Miracle-dz/UniFAR-FTUs huggingface dataset:
An In Vitro Model of the Horse Gut Microbiome Enables Identification of Lactate-Utilizing Bacteria That Differentially Respond to Starch Induction

Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaera elsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonella montpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions.
Thrombectomy versus medical management for large vessel occlusion strokes with minimal symptoms: an analysis from STOPStroke and GESTOR cohorts

Introduction It remains unclear whether patients presenting with large vessel occlusion strokes and mild symptoms benefit from thrombectomy. Objective To compare outcomes of endovascular therapy versus medical management in patients with large vessel occlusion strokes and National Institute of Health Stroke Scale (NIHSS) score ≤5. Methods This was a retrospective analysis combining two large prospectively collected datasets including patients with (1) admission NIHSS score ≤5, (2) premorbid modified Rankin Scale (mRS) score 0–2, and (3) middle cerebral-M1/M2, intracranial carotid, anterior cerebral or basilar artery occlusions. Groups receiving (1) endovascular treatment and (2) medical management were compared. The primary and secondary outcome measures were NIHSS shift (discharge NIHSS minus admission NIHSS) and the rates of mRS 0–2 at discharge and 3–6 months, respectively. Univariate, multivariate, and matched analyses were performed. Results Eighty-eight patients received medical management and 30 thrombectomy. Multivariable analysis indicated thrombectomy was the only predictor of favorable NIHSS shift (β −3.7, 95% CI −6.0 to −1.5, p=0.02), as well as independence at discharge (β −21.995% CI −41.4to −20.8, p<0.01) and 3–6-month follow-up (β −21.1, 95% CI −39.1 to −19.7, p<0.01). A matched analysis (based on age, baseline NIHSS and intravenous tissue plasminogen activator use) produced 26 pairs. Endovascular therapy was statistically associated with lower NIHSS at discharge (p=0.04), favorable NIHSS shift (p=0.03), and increased independence rates at discharge (p=0.03) and 3–6-month follow-up (p=0.04). Conclusion In patients presenting with minimal stroke symptoms (NIHSS score ≤5) and large vessel occlusion strokes, mechanical thrombectomy appears to be associated with a favorable shift of NIHSS at discharge, as well as higher rates of independence at discharge and long-term follow-up. Confirmatory prospective studies are warranted.
Association of Frailty and 1-Year Postoperative Mortality Following Major Elective Noncardiac Surgery: A Population-Based Cohort Study.

IMPORTANCE Single-center studies identify frailty as a risk factor for 30-day postoperative mortality. The long-term and population-level effect of frailty on postoperative mortality is, to our knowledge, poorly described, as are the interactions of frailty with important predictors of mortality. OBJECTIVE To measure the population-level effect of patient frailty on, and its association with, 1-year postoperative mortality. DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study in Ontario, Canada, with data collected between April 1, 2002 and March 31, 2012. Analysis was performed from December 2014 to March 2015. All patients were community-dwelling individuals aged 65 years or older on the day of elective, major noncardiac surgery. EXPOSURE Frailty, as defined by the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. The ACG frailty-defining diagnoses indicator is a binary variable that uses 12 clusters of frailty-defining diagnoses. MAIN OUTCOMES AND MEASURES One-year all-cause postoperative mortality. RESULTS Of 202 811 patients, 6289 (3.1%) were frail (mean [SD] age, 77 [7] years). Within 1 year, 13.6% (n = 855) of frail and 4.8% (n = 9433) of nonfrail patients died. Adjustment for sociodemographic and surgical confounders resulted in a hazard ratio of 2.23 (95% CI, 2.08-2.40). The interaction between frailty and postoperative time demonstrated an increased relative hazard for death in frail patients (hazard ratio, 35.58; 95% CI, 29.78-40.19) on postoperative day 3. The association between frailty and increased risk of death decreased with patient age (HR, 2.66; 95% CI, 2.28-3.10 at age 65; HR, 1.63; 95% CI, 1.36-1.95 at age 90). Significant variations in the increased risk for death in frail patients existed between different surgery types and was strongest after total joint arthroplasty (HR, 3.79; 95% CI, 3.21-4.47 for hip replacement; HR, 2.68; 95% CI, 2.10-3.42 for knee replacement). CONCLUSIONS AND RELEVANCE At a population level, preoperative frailty-defining diagnoses were associated with a significantly increased risk of 1-year mortality that was particularly notable in the early postoperative period, in younger patients, and after joint arthroplasty.
Scan Order in Gibbs Sampling: Models in Which it Matters and Bounds on How Much

