Miracle-dz/UniFAR-FTUs huggingface dataset:
Gold-based nanomaterials for the treatment of brain cancer

Brain cancer, also known as intracranial cancer, is one of the most invasive and fatal cancers affecting people of all ages. Despite the great advances in medical technology, improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier (BBB). Fortunately, recent endeavors using gold-based nanomaterials (GBNs) have indicated the potential of these materials to cross the BBB. Therefore, GBNs might be an attractive therapeutic strategy against brain cancer. Herein, we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment. Furthermore, the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized, with an emphasis on the mechanism of their effective BBB penetration. Finally, the challenges and future outlook in using GBNs for brain cancer treatment are discussed. We hope that this review will spark researchers’ interest in constructing more powerful nanoplatforms for brain disease treatment.
Xenogeneic Silencing and Bacterial Genome Evolution: Mechanisms for DNA Recognition Imply Multifaceted Roles of Xenogeneic Silencers

Abstract Horizontal gene transfer (HGT) is a major driving force for bacterial evolution. To avoid the deleterious effects due to the unregulated expression of newly acquired foreign genes, bacteria have evolved specific proteins named xenogeneic silencers to recognize foreign DNA sequences and suppress their transcription. As there is considerable diversity in genomic base compositions among bacteria, how xenogeneic silencers distinguish self- from nonself DNA in different bacteria remains poorly understood. This review summarizes the progress in studying the DNA binding preferences and the underlying molecular mechanisms of known xenogeneic silencer families, represented by H-NS of Escherichia coli, Lsr2 of Mycobacterium, MvaT of Pseudomonas, and Rok of Bacillus. Comparative analyses of the published data indicate that the differences in DNA recognition mechanisms enable these xenogeneic silencers to have clear characteristics in DNA sequence preferences, which are further correlated with different host genomic features. These correlations provide insights into the mechanisms of how these xenogeneic silencers selectively target foreign DNA in different genomic backgrounds. Furthermore, it is revealed that the genomic AT contents of bacterial species with the same xenogeneic silencer family proteins are distributed in a limited range and are generally lower than those species without any known xenogeneic silencers in the same phylum/class/genus, indicating that xenogeneic silencers have multifaceted roles on bacterial genome evolution. In addition to regulating horizontal gene transfer, xenogeneic silencers also act as a selective force against the GC to AT mutational bias found in bacterial genomes and help the host genomic AT contents maintained at relatively low levels.
Evaluating user-personas as supplementary tools in AAC intervention and clinician decision making

ABSTRACT Models used for the design and service delivery of Augmentative and Alternative Communication (AAC) systems are limited. There are no standardized protocols for gathering user requirements beyond clinical/diagnostic information relating to AAC access needs (i.e., physical and cognitive capabilities). Nonetheless, information on the social, cultural, and psychological aspects of technology orientation and use are important to understanding how an AAC system will complement the user’s lifestyle, personal goals, values, and activities. Persona development is a user-centered design method that creates descriptive user models of different segments of a user population. Personas describe users’ personal characteristics, and the ways in which they think, behave, and engage in activities (with or without technology). The objective of this study is to investigate the utility of user personas as a supplementary tool to aid SLPs in AAC assessment and service delivery. Three personas of individuals with Amyotrophic Lateral Sclerosis (ALS) were developed and validated in our prior research. Twelve SLPs engaged in mock AAC assessments of the three ALS case studies under two conditions: with or without the use of personas as a supplemental informational tool. By and large, there were no statistically significant differences between groups across objective measures; however, interview sessions with the SLP participants revealed benefits to using personas during clinical decision-making, particularly for training novice SLPs. Discussion also focuses on ways in which user personas can be adapted and improved to mitigate some of the challenges and risks identified.
The colorectal cancer lipidome - identification of a robust tumor-specific lipid species signature.

