Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials

ABSTRACT Background: In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). Methods: To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Results: Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Conclusions: Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.
Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

Aggregatibacter actinomycetemcomitans generates citrullinated autoantigens involved in rheumatoid arthritis through its pore-forming toxin leukotoxin A. A joint effect of bacteria and genetics Although rheumatoid arthritis is an autoimmune disease, scientists have long suspected that bacterial infections (and in particular, periodontal infections) may play a role in its pathogenesis. Konig et al. now demonstrate that a particular periodontal pathogen called Aggregatibacter actinomycetemcomitans (Aa) induces changes in neutrophil function, including hypercitrullination of host proteins, an abnormality that is also observed in the joints of patients with rheumatoid arthritis. Moreover, the effect of HLA-DRB1, an allele associated with increased risk of rheumatoid arthritis, was only observed in patients exposed to Aa, suggesting the possibility of eventually using these results to identify and possibly even treat high-risk patients. A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls. Periodontitis was characterized by the presence of citrullinated autoantigens that are primary immune targets in RA. The citrullinome in periodontitis mirrored patterns of hypercitrullination observed in the rheumatoid joint, implicating this mucosal site in RA pathogenesis. Proteomic signatures of several microbial species were detected in hypercitrullinated periodontitis samples. Among these, Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils. We identified the pore-forming toxin leukotoxin A (LtxA) as the molecular mechanism by which Aa triggers dysregulated activation of citrullinating enzymes in neutrophils, mimicking membranolytic pathways that sustain autoantigen citrullination in the RA joint. Moreover, LtxA induced changes in neutrophil morphology mimicking extracellular trap formation, thereby releasing the hypercitrullinated cargo. Exposure to leukotoxic Aa strains was confirmed in patients with RA and was associated with both anticitrullinated protein antibodies and rheumatoid factor. The effect of human lymphocyte antigen–DRB1 shared epitope alleles on autoantibody positivity was limited to RA patients who were exposed to Aa. These studies identify the periodontal pathogen Aa as a candidate bacterial trigger of autoimmunity in RA.
Human T-cell leukaemia virus type 1: parasitism and pathogenesis

Human T-cell leukaemia virus type 1 (HTLV-1) causes not only adult T-cell leukaemia-lymphoma (ATL), but also inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 transmits primarily through cell-to-cell contact, and generates abundant infected cells in the host in order to survive and transmit to a new host. The resulting high proviral load is closely associated with the development of ATL and inflammatory diseases. To increase the number of infected cells, HTLV-1 changes the immunophenotype of infected cells, induces proliferation and inhibits apoptosis through the cooperative actions of two viral genes, tax and HTLV-1 bZIP factor (HBZ). As a result, infected cells survive, proliferate and infiltrate into the tissues, which is critical for transmission of the virus. Thus, the strategy of this virus is indivisibly linked with its pathogenesis, providing a clue for prevention and treatment of HTLV-1-induced diseases. This article is part of the themed issue ‘Human oncogenic viruses’.
FORMULATIO AND EVALUATION OF ZOLMITRIPTAN BILAYER ORAL STRIP

Oral strip is one of acceptable and palatable delivery system assist patients in any age to be easily administered. Zolmitriptan is a 5HT receptor agonist used to relief migraine attack was studied to formulate it as a bilayer oral strip, both layers disintegrates within seconds but each layer has its own drug release (the first layer formulate to release drug rapidly while the second layer release its drug in a sustained release manner) the first release to get rapid mask the migraine attack and the second release to prevent recurrent attack for certain time period, this strip formulated by casting and spraying techniques to get bilayer film with sufficient physical and mechanical properties using different hydrophilic and hydrophobic polymers with different plasticizers in different ratios and concentrations and study their effects on the in-vitro disintegration time, the mechanical properties of the film and also the in-vitro release profile, other studied parameters such as drug-excipients compatibility were evaluated. The disintegration time of the optimized formula (Fx10) was 32 sec. ; release 50% of the drug within first 15 minutes and the remaining drug released as sustained reach to 4 hours. The fast release profile compared with the marketed zolmitriptan oral dispersible tablet. FTIR and DSC thermogram studies indicate no presence of incompatibility with the excipients either during mixing or during casting.
Time-resolved 3D rotational angiography: display of detailed neurovascular anatomy in patients with intracranial vascular malformations

