Miracle-dz/UniFAR-FTUs huggingface dataset:
A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.
Imaging Transcranial Doppler Ultrasound to Measure Middle Cerebral Artery Blood Flow: The Importance of Measuring Vessel Diameter.

Cerebral blood flow (CBF) is commonly inferred from blood velocity measurements in the middle cerebral artery (MCA), using, non-imaging, transcranial Doppler ultrasound (TCD). However, both blood velocity and vessel diameter are critical components required to accurately determine blood flow, and there is mounting evidence that the MCA is vasoactive. Therefore, the aim of this study was to employ imaging TCD (ITCD), utilizing color flow images and pulse wave velocity, as a novel approach to measure both MCA diameter and blood velocity to accurately quantify changes in MCA blood flow. ITCD was performed at rest in 13 healthy participants (7M/6F; 28 ± 5 yr) with pharmaceutically-induced vasodilation (nitroglycerin (NTG), 0.8 mg) and without (CON). Measurements were taken for 2 minutes prior, and for 5 minutes following NTG or sham delivery (CON). There was more than a 5-fold, significant, fall in MCA blood velocity in response to NTG (∆-4.95 ± 4.6 cm/s) comparted to negligible fluctuation in CON (∆-0.88 ± 4.7 cm/s) (p<0.001). MCA diameter increased significantly in response to NTG (∆0.09 ± 0.04 cm) compared to the basal variation in CON (∆0.00 ± 0.04 cm) (p=0.018). Interestingly, the product of the NTG-induced fall in MCA blood velocity and increase in diameter was a significant increase in MCA blood flow following NTG (∆144 ± 159 ml/min) compared to CON (∆-5 ± 130 ml/min) (p=0.005). These juxtaposed findings highlight the importance of measuring both MCA blood velocity and diameter when assessing CBF and document ITCD as a novel approach to achieve this goal.
Simple sensitivity analysis for control selection bias.

e44 | www.epidem. com © 2020 Wolters Kluwer Health, Inc. All rights reserved. Simple Sensitivity Analysis for Control Selection Bias ACM SIGKDD Explorations Newsletter. 2004;6:1–6. 3. Naimi AI, Balzer LB. Stacked generalization: an introduction to super learning. Eur J Epidemiol. 2018;33:459–464. 4. SuperLearner: Super Learner Prediction. [computer program]. Version R package version 2.02. 4. Available at: https://CRAN.R-project.org/ package=SuperLearner2018. Accessed 1 October 2019. 5. Batista G, Prati RC, Monard MC. A study of the behavior of several methods for balancing machine learning training data. ACM SIGKDD Explorations Newsletter. 2004;6:20–29. 6. Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP. SMOTE: synthetic minority over-sampling technique. J Artifi Intell Res. 2002;16:321–357. 7. Kuhn M. Building predictive models in R using the caret package. J Stat Soft. 2008;28:1–26. 8. pROC: an open-source package for R and S+ to analyze and compare ROC curves [computer program]. BMC Bioinformatics. 2011;12:77.
Hepsin enhances liver metabolism and inhibits adipocyte browning in mice

Significance Hepsin is a cell membrane-bound enzyme discovered in the human liver. To date, the function of hepsin in the body remains unclear. Here we show that hepsin increases glycogen and lipid production in the liver and lowers metabolic rates and adipose tissue browning in mice. This function is medicated by the activation of hepatocyte growth factor and downstream Met signaling in both hepatocytes and adipocytes. Hepsin-deficient mice are resistant to obesity, hyperglycemia, and hyperlipidemia caused by a high-fat diet or leptin receptor deficiency. Our findings identify hepsin as a key regulator in the liver and energy metabolism, suggesting that hepsin may be a novel therapeutic target for obesity, dyslipidemia, and diabetes. Hepsin is a transmembrane serine protease primarily expressed in the liver. To date, the physiological function of hepsin remains poorly defined. Here we report that hepsin-deficient mice have low levels of blood glucose and lipids and liver glycogen, but increased adipose tissue browning and basal metabolic rates. The phenotype is caused by reduced hepatocyte growth factor activation and impaired Met signaling, resulting in decreased liver glucose and lipid metabolism and enhanced adipocyte browning. Hepsin-deficient mice exhibit marked resistance to high-fat diet-induced obesity, hyperglycemia, and hyperlipidemia. In db/db mice, hepsin deficiency ameliorates obesity and diabetes. These data indicate that hepsin is a key regulator in liver metabolism and energy homeostasis, suggesting that hepsin could be a therapeutic target for treating obesity and diabetes.
Pan-Genome Analyses of Geobacillus spp. Reveal Genetic Characteristics and Composting Potential

