Miracle-dz/UniFAR-FTUs huggingface dataset:
A new rapid and simple colorimetric method to detect pyrazinamide resistance in Mycobacterium tuberculosis using nicotinamide.

OBJECTIVES The purpose of this study was to develop and assess a rapid method for pyrazinamide resistance detection in Mycobacterium tuberculosis using nicotinamide in a colorimetric resazurin assay. METHODS We have tested M. tuberculosis isolates using nicotinamide in a 96-well format with the redox indicator resazurin (REMA) and compared results using the BACTEC 460-TB system with two concentrations of pyrazinamide (100 and 300 mg/L), as well as the Wayne method for detecting pyrazinamidase activity. Mutations in the pncA gene were detected by DNA sequencing of the pyrazinamide-resistant strains. RESULTS Out of 95 clinical isolates of M. tuberculosis tested, 25 were determined to be resistant by the Wayne, BACTEC (300 mg/L), and the REMA nicotinamide methods. Using a nicotinamide MIC>250 mg/L as the cut-off for defining resistance, only one strain was falsely labelled as resistant. The REMA nicotinamide assay demonstrated a sensitivity of 100% and a specificity of 98%. The BACTEC (100 mg/L) falsely classified 8 strains as resistant. DNA sequencing detected mutations in 18/22 of the pncA genes from pyrazinamide-resistant strains. CONCLUSIONS The REMA plate using nicotinamide to detect resistance to pyrazinamide is a simple and rapid method that could be useful in limited-resource countries.
Hypertrophic Neuropathies and Malignant Peripheral Nerve Sheath Tumors in Transgenic Mice Overexpressing Glial Growth Factor β3 in Myelinating Schwann Cells

The neuregulin-1 (NRG-1) family of growth and differentiation factors exerts a variety of effects on Schwann cells and their precursors during nervous system development; however, NRG-1 effects on adult Schwann cells are poorly defined. Several lines of evidence suggest that NRG-1 actions on adult Schwann cells are distinct from those observed during development. To test this hypothesis, we generated transgenic mice overexpressing the NRG-1 isoform glial growth factor β3 (GGFβ3) in myelinating Schwann cells [protein zero (P0)GGFβ3 mice]. P0-GGFβ3 mice develop resting tremors, gait abnormalities, decreased hindlimb strength, and paralysis by ∼7 months of age. Sciatic nerves from these animals show a hypertrophic neuropathy characterized by demyelination, remyelination, and “onion bulb” formation. Development of this hypertrophic neuropathy is preceded by Schwann cell hyperplasia that is prominent in 1-month-old mice and present but decreased in 2- and 4-month-old animals. P0-GGFβ3 mice also develop peripheral ganglion-associated malignant peripheral nerve sheath tumors. Motor, sensory, and sympathetic ganglia from 1-, 2-, and 4-month-old P0-GGFβ3 mice uniformly contain intraganglionic, likely preneoplastic, Schwann cell proliferations. Examination of bromodeoxyuridine incorporation and caspase-3 activation in sciatic nerves and trigeminal ganglia indicates that Schwann cell hyperplasia in P0-GGFβ3 mice reflects increased proliferation rather than decreased apoptosis. These observations are consistent with the hypothesis that GGFβ3 induces proliferation of adult Schwann cells and demyelination of peripheral nerve axons. Furthermore, overexpression of this NRG-1 isoform frequently induces neoplastic Schwann cell proliferation within PNS ganglia, suggesting that NRG-1 may contribute to human Schwann cell neoplasia.
The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae

For bacterial pathogens whose sole environmental reservoir is the human host, the acquisition of essential nutrients, particularly transition metals, is a critical aspect of survival due to tight sequestration and limitation strategies deployed to curtail pathogen outgrowth. As such, these bacteria have developed diverse, specialized acquisition mechanisms to obtain these metals from the niches of the body in which they reside. To oppose the spread of infection, the human host has evolved multiple mechanisms to counter bacterial invasion, including sequestering essential metals away from bacteria and exposing bacteria to lethal concentrations of metals. Hence, to maintain homeostasis within the host, pathogens must be able to acquire necessary metals from host proteins and to export such metals when concentrations become detrimental. Furthermore, this acquisition and efflux equilibrium must occur in a tissue-specific manner because the concentration of metals varies greatly within the various microenvironments of the human body. In this review, we examine the functional roles of the metal import and export systems of the Gram-positive pathogen Streptococcus pneumoniae in both signaling and pathogenesis.
Name Tagging for Low-resource Incident Languages based on Expectation-driven Learning