OBJECTIVE Lipidomic changes were causally linked to metabolic diseases, but the scenario for colorectal cancer (CRC) is less clear. We investigated the CRC lipidome for putative tumour-specific alterations through analysis of three independent retrospective patient cohorts from two clinical centers, to derive a clinically useful signature. DESIGN Quantitative comprehensive lipidomic analysis was performed by direct infusion electrospray ionization coupled to tandem mass spectrometry (ESI-MS/MS) and high-resolution mass spectrometry (HR-MS) on matched non-diseased mucosa and tumor tissue in a discovery cohort (n=106). Results were validated in two independent cohorts (n=28, and n=20), associated with genomic and clinical data, and lipidomic data from a genetic mouse tumor model (Apc1638N). RESULTS Significant differences were found between tumor and normal tissue for glycero-, glycerophospho- and sphingolipids in the discovery cohort. Comparison to the validation collectives unveiled that glycerophospholipids showed high interpatient variation and were strongly affected by preanalytical conditions, whereas glycero- and sphingolipids appeared more robust. Signatures of sphingomyelin (SM) and triacylglycerol (TG) species significantly differentiated cancerous from non-diseased tissue in both validation studies. Moreover, lipogenic enzymes were significantly upregulated in CRC, and FASN gene expression was prognostically detrimental. The TG profile was significantly associated with post-operative disease-free survival and lymphovascular invasion, and was essentially conserved in murine digestive cancer, but not associated with microsatellite status, KRAS or BRAF mutations, or T-cell infiltration. CONCLUSION Analysis of the CRC lipidome revealed a robust TG-species signature with prognostic potential. A better understanding of the cancer-associated glycerolipid and sphingolipid metabolism may lead to novel therapeutic strategies.
Anaerobic toxicity evaluation by batch and semi-continuous assays

Toxic materials are frequently blamed for causing imbalance in anaerobic sludge diges tion. However, when a digester failure occurs, the cause is generally difficult to determine because sludge is a complex mixture of ma terials. Chemical analysis by itself is of little value unless available evidence suggests a particular chemical is the most likely cause of the problem. Biological assay procedures generally offer the most promise for determin ing whether or not digester imbalance is in deed caused by toxic materials, and can aid in the evaluation of toxicity thresholds for suspect chemicals. Either batch or semi-continuous feed bio assays can be used. Each has advantages and disadvantages, and the objective of this study was to explore relative advantages of each in the evaluation of four different organic ma terials: m? thyl? ne chloride (MC), vinyl ace tate (VA), ethylene dichloride (EDC), and vinyl chloride (VC). These chemicals are of considerable commercial interest, and in 1974 their combined sales were $490 million, with ethylene dichloride being the third leading organic in terms of sale value.1
Mining of linear B cell epitopes of SARS-CoV-2 ORF8 protein from COVID-19 patients

ABSTRACT Given the on-going SARS-CoV-2 pandemic, identification of immunogenic targets against the viral protein will provide crucial advances towards the development of sensitive diagnostic tools and vaccination strategies. Our previous study has found that ORF8 protein of SARS-CoV-2 is highly immunogenic and shows high sensitivity in identifying COVID-19 disease. In this study, by employing overlapping linear peptides, we characterized the IgG immunodominant regions on SARS-CoV-2 ORF8 protein that are seropositive in the sera from SARS-CoV-2-infected patients. The major immunogenic epitopes are localized at (1) N-termini alpha helix, (2) the resides spanning beta 2 and 3 sheets, and (3) the loop between beta 4 and 5 sheets. Additionally, hamster model infected by SARS-CoV-2 further validates the seropositivity of the linear epitopes in vivo, demonstrating a potential application of the linear peptide-based immunization strategy. Taken together, identification and validation of these B-cell linear epitopes will provide insights into the design of serological diagnostics and peptide-based vaccination approach against this pandemic virus of high priority.
Multi-step vs. single-step resistance evolution under different drugs, pharmacokinetics, and treatment regimens