The genus Geobacillus is abundant in ecological diversity and is also well-known as an authoritative source for producing various thermostable enzymes. Although it is clear now that Geobacillus evolved from Bacillus, relatively little knowledge has been obtained regarding its evolutionary mechanism, which might also contribute to its ecological diversity and biotechnology potential. Here, a statistical comparison of thirty-two Geobacillus genomes was performed with a specific focus on pan- and core genomes. The pan-genome of this set of Geobacillus strains contained 14,913 genes, and the core genome contained 940 genes. The Clusters of Orthologous Groups (COG) and Carbohydrate-Active Enzymes (CAZymes) analysis revealed that the Geobacillus strains had huge potential industrial application in composting for agricultural waste management. Detailed comparative analyses showed that basic functional classes and housekeeping genes were conserved in the core genome, while genes associated with environmental interaction or energy metabolism were more enriched in the pan-genome. Therefore, the evolution of Geobacillus seems to be guided by environmental parameters. In addition, horizontal gene transfer (HGT) events among different Geobacillus species were detected. Altogether, pan-genome analysis was a useful method for detecting the evolutionary mechanism, and Geobacillus’ evolution was directed by the environment and HGT events.
Comparing Light-Driven Contact Hearing Aids with Acoustic Hearing Aids: Data and Clinical Tips

Introduction: Contact hearing aids (CHA) offer potential advantages over conventional acoustic hearing aids (AHA) in terms of sound quality, reduced occlusion, and increased high-frequency gain. This study evaluates objective and subjective outcome data for CHA compared to AHA. Methods: Clinical outcome data were retrospectively reviewed for patients wearing CHA. Individual and group data were analyzed and then compared to unaided and AHA data. Adverse effects, device complaints, and clinical utility were documented throughout the device fitting and follow-up process. Results: CHA outcomes were better than unaided hearing and AHA for all patients completing the 3-month CHA trial period (45%). However, CHA return rate was high (55%), most often due to device repair and fit issues. Two patients returned the devices due to poor hearing benefit, though both were off-label audiometric candidates. Significantly more clinical time was required from both audiologists and otolaryngologists to successfully fit and maintain maximum device benefit. Conclusions: For proper audiometric and otologic candidates, this light-driven CHA can offer significant improvements in high-frequency sound fidelity, word recognition, and sound quality compared to AHA technology. Administering questionnaires was helpful in illuminating real-world improvements. Device fit, alignment, and quality control issues are improving, though still contributing to high device return rates at this time. Operational factors should be considered when incorporating CHA into a hearing health care practice.
Creating Backup Management Resources for Spine Care during the Coronavirus Disease 2019 Pandemic

During this unprecedented time of the coronavirus disease 2019 (COVID 19) pandemic, most countries are struggling to optimize their healthcare resources. Although the prevention and treatment of COVID 19 has become the priority for the majority of the population, most medical professionals are facing the challenge of balancing the management of this pandemic and treating patients with other diseases. Healthcare professionals from all specialties are facing this situation and designing guidelines and recommendations that are contributing to the literature that is crucial for disease management at the current time. We share our experience with two ends of the spectra that we currently observe in spine patients. One group of patients included the non-operative cases that presented with back pain. Further, we discuss our experience with operative precautions and digitally assisted discharge.
Consumption of acidic drinks, knowledge and concern about dental erosive wear in Norwegian high school students

