Miracle-dz/UniFAR-FTUs huggingface dataset:
Indole toxicity in cattle

Indole and 3-methylindole (3MI) are ruminal metabolites of L-tryptophan (TRP) and have similar physical and chemical properties. 3-Methylindole causes acute bovine pulmonary emphysema (ABPE). The effects of indole when administered orally to cows were determined. Four mature Holstein cows were given increasing doses of 0.05, 0.1 and 0.2 g indole per kg body-weight orally at two-week intervals. The animals were killed one week after the last dose. Plasma indole concentrations peaked three house after administration at 4.5, 8.8 and 19.8 microgram per ml after the 0.05, 0.1 and 0.2 doses, respectively. Detectable concentrations of indole (more than 0.02 microgram per ml) persisted in the plasma from three to 25 hours after dosing. Packed cell volume was decreased (P less than 0.01) at 48 and 72 hours after the 0.2 g per kg dose and at 72 hours after the 0.1 g per kg dose. Plasma haemoglobin was increased (P less than 0.05) at 48 hours after the 0.2 and 0.1 g per kg doses. By 72 hours after the 0.2 g per kg dose, all cows had mild diarrhoea and haemolysis and two of the cows had haemoglobinuria. At necropsy, microscopic lesions of haemoglobinuric nephrosis were seen in all four cows. No lesions of ABPE were found in any of the animals.
L20B cells simplify culture of polioviruses from clinical samples

Culture of polioviruses from clinical samples is the gold‐standard method for virological surveillance in the world‐wide initiative to eradicate wild‐type polioviruses. Two poliovirus‐sensitive cell lines of human origin were used originally by the laboratories of the World Health Organisation (WHO) global poliovirus network. However, the cell lines used, Hep2 and RD, also support cytopathic growth of a variety of non‐poliovirus enteroviruses. This can make detection of polioviruses in samples with mixtures of viruses difficult and time consuming. The development of mouse cell lines that express the gene for the human cellular receptor for polioviruses allows selective poliovirus culture, because very few non‐poliovirus enteroviruses grow in these murine cells. A WHO Collaborative Study was initiated to test one such cell line, L20B, and to compare under routine conditions the sensitivity and selectivity of L20B cells against RD and Hep2 cells. Five laboratories in countries endemic or recently endemic for wild polioviruses participated. A total of 425 samples were tested prospectively in all three cell lines and there was a clear and consistent trend for greater sensitivity for polioviruses in L20B cells. Overall, 148/160 polioviruses were detected in L20B cells compared with 89/160 in RD and 98/160 in Hep2. In part, this finding was due to detection in L20B cells of polioviruses from samples that also contained non‐poliovirus enteroviruses in which the poliovirus was masked in RD or Hep2 cells. However, L20B cells were also significantly more sensitive for poliovirus than either RD or Hep2 cells in three of the five study laboratories. The L20B cells were completely selective for polioviruses, as 0/89 wild type non‐poliovirus enteroviruses produced cytopathic effect in L20B cells. Finally, L20B cells provided a diagnosis of poliovirus infection in the same time as RD and Hep2 cells from samples that contained poliovirus only, but substantially more quickly for samples that contained another enterovirus. Taken together, these data indicate that L20B cells simplify primary diagnosis of poliovirus from clinical samples and as a result they have been introduced for routine use by laboratories of the WHO global poliovirus network. J. Med. Virol. 58:188–192, 1999. © 1999 Wiley‐Liss, Inc.
Precarious Work, Insecure Workers: Employment Relations in Transition

The growth of precarious work since the 1970s has emerged as a core contemporary concern within politics, in the media, and among researchers. Uncertain and unpredictable work contrasts with the relative security that characterized the three decades following World War II. Precarious work constitutes a global challenge that has a wide range of consequences cutting across many areas of concern to sociologists. Hence, it is increasingly important to understand the new workplace arrangements that generate precarious work and worker insecurity. A focus on employment relations forms the foundation of theories of the institutions and structures that generate precarious work and the cultural and individual factors that influence people's responses to uncertainty. Sociologists are well-positioned to explain, offer insight, and provide input into public policy about such changes and the state of contemporary employment relations.
Association Between PAX9 Single-Nucleotide Polymorphisms and Nonsyndromic Cleft Lip With or Without Cleft Palate