Gibbs sampling is a Markov Chain Monte Carlo sampling technique that iteratively samples variables from their conditional distributions. There are two common scan orders for the variables: random scan and systematic scan. Due to the benefits of locality in hardware, systematic scan is commonly used, even though most statistical guarantees are only for random scan. While it has been conjectured that the mixing times of random scan and systematic scan do not differ by more than a logarithmic factor, we show by counterexample that this is not the case, and we prove that that the mixing times do not differ by more than a polynomial factor under mild conditions. To prove these relative bounds, we introduce a method of augmenting the state space to study systematic scan using conductance.
Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology

ABSTRACT Excessive hydrogen sulfide (H2S) production from gut microbial metabolism may have clinically important relevance in the pathogenesis of gut disorders, including ulcerative colitis. However, little is known regarding factors that alter its production. Using a newly-designed in vitro gas-profiling technology, the study aimed to verify real-time H2S measurement reproducibility and thereafter, assess its production following exposure to dietary factors and 5-aminosalicylate acid (5-ASA). Measurements of H2S, carbon dioxide, hydrogen and methane measurements were compared between gas-profiling systems. Homogenized slurries were prepared from freshly-passed healthy human feces. Fifty ml slurries were aliquoted into separate fermentation chambers and substrates added including 1 g highly fermentable fructo-oligosaccharides (FOS) or resistant starch Hi-Maize (RS), or minimally fermentable psyllium or sterculia, 1 g cysteine, 0.9 g sodium sulfate or 1.2 mL of 1 M 5-ASA alone or in combinations. H2S release was sampled every 5 mins over 4-h and expressed relative to unspiked controls. RS suppressed H2S production by a mean 89.0 (SEM 4.8)% and FOS by 82.2 (6.2)% compared to <35 (17)% by psyllium and sterculia (p<0.001, two-way ANOVA). Cysteine stimulated H2S production by 1557 (532)%. The addition of FOS to slurries containing cysteine significantly suppressed H2S by 90 (2)% over the addition of 5-ASA (0.3 (2)%, p<0.001). Sulfate and 5-ASA had minimal overall effects. In conclusion, the H2S-profiling technology is a reproducible tool. Production of H2S is greatly enhanced by sulfur-amino acids but not inorganic sulfate, and is effectively suppressed by readily fermentable fibers. These findings inform potential designs of dietary therapies to reduce H2S production in vivo.
Antibiotic perturbation of the preterm infant gut microbiome and resistome

ABSTRACT The gut microbiota plays important roles in nutrient absorption, immune system development, and pathogen colonization resistance. Perturbations early in life may be detrimental to host health in the short and the long-term. Antibiotics are among the many factors that influence the development of the microbiota. Because antibiotics are heavily administered during the first critical years of gut microbiota development, it is important to understand the effects of these interventions. Infants, particularly those born prematurely, represent an interesting population because they receive early and often extensive antibiotic therapy in the first months after birth. Gibson et al. recently demonstrated that antibiotic therapy in preterm infants can dramatically affect the gut microbiome. While meropenem, ticarcillin-clavulanate, and cefotaxime treatments were associated with decreased species richness, gentamicin and vancomycin had variable effects on species richness. Interestingly, the direction of species richness response could be predicted based on the abundance of 2 species and 2 genes in the microbiome prior to gentamicin or vancomycin treatment. Nonetheless, all antibiotic treatments enriched the presence of resistance genes and multidrug resistant organisms. Treatment with different antibiotics further resulted in unique population shifts of abundant organisms and selection for different sets of resistance genes. In this addendum, we provide an extended discussion of these recent findings, and outline important future directions for elucidating the interplay between antibiotics and preterm infant gut microbiota development.
Acute Invasive Fungal Rhinosinusitis in Immunocompromised Patients: Role of an Early Diagnosis