The success of antimicrobial treatment is threatened by the evolution of drug resistance. Population genetic models are an important tool in mitigating that threat. However, most such models consider resistance emergence via a single mutational step. Here, we assembled experimental evidence that drug resistance evolution follows two patterns: (i) a single mutation, which provides a large resistance benefit, or (ii) multiple mutations, each conferring a small benefit, which combine to yield high-level resistance. Using stochastic modeling, we then investigated the consequences of these two patterns for treatment failure and population diversity under various treatments. We find that resistance evolution is substantially limited if more than two mutations are required and that the extent of this limitation depends on the combination of drug type and pharmacokinetic profile. Further, if multiple mutations are necessary, adaptive treatment, which only suppresses the bacterial population, delays treatment failure due to resistance for a longer time than aggressive treatment, which aims at eradication.
Mental Fatigue From Smartphone Use Reduces Volume-Load in Resistance Training: A Randomized, Single-Blinded Cross-Over Study

We investigated the acute effects of mental fatigue induced by 30-minute use of smartphone social network apps on volume load in resistance training among recreationally trained adults. Sixteen (n = 16) adults of both sexes performed three sets of a half back-squat exercise to failure with 80% of 15RM, interspersed with 3-minutes of passive recovery between sets, before and after two different cognitive tasks: (a) use of smartphone social network apps; and (b) watching a documentary. We assessed mechanical variables and ratings of perceived exertion during the strength exercise. Relative to the documentary-viewing control condition, a 30-minute exposure to smartphone social network apps led participants toward increased perception of mental fatigue (p = 0.004) and lower volume-load during the strength exercise (p = 0.006). There were no significant differences in perceived exertion between conditions (p = 0.54), participants’ motivation (p = 0.277), intra-set mechanical variables (p > 0.05), or blood lactate concentrations (p = 0.36). Our findings of an isolated possible higher-than normal RPE without changes in physiological variables, accompanying the lower volume-load in the mentally-fatigued participants support psychological, rather than physiological, bases for mental fatigue effects.
Influence of parameters and characteristics of complete denture bases fabricated by 3D printing on evaluated properties: a scoping review.

PURPOSE To verify the parameters and characteristics evaluated in printed complete denture bases and how they influence properties. MATERIALS AND METHODS This work was registered in Open Science Framework (osf.io/4um6v) and followed the PRISMA Extension for Scoping Reviews (PRISMA-ScR). A search of peer-reviewed articles published up to April 9, 2020 was performed on the PubMed, Lilacs, Cochrane Library, and Science Direct databases. The review question based on the population, concept, and context (PCC) was: What printing parameters and characteristics of complete denture bases can influence properties? RESULTS The database search resulted in 1,945 articles, and 1,390 article titles and abstracts were screened. A total of 17 articles were included. The summarized findings included: cleaning prostheses with alcohol after printing and a postcuring cycle influence biocompatibility and residual monomers; the printing angle influences physical/mechanical properties, microbial adhesion, and tissue adaptation; accuracy is influenced by layer thickness and the manufacturing technique, which also influences retention and tissue adaptation; the incorporation of antimicrobial agents influences physical/mechanical properties and antimicrobial activity; and the method of union between the base and the teeth influences mechanical strength. CONCLUSION Printed denture bases of 100-μm layer thickness showed good adaptation to tissues and accuracy, and it can be recommended that the prosthesis be cleaned in ethanol followed by postcuring for better biocompatibility. Nanoand microparticles can be added to provide antimicrobial activity and better resistance. Printing angle and mechanical properties must be better evaluated.
Beneficial effects of folic acid supplementation on lipid markers in adults: A GRADE-assessed systematic review and dose-response meta-analysis of data from 21,787 participants in 34 randomized controlled trials