Abstract The purpose of this study was to investigate the contribution of PAX9 gene to the risk of nonsyndromic cleft lip with or without cleft palate (NS-CL/P). The samples consisted of 142 Korean NS-CL/P families (90 males and 52 females; 9 cleft lip, 26 cleft lip and alveolus, and 107 cleft lip and palate; 76 trios and 66 dyads). A total of 10 single-nucleotide polymorphisms (SNPs) were tested for association with Korean CL/P case-parent trios using transmission disequilibrium test (TDT) and conditional logistic regression models. The minor allele frequency, heterozygosity, and a &khgr;2 test for Hardy-Weinberg equilibrium at each SNP were computed between parents. Pairwise linkage disequilibrium was computed as both D′ and r 2 for all SNPs. Both allelic and genotypic TDTs were performed for individual SNPs using family-based association test program. Sliding windows of haplotypes consisting of 2 to 8 SNPs were tested using haplotype-based association test program. Genotypic odd ratios were obtained from conditional logistic regression models using STATA software. The family-based TDT using individual SNPs and 2- to 8-SNP haplotypes of the gene indicated a significant association at rs17104928 (P = 0.014). The haplotype analysis revealed that the association was most significant for the haplotype consisting of 3 SNPs (rs2073247, rs17104928, and rs17176643; P = 0.007). G/A heterozygote at rs17104928 had a significantly increased association with NS-CL/P (genotypic odd ratio, 2.88; 95% confidence interval, 1.42–5.84; P = 0.0014, dominant model). The high-risk SNP and genotype may provide a better understanding of the etiologic role of PAX9 gene in NS-CL/P and potential options for genetic counseling.
Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats

Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34–59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.
Assessment of Mobility in Older People Hospitalized for Medical Illness Using the de Morton Mobility Index and Cumulated Ambulation Score-Validity and Minimal Clinical Important Difference

Background and Purpose: Older adults acutely hospitalized for medical illness typically have comorbidity and disability, and in-hospital physical inactivity greatly increases the likelihood of developing new disability. Thus, assessment of the patients' mobility status is crucial for planning and carrying out targeted interventions that ensure mobilization during hospital admission. The aim of this study was to determine convergent validity, known group validity, floor and ceiling effects, and anchor-based minimal clinically important difference (MCID) of the more time-consuming de Morton Mobility Index (DEMMI) and the less time-consuming Cumulated Ambulation Score (CAS) in older adults acutely hospitalized for medical illness. Methods: In this multicenter cohort study, 235 older hospitalized adults, with a mean (standard deviation) age of 84.8 (7.1) years, were consecutively included. Assessments of mobility using the DEMMI (score range 0-100), the CAS (score range 0-6), and the Barthel Index (BI, score range 0-100) were performed by physical or occupational therapists at hospital admission and discharge. In addition, at discharge patients and therapists were independently asked to assess the patients' current mobility status compared with their mobility status at hospital admission using the Global Rating of Change scale. Results and Discussion: Complete data sets were obtained for 155 patients. Baseline characteristics of those with complete data sets did not differ from those with incomplete data sets, except for the number of secondary diagnoses, which was lower in the latter. Significant and moderate relationships existed both at admission and at discharge between scores in the DEMMI and the BI (rs = 0.68, P < .0001, and rs = 0.71, P < .0001), and between scores in the CAS and the BI (rs = 0.60, P < .0001, and rs = 0.57, P < .0001). Use of a gait aid and discharge to inpatient rehabilitation or nursing home were associated with significantly lower DEMMI and CAS scores. No floor or ceiling effects were present in the DEMMI, while a ceiling effect was present in the CAS. The MCID scores based on patients' assessments were 10.7 points for the DEMMI and 0.67 for the CAS. Conclusions: These data show that the DEMMI is valid and responsive to changes in mobility and can be considered to have the required properties for measuring mobility in older adults who are hospitalized in medical and geriatric wards. In contrast, the CAS appears to be appropriate to identify whether a patient is independently mobile or needs assistance, while the measure is less suitable for measuring improvements in mobility.
Prospects for recombinant vaccines against Babesia bovis and related parasites

Babesial parasites infect cattle in tropical and temperate regions of the world and cause significant morbidity and mortality. Discovery of protective antigens that could be used in a killed vaccine has been slow and to date there are few promising vaccine candidates for cattle Babesia. This review describes mechanisms of protective innate and adaptive immune responses to babesial parasites and different strategies to identify potentially protective protein antigens of B. bovis, B. bigemina, and B. divergens. Successful parasites often cause persistent infection, and this paper also discusses how B. bovis evades and regulates the immune response to promote survival of parasite and host. Development of successful non‐living recombinant vaccines will depend on increased understanding of protective immune mechanisms and availability of parasite genomes.
Spiritual Intimacy, Marital Intimacy, and Physical/Psychological Well-Being: Spiritual Meaning as a Mediator.