In this paper we tackle a challenging name tagging problem in an emergent setting the tagger needs to be complete within a few hours for a new incident language (IL) using very few resources. Inspired by observing how human annotators attack this challenge, we propose a new expectation-driven learning framework. In this framework we rapidly acquire, categorize, structure and zoom in on ILspecific expectations (rules, features, patterns, gazetteers, etc.) from various non-traditional sources: consulting and encoding linguistic knowledge from native speakers, mining and projecting patterns from both mono-lingual and cross-lingual corpora, and typing based on cross-lingual entity linking. We also propose a cost-aware combination approach to compose expectations. Experiments on seven low-resource languages demonstrate the effectiveness and generality of this framework: we are able to setup a name tagger for a new IL within two hours, and achieve 33.8%-65.1% F-score 1.
Synaptically-Competent Neurons Derived from Canine Embryonic Stem Cells by Lineage Selection with EGF and Noggin

Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGFαα) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABAA- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model.
Understanding Group Therapists’ Use of Spiritual and Religious Interventions in Group Therapy

Abstract The current study examined therapist characteristics that are related to the use of spiritual and religious interventions in group therapy and to perceived barriers to attending to spirituality in group therapy among a sample of experienced group therapists. Results demonstrated that greater therapist spirituality was associated with more frequent use of both spiritual and religious interventions, as well as lower perceived barriers to attending to spirituality in group therapy. Religious commitment was only uniquely related to perceived barriers, such that therapists with higher religious commitment actually perceived greater barriers. Training in religion and spirituality and comfort with spiritual discussions was also related to therapists’ use of religious and spiritual interventions and perceived barriers.
Bioassay Research Methodology: Measuring CRH in Pregnancy

Background. There are documented associations between elevated maternal corticotropin-releasing hormone (CRH) levels and adverse pregnancy outcomes. However, reports of these findings often lack sufficient detail and rationale regarding the bioassay methodology. This shortcoming can be problematic for researchers who do not possess in-depth laboratory sciences knowledge but who want to include bioassays in their investigations or to evaluate published reports. The quality and reliability of CRH measurement results can be significantly affected by variables encountered during sample collection, processing, storage, and bioassay. Thus, it is important to establish research laboratory protocols that are based on well-informed rationales and to carefully consider and control for relevant variables. Approach. A synthesis of laboratory sciences literature regarding variables affecting CRH measurement in pregnancy is presented. Additionally, consultation with experienced researchers provided an in-depth understanding of CRH measurement. From these sources, a laboratory protocol for clinical research was developed. Results. Multiple variables that are specific to the reliability of CRH measurement in pregnancy have been identified. These include sample collection methods, sample processing, sample integrity, sample storage, and the actual assay selected. Conclusion. The reliability of CRH measurements can be significantly improved by identifying and controlling for variables encountered during sample collection, processing, storage, and bioassay. Adequate methodological details are difficult to glean solely from the published literature, thus consultation with well-informed researchers is necessary. A protocol for CRH bioassay in clinical research is proposed.
Molecular mechanisms of asymmetric divisions in mammary stem cells

Stem cells have the remarkable ability to undergo proliferative symmetric divisions and self‐renewing asymmetric divisions. Balancing of the two modes of division sustains tissue morphogenesis and homeostasis. Asymmetric divisions of Drosophila neuroblasts (NBs) and sensory organ precursor (SOP) cells served as prototypes to learn what we consider now principles of asymmetric mitoses. They also provide initial evidence supporting the notion that aberrant symmetric divisions of stem cells could correlate with malignancy. However, transferring the molecular knowledge of circuits underlying asymmetry from flies to mammals has proven more challenging than expected. Several experimental approaches have been used to define asymmetry in mammalian systems, based on daughter cell fate, unequal partitioning of determinants and niche contacts, or proliferative potential. In this review, we aim to provide a critical evaluation of the assays used to establish the stem cell mode of division, with a particular focus on the mammary gland system. In this context, we will discuss the genetic alterations that impinge on the modality of stem cell division and their role in breast cancer development.
Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years' duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.
Antenatal spectrum of CHARGE syndrome in 40 fetuses with CHD7 mutations