Abstract Objectives The objectives of the present study were to assess the consumption of acidic beverages, knowledge and concern about preventing dental erosive wear, and to examine potential associations between these variables, in a sample of high school students. Materials and methods A survey measuring acidic beverage consumption, knowledge and concern about erosive tooth wear was conducted at 13 high schools in Rogaland county, Norway. Results Of the 850 students who completed the questionnaire, 26% reported that they drink acidic beverages every day. There were significant gender differences for the consumption of acidic drinks. The survey also demonstrated that a high proportion of students lacks basic knowledge of what erosive tooth wear is, and that this lack of knowledge is associated with a more frequent intake of acidic beverages. However, students who responded that they are concerned about preventing dental erosive wear reported that they drink soft drinks and energy drinks less frequently than students who are not concerned about this. Conclusions Results from this study support assumptions about a lack of knowledge about dental erosive wear in youth, and that this lack of knowledge is associated with a more frequent intake of acidic drinks.
Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.
Multiple weak interactions between BvgA~P and ptx promoter DNA strongly activate transcription of pertussis toxin genes in Bordetella pertussis

Pertussis toxin is the preeminent virulence factor and major protective antigen produced by Bordetella pertussis, the human respiratory pathogen and etiologic agent of whooping cough. Genes for its synthesis and export are encoded by the 12 kb ptx-ptl operon, which is under the control of the pertussis promoter, Pptx. Expression of this operon, like that of all other known protein virulence factors, is regulated by the BvgAS two-component global regulatory system. Although Pptx has been studied for years, characterization of its promoter architecture vis-à-vis BvgA-binding has lagged behind that of other promoters, mainly due to its lower affinity for BvgA~P. Here we take advantage of a mutant BvgA protein (Δ127–129), which enhances ptx transcription in B. pertussis and also demonstrates enhanced binding affinity to Pptx. By using this mutant protein labeled with FeBABE, binding of six head-to-head dimers of BvgA~P was observed, with a spacing of 22 bp, revealing a binding geometry similar to that of other BvgA-activated promoters carrying at least one strong binding site. All of these six BvgA-binding sites lack sequence features associated with strong binding. A genetic analysis indicated the degree to which each contributes to Pptx activity. Thus the weak/medium binding affinity of Pptx revealed in this study explains its lower responsiveness to phosphorylated BvgA, relative to other promoters containing a high affinity binding site, such as that of the fha operon.
Sex Biases in Avian Dispersal: A Reappraisal

We reviewed the avian literature for quantitative studies of sex biases in dispersal and found continued and strengthened support for the general pattern of female biased dispersal established by Greenwood in 1980. We report sex differences in dispersal patterns in natal and breeding dispersal as measured by 1) proportion leaving and 2) distance moved. Greenwood's review found evidence for male biased dispersal only within four species of the Anatidae. We find there is now evidence for male biased dispersal in twenty-two species representing twelve families.
Rapidly assessing cobenefits to advance threat‐management alliances

Conservation strategies aimed at reducing threats to biodiversity can have significant implications for multiple sectors in a socioeconomic system, but these cobenefits are often poorly understood. For example, many of the threats to native species also impede agricultural production, yet agriculture is typically perceived as in competition with conservation objectives. Although a comprehensive, multiobjective decision analysis is usually beyond the scope and capacity of conservation decision makers, failing to incorporate key socioeconomic costs and benefits into conservation decision‐making processes can result in missed opportunities for diversifying outcomes and creating cost‐sharing multisectoral partnerships. We devised a straightforward and readily interpretable approach to incorporate cobenefits into a threat‐management prioritization approach. We used it to analyze the agricultural cobenefits of implementing 9 invasive animal management strategies designed to ensure the persistence of 148 threatened species across Australia's Lake Eyre Basin over 50 years. A structured elicitation process with 24 participants (scientists, land managers, agriculturalists, and other stakeholders) was used to collect information on each strategy, including costs, technical and social feasibility, benefits to native threatened species, and cobenefits to agricultural production systems. The costs of targeted invasive animal management to save threatened species across the basin (AU$33 million/year) outweighed the overall benefits to the agricultural industry (estimated AU$226 million/year). The return on investment for these management strategies varied substantially when agricultural cobenefits were considered alongside threatened species benefits and showed synergies and challenges. Our approach demonstrates the value of incorporating cobenefits of conservation actions into cost‐effectiveness analyses to guide potential investment and partnerships and to diversify implementation pathways.
Legume and Nuts Consumption in Relation to Glioma: A Case- Control Study