Purpose The purpose of this pilot study was to demonstrate the applicability of time-resolved three-dimensional (3D) reconstructions from 3D digital subtraction angiography (DSA) rotational angiography (RA) datasets (four-dimensional (4D) DSA) to provide a more detailed display of the architecture of intracranial vascular malformations. Methods The experimental reconstruction software was applied to the existing 3D DSA datasets obtained with Siemens Artis zee biplane neuroangiography equipment. We included 27 patients with clinical indications for 3DRA for preinterventional or preoperative evaluation of intracranial dural arteriovenous fistulas (dAVFs, n=8) or arteriovenous malformations (AVMs, n=19). A modified DSA acquisition protocol covering an extended rotation angle of the C-arm of 260° during a scan time of 12 s was used. 4D volumes were displayed with up to 30 frames/s in a transparent volume rendering (VRT) mode and time-resolved multiplanar reconstructions (MPRs). Arterial feeders, fistulous points, or the shunt zone within the AVM nidus and venous drainage patterns as well as associated aneurysms were assessed after definition of a standardized evaluation procedure by consensus of two reviewers in comparison with 2D DSA and conventional 3D reconstructions. Results In all cases calculation of 4D reconstructions were technically feasible and evaluable. In two cases image quality was slightly compromised by movement artifacts. Compared with standard DSA projection images and 3D reconstructions, 4D VRTs and MPRs were rated significantly superior to define a proper projection and display of the shunt zone. In 12 out of 27 cases 4D reconstructions showed details of the angioarchitecture at the fistulous point or the nidus better than the other modalities and came close to the quality of superselective angiography. The efficacy of 3D and 4D applications was equal in the detection of pre- and intranidal aneurysms. The course of long arterial feeders and draining veins was difficult to assess on VRTs and MPRs. Especially for dAVFs, 2D DSA was clearly superior in identifying meningeal feeders. For detecting smaller vessels and for distinction between angiographic phases, 2D DSA is still considered to be superior to 4D imaging. Venous drainage was slightly better displayed in 4D reconstructions. Conclusions Time-resolved 3DRA with 4D VRTs and MPRs is technically feasible and provides a detailed display of the angioarchitecture at the fistulous point or the nidus. Visualization of all angiographic features demands additional post-processing. Further standardization of evaluation tools and studies with blinded independent reviewers are necessary before the new technique can replace conventional neuroangiographic approaches.
New insights into the function of Rab GTPases in the context of exosomal secretion

ABSTRACT In the last two decades, extracellular vesicle-mediated communication between cells has become a major field in cell biology. However, the function of extracellular vesicles is far from clear, especially due to the disparity of released vesicles by cells. Basically, one must consider vesicles budding from the cell plasma membrane (ectosomes) and vesicles released upon fusion of an endosomal multivesicular compartment (exosomes). Moreover, even for exosomes, we report and discuss here the possibility that different routes regulated by specific Rab GTPases might produce exosomes having various biologic functions.
Beyond Sodium, Phosphate and Potassium: Potential Dietary Interventions in Kidney Disease

People with kidney disease are advised to restrict individual nutrients, such as sodium, potassium, and phosphate, in line with current best practice guidelines. However, there is limited evidence to support the efficacy of single nutrient strategies, and compliance remains a challenge for clinicians to overcome. Many factors contribute to poor compliance with dietary prescriptions, including conflicting priorities for single nutrient restriction, the arduous self‐monitoring required, and the health‐related knock‐on effects resulting from targeting these nutrients in isolation. This paper reviews the evidence base for the overall pattern of eating as a potential tool to deliver a diet intervention in which all the nutrients and foods work cumulatively and synergistically to improve clinical outcomes. These interventions may assist in kidney disease management and overcome these innate challenges that single nutrient interventions possess. Healthy dietary patterns are typically plant‐based and lower in sodium and animal proteins. These patterns may have numerous mechanistic benefits for cardiovascular health in kidney disease, most notably through the increase in fruit, vegetables, and plant‐based protein, as well as improved gut health through the increase in dietary fiber. The evidence to date on optimal dietary patterns points toward use of a predominantly plant‐based diet, and suggests its adoption may improve clinical outcomes in dialysis patients. However, clinical trials are needed to determine whether these diet interventions are feasible, safe, and effective in this patient population.
Genetic and metabolic engineering in diatoms