Background CHARGE syndrome is a rare, usually sporadic disorder of multiple congenital anomalies ascribed to a CHD7 gene mutation in 60% of cases. Although the syndrome is well characterised in children, only one series of 10 fetuses with CHARGE syndrome has been reported to date. Therefore, we performed a detailed clinicopathological survey in our series of fetuses with CHD7 mutations, now extended to 40 cases. CHARGE syndrome is increasingly diagnosed antenatally, but remains challenging in many instances. Method Here we report a retrospective study of 40 cases of CHARGE syndrome with a CHD7 mutation, including 10 previously reported fetuses, in which fetal or neonatal clinical, radiological and histopathological examinations were performed. Results Conversely to postnatal studies, the proportion of males is high in our series (male to female ratio 2.6:1) suggesting a greater severity in males. Features almost constant in fetuses were external ear anomalies, arhinencephaly and semicircular canal agenesis, while intrauterine growth retardation was never observed. Finally, except for one, all other mutations identified in our antenatal series were truncating, suggesting a possible phenotype–genotype correlation. Conclusions Clinical analysis allowed us to refine the clinical description of CHARGE syndrome in fetuses, describe some novel features and set up diagnostic criteria in order to help the diagnosis of CHARGE syndrome after termination of pregnancies following the detection of severe malformations.
Dynamical Constants and Time Universals: A First Step toward a Metrical Definition of Ordered and Abnormal Cognition

From the point of view of the cognitive dynamicist the organization of brain circuitry into assemblies defined by their synchrony at particular (and precise) oscillation frequencies is important for the correct correlation of all independent cortical responses to the different aspects of a given complex thought or object. From the point of view of anyone operating complex mechanical systems, i.e., those comprising independent components that are required to interact precisely in time, it follows that the precise timing of such a system is essential – not only essential but measurable, and scalable. It must also be reliable over observations to bring about consistent behavior, whatever that behavior is. The catastrophic consequence of an absence of such precision, for instance that required to govern the interference engine in many automobiles, is indicative of how important timing is for the function of dynamical systems at all levels of operation. The dynamics and temporal considerations combined indicate that it is necessary to consider the operating characteristic of any dynamical, cognitive brain system in terms, superficially at least, of oscillation frequencies. These may, themselves, be forensic of an underlying time-related taxonomy. Currently there are only two sets of relevant and necessarily systematic observations in this field: one of these reports the precise dynamical structure of the perceptual systems engaged in dynamical binding across form and time; the second, derived both empirically from perceptual performance data, as well as obtained from theoretical models, demonstrates a timing taxonomy related to a fundamental operator referred to as the time quantum. In this contribution both sets of theory and observations are reviewed and compared for their predictive consistency. Conclusions about direct comparability are discussed for both theories of cognitive dynamics and time quantum models. Finally, a brief review of some experimental data measuring sensitivity to visual information presented to the visual blind field (blindsight), as well as from studies of temporal processing in autism and schizophrenia, indicates that an understanding of a precise and metrical dynamic structure may be very important for an operational understanding of perception as well as more general cognitive function in psychopathology.
Efficacy of expiratory tracheal gas insufflation in a canine model of lung injury.

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination by reducing the CO2-laden dead space of the airways. The effect of TGI on PaCO2 diminishes in the setting of acute lung injury (ALI) because an increased alveolar component dominates the total physiologic dead space. Nevertheless, adopting a strategy of permissive hypercapnia should partially offset the decreased efficacy of TGI by increasing CO2 concentration in the proximal airways. To examine these issues we studied the CO2 removal efficacy of expiratory TGI as an adjunct to conventional mechanical ventilation (CMV) before and after oleic acid-induced lung injury (OAI). We first examined the effect of TGI before and after OAI, keeping tidal volume (VT) and frequency constant, and allowing PaCO2 to increase after OAI. We then tested TGI efficiency after matching PaCO2 after OAI to its pre-OAI level by increasing VT (post-OA/VT stage). PaCO2 was 53 +/- 3, 79 +/- 21, and 52 +/- 4 mm Hg in the pre-OAI, post-OAI, and post-OA/VT stages of CMV, respectively. The corresponding decrements in PaCO2 produced by TGI at a flow rate of 10 L/min were 16 +/- 3, 24 +/- 10, and 10 +/- 2 mm Hg, respectively. TGI decreased total physiologic dead space per breath (VD) by 56, 31, and 28 ml during the pre-OAI, post-OAI, and post-OA/VT stages, respectively. Despite a smaller reduction in VD during the post-OAI stage, the effect of TGI on PaCO2 was preserved because of the relatively high PaCO2 prior to its initiation. (ABSTRACT TRUNCATED AT 250 WORDS)
Perceptions and competence in evidence-based medicine: Are surgeons getting better? A questionnaire survey of members of the Dutch Orthopaedic Association.

