Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults

Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC). Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days. Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF. Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health. Clinical Trial Registration: ClinicalTrials.gov, NCT03904433.
Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.
The Weekend Drug; Recreational Use of Sildenafil Citrate and Concomitant Factors: A Cross-Sectional Study

Background: Men who use erectile dysfunction medications for recreational purposes may be at increased risk of becoming psychologically dependent, which in turn could lead to psychogenic-based erectile dysfunction symptoms. Sildenafil has become one of the most commonly prescribed and abused drugs available today. Objectives: This study aimed to describe the utilization pattern and associated factors of sildenafil citrate among its users visiting community pharmacies in Gondar, Ethiopia. Methods: A facility-based cross-sectional study was conducted from March 20, 2017 to May 10, 2017, among male clients who visited community pharmacies in Gondar town, North West Ethiopia. A self-administered, structured questionnaire was used to collect data from Sildenafil users older than 18 years, that started using the drug (Sildenafil) for at least 6 months before the data collection period. A regression analysis was conducted to determine the association between study variables, and a P-value of <0.05 was considered to declare statistical significance. Results: A total of 65 men participated in the study. Of the total study participants, 33.8% were aged 25–34 years and about 40% of them had multiple sexual partners. The use of sildenafil for recreational purposes was 66.2% and was found to be higher than its use for medical purposes 33.8%. Use of the drug for <1-year duration (AOR = 34.086, 95% CI [2.90, 401.37]) and 2 years duration (AOR = 21.42: 95% CI [2.10, 218.82]) were significantly associated with its use for recreational purpose. Non-recreational use of sildenafil includes erectile problems associated with diabetes mellitus (27.1%), heart disease (9.2%), hyperlipidemia (4.2%), and relationship problems due to stress and poor communication (3.1%). Conclusion: Most men who use sildenafil citrate do so for recreational purposes, and use of sildenafil citrate for 2 years or less was associated with recreational use. There should be a collaborative effort among pharmacists, health professionals, and policymakers to improve the rational use of sildenafil.
Genomic Variation Influences Methanothermococcus Fitness in Marine Hydrothermal Systems

Hydrogenotrophic methanogens are ubiquitous chemoautotrophic archaea inhabiting globally distributed deep-sea hydrothermal vent ecosystems and associated subseafloor niches within the rocky subseafloor, yet little is known about how they adapt and diversify in these habitats. To determine genomic variation and selection pressure within methanogenic populations at vents, we examined five Methanothermococcus single cell amplified genomes (SAGs) in conjunction with 15 metagenomes and 10 metatranscriptomes from venting fluids at two geochemically distinct hydrothermal vent fields on the Mid-Cayman Rise in the Caribbean Sea. We observed that some Methanothermococcus lineages and their transcripts were more abundant than others in individual vent sites, indicating differential fitness among lineages. The relative abundances of lineages represented by SAGs in each of the samples matched phylogenetic relationships based on single-copy universal genes, and genes related to nitrogen fixation and the CRISPR/Cas immune system were among those differentiating the clades. Lineages possessing these genes were less abundant than those missing that genomic region. Overall, patterns in nucleotide variation indicated that the population dynamics of Methanothermococcus were not governed by clonal expansions or selective sweeps, at least in the habitats and sampling times included in this study. Together, our results show that although specific lineages of Methanothermococcus co-exist in these habitats, some outcompete others, and possession of accessory metabolic functions does not necessarily provide a fitness advantage in these habitats in all conditions. This work highlights the power of combining single-cell, metagenomic, and metatranscriptomic datasets to determine how evolution shapes microbial abundance and diversity in hydrothermal vent ecosystems.
Antibiotic Resistance Profiles and Molecular Characteristics of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella pneumoniae Isolated From Shrimp Aquaculture Farms in Kerala, India