Abstract Folic acid supplementation has received considerable attention in the literature, yet there is a large discrepancy in its effects on lipid markers in adults. Therefore, this systematic review and meta-analysis of 34 randomized controlled trials (RCTs) evaluated the effects of folic acid supplementation on triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations in a cohort of 21,787 participants. A systematic search current as of March 2021 was performed in PubMed/Medline, Scopus, Web of Science, and Embase using relevant keywords to identify eligible studies. A fix or random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence intervals (CIs). Thirty-four RCTs were included in this meta-analysis. The pooled analysis revealed that serum TG (WMD: −9.78 mg/dL; 95% CI: −15.5 to −4.00; p = 0.001, I2=0.0%, p = 0.965) and TC (WMD: −3.96 mg/dL; 95% CI: −6.71 to −1.21; p = 0.005, I2=46.9%, p = 0.001) concentrations were significantly reduced following folic acid supplementation compared to placebo. However, folic acid supplementation did not affect serum concentrations of LDL (WMD: −0.97 mg/dL; 95% CI: −6.82 to 4.89; p = 0.746, I2=60.6%, p < 0.001) or HDL cholesterol (WMD: 0.44 mg/dL; 95% CI: −0.53 to 1.41; p = 0.378, I2= 0.0%, p = 0.831). A significant dose-response relationship was observed between the dose of folic acid supplementation and serum concentrations of HDL cholesterols (r = 2.22, p = 0.047). Folic acid supplementation reduced serum concentrations of TG and TC without affecting LDL or HDL cholesterols. Future large RCTs on various populations are needed to show further beneficial effects of folic acid supplementation on lipid profile.
Are efforts to recruit to psychiatry closing the stable door after the horse has bolted? Knowledge and attitudes towards a career in psychiatry amongst secondary (high) school students: a UK-based cross-sectional survey

Abstract Background Internationally there is a shortage of psychiatrists, whilst clinical psychology training is generally oversubscribed. School students interested in psychological health may not be aware of the possibility of studying medicine before specialising in psychiatry. This has implications for the mental health workforce. Aims To evaluate the knowledge and attitudes relating to a potential career in psychiatry amongst secondary (high) school students. Method A cross-sectional survey evaluated attitudes and knowledge relating to psychiatry and clinical psychology, targeting students from five schools who were studying chemistry, biology and/or psychology at an advanced level. Results 186 students completed the survey (response rate 41%). Knowledge was generally poor with only 57% of respondents knowing that psychiatrists had medical degrees, and most participants substantially underestimating the salaries of consultant psychiatrists. Attitudinal response patterns were explained by two underlying factors, relating to generally negative attitudes towards psychiatry and positive attitudes towards the effectiveness of psychiatric treatments. Females and those studying psychology reported more positive attitudes towards psychiatry. Those studying chemistry reported more negative attitudes towards the effectiveness of mental health treatment. Conclusions Studying psychology predicted positive attitudes towards psychiatry. Such students could be targeted by recruitment campaigns, which emphasise factual information about the specialty.
Cortical propagation tracks functional recovery after stroke

Stroke is a debilitating condition affecting millions of people worldwide. The development of improved rehabilitation therapies rests on finding biomarkers suitable for tracking functional damage and recovery. To achieve this goal, we perform a spatiotemporal analysis of cortical activity obtained by wide-field calcium images in mice before and after stroke. We compare spontaneous recovery with three different post-stroke rehabilitation paradigms, motor training alone, pharmacological contralesional inactivation and both combined. We identify three novel indicators that are able to track how movement-evoked global activation patterns are impaired by stroke and evolve during rehabilitation: the duration, the smoothness, and the angle of individual propagation events. Results show that, compared to pre-stroke conditions, propagation of cortical activity in the subacute phase right after stroke is slowed down and more irregular. When comparing rehabilitation paradigms, we find that mice treated with both motor training and pharmacological intervention, the only group associated with generalized recovery, manifest new propagation patterns, that are even faster and smoother than before the stroke. In conclusion, our new spatiotemporal propagation indicators could represent promising biomarkers that are able to uncover neural correlates not only of motor deficits caused by stroke but also of functional recovery during rehabilitation. In turn, these insights could pave the way towards more targeted post-stroke therapies.
PHYTOCHEMICAL ANALYSIS OF FUMARIA OFFICINALIS L. (FUMARIACEAE)