Diatoms have attracted considerable attention due to their success in diverse environmental conditions, which probably is a consequence of their complex origins. Studies of their metabolism will provide insight into their adaptation capacity and are a prerequisite for metabolic engineering. Several years of investigation have led to the development of the genome engineering tools required for such studies, and a profusion of appropriate tools is now available for exploring and exploiting the metabolism of these organisms. Diatoms are highly prized in industrial biotechnology, due to both their richness in natural lipids and carotenoids and their ability to produce recombinant proteins, of considerable value in diverse markets. This review provides an overview of recent advances in genetic engineering methods for diatoms, from the development of gene expression cassettes and gene delivery methods, to cutting-edge genome-editing technologies. It also highlights the contributions of these rapid developments to both basic and applied research: they have improved our understanding of key physiological processes; and they have made it possible to modify the natural metabolism to favour the production of specific compounds or to produce new compounds for green chemistry and pharmaceutical applications. This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Ethnic disparities in educational and occupational gradients of estimated cardiovascular disease risk: The Healthy Life in an Urban Setting study

Background: European societies are becoming increasingly ethnically diverse. This may have important implications for socio-economic inequalities in health due to the often disadvantaged position of ethnic minority groups in both socio-economic status (SES) and disease, especially cardiovascular disease (CVD). Objective: The aim of this study was to determine whether the socio-economic gradient of estimated CVD risk differs between ethnic groups. Methods: Using the Healthy Life in an Urban Setting study, we obtained data on SES and CVD risk factors among participants from six ethnic backgrounds residing in Amsterdam. SES was measured using educational level and occupational level. CVD risk was estimated based on the occurrence of CVD risk factors using the Dutch version of the systematic coronary risk evaluation algorithm. Ethnic disparities in socio-economic gradients for estimated CVD risk were determined using the relative index of inequality (RII). Results: Among Dutch-origin men, the RII for estimated CVD risk according to educational level was 6.15% (95% confidence interval [CI] 4.35–7.96%), indicating that those at the bottom of the educational hierarchy had a 6.15% higher estimated CVD risk relative than those at the top. Among Dutch-origin women, the RII was 4.49% (CI 2.45–6.52%). The RII was lower among ethnic minority groups, ranging from 0.83% to 3.13% among men and −0.29% to 5.12% among women, indicating weaker associations among these groups. Results were similar based on occupational level. Conclusions : Ethnic background needs to be considered in associations between SES and disease. The predictive value of SES varies between ethnic groups and may be quite poor for some groups.
Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin

In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5–38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2–2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.
Influence of Afforestation on the Species Diversity of the Soil Seed Bank and Understory Vegetation in the Hill-Gullied Loess Plateau, China

The Chinese Loess Plateau region has long been suffering from serious soil erosion. Thus, large-scale afforestation has continued during the past decades in order to control soil erosion. Afforestation can dramatically alter nutrient cycles, affect soil-carbon storage, and change hydrology. However, it is unknown how afforestation influences species diversity of the soil seed bank and understory vegetation compared with spontaneous restoration of abandoned land. Forest land with trees planted 30 years ago, abandoned slope land restored spontaneously for 30 years, and the corresponding slopes with remnant natural vegetation were selected as sampling sites. The species richness both in the soil seed bank and vegetation was significantly higher on the afforested slope compared to the spontaneously restored abandoned land. The species similarity between the afforested slope and the remnant slope land was high both in the soil seed bank and standing vegetation compared to the abandoned land. The soil seed bank density varied from 1778 ± 187 to 3896 ± 221 seeds/m2, and more than half of it was constituted by annual and biennial species, with no significant difference among sampling habitats. However, the afforested slope had higher seed density of grass and shrub/subshrubs compared to the abandoned slope. The present study indicates that in the study region, characterized by serious soil erosion, afforestation can better facilitate vegetation succession compared to spontaneously restoration of abandoned slope land.
Do More Active Children Sleep More? A Repeated Cross-Sectional Analysis Using Accelerometry