Objective The aims of the present study were to evaluate the clinical significance of the delay for surgical treatment and the prognostic value of other clinical, pathologic, and microbiological variables among hematologic patients affected by acute invasive fungal rhinosinusitis (AIFRS). Furthermore, we propose our early diagnosis and treatment protocol, reporting its 10-year results. Study Design Monocentric retrospective analysis. Setting The study was conducted from 2001 to 2017 at the University Hospital of Bologna, Italy. Subjects and Methods The impact of time to treatment and clinical, pathologic, and microbiological variables were analyzed among patients with histologically and microbiologically proven AIFRS. The outcomes of patients treated before the introduction of the early diagnosis protocol were compared with those treated afterward. Results Nineteen patients affected by AIFRS were eligible for the study. Treatment delay >4 days (P = .002), infection caused by Mucorales (P = .015), and extension of the disease were negative prognostic variables (P = .017). The application of our protocol significantly reduced the delay for diagnosis and appropriate treatment by an average of 7.3 days (P = .02). Conclusion The promptness of the diagnosis and surgical treatment may play a significant role in the management of AIFRS, as it appears to be significantly associated with the disease outcome. Our protocol may help to reduce the time required for diagnosis of high-risk hematologic patients.
The Ontogeny of Bumblebee Flight Trajectories: From Naïve Explorers to Experienced Foragers

Understanding strategies used by animals to explore their landscape is essential to predict how they exploit patchy resources, and consequently how they are likely to respond to changes in resource distribution. Social bees provide a good model for this and, whilst there are published descriptions of their behaviour on initial learning flights close to the colony, it is still unclear how bees find floral resources over hundreds of metres and how these flights become directed foraging trips. We investigated the spatial ecology of exploration by radar tracking bumblebees, and comparing the flight trajectories of bees with differing experience. The bees left the colony within a day or two of eclosion and flew in complex loops of ever-increasing size around the colony, exhibiting Lévy-flight characteristics constituting an optimal searching strategy. This mathematical pattern can be used to predict how animals exploring individually might exploit a patchy landscape. The bees’ groundspeed, maximum displacement from the nest and total distance travelled on a trip increased significantly with experience. More experienced bees flew direct paths, predominantly flying upwind on their outward trips although forage was available in all directions. The flights differed from those of naïve honeybees: they occurred at an earlier age, showed more complex looping, and resulted in earlier returns of pollen to the colony. In summary bumblebees learn to find home and food rapidly, though phases of orientation, learning and searching were not easily separable, suggesting some multi-tasking.
Influence of Graded Levels of l-Theanine Dietary Supplementation on Growth Performance, Carcass Traits, Meat Quality, Organs Histomorphometry, Blood Chemistry and Immune Response of Broiler Chickens

l-theanine is a water-soluble non-proteinous amino acid mainly found in green tea leaves. Despite the availability of abundant literature on green tea, studies on the use of l-theanine as a feed additive in animals, and especially broilers are limited. The objective of this study was, therefore, to evaluate the effect of different dietary levels of l-theanine on meat quality, growth performance, immune response, and blood metabolites in broilers. A total of 400 day-old broiler chicks were randomly divided into four treatment groups using a completely randomized design; C-control, basal diet; 100LT-basal diet + 100 mg l-theanine/kg diet; 200LT-basal diet + 200 mg l-theanine/kg diet; and 300LT-basal diet + 300 mg l-theanine/kg diet. Results revealed that the intermediate level of l-theanine (200 mg/kg diet) showed better results in terms of body weight gain (BWG), feed consumed (FC), and feed conversion ratio (FCR) as compared with the other supplemented groups and the control. The live weight eviscerated weight and gizzard weight were higher in all l-theanine levels as compared to those of the control group. Increased weight (p ≤ 0.05) of spleen and bursa were found in group 200LT (200 mg l-theanine/kg diet). Concerning meat color parameters, values for yellowness (b*), and redness (a*) were greater in l-theanine-supplemented groups than the control. Supplementing broiler diet with l-theanine reduced (p = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines (IL-2 and INF-γ) and reduced mRNA expression of TNF-α and IL-6 in thymus, and IFN-γ and IL-2 in spleen in the treated group. Moreover, supplementation with 200 mg/kg of l-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level of l-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels of l-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens.
Intrapulmonary Pharmacokinetics of Levonadifloxacin following Oral Administration of Alalevonadifloxacin to Healthy Adult Subjects

