Miracle-dz/UniFAR-FTUs huggingface dataset:
Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico–chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.
PrEP Implementation for Mothers in Antenatal Care (PrIMA): study protocol of a cluster randomised trial

Introduction Women in regions with high HIV prevalence are at high risk of HIV acquisition during pregnancy and postpartum, and acute maternal HIV contributes a substantial proportion of infant HIV infections. Pre-exposure prophylaxis (PrEP) could prevent HIV during pregnancy/postpartum; however, identifying women who would most benefit from PrEP in this period is challenging. Women may not perceive risk, may not know partner HIV status and partners may have external partners during this period. PrEP offer in pregnancy could be universal or risk guided. Methods and analysis The PrEP Implementation for Mothers in Antenatal Care (PrIMA) study is a cluster randomised trial that aims to determine the best model for PrEP implementation in pregnancy, among women attending public sector maternal child health clinics in Western Kenya (HIV prevalence >25%). Twenty clinics are randomised to either universal PrEP offer following standardised counselling (‘Universal arm’ 10 clinics) or risk screening with partner self-test option (‘Targeted arm’ 10 clinics). Four thousand women will be enrolled and followed through 9-month postpartum. The primary analysis will be intention to treat. Outcomes reflect the balance between HIV preventive effectiveness and avoiding unnecessary PrEP exposure to women at low risk and include: maternal HIV incidence, PrEP uptake, PrEP adherence, PrEP duration, ‘appropriate’ PrEP use (among women with objective evidence of potential risk), infant birth outcomes, infant growth and partner self-testing uptake. To better understand the feasibility and acceptability of the provision of PrEP in these settings, qualitative interviews and cost-effectiveness analyses will be conducted. Ethics and dissemination The protocol was approved by the institutional review boards at Kenyatta National Hospital and the University of Washington. An external advisory panel monitors adverse and social harm events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy makers, community and participants. Trial registration number NCT03070600.
Lipoprotein Apheresis in Patients With Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)-Hyperlipoproteinemia, and Progressive Cardiovascular Disease: Prospective Observational Multicenter Study

Background— Lipoprotein(a) (Lp(a)) hyperlipoproteinemia is a major risk factor for cardiovascular disease, which is not affected by treatment of other cardiovascular risk factors. This study sought to assess the effect of chronic lipoprotein apheresis (LA) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment. Methods and Results— In a prospective observational multicenter study, 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease. Patients were characterized regarding plasma lipid status, lipid-lowering drug treatment, and variants at the LPA gene locus. The incidence rates of cardiovascular events 2 years before (y-2 and y-1) and prospectively 2 years during LA treatment (y+1, y+2) were compared. The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA. Before LA, mean low-density lipoprotein cholesterol and Lp(a) were 2.56±1.04 mmol·L−1 (99.0±40.1 mg·dL−1) and Lp(a) 3.74±1.63 µmol·L−1 (104.9±45.7 mg·dL−1), respectively. Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA (P<0.0001). Event rates including all vascular beds declined from 0.61 to 0.16 (P<0.0001). Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 (P=0.001) for y-2 to y-1 before LA, decline to 0.14 from y-1 to y+1 (P<0.0001) and to 0.05 from y+1 to y+2 (P=0.014). Conclusions— In patients with Lp(a)-hyperlipoproteinemia, progressive cardiovascular disease, and maximally tolerated lipid-lowering medication, LA effectively lowered the incidence rate of cardiovascular events. Clinical Trial Registration— URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00003119.
Overlap between hippocampal pre‐encoding and encoding patterns supports episodic memory

It is well‐established that whether the information will be remembered or not depends on the extent to which the learning context is reinstated during post‐encoding rest and/or at retrieval. It has yet to be determined, however, if the fundamental importance of contextual reinstatement to memory extends to periods of spontaneous neurocognitive activity prior to learning. We thus asked whether memory performance can be predicted by the extent to which spontaneous pre‐encoding neural patterns resemble patterns elicited during encoding. Individuals studied and retrieved lists of words while undergoing fMRI‐scanning. Multivoxel hippocampal patterns during resting periods prior to encoding resembled hippocampal patterns at encoding most strongly for items that were subsequently remembered. Furthermore, across subjects, the magnitude of similarity correlated with a behavioral measure of episodic recall. The results indicate that the neural context before learning is an important determinant of memory.
Application of Hepatocyte Growth Factor for Acute Spinal Cord Injury: The Road from Basic Studies to Human Treatment

Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.
Epitypification of Fusisporium (Fusarium) solani and its assignment to a common phylogenetic species in the Fusarium solani species complex