This study was undertaken to evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae in selected shrimp aquaculture farms (n = 37) in Kerala, South India and to characterize the isolates using molecular tools. Overall, a low prevalence of ESBL-producers was found in the farms, most likely due to the reduced antibiotic usage in the shrimp farming sector. Out of the 261 samples (77 shrimp and 92 each of water and sediment), 14 (5.4%) tested positive for ESBL-E. coli or ESBL-K. pneumoniae. A total of 32 ESBL-E. coli and 15 ESBL- K. pneumoniae were recovered from these samples. All ESBL isolates were cefotaxime-resistant with minimal inhibitory concentration (MIC) ≥32 μg/ml. Of all isolates, 9 (28.1%) E. coli and 13 (86.7%) K. pneumoniae showed simultaneous resistance to tetracycline, ciprofloxacin, and trimethoprim-sulfamethoxazole. PCR analysis identified CTX-M group 1 (blaCTX–M–15) as the predominant ESBL genotype in both E. coli (23, 71.9%) and K. pneumoniae (15, 100%). Other beta-lactamase genes detected were as follows: blaTEM and blaSHV (11 K. pneumoniae), blaCTX–M group 9 (9 E. coli), and blaCMY–2 (2 E. coli). Further screening for AMR genes identified tetA and tetB (13, 40.6%), sul1 (11, 34.4%), sul2 (9, 28.1%), catA and cmlA (11, 34.4%), qepA and aac(6′)-Ib-cr (9, 28.1%) and strAB and aadA1 (2, 6.3%) in E. coli, and qnrB (13, 86.7%), qnrS (3, 20%), oqxB (13, 86.7%), tetA (13, 86.7%), and sul2 (13, 86.7%) in K. pneumoniae isolates. Phylogenetic groups identified among E. coli isolates included B1 (4, 12.5%), B2 (6, 18.8%), C (10, 31.3%), D (3, 9.4%), and E (9, 28.1%). PCR-based replicon typing (PBRT) showed the predominance of IncFIA and IncFIB plasmids in E. coli; however, in K. pneumoniae, the major replicon type detected was IncHI1. Invariably, all isolates of K. pneumoniae harbored virulence-associated genes viz., iutA, entB, and mrkD. Epidemiological typing by pulsed-field gel electrophoresis (PFGE) revealed that E. coli isolates recovered from different farms were genetically unrelated, whereas isolates of K. pneumoniae showed considerable genetic relatedness. In conclusion, our findings provide evidence that shrimp aquaculture environments can act as reservoirs of multi-drug resistant E. coli and K. pneumoniae.
Caveolin-1, a Key Mediator Across Multiple Pathways in Glioblastoma and an Independent Negative Biomarker of Patient Survival

Glioblastoma (GB) remains an aggressive malignancy with an extremely poor prognosis. Discovering new candidate drug targets for GB remains an unmet medical need. Caveolin-1 (Cav-1) has been shown to act variously as both a tumour suppressor and tumour promoter in many cancers. The implications of Cav-1 expression in GB remains poorly understood. Using clinical and genomic databases we examined the relationship between tumour Cav-1 gene expression (including its spatial distribution) and clinical pathological parameters of the GB tumour and survival probability in a TCGA cohort (n=155) and CGGA cohort (n=220) of GB patients. High expression of Cav-1 represented a significant independent predictor of shortened survival (HR = 2.985, 5.1 vs 14.9 months) with a greater statistically significant impact in female patients and in the Proneural and Mesenchymal GB subtypes. High Cav-1 expression correlated with other factors associated with poor prognosis: IDH w/t status, high histological tumour grade and low KPS score. A total of 4879 differentially expressed genes (DEGs) in the GB tumour were found to correlate with Cav-1 expression (either positively or negatively). Pathway enrichment analysis highlighted an over-representation of these DEGs to certain biological pathways. Focusing on those that lie within a framework of epithelial to mesenchymal transition and tumour cell migration and invasion we identified 27 of these DEGs. We then examined the prognostic value of Cav-1 when used in combination with any of these 27 genes and identified a subset of combinations (with Cav-1) indicative of co-operative synergistic mechanisms of action. Overall, the work has confirmed Cav-1 can serve as an independent prognostic marker in GB, but also augment prognosis when used in combination with a panel of biomarkers or clinicopathologic parameters. Moreover, Cav-1 appears to be linked to many signalling entities within the GB tumour and as such this work begins to substantiate Cav-1 or its associated signalling partners as candidate target for GB new drug discovery.
Characterization of Vaginal Microbiota in Women With Recurrent Spontaneous Abortion That Can Be Modified by Drug Treatment