ABSTRACT Alalevonadifloxacin (WCK 2349) is a novel l-alanine ester prodrug of levonadifloxacin that is being developed as an oral fluoroquinolone antibiotic. The primary objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levonadifloxacin following oral administration of alalevonadifloxacin to healthy adult subjects. Levonadifloxacin concentrations in plasma, ELF, and AM samples from 30 healthy subjects were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following oral dosing of alalevonadifloxacin (1,000 mg twice daily for 5 days). Six subjects were assigned to each bronchoalveolar lavage (BAL) fluid sampling time, i.e., 2, 4, 6, 8, or 12 h after the ninth oral dose. Noncompartmental pharmacokinetic (PK) parameters were determined from serial total plasma concentrations collected over a 12-h interval following the first and ninth oral doses. Penetration ratios were calculated from the areas under the concentration-time curves from 0 to 12 h (AUC0–12) for plasma, ELF, and AM by using mean (and median) concentrations at each BAL sampling time. Unbound plasma concentrations (∼85% plasma protein binding) were used to determine site-to-plasma penetration ratios. Plasma PK parameter values for levonadifloxacin were similar after the first and ninth doses. The respective AUC0–12 values based on mean ELF and AM concentrations were 172.6 and 35.3 mg · h/liter, respectively. The penetration ratios for ELF and AM levonadifloxacin concentrations to unbound plasma levonadifloxacin concentrations were 7.66 and 1.58, respectively. Similar penetration ratios were observed with median concentrations. The observed plasma, ELF, and AM concentrations of levonadifloxacin support further studies of alalevonadifloxacin for treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02253342.)
Impacts of maternal dietary protein intake on fetal survival, growth, and development

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.
The female aging body: A systematic review of female perspectives on aging, health, and body image

ABSTRACT While most body image research has focused on young female populations, evidence has shown that as few as 12% of older women are satisfied with their body size. Recent studies have also highlighted how anti-aging discourses are promoting unrealistic body norms, which have shown to contribute to poor body image and altered health behaviors. A systematic review of empirical studies focused on older women’s perspectives of health, body image, and the aging body is presented. Findings support that body image is a persistent, lifelong issue for women and should be considered when implementing healthy aging policies and practices.
Mapping the Shapes of Phylogenetic Trees from Human and Zoonotic RNA Viruses

A phylogeny is a tree-based model of common ancestry that is an indispensable tool for studying biological variation. Phylogenies play a special role in the study of rapidly evolving populations such as viruses, where the proliferation of lineages is constantly being shaped by the mode of virus transmission, by adaptation to immune systems, and by patterns of human migration and contact. These processes may leave an imprint on the shapes of virus phylogenies that can be extracted for comparative study; however, tree shapes are intrinsically difficult to quantify. Here we present a comprehensive study of phylogenies reconstructed from 38 different RNA viruses from 12 taxonomic families that are associated with human pathologies. To accomplish this, we have developed a new procedure for studying phylogenetic tree shapes based on the ‘kernel trick’, a technique that maps complex objects into a statistically convenient space. We show that our kernel method outperforms nine different tree balance statistics at correctly classifying phylogenies that were simulated under different evolutionary scenarios. Using the kernel method, we observe patterns in the distribution of RNA virus phylogenies in this space that reflect modes of transmission and pathogenesis. For example, viruses that can establish persistent chronic infections (such as HIV and hepatitis C virus) form a distinct cluster. Although the visibly ‘star-like’ shape characteristic of trees from these viruses has been well-documented, we show that established methods for quantifying tree shape fail to distinguish these trees from those of other viruses. The kernel approach presented here potentially represents an important new tool for characterizing the evolution and epidemiology of RNA viruses.