Miracle-dz/UniFAR-FTUs huggingface dataset:
Major environmental characteristics of swine husbandry that affect exposure to dust and airborne endotoxins

ABSTRACT Inhalation of organic dust or endotoxin in the dust is considered a major risk factor for occupational respiratory illnesses. Eighteen environmental characteristics associated with animal husbandry were surveyed at 36 swine farms in seven provinces throughout South Korea. Association of these factors with levels of indoor inhalable or respirable dust or endotoxin in each type of dust was analyzed using backward stepwise multiple linear regression models. Mean levels of inhalable and respirable dust were 0.5 ± 0.35 and 0.13 ± 0.12 mg/m3 air, respectively, and mean endotoxin levels were 676 ± 463 and 48.4 ± 68.2 EU/m3, respectively, in each dust. Factors negatively associated with inhalable dust levels included pig age, indoor farm temperature, number of pigs in the building, hr/week of indoor farm work, and partly slatted floor. Factors positively associated with inhalable dust levels included floor cleaning by manual scraping and slurry deposit duration. Factors negatively associated with the level of endotoxin in inhalable dust included pig age, temperature, number of pigs, hr/week of indoor farm work, and partly slatted floor. Factors negatively associated with respirable dust level included area of the confinement building, whereas factors positively associated with respirable dust level included the number of pigs and stocking density. Endotoxin levels in respirable dust were negatively associated with h/week of indoor farm work and partly slatted floor. Overall, data suggest that husbandry variables may be adjusted to control dust and airborne endotoxin levels in swine farms.
Risk Factors That Determine Removal of the Catheter in Bacterial Peritonitis in Peritoneal Dialysis

dialysis–related peritonitis caused by vancomycin-resistant Enterococcus faecium. Ther apher Dial 2011; 15:115–16. 13. Yang JW, Kim YS, Choi SO, Han BG. Successful use of intravenous linezolid in CAPD patient with vancomycinresistant enterococcal peritonitis. Perit Dial Int 2011; 31:209–10. 14. Li PK, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, et al. on behalf of the International Society for Peritoneal Dialysis. Peritoneal dialysis–related infections recommendations: 2010 update. Perit Dial Int 2010; 30:393–423. [Erratum in: Perit Dial Int 2011; 31:512] 15. Murray BE. Vancomycin-resistant enterococcal infections. N Engl J med 2000; 342:710–21. 16. Kang CI, Song JH. Antimicrobial resistance in Asia: current epidemiology and clinical implications. Infect chemother 2013; 45:22–31. 17. Diaz–Buxo JA, Wick GS, Pesich AA. Using CQI techniques for managing infections in PD patients. Nephrol News Issues 1998; 12:22–4. 18. Barbosa D, Lima L, Silbert S, Sader H, Cendoroglo M, Draibe S, et al. Evaluation of the prevalence and risk factors for colonization by vancomycin-resistant Enterococcus among patients on dialysis. am J Kidney Dis 2004; 44:337–43. 19. roghmann MC, Fink JC, Polish L, Maker T, Brewrink J, Morris JG Jr, et al. Colonization with vancomycin-resistant enterococci in chronic hemodialysis patients. am J Kidney Dis 1998; 32:254–7. 20. Chavers LS, Moser SA, Benjamin WH, Banks SE, Steinhauer Jr, Smith AM, et al. Vancomycin-resistant enterococci: 15 years and counting. J hosp Infect 2003; 53:159–71. doi:10.3747/pdi.2013. 00076
Perspective: What Does Stunting Really Mean? A Critical Review of the Evidence