Objective The role of vaginal microbiota in recurrent spontaneous abortion (RSA) remains unknown. The purpose of this study was to investigate characteristics of vaginal microbiota and the effects of drug treatment on vaginal microbiota of patients with RSA. Methods A case-control study was performed, in which non-pregnant patients who experienced RSA were selected and divided into untreated and drug-treated groups. Drug-treated patients were subdivided into the metformin group, metformin plus aspirin group, and other drugs group. Healthy women who had live births and never experienced spontaneous abortion were enrolled in the control group. Characteristics of vaginal microbiomes of patients with RSA and healthy women and the impact of drug treatment on the microbiome was evaluated via 16S rRNA gene sequencing of the V3-V4 region using the Illumina MiSeq platform. Results Women who underwent RSA had lower microbial richness than healthy women. Compared to controls, the relative abundance of seven taxa (Megasphaera, Sneathia sanguinegens, Pseudomonas, Sphingomonas, Rhodococcus, Burkholderia- Caballeronia-Paraburkholderia, and Corynebacterium_1) in the patient’s vaginal microbiota changed significantly, which may be closely related to RSA. The composition of the vaginal microbial community in RSA patients was altered by drug treatment. Metformin combined with aspirin treatment significantly increased the relative abundance of vaginal Lactobacillus spp. in patients. Conclusion An altered vaginal microbiome composition might be associated with RSA, which could be modified by drug treatment. The effect of metformin combined with aspirin on vaginal Lactobacillus is worthy of attention.
Research Progress on the Mechanism of Cochlear Hair Cell Regeneration

Mammalian inner ear hair cells do not have the ability to spontaneously regenerate, so their irreversible damage is the main cause of sensorineural hearing loss. The damage and loss of hair cells are mainly caused by factors such as aging, infection, genetic factors, hypoxia, autoimmune diseases, ototoxic drugs, or noise exposure. In recent years, research on the regeneration and functional recovery of mammalian auditory hair cells has attracted more and more attention in the field of auditory research. How to regenerate and protect hair cells or auditory neurons through biological methods and rebuild auditory circuits and functions are key scientific issues that need to be resolved in this field. This review mainly summarizes and discusses the recent research progress in gene therapy and molecular mechanisms related to hair cell regeneration in the field of sensorineural hearing loss.
Greater Knowledge Enhances Complainant Credibility and Increases Jury Convictions for Child Sexual Assault

Child sexual assault (CSA) cases reliant on uncorroborated testimony yield low conviction rates. Past research demonstrated a strong relationship between verdict and juror CSA knowledge such as typical delays in reporting by victims, and perceived victim credibility. This trial simulation experiment examined the effectiveness of interventions by an expert witness or an educative judicial direction in reducing jurors' CSA misconceptions. Participants were 885 jurors in New South Wales, Australia. After viewing a professionally acted video trial, half the jurors rendered individual verdicts and half deliberated in groups of 8–12 before completing a post-trial questionnaire. Multilevel structural equation modeling exploring the relationship between CSA knowledge and verdict demonstrated that greater CSA knowledge after the interventions increased the odds ratio to convict by itself, and that the judicial direction predicted a higher level of post-trial CSA knowledge in jurors than other expert interventions. Moreover, greater CSA knowledge was associated with heightened credibility perceptions of the complainant and a corroborating witness. At the conclusion of the trial, the more jurors knew about CSA, the higher the perceived credibility of both the complainant and her grandmother, and the more likely jurors were to convict the accused.
Biochemical Origin of Raman-Based Diagnostics of Huanglongbing in Grapefruit Trees

Biotic and abiotic stresses cause substantial changes in plant biochemistry. These changes are typically revealed by high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS). This information can be used to determine underlying molecular mechanisms of biotic and abiotic stresses in plants. A growing body of evidence suggests that changes in plant biochemistry can be probed by Raman spectroscopy, an emerging analytical technique that is based on inelastic light scattering. Non-invasive and non-destructive detection and identification of these changes allow for the use of Raman spectroscopy for confirmatory diagnostics of plant biotic and abiotic stresses. In this study, we couple HPLC and HPLC-MS findings on biochemical changes caused by Candidatus Liberibacter spp. (Ca. L. asiaticus) in citrus trees to the spectroscopic signatures of plant leaves derived by Raman spectroscopy. Our results show that Ca. L. asiaticus cause an increase in hydroxycinnamates, the precursors of lignins, and flavones, as well as a decrease in the concentration of lutein that are detected by Raman spectroscopy. These findings suggest that Ca. L. asiaticus induce a strong plant defense response that aims to exterminate bacteria present in the plant phloem. This work also suggests that Raman spectroscopy can be used to resolve stress-induced changes in plant biochemistry on the molecular level.
Shifting of Physicochemical and Biological Characteristics of Coffee Roasting Under Ultrasound-Assisted Extraction