Aim To determine whether levels of daytime physical activity are associated with sleep duration and night waking in children assessed using accelerometry, and if these associations change over time. Methods 24-hour accelerometry data were obtained from 234 children at 3, 5 and 7 years of age for at least 5 days at each time. Sleep duration was estimated using the Sadeh algorithm. Time spent in sedentary, light and moderate-vigorous (MVPA) activity was established using published cut-points. Appropriate statistical techniques were utilised to account for the closed nature of the data (24-hour periods). Results Time spent asleep was related more to sedentary or light activity and not to MVPA. The most active (95th percentile) children spent 55–84 fewer minutes asleep and 16–19 more minutes awake at night compared to the least active (5th percentile) children. Children with later bedtimes slept less at night (30–40 minutes) and undertook more sedentary (10–15 minutes) but also more light (18–23 minutes) activity during the day. However, no differences in MVPA were apparent according to bedtime. Children slept slightly less on weekend nights (11 minutes) compared with week-nights, but only at 3 years of age. Most relationships were broadly similar at 3, 5 and 7 years of age. Conclusion Children who are more physically active during the day have shorter total sleep time and are more awake at night than less active children. The protective effect of sleep on obesity does not appear to be mediated by increased physical activity.
Twin-induced template effect on the inelastic deformation of hierarchically nanotwinned copper under indentation and scratch

The inelastic deformation of hierarchically nanotwinned copper that is composed of primary and secondary twins under indentation and scratch has been investigated by using large-scale molecular dynamics simulations. Simulation results show that the partial dislocation activities are the main factor that dominates the inelastic deformation. Both the indentation and scratch processes show arrest and burst behaviors of partial dislocations, which indicates that the twin boundaries have a template effect on the inelastic deformations. Moreover, it is found that the characteristic size of the inelastic deformation zone increases, respectively, with the increase of the primary and secondary twin spacings.
Using the Stable Carbon and Nitrogen Isotope Compositions of Vervet Monkeys (Chlorocebus pygerythrus) to Examine Questions in Ethnoprimatology

This study seeks to understand how humans impact the dietary patterns of eight free-ranging vervet monkey (Chlorocebus pygerythrus) groups in South Africa using stable isotope analysis. Vervets are omnivores that exploit a wide range of habitats including those that have been anthropogenically-disturbed. As humans encroach upon nonhuman primate landscapes, human-nonhuman primate interconnections become increasingly common, which has led to the rise of the field of ethnoprimatology. To date, many ethnoprimatological studies have examined human-nonhuman primate associations largely in qualitative terms. By using stable carbon (δ13C) and nitrogen (δ15N) isotope analysis, we use quantitative data to understand the degree to which humans impact vervet monkey dietary patterns. Based on initial behavioral observations we placed the eight groups into three categories of anthropogenic disturbance (low, mid, and high). Using δ13C and δ15N values we estimated the degree to which each group and each anthropogenically-disturbed category was consuming C4 plants (primarily sugar cane, corn, or processed foods incorporating these crops). δ13C values were significantly different between groups and categories of anthropogenic-disturbance. δ15N values were significantly different at the group level. The two vervet groups with the highest consumption of C4 plants inhabited small nature reserves, appeared to interact with humans only sporadically, and were initially placed in the mid level of anthropogenic-disturbance. However, further behavioral observations revealed that the high δ13C values exhibited by these groups were linked to previously unseen raiding of C4 crops. By revealing these cryptic feeding patterns, this study illustrates the utility of stable isotopes analysis for some ethnoprimatological questions.