ABSTRACT The past decade has seen an unprecedented increase in attention to undernutrition, and drastically reducing child stunting has become a global development objective. The strong focus on linear growth retardation and stunting has enabled successful advocacy for nutrition, but with this focus has come some confusion and misunderstanding about the meaning of linear growth retardation and stunting among researchers, donors, and agencies active in nutrition. Motivated by the belief that a sharp focus will further accelerate progress in reducing undernutrition, we critically reviewed the evidence. The global attention to stunting is based on the premise that any intervention aimed at improving linear growth will subsequently lead to improvements in the correlates of linear growth retardation and stunting. Current evidence and understanding of mechanisms does not support this causal thinking, with 2 exceptions: linear growth retardation is a cause of difficult births and poor birth outcomes. Linear growth retardation is associated with (but does not cause) delayed child development, reduced earnings in adulthood, and chronic diseases. We thus propose distinguishing 2 distinctly different meanings of linear growth retardation and stunting. First, the association between linear growth retardation (or stunting) and other outcomes makes it a useful marker. Second, the causal links with difficult births and poor birth outcomes make linear growth retardation and stunting outcomes of intrinsic value. In many cases a focus on linear growth retardation and stunting is not necessary to improve the well-being of children; in many other cases, it is not sufficient to reach that goal; and for some outcomes, promoting linear growth is not the most cost-efficient strategy. We appeal to donors, program planners, and researchers to be specific in selecting nutrition outcomes and to target those outcomes directly.
New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Microorganisms in the environment can produce a diverse range of secondary metabolites (SM), which are also known as natural products. Bioactive SMs have been crucial in the development of antibiotics and can also act as useful compounds in the biotechnology industry. These natural products are encoded by an extensive range of biosynthetic gene clusters (BGCs). The developments in omics technologies and bioinformatic tools are contributing to a paradigm shift from traditional culturing and screening methods to bioinformatic tools and genomics to uncover BGCs that were previously unknown or transcriptionally silent. Natural product discovery using bioinformatics and omics workflow in the environment has demonstrated an extensive distribution of BGCs in various environments, such as soil, aquatic ecosystems and host microbiome environments. Computational tools provide a feasible and culture-independent route to find new secondary metabolites where traditional approaches cannot. This review will highlight some of the advances in the approaches, primarily bioinformatic, in identifying new BGCs, especially in environments where microorganisms are rarely cultured. This has allowed us to tap into the huge potential of microbial dark matter.
Medications for Early Life Epilepsy: Evidence Versus Experience?

Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017. 5211. Importance: More than half of infants with new-onset epilepsy have electroencephalographic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown. Objective: To compare the effectiveness of levetiracetam versus phenobarbital for nonsyndromic infantile epilepsy. Design, Setting, and Participants: The Early Life Epilepsy Study—a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers—enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age. Exposures: Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. Main Outcomes and Measures: The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations. Results: Of the 155 infants in the study (81 girls and 74 boys; median age, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n = 117) were older at the time of the first seizure than those treated with phenobarbital (n = 38; median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P < .001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P = .01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). Conclusions and Relevance: Levetiracetam may have superior effectiveness compared to phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.
Distractor-resistant Short-Term Memory Is Supported by Transient Changes in Neural Stimulus Representations

Goal-directed behavior in a complex world requires the maintenance of goal-relevant information despite multiple sources of distraction. However, the brain mechanisms underlying distractor-resistant working or short-term memory (STM) are not fully understood. Although early single-unit recordings in monkeys and fMRI studies in humans pointed to an involvement of lateral prefrontal cortices, more recent studies highlighted the importance of posterior cortices for the active maintenance of visual information also in the presence of distraction. Here, we used a delayed match-to-sample task and multivariate searchlight analyses of fMRI data to investigate STM maintenance across three extended delay phases. Participants maintained two samples (either faces or houses) across an unfilled pre-distractor delay, a distractor-filled delay, and an unfilled post-distractor delay. STM contents (faces vs. houses) could be decoded above-chance in all three delay phases from occipital, temporal, and posterior parietal areas. Classifiers trained to distinguish face versus house maintenance successfully generalized from pre- to post-distractor delays and vice versa, but not to the distractor delay period. Furthermore, classifier performance in all delay phases was correlated with behavioral performance in house, but not face, trials. Our results demonstrate the involvement of distributed posterior, but not lateral prefrontal, cortices in active maintenance during and after distraction. They also show that the neural code underlying STM maintenance is transiently changed in the presence of distractors and reinstated after distraction. The correlation with behavior suggests that active STM maintenance is particularly relevant in house trials, whereas face trials might rely more strongly on contributions from long-term memory.
Opening the field of integrin biology to "biased agonism".