Ultrasound-assisted extraction (UAE) is an effective tool for the extraction of natural antioxidants. Thus, differentially roasted Arabica-coffee beans known as light (LC), medium (MC), and dark coffee (DC) were prepared and extracted under the influence of UAE. Following that, they were examined specifically on theirs physicochemical and biological characteristics: nutritional values, pH, °Brix, antioxidant activities, polyphenol content, caffeine, and chlorogenic-acid levels. Various parameters, such as extraction temperatures (20, 40, and 80°C) and extraction time periods (5, 10, and 20 min), were examined. DC extract was less acidic than those on MC and LC extracts. LC showed higher moisture content than the MC and DC (1.56, 1.3, and 0.92%, respectively). MC displayed the highest polyphenol content and potent antioxidant activity. Caffeine and chlorogenic acid contents trend to decrease during roasting. The maximum caffeine level was found in MC at 80°C for 5 min (27.65 mg/g extract). The highest chlorogenic acid content was in LC at 80°C for 10 min (16.67 mg/g extract). The caffeine and chlorogenic acid contents were related to the polyphenol content and depended on the roasting and extraction conditions. These results suggest that the UAE at various temperature and extraction time period may alter the physicochemical and biological characteristics of different coffee roasts.
N-Truncated Aβ Starting at Position Four—Biochemical Features, Preclinical Models, and Potential as Drug Target in Alzheimer’s Disease

The discussion of whether amyloid plaque Aβ is a valid drug target to fight Alzheimer’s disease (AD) has been a matter of scientific dispute for decades. This question can only be settled by successful clinical trials and the approval of disease-modifying drugs. However, many clinical trials with antibodies against different regions of the amyloid Aβ peptide have been discontinued, as they did not meet the clinical endpoints required. Recently, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate Aβ, showed beneficial effects in a phase II trial, supporting the concept that N-truncated Aβ is a relevant target for AD therapy. There is long-standing evidence that N-truncated Aβ variants are the main variants found in amyloid plaques besides full-length Aβ1–42, t, therefore their role in triggering AD pathology and as targets for drug development are of interest. While the contribution of pyroglutamate Aβ3–42 to AD pathology has been well studied in the past, the potential role of Aβ4–42 has been largely neglected. The present review will therefore focus on Aβ4–42 as a possible drug target based on human and mouse pathology, in vitro and in vivo toxicity, and anti-Aβ4-X therapeutic effects in preclinical models.
Pseudomonas palmensis sp. nov., a Novel Bacterium Isolated From Nicotiana glauca Microbiome: Draft Genome Analysis and Biological Potential for Agriculture

A novel Pseudomonas, designated strain BBB001T, an aerobic, rod-shaped bacterium, was isolated from the rhizosphere of Nicotiana glauca in Las Palmas Gran Canaria, Spain. Genomic analysis revealed that it could not be assigned to any known species of Pseudomonas, so the name Pseudomonas palmensis sp. nov. was proposed. A 16S rRNA gene phylogenetic analysis suggested affiliation to the Pseudomonas brassicae group, being P. brassicae MAFF212427 T the closest related type strain. Upon genomic comparisons of both strains, all values were below thresholds established for differentiation: average nucleotide identity (ANI, 88.29%), average amino acid identity (AAI, 84.53%), digital DNA-DNA hybridization (dDDH, 35.4%), and TETRA values (0.98). When comparing complete genomes, a total of 96 genes present exclusively in BBB001T were identified, 80 of which appear associated with specific subsystems. Phenotypic analysis has shown its ability to assimilate glucose, potassium gluconate, capric acid malate, trisodium citrate, and phenylacetic acid; it was oxidase positive. It is able to produce auxins and siderophores in vitro; its metabolic profile based on BIOLOG Eco has shown a high catabolic capacity. The major fatty acids accounting for 81.17% of the total fatty acids were as follows: C16:0 (33.29%), summed feature 3 (22.80%) comprising C16:1 ω7c and C16:1 ω6c, summed feature 8 (13.66%) comprising C18:1 ω7c, and C18:1ω6c and C17:0 cyclo (11.42%). The ability of this strain to improve plant fitness was tested on tomato and olive trees, demonstrating a great potential for agriculture as it is able to trigger herbaceous and woody species. First, it was able to improve iron nutrition and growth on iron-starved tomatoes, demonstrating its nutrient mobilization capacity; this effect is related to its unique genes related to iron metabolism. Second, it increased olive and oil yield up to 30% on intensive olive orchards under water-limiting conditions, demonstrating its capacity to improve adaptation to adverse conditions. Results from genomic analysis together with differences in phenotypic features and chemotaxonomic analysis support the proposal of strain BBB001T (=LMG 31775T = NCTC 14418T) as the type strain of a novel species for which the name P. palmensis sp. nov is proposed.