Nondeletional Hb H disease due to the αPA1 mutation is the most common in Omanis. Molecular diagnosis is necessary for accurate confirmation of the diagnosis of α-thal, determination of underlying genotypes, follow-up and counseling.
High muscle‐to‐fat ratio is associated with lower risk of chronic kidney disease development

Obesity, a known risk factor for chronic kidney disease (CKD), is generally assessed using body mass index (BMI). However, BMI may not effectively reflect body composition, and the impact of muscle‐to‐fat (MF) mass balance on kidney function has not been elucidated. This study evaluated the association between body muscle and fat mass balance, represented as the MF ratio, and incident CKD development.
EMRE is essential for mitochondrial calcium uniporter activity in a mouse model.

The mitochondrial calcium uniporter is widely accepted as the primary route of rapid calcium entry into mitochondria, where increases in matrix calcium contribute to bioenergetics but also mitochondrial permeability and cell death. Hence, regulation of uniporter activity is critical to mitochondrial homeostasis. The uniporter subunit EMRE is known to be an essential regulator of the channel-forming protein MCU in cell culture, but EMRE's impact on organismal physiology is less understood. Here we characterize a novel mouse model of EMRE deletion and show that EMRE is indeed required for mitochondrial calcium uniporter function in vivo. EMRE-/- mice are born less frequently; however, the mice which are born are viable, healthy, and do not manifest overt metabolic impairment, at rest or with exercise. Finally, to investigate the role of EMRE in disease processes, we examine the effects of EMRE deletion in a muscular dystrophy model associated with mitochondrial calcium overload.
The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I

Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB.
Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice

Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% of diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording in hippocampal brain slices from male mice, we determined the electrophysiological properties of stratum radiatum astrocytes and CA1 pyramidal neurons. In diabetic mice, astrocytic Kir4.1 channels were functionally downregulated as evidenced by multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents and impaired potassium uptake capabilities of hippocampal astrocytes. Furthermore, CA1 pyramidal neurons from diabetic mice displayed increased spontaneous activity: action potential frequency was ≈9 times higher in diabetic compared with non-diabetic mice and small EPSC event frequency was significantly higher in CA1 pyramidal cells of diabetics compared to non-diabetics. These differences were apparent in control conditions and largely pronounced in response to the pro-convulsant 4-aminopyridine. Our data suggest that astrocytic dysfunction due to downregulation of Kir4.1 channels may increase seizure susceptibility by impairing astrocytic ability to maintain proper extracellular homeostasis.
A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients.

BACKGROUND In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens. PATIENTS AND METHODS This multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m2 and 1 g/m2) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m2). RESULTS Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62-1.51]}, with a median survival of 16.1 (CI 11.8-20.5) and 13.8 months (CI 10.8-16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60-1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9-15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1-14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001). CONCLUSIONS In this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.
Prenatal and childhood predictors of hair cortisol concentration in mid-childhood and early adolescence

Background Hair cortisol concentration (HCC) is an increasingly used measure of systemic cortisol concentration. However, determinants of HCC in children and adolescents are unclear because few prospective studies have been conducted to date. Study design We followed 725 children in Project Viva, a pre-birth cohort study of mothers and children, who provided hair samples at mid-childhood (median age: 7.7 years) or early adolescence (median age: 12.9 years). We examined associations of various factors measured from pregnancy to mid-childhood with HCC in mid-childhood and early adolescence, as well as change in HCC between these time points (ΔHCC). Results There were 426 children with HCC measurements in both mid-childhood and early adolescence, 173 children with measures only in mid-childhood, and 126 with measures only in early adolescence. HCC was lower in mid-childhood (median 1.0pg/mg [interquartile range, IQR: 0.5, 2.4]) than early adolescence (2.2pg/mg [1.1, 4.4]). In multivariable-adjusted regression models, female sex (β = -0.41, 95% CI: -0.67, -0.15) and birth weight-for-gestational age z-score (β = -0.19, 95% CI: -0.33, -0.04) were associated with lower mid-childhood HCC, while prenatal smoking was associated with higher mid-childhood HCC (β = 0.53, 95% CI: 0.04, 1.01). In early adolescence, child age (β = 0.34 per year, 95% CI: 0.21, 0.46) female sex (β = 0.33, 95% CI: 0.10, 0.57), and maternal pre-pregnancy body mass index (β = 0.15 per 5-kg/m2, 95% CI: 0.01, 0.29) were positively associated with HCC. Child anthropometric measures and biomarker concentrations were not associated with HCC. Conclusion Maternal pre-pregnancy BMI, maternal prenatal smoking, and low birth weight were associated with higher mid-childhood and adolescent HCC. However, few postnatal characteristics were associated with HCC.