Fusisporium solani was described as the causal agent of a dry rot of potato in Germany in the mid 19th century. As Fusarium solani, the species became known as a plurivorous plant pathogen, endophyte, decomposer, and opportunistic pathogen of humans and nutritional symbiont of insects. In parallel, it became evident that the morphologically defined species F. solani represents a phylogenetically and biologically complex group of often morphologically cryptic species that has come to be known in part as the F. solani species complex (FSSC), accommodating several formae speciales and mating populations/biological species. The FSSC currently includes more than 60 phylogenetic species. Several of these have been named, but the majority remains unnamed and the identity of F. solani sensu stricto is unclear. To promote further taxonomic developments in the FSSC, lectoand epitypification is proposed for Fusisporium solani. Although no type material for F. solani is known to exist, the species was abundantly illustrated in the protologue. Thus, a relevant illustration provided by von Martius is selected as the lectotype. The epitype selected here originates from a rotting potato collected in a field in Slovenia. This strain causes a dry rot of artificially inoculated potatoes. It groups in the heretofore unnamed phylogenetic species 5, which is nested within clade 3 of the FSSC (FSSC 5). Members of this phylogenetic species have a wide geographic distribution and include soil saprotrophs and plant and opportunistic human pathogens. This typification is consistent with the original description of Fusisporium solani and the concept of F. solani as a widely distributed soil inhabitant and pathogen.
Linkage disequilibrium and past effective population size in native Tunisian cattle

Abstract To carry out effective genome-wide association studies, information about linkage disequilibrium (LD) is essential. Here, we used medium-density SNP chips to provide estimates of LD in native Tunisian cattle. The two measures of LD that were used, mean r2 and D’, decreased from 0.26 to 0.05 and from 0.73 to 0.40, respectively, when the distance between markers increased from less than 20 Kb to 200 Kb. The decay in LD over physical distance occurred at a faster rate than that reported for European and other indigenous breeds, and reached background levels at less than 500 Kb distance. This is consistent with the absence of strong selective pressure within the Tunisian population and suggests that, in order to be effective, any potential genome-wide association mapping studies will need to use chips with higher marker density. An analysis of effective population size (Ne) based on LD data showed a decline in past Ne, with a sudden drop starting about eight generations ago. This finding, combined with the high levels of recent inbreeding revealed by runs of homozygosity (ROH) analysis, indicate that this population is endangered and may be in urgent need of a conservation plan that includes a well-designed genetic management program.
Polymer-to-Carbon Conversion: From Nature to Technology

Glassy carbon is derived from synthetic organic polymers that undergo the process of coking during their pyrolysis. Polymer-to-carbon conversion (hereafter referred to as PolyCar) also takes place in nature, and is indeed responsible for the formation of various naturally occurring carbon allotropes. In the last few decades the PolyCar concept has been utilized in technological applications, i.e., specific polymers are patterned into the desired shapes and intentionally converted into carbon by a controlled heat-treatment. Device fabrication using glassy carbon is an excellent example of the use of the PolyCar process in technology, which has rapidly progressed from conventional to micro- and nanomanufacturing. While the technique itself is simple, one must have a good understanding of the carbonization mechanism of the polymer, which in turn determines whether or not the resulting material will be glassy carbon. Publications that comprise this special issue shed light on several aspects of the formation, properties and performance of glassy carbon in the cutting-edge technological applications. The results of detailed material characterization pertaining to two important research areas, namely neural electrodes and precision glass molding, are presented as examples. I hope that the readers will enjoy as well as benefit from this collection.
Nephropharmacology for the Clinician Clinical Pharmacology Considerations in Pain Management in Patients with Advanced Kidney Failure

Painiscommon andpoorlymanagedinpatientswithadvancedCKD,likelyduetobothunderandoverprescription ofappropriateanalgesics.Poorlymanagedpaincontributestopatients’poorqualityoflifeandexcessivehealthcareuse.Thereistremendousvariabilitywithinandbetweencountriesinprescribingpatternsofanalgesics,suggesting that factors other than patient characteristics account for these differences. This article discusses the pharmacologic management of acute and chronic pain in patients with advanced CKD, and the role analgesics, including opioids, play in the overall approach to pain management. morphine and constipation and high levels of M3G and cognitive impairment (26). There are many reports in the literature of profound toxicity in patients with advanced CKD.
Structural basis of dimerization and dual W-box DNA recognition by rice WRKY domain