The present study describes the investigation of active compounds from several samples of Fumaria officinalis L. (Fumariaceae). The identification of the isoquinoline alkaloids (allocryptopine, chelidonine, protopine, bicuculline, sanguinarine, cheleritrine, stylopine and hydrastine) was performed by comparison with reference standards using an HPLCDAD method, and their quantification by LC-DAD and spectrophotometric methods. The presence of polyphenolic compounds was simultaneously assessed by HPLC. Protopine and sanguinarine were identified in all extracts. The major alkaloids were protopine and chelidonine (258.3 mg/100 g and respectively 94.13 mg/100 g). The spectrophotometric determinations of alkaloids showed minor differences between commercial samples and those harvested from spontaneous flora. The concentration of isoquinoline alkaloids expressed in chelidonine was between 0.69 and 0.76% in all samples. The pattern of phenol carboxylic acids showed the presence of cynarin, chlorogenic, isochlorogenic and ferulic acids. The flavonoids isovitexin, rutin, isoquercitrin and quercitrin were found in all assessed samples of Fumaria officinalis aerial parts.
Distribution of the Noradrenaline Innervation and Adrenoceptors in the Macaque Monkey Thalamus

Abstract Noradrenaline (NA) in the thalamus has important roles in physiological, pharmacological, and pathological neuromodulation. In this work, a complete characterization of NA axons and Alpha adrenoceptors distributions is provided. NA axons, revealed by immunohistochemistry against the synthesizing enzyme and the NA transporter, are present in all thalamic nuclei. The most densely innervated ones are the midline nuclei, intralaminar nuclei (paracentral and parafascicular), and the medial sector of the mediodorsal nucleus (MDm). The ventral motor nuclei and most somatosensory relay nuclei receive a moderate NA innervation. The pulvinar complex receives a heterogeneous innervation. The lateral geniculate nucleus (GL) has the lowest NA innervation. Alpha adrenoceptors were analyzed by in vitro quantitative autoradiography. Alpha-1 receptor densities are higher than Alpha-2 densities. Overall, axonal densities and Alpha adrenoceptor densities coincide; although some mismatches were identified. The nuclei with the highest Alpha-1 values are MDm, the parvocellular part of the ventral posterior medial nucleus, medial pulvinar, and midline nuclei. The nucleus with the lowest Alpha-1 receptor density is GL. Alpha-2 receptor densities are highest in the lateral dorsal, centromedian, medial and inferior pulvinar, and midline nuclei. These results suggest a role for NA in modulating thalamic involvement in consciousness, limbic, cognitive, and executive functions.
Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder

The study of sensory phenotypes has great potential for increasing research translation between species, a necessity to decipher the neural mechanisms that contribute to higher‐order differences in neurological conditions such as autism spectrum disorder (ASD). Over the past decade, despite separate advances in our understanding of the structural and functional differences within the brain of autistic and non‐autistic individuals and in rodent models for ASD, researchers have had difficulty translating the findings in murine species to humans, mostly due to incompatibility in experimental methodologies used to screen for ASD phenotypes. Focusing on sensory phenotypes offers an avenue to close the species gap because sensory pathways are highly conserved across species and are affected by the same risk‐factors as the higher‐order brain areas mostly responsible for the diagnostic criteria for ASD. By first reviewing how sensory processing has been studied to date, we direct our focus to electrophysiological and behavioral techniques that can be used to study sensory phenotypes consistently across species. Using auditory sensory phenotypes as a template, we seek to improve the accessibility of translational methods by providing a framework for collecting cohesive data in both rodents and humans. Specifically, evoked‐potentials, acoustic startle paradigms, and psychophysical detection/discrimination paradigms can be created and implemented in a coordinated and systematic fashion across species. Through careful protocol design and collaboration, sensory processing phenotypes can be harnessed to bridge the gap that exists between preclinical animal studies and human testing, so that mutually held questions in autism research can be answered.