OBJECTIVE Intimacy is an essential part of marital relationships, spiritual relationships, and is also a factor in well-being, but there is little research simultaneously examining the links among spiritual intimacy, marital intimacy, and well-being. METHODS Structural equation modeling was used to examine associations among the latent variables-spiritual intimacy, marital intimacy, spiritual meaning, and well-being-in a cross-sectional study of 5,720 married adults aged 29-100 years (M = 58.88, SD = 12.76, 59% female). All participants were from the Adventist Health Study-2, Biopsychosocial Religion and Health Study. RESULTS In the original structural model, all direct associations between the three latent variables of spiritual intimacy, marital intimacy, and well-being were significantly positive indicating that there was a significant relationship among spiritual intimacy, marital intimacy, and well-being. When spiritual meaning was added as a mediating variable, the direct connections of spiritual intimacy to marital intimacy and to well-being became weakly negative. However, the indirect associations of spiritual intimacy with marital intimacy and with well-being were then strongly positive through spiritual meaning. This indicates that the relationship among spiritual intimacy, marital intimacy, and well-being was primarily a result of the meaning that spiritual intimacy brought to one's marriage and well-being, and that without spiritual meaning greater spirituality could negatively influence one's marriage and well-being. CONCLUSIONS These findings suggest the central place of spiritual meaning in understanding the relationship of spiritual intimacy to marital intimacy and to well-being.
Genetically encodable fluorescent biosensors for tracking signaling dynamics in living cells.

Fluorescence has long been recognized as a powerful tool for probing biological structure and function. Nearly sixty-five years ago, Coons and colleagues introduced the first fluorescent-antibody techniques as a means of detecting pneumococcal antigens in mouse tissue.1 In the years that followed, studies have been conducted in hundreds of cellular contexts using immunofluorescence and related techniques such as fluorescence in situ hybridization.2 Together, these studies have provided cell biologists with a unique glimpse into the molecular organization of cells and tissues. However, because such approaches typically require fixation prior to detection, they provide only a snapshot of the highly dynamic cellular processes that govern cell physiology at the molecular level. To add a crucial temporal component to the study of cell biology, researchers have developed a diverse set of genetically-encodable biosensors designed to probe dynamic cellular events in living cells with high spatial and temporal resolution. These sensors, which generally involve the incorporation of a fluorescent tag into the primary amino acid sequence of a protein or a selected protein domain, have enabled researchers to track various components of intracellular signaling networks in real time within the native cellular environment. In this review, we will first explore the molecular basis of several genetically-targetable fluorescent tags amenable to live cell imaging. We will then turn our attention to the development and use of fluorescent biosensors for studying dynamic signaling processes in living cells.
World Heart Day 2002: the international burden of cardiovascular disease: responding to the emerging global epidemic.

World Heart Day is September 29, 2002. This occasion provides an opportunity to recognize our successes in science and clinical care, to survey the present and future challenges at home and abroad, and to seek opportunities for international partnerships in addressing the burgeoning global epidemic of cardiovascular disease. The final decades of the twentieth century represented a period of unprecedented success for the cardiovascular biomedical enterprise in advancing the knowledge of cardiovascular disease. Scientific progress in understanding the mechanisms of cardiovascular diseases fueled the proliferation of new methods for prevention and treatment, clinical trials to critically test these interventions, and evidence-based practice guidelines to distill these scientific advances broadly into clinical practice. Despite major steps forward in the fight against cardiovascular disease, there is compelling evidence in the United States that we have not been fully effective in translating, disseminating, and expediting the adoption of scientific advances to improve outcomes for our society. We have failed to develop public health infrastructures and healthcare systems in parallel with the scientific progress to implement effective, evidence-based prevention and treatment strategies. Hence, we have not realized the potential of our scientific discoveries for improved cardiovascular health. A recent Institute of Medicine report1 underscored this dilemma, indicating that “between the care we have and the care we could have lies not just a gap, but a chasm. ” The chasm may impede our efforts to achieve the Healthy People 2010 Objectives for the US population, as established by the Department of Health and Human Services.2 The US healthcare system is facing serious access and quality issues. Large segments of the US population do not have access to mainstream health care. These include the uninsured, a segment of the population that includes not only the unemployed but also many self-employed and low-wage earners. It …
Soluble Fms-like Tyrosine Kinase 1 and Endothelial Dysfunction in the Pathogenesis of Preeclampsia