Abstract Data on the link between legume and nuts consumption and risk of glioma are controversial. The current study aimed to investigate the relation between legume and nuts consumption and glioma in a case-control study in Iranian adults. In this hospital-based case-control study, we enrolled 128 pathologically confirmed new cases of glioma and 256 age and sex-matched controls. Dietary intakes of study participants were assessed using the validated Block-format 123-item semi-quantitative FFQ. Data on potential confounders were also collected through the use of a pre-tested questionnaire. Mean age of cases and controls were 43.4 and 42.8 years, respectively. Individuals with the greatest legume and nuts consumption were less likely to have glioma compared with those with the lowest consumption (0.52; 95% CI: 0.30–0.88). This inverse association was not changed after controlling for age, sex and energy intake (0.46; 95% CI: 0.26–0.81). The association remained statistically significant even after taking other potential confounders, including dietary intakes into account (0.32; 95% CI: 0.14–0.72). Additional adjustments for BMI did not alter the association; such that individuals in the top category of legume and nuts consumption were 66% less likely to have glioma compared with those in the bottom category (0.34; 95% CI: 0.15–0.76). We found an inverse association between legume and nuts consumption and odds of glioma, even after controlling for a wide range of confounders.
Tumor‐associated macrophages promote prostate cancer progression via exosome‐mediated miR‐95 transfer

Tumor‐associated macrophages (TAMs) are vital constituents in mediating cell‐to‐cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of “onco‐vesicles” is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP‐1 and M2 macrophages and found a significant increase in miR‐95 levels in TAM‐derived exosomes, demonstrating the direct uptake of miR‐95 by recipient PCa cells. In vitro and in vivo loss‐of‐function assays suggested that miR‐95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial–mesenchymal transition. The clinical data analyses further revealed that higher miR‐95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM‐mediated PCa progression is partially attributed to the aberrant expression of miR‐95 in TAM‐derived exosomes, and the miR‐95/JunB axis provides the groundwork for research on TAMs to further develop more‐personalized therapeutic approaches for patients with PCa.
Multivalent ions and biomolecules: Attempting a comprehensive perspective

Abstract Ions are ubiquitous in nature. They play a key role for many biological processes on the molecular scale, from molecular interactions, to mechanical properties, to folding, to self‐organisation and assembly, to reaction equilibria, to signalling, to energy and material transport, to recognition etc. Going beyond monovalent ions to multivalent ions, the effects of the ions are frequently not only stronger (due to the obviously higher charge), but qualitatively different. A typical example is the process of binding of multivalent ions, such as Ca2+, to a macromolecule and the consequences of this ion binding such as compaction, collapse, potential charge inversion and precipitation of the macromolecule. Here we review these effects and phenomena induced by multivalent ions for biological (macro)molecules, from the “atomistic/molecular” local picture of (potentially specific) interactions to the more global picture of phase behaviour including, e. g. , crystallisation, phase separation, oligomerisation etc. Rather than attempting an encyclopedic list of systems, we rather aim for an embracing discussion using typical case studies. We try to cover predominantly three main classes: proteins, nucleic acids, and amphiphilic molecules including interface effects. We do not cover in detail, but make some comparisons to, ion channels, colloidal systems, and synthetic polymers. While there are obvious differences in the behaviour of, and the relevance of multivalent ions for, the three main classes of systems, we also point out analogies. Our attempt of a comprehensive discussion is guided by the idea that there are not only important differences and specific phenomena with regard to the effects of multivalent ions on the main systems, but also important similarities. We hope to bridge physico‐chemical mechanisms, concepts of soft matter, and biological observations and connect the different communities further.
An evaluation of taxonomic characters in the Vaucheria prona complex (Vaucheriaceae, Chrysophyta)

Abstract Taxonomic characters have been evaluated in plants referable to the Vaucheria prona complex of Vaucheria. Three isolates were tested under a range oftemperatures, photon flux densities, salinities and substrate gradients, and compared with 32 field populations. Oospore shape, oospore wall thickness and texture in transverse section, and gametangial orientation were found to be good taxonomic characters. V. frigida has been distinguished from V. prona in having oospore walls lamellate rather than evenly textured and > 5 μm thick, dimidiate-globose oospores with a large conical protuberance rather than ovoid-reniform with a small distal prominence, and oogonia distal rather than lateral to antheridium when there is only one oogonium per gametophore. Descriptions and nomenclatural data are provided for both species, and their relationships with V. terrestris and V. racemosa are considered.