BACKGROUND The Journal of Bone and Joint Surgery, American Volume (The Journal) recently initiated a section called "Evidence-Based Orthopaedics. " Furthermore, a level-of-evidence rating is now used in The Journal to help readers in clinical decision-making. Little is known about whether this recent emphasis has influenced surgeons' perceptions about and competence in evidence-based medicine. Therefore, we examined perceptions and competence in evidence-based medicine among Dutch orthopaedic surgeons. METHODS Members of the Dutch Orthopaedic Association were surveyed to examine their attitudes toward evidence-based medicine and their competence in evidence-based medicine. We evaluated competences using a newly developed instrument tailored to surgical practice. RESULTS Of the 611 members, 367 surgeons (60%) responded. Orthopaedic surgeons welcomed evidence-based medicine. Practical evidence-based medicine resources were perceived as the best method to move from opinion-based or experience-based to evidence-based practice. Four variables were significantly and positively associated with the competence instrument: (1) a younger age, particularly between thirty-six and forty-five years (p = 0.007), (2) experience of less than ten years (p = 0.032), (3) having a PhD degree (p < 0.001), and (4) working in an academic or teaching setting (p = 0.004). The majority of the respondents were aware of The Journal's evidence-based medicine section (84%) and level-of-evidence ratings (65%), and 20% used The Journal's evidence-based medicine abstracts in clinical decision-making. This increased awareness of evidence-based medicine was also reflected in the frequent use of Cochrane reviews in clinical decision-making (27% of the respondents). Surgeons who used and those who were aware of but did not use The Journal's evidence-based medicine abstracts or Cochrane reviews in clinical decision-making had significantly higher competence instrument scores than those who were unaware of these resources (p = 0.03 and p < 0.001, respectively). CONCLUSIONS Evidence-based medicine is welcomed by Dutch orthopaedic surgeons. The recent emphasis on evidence-based medicine is reflected in an increased awareness about The Journal's evidence-based medicine section, levels of evidence, and the largest evidence-based medicine resource: the Cochrane reviews. Younger orthopaedic surgeons had better knowledge about evidence-based medicine. The development and use of evidence-based resources as well as preappraised summaries such as The Journal's evidence-based medicine abstracts and Cochrane reviews were perceived as the best way to move from opinion-based to evidence-based orthopaedic practice.
Effects of acute alcohol consumption on alcohol-related cognitive biases in light and heavy drinkers are task-dependent

We investigated (1) the effects of alcohol on cognitive biases for alcohol-related cues, (2) the effects of drinking status on alcohol-related cognitive biases and (3) the similarity of any effects of alcohol across two measures of alcohol cognitive bias. Healthy, heavy and light social alcohol users (n = 72) were examined in a single-blind placebo-controlled design. Participants received 0.00 g/kg, 0.13 g/kg or 0.40 g/kg of alcohol in a between-subjects design and then completed both a modified Stroop task and a visual probe task. Modified Stroop data indicated a main effect of cue type, which was qualified by drinking status, with heavier drinkers slower to respond to alcohol-related cues. Visual probe data, in contrast, indicated a significant interaction effect between validity (valid: alcohol-related, invalid: neutral) and drink condition. Participants receiving a moderate dose of alcohol (0.40 g/kg) were faster to respond to alcohol-related stimuli compared with participants receiving a low dose of alcohol or placebo. These data indicate that the cognitive processes assayed by the visual probe and Stroop tasks may not be mediated by a common underlying mechanism.