Preeclampsia, a pregnancy-specific syndrome of hypertension and proteinuria, is characterized by defective placental vasculogenesis and widespread maternal endothelial dysfunction. Although the manifestations of preeclampsia are primarily maternal, the burden of morbidity and mortality is often on the neonate, since the only effective treatment—delivery of the fetus and placenta—often results in iatrogenic prematurity. In this review, we summarize recent advances in our understanding of the pathophysiology of preeclampsia, including normal and aberrant placental vascular development and evidence for endothelial dysfunction. We describe recent evidence that supports a novel mechanism in which a maladaptive shift in placental production of angiogenic factors such as soluble fms-like tyrosine kinase 1 (a circulating antiangiogenic protein) may play an important role in the pathogenesis of preeclampsia.
Diabetes impairs the neuroprotective properties of retinal alpha-crystallins.

PURPOSE α-Crystallins are small heat shock proteins that regulate cellular damage and cell survival. Expression of the proteins of the crystallin superfamily in the retina and their role in neuronal cell survival were investigated in two animal models of diabetes and retinal neurons in culture. METHODS Crystallin expression was assessed in streptozotocin-induced and Ins2(Akita) diabetic mice using iTRAQ methodology and validated using immunoblotting. Protein-protein interactions, solubility properties, and subcellular localization of αA- and αB-crystallins were further analyzed in vivo and in a retinal neuronal cell model using immunoprecipitation and fractionation METHODS Survival of retinal neurons to metabolic stress after overexpression and knock-down of α-crystallins was used to measure their neuroprotective properties. RESULTS All 10 of the crystallins identified in retinal lysates from both models of type 1 diabetes were strongly upregulated, coinciding with increased retinal cell death and expression of proapoptotic proteins Bax and Bcl-Xs. Diabetes strongly reduces the chaperone function of α-crystallins by reducing their solubility and disrupting the normal interaction of α-crystallins with Bax. The same properties disrupted by diabetes were confirmed to be critical for the neuroprotective effect of the overexpression of α-crystallins in retinal neurons in culture. CONCLUSIONS Both chemically and genetically induced diabetic models are characterized by upregulation of α-, β-, and γ-crystallins in the retina. Despite being overexpressed, the molecular properties of α-crystallins are disrupted by diabetes and contribute to the loss of neuroprotective function. Identification and prevention of these alterations could lead to the emergence of new therapies for diabetic retinopathy.
Classification Similarity Learning Using Feature-Based and Distance-Based Representations: A Comparative Study

Automatically measuring the similarity between a pair of objects is a common and important task in the machine learning and pattern recognition fields. Being an object of study for decades, it has lately received an increasing interest from the scientific community. Usually, the proposed solutions have used either a feature-based or a distance-based representation to perform learning and classification tasks. This article presents the results of a comparative experimental study between these two approaches for computing similarity scores using a classification-based method. In particular, we use the Support Vector Machine as a flexible combiner both for a high dimensional feature space and for a family of distance measures, to finally learn similarity scores. The approaches have been tested in a content-based image retrieval context, using three different repositories. We analyze both the influence of the different input data formats and the training size on the performance of the classifier. Then, we found that a low-dimensional, multidistance-based representation can be convenient for small to medium-size training sets, whereas it is detrimental as the training size grows.
Letrozole: Advancing Hormone Therapy in Breast Cancer

Letrozole is a type 2 aromatase inhibitor, which reduces availability of estrogen in postmenopausal women, thereby decreasing its ability to stimulate breast cancer cells. Phase III trials in both the advanced and early breast cancer setting have shown an improvement in disease-free survival compared with other compounds, including tamoxifen. Letrozole is well-tolerated, with the main adverse effects reported as hot flushes, arthritis, arthralgia and myalgia, and a trend towards increased risk of fracture.