See related article, pages 1269–1279 Integrins are α- and β-subunit heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands central to inflammation, immunity, hemostasis, and tumor metastasis.1 Integrins have been viewed to function within a 2-state model. In response to cell activation signals, integrins switch from a low-affinity to a high-affinity ligand-binding state. These inactive and active integrin conformations have been corroborated structurally.2 In this issue of Circulation Research , Wolf and coworkers3 have mapped a novel interaction site within the ligand-binding I-domain of the αM-subunit. Taken with the synthesis herein, these data provide tantalizing evidence that the 2-state model of integrin activation and deactivation may be oversimplified. Recruitment of circulating leukocytes in inflammation requires multistep adhesive and signaling events mediated, in part, by members of the β2-integrin family, LFA-1 (αLβ2, CD11a/CD18), Mac-1 (αMβ2, CD11b/CD18), p150,95 (αMβ2, CD11c/CD18), and αDβ2 (CD11d/CD18). 4 Mac-1 is the most abundant β2-integrin on neutrophils and monocytes and is a highly promiscuous receptor, capable of binding a broad repertoire of ligands (Figure, A) and facilitating key leukocyte functions including migration, coagulation, proteolysis, phagocytosis, oxidative burst, and signaling.5–9 Elegant structural studies by several groups have begun to elucidate the molecular basis for such broad ligand recognition by Mac-1. A subset of integrin α-subunits, including αM of Mac-1, contains an inserted domain (I domain) of ≈200 amino acids that is implicated in ligand binding. The αMI-domain contributes broadly to the recognition of ligands by αMβ …
Weak spatiotemporal response of prey to predation risk in a freely interacting system

The extent to which prey space use actively minimises predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured, and lack of robust null expectations. We addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by grey wolves (Canis lupus) during winter in northern Yellowstone, USA. We quantified spatial overlap between the winter home ranges of GPS-collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf-killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterised by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach. Although a small proportion of elk did show a tendency to minimise use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone. Our results suggest that predator-prey interactions may not always result in strong spatiotemporal patterns of avoidance.
Tracer: Taming Anomalous Events with CRFID Tags for Trajectory Management

Mitigating anomalies are crucial for trajectory management in logistics and supply chain systems. Among variant devices for trace detection, computational radio frequency identification (CRFID) tags are promising to draw precise trajectory from the data reported by their accelerometers. However, full coverage of the processing flow using RFID readers is usually cost inefficient, sometimes impractical. In this paper, we propose to employ CRFID tags as tagging devices and develop a working system, Tracer, for precise trajectory detection. Instead of covering the entire processing area, Tracer only deploys RFID readers in essential regions to detect the mishandling, loss, and other abnormal states of items. We design a tree-indexed Markov chain framework, which leverages statistical methods to enable fine-grained and dynamic trajectory management. Results from a preliminarily deployment on a real baggage handling system and trace-driven simulations demonstrate that Tracer is effective to detect the anomalous events with low cost and high accuracy.
Developments in depression in epilepsy: screening, diagnosis, and treatment

ABSTRACT Introduction: Depression is one of the most frequent comorbidities in epilepsy affecting between 17% and 22% of patients, but it is still underdiagnosed and undertreated. Areas covered: This paper discusses recent advances about screening, diagnosis, and treatment of depression in epilepsy taking into account the heterogeneity of clinical scenarios where depression can occur. Expert opinion: A number of screening instruments are now validated for adults with epilepsy, and their psychometric properties are discussed but the NDDI-E is the most practical and cost-effective. Challenges in diagnosing depression in epilepsy are discussed including reasons for the atypical features of mood disorders in epilepsy. Psychological treatments and/or SSRIs are indicated, but the level of evidence is still low. Even if there is no reason to hypothesise that internationally accepted guidelines of treatment of depression outside epilepsy may not be valid, rigorous studies are needed in order to have proper outcome measures. Epilepsy centers should have well-defined care pathways for depression in order to provide access to mental health support when needed.
Incidence and survival of laryngeal cancer in Denmark: a nation-wide study from 1980 to 2014

Abstract Background: The purpose of this registry study was to evaluate trends in incidence and survival of laryngeal cancer in the Danish population from 1980 to 2014. Methods: This study includes all patients with laryngeal cancer registered in the Danish Cancer Registry (DCR) in the period 1980–2014. The age-adjusted incidence rate (AAIR) per 100,000 and average annual percent change (AAPC) were calculated. We evaluated the relative survival at five years in relation to gender, anatomical location, year at diagnosis, and histological type. Further, an age-period-cohort (APC) model of incidence was constructed. Results: A total of 8748 patients (82% males) were included. The median age at diagnosis was 60 years, range 18–101 years. The AAIR decreased from 3.6 per 100,000 in 1980 to 2.3 per 100,000 in 2014 with an AAPC of –0.8% (p < .008). Considering the anatomic location, we found that glottic cancer had a significantly better survival at five years compared to the other locations. We observed no significant difference in survival for supraglottic, subglottic and larynx unspecified cancer during the observation period. During the period 1980–2014, we found no improvement in five year relative survival. Conclusions: This nation-wide study reports a significant decrease in the incidence of laryngeal cancer. Glottic cancer had a significantly better survival at five years compared to other locations.
Reflecting on Concepts Relevant to Contemplating the Relationships Between Glucose–Insulin Perturbations, Nutrition, and Aging

Abstract Background: Medical professionals attribute a crucial role in the development of several age-related, chronic health maladies to glucose-insulin perturbations – particularly, discernible insulin resistance (IR). However, little information is available concerning the degree to which relatively minor changes in IR participate over time in overall aging population, e.g., when circulating glucose and/or insulin concentrations are consistently within the higher end of normally accepted ranges. Objective: Obtaining precise knowledge is important, because proper nutritional management has the distinct capability of ameliorating the consequences. Methods: Five key concepts are suggested to underpin current thinking as to the applicable mechanisms and these are (1) the practical use of fasting blood glucose (FBG) levels as an estimate of IR, (2) the potential role of even slightly aberrant insulin regulation over time in the aging process, (3) the implementation of “continuum of risks” rather than checkpoints in considering prevention, (4) the presence and meaning of an aging paradox discovered in a recent study, and (5) the importance nutritional considerations in the “deadly triangle” as key factors in aging. Conclusions: Maintaining relatively low levels of FBG representing IR during aging via nutritional means has the potential to deliver a longer, more healthful lifespan as well as ameliorate many adverse manifestations of aging.
Podocyte-specific expression of Cre recombinase promotes glomerular basement membrane thickening.

Conditional gene targeting using Cre recombinase has offered a powerful tool to modify gene function precisely in defined cells/tissues and at specific times. However, in mammalian cells, Cre recombinase can be genotoxic. The importance of including Cre-expressing control mice to avoid misinterpretation and to maximize the validity of the experimental results has been increasingly recognized. While studying the role of podocytes in the pathogenesis of glomerular basement membrane (GBM) thickening, we used Cre recombinase driven by the podocyte-specific podocin promoter (NPHS2-Cre) to generate a conditional knockout. By conventional structural and functional measures (histology by periodic acid-Schiff staining, albuminuria, and plasma creatinine), we did not detect significant differences between NPHS2-Cre transgenic and wild-type control mice. However, surprisingly, the group that expressed Cre transgene alone developed signs of podocyte toxicity, including marked GBM thickening, loss of normal foot process morphology, and reduced Wilms tumor 1 expression. GBM thickening was characterized by altered expression of core structural protein laminin isoform α5β2γ1. RNA sequencing analysis of extracted glomeruli identified 230 genes that were significant and differentially expressed (applying a q < 0.05-fold change ≥ ±2 cutoff) in NPHS2-Cre mice compared with wild-type control mice. Many biological processes were reflected in the RNA sequencing data, including regulation of the extracellular matrix and pathways related to apoptosis and cell death. This study highlights the importance of including the appropriate controls for potential Cre-mediated toxicity in conditional gene-targeting experiments. Indeed, omitting the Cre transgene control can result in critical errors during interpretation of experimental data.
NKAP Must Associate with HDAC3 to Regulate Hematopoietic Stem Cell Maintenance and Survival

Key Points NKAP Y352 is required for association with HDAC3. The interaction between NKAP and HDAC3 is critical for its function in HSCs. The interaction between NKAP and HDAC3 is unimportant in some cell types. NKAP is a multifunctional nuclear protein that associates with the histone deacetylase HDAC3. Although both NKAP and HDAC3 are critical for hematopoietic stem cell (HSC) maintenance and survival, it was not known whether these two proteins work together. To assess the importance of their association in vivo, serial truncation and alanine scanning was performed on NKAP to identify the minimal binding site for HDAC3. Mutation of either Y352 or F347 to alanine abrogated the association of NKAP with HDAC3, but did not alter NKAP localization or expression. Using a linked conditional deletion/re-expression system in vivo, we demonstrated that re-expression of the Y352A NKAP mutant failed to restore HSC maintenance and survival in mice when endogenous NKAP expression was eliminated using Mx1-cre and poly-IC, whereas re-expression of wild type NKAP maintained the HSC pool. However, Y352A NKAP did restore proliferation in murine embryonic fibroblasts when endogenous NKAP expression was eliminated using ER-cre and tamoxifen. Therefore, Y352 in NKAP is critical for association with HDAC3 and for HSC maintenance and survival but is not important for proliferation of murine embryonic fibroblasts, demonstrating that NKAP functions in different complexes in different cell types.