Abstract In rice, the critical regulator of the salicylic acid signalling pathway is OsWRKY45, a transcription factor (TF) of the WRKY TF family that functions by binding to the W-box of gene promoters, but the structural basis of OsWRKY45/W-box DNA recognition is unknown. Here, we show the crystal structure of the DNA binding domain of OsWRKY45 (OsWRKY45–DBD, i.e. the WRKY and zinc finger domain) in complex with a W-box DNA. Surprisingly, two OsWRKY45–DBD molecules exchange β4-β5 strands to form a dimer. The domain swapping occurs at the hinge region between the β3 and β4 strands, and is bridged and stabilized by zinc ion via coordinating residues from different chains. The dimer contains two identical DNA binding domains that interact with the major groove of W-box DNA. In addition to hydrophobic and direct hydrogen bonds, water mediated hydrogen bonds are also involved in base-specific interaction between protein and DNA. Finally, we discussed the cause and consequence of domain swapping of OsWRKY45–DBD, and based on our work and that of previous studies present a detailed mechanism of W-box recognition by WRKY TFs. This work reveals a novel dimerization and DNA-binding mode of WRKY TFs, and an intricate picture of the WRKY/W-box DNA recognition.
Preconceptual Spectral and Temporal Cues as a Source of Meaning in Speech and Music

This paper explores the importance of preconceptual meaning in speech and music, stressing the role of affective vocalizations as a common ancestral instrument in communicative interactions. Speech and music are sensory rich stimuli, both at the level of production and perception, which involve different body channels, mainly the face and the voice. However, this bimodal approach has been challenged as being too restrictive. A broader conception argues for an action-oriented embodied approach that stresses the reciprocity between multisensory processing and articulatory-motor routines. There is, however, a distinction between language and music, with the latter being largely unable to function referentially. Contrary to the centrifugal tendency of language to direct the attention of the receiver away from the text or speech proper, music is centripetal in directing the listener’s attention to the auditory material itself. Sound, therefore, can be considered as the meeting point between speech and music and the question can be raised as to the shared components between the interpretation of sound in the domain of speech and music. In order to answer these questions, this paper elaborates on the following topics: (i) The relationship between speech and music with a special focus on early vocalizations in humans and non-human primates; (ii) the transition from sound to meaning in speech and music; (iii) the role of emotion and affect in early sound processing; (iv) vocalizations and nonverbal affect burst in communicative sound comprehension; and (v) the acoustic features of affective sound with a special emphasis on temporal and spectrographic cues as parts of speech prosody and musical expressiveness.
Advances in identification of genes involved in autosomal recessive intellectual disability: a brief review

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1%–3% of the general population. The number of ID-causing genes is high. Many X-linked genes have been implicated in ID. Autosomal dominant genes have recently been the focus of several large-scale studies. The total number of autosomal recessive ID (ARID) genes is estimated to be very high, and most are still unknown. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause ARID has lagged behind, predominantly due to non-availability of sizeable families. A commonly used approach to identify genetic loci for recessive disorders in consanguineous families is autozygosity mapping and whole-exome sequencing. Combination of these two approaches has recently led to identification of many genes involved in ID. These genes have diverse function and control various biological processes. In this review, we will present an update regarding genes that have been recently implicated in ID with focus on ARID.
Anterior hippocampal volume predicts affect-focused psychotherapy outcome

Abstract Background The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)]. Methods Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes. Results Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome. Conclusions This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the ‘limbic’ AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.
Intrinsic default—executive coupling of the creative aging brain

Abstract Creativity refers to the ability to generate novel associations and has been linked to better problem‐solving and real‐world functional abilities. In younger adults, creative cognition has been associated with functional connectivity among brain networks implicated in executive control [fronto‐parietal network (FPN) and salience network (SN)] and associative or elaborative processing default network (DN). Here, we investigate whether creativity is associated with the intrinsic network architecture of the brain and how these associations may differ for younger and older adults. Young (mean age: 24.76, n = 22) and older (mean age: 70.03, n = 44) adults underwent multi‐echo functional magnetic resonance image scanning at rest and completed a divergent‐thinking task to assess creative cognition outside the scanner. Divergent thinking in older adults, compared to young adults, was associated with functional connectivity between the default and both executive control networks (FPN and SN) as well as more widespread default‐executive coupling. Finally, the ventromedial prefrontal cortex appears to be a critical node involved in within‐ and between‐network connectivity associated with creative cognition in older adulthood. Patterns of intrinsic network coupling revealed here suggest a putative neural mechanism underlying a greater role for mnemonic processes in creative cognition in older adulthood.
Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study.

AIMS Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use. METHODS AND RESULTS From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = -0.194, P = 0.026). CONCLUSION In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins.