Miracle-dz/UniFAR-FTUs huggingface dataset:
BCG vaccination: 90 years on and still so much to learn …

The history of vaccination against tuberculosis abounds with instances of scientific discovery and rediscovery. At the end of the 19th and beginning of the 20th century, following Robert Koch's announcement of his discovery of Mycobacterium tuberculosis in 1882, scientists across the world, including Koch himself, set out to invent a vaccine against tuberculosis. In 1908 Leon Calmette, a bacteriologist, and Camille Guerin, a veterinarian at the Pasteur Institute, Lille began an experiment to devise a vaccine by attenuating a Mycobacterium bovis strain until it lost its virulence. Thirteen years and 230 passages later, they were able to show that the strain was protective in animal models and no longer caused disease which was subsequently discovered to be primarily due to the loss of the genes in the region of difference 1 (RD1) region of the M bovis genome.1 That same year, an infant tuberculosis contact was given the first dose of this live attenuated vaccine, M bovis Bacille Calmette-Geurin (BCG). Now, with over 3 billion doses administered, BCG is the most widely used vaccine worldwide. Since its first use 90 years ago, BCG has been recommended as a vaccine because of its partial protective effect against active tuberculosis and death, albeit with greater efficacy against disseminated and meningeal disease in children than pulmonary disease in adolescents and adults.2 3 This, taken together with autopsy studies suggesting BCG decreases the size of pulmonary tuberculous foci thereby limiting bacillary multiplication and spread4 and animal models where BCG vaccination reduces bacillary burden after M tuberculosis challenge but does not protect against infection, led to the longstanding dogma that BCG protects against dissemination and disease but not against infection. It was only 5 years ago that the first report5 of the ability of BCG to protect against the acquisition of infection changed …
High-mobility group box 1 inhibits HCO 3 absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na / H exchange

Watts BA 3rd, George T, Badalamenti A, Good DW. Highmobility group box 1 inhibits HCO3 absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na /H exchange. Am J Physiol Renal Physiol 311: F600 –F613, 2016. First published June 29, 2016; doi:10.1152/ajprenal.00185. 2016. —High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III. Am J Physiol Renal Physiol 309: F720– F730, 2015). Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3 absorption by HMGB1 was eliminated by the Rho-associated kinase (ROCK) inhibitor Y27632 and by a specific inhibitor of Rho, the major upstream activator of ROCK. HMGB1 increased RhoA and ROCK1 activity. HMGB1-induced ROCK1 activation was eliminated by the RAGE antagonist FPS-ZM1 and by inhibition of Rho. The Rho and ROCK inhibitors had no effect on inhibition of HCO3 absorption by bath LPS. Inhibition of HCO3 absorption by HMGB1 was eliminated by bath amiloride, 0 Na bath, and the F-actin stabilizer jasplakinolide, three conditions that selectively prevent inhibition of MTAL HCO3 absorption mediated through NHE1. HMGB1 decreased basolateral Na /H exchange activity through activation of ROCK. We conclude that HMGB1 inhibits HCO3 absorption in the MTAL through a RAGE-RhoA-ROCK1 signaling pathway coupled to inhibition of NHE1. The HMGB1-RAGE-RhoA-ROCK1 pathway thus represents a potential target to attenuate MTAL dysfunction during sepsis and other inflammatory disorders. HMGB1 and LPS inhibit HCO3 absorption through different receptor signaling and transport mechanisms, which enables these pathogenic mediators to act directly and independently to impair MTAL function.
Measuring single constructs by single items: Constructing an even shorter version of the “Short Five” personality inventory

The aim of this study was to construct a short, 30-item personality questionnaire that would be, in terms of content and meaning of the scores, as comparable as possible with longer, well-established inventories such as NEO PI-R and its clones. To do this, we shortened the formerly constructed 60-item “Short Five” (S5) by half so that each subscale would be represented by a single item. We compared all possibilities of selecting 30 items (preserving balanced keying within each domain of the five-factor model) in terms of correlations with well-established scales, self-peer correlations, and clarity of meaning, and selected an optimal combination for each domain. The resulting shortened questionnaire, XS5, was compared to the original S5 using data from student samples in 6 different countries (Estonia, Finland, UK, Germany, Spain, and China), and a representative Finnish sample. The correlations between XS5 domain scales and their longer counterparts from well-established scales ranged from 0.74 to 0.84; the difference from the equivalent correlations for full version of S5 or from meta-analytic short-term dependability coefficients of NEO PI-R was not large. In terms of prediction of external criteria (emotional experience and self-reported behaviours), there were no important differences between XS5, S5, and the longer well-established scales. Controlling for acquiescence did not improve the prediction of criteria, self-peer correlations, or correlations with longer scales, but it did improve internal reliability and, in some analyses, comparability of the principal component structure. XS5 can be recommended as an economic measure of the five-factor model of personality at the level of domain scales; it has reasonable psychometric properties, fair correlations with longer well-established scales, and it can predict emotional experience and self-reported behaviours no worse than S5. When subscales are essential, we would still recommend using the full version of S5.
Remembering to remember: adult age differences in prospective memory.

Age-related differences in prospective memory were examined in a laboratory-based task in which younger and older adults performed different actions whenever a semantically defined target word occurred in the context of a free-association task. Requirements for self-initiated retrieval operations were manipulated by presenting target words that were typical or atypical instances (e.g., milk vs ink) of a given semantic category (liquid). The results showed that age differences in prospective memory were accentuated when atypical items were used as targets, but reduced when highly typical targets were presented. Furthermore, age differences were not limited to remembering when to perform action, but young subjects also showed better performance in remembering what was to be done. These findings indicate that the magnitude of age difference in prospective memory interacts with task complexity, and support the view that prospective memory failures are accentuated in tasks with high resource demands on self-initiated retrieval operations.
Evaluation of Threat by Police Officers: Initial Findings

Police officers' threat perception of static images was examined using images reflecting the range of five threat categories on which police officers are trained. Thirteen experienced officers from a police departments in the southeastern United States participated in this study. Officers rated their perceived threat level for 110 images that were presented to them on a laptop computer. Each of these images was rated twice by each officer. Officers used all five categories to rate the stimuli, and their responses to the extremes (images rated as 1 or 5) were faster than responses to more ambiguous stimuli in the other categories. These results were generally consistent with predictions based on Fuzzy Signal Detection Theory. Further studies will evaluate performance with these images in the context of a signal detection task. Once fully developed, this tool could be used to evaluate new recruits' decision-making process before given the green light to carry a badge. These assessments could also be used as a modified training tool for experienced officers if the stimuli were to be placed in a semiimmersive environment.
Adipokines and Cardiovascular Risk in Cushing’s Syndrome

Cushing’s syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or ‘cured’ CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.
Epicentral Disruption of Structural Connectivity in Alzheimer's Disease

Neurodegenerative changes observed in Alzheimer's disease (AD) have been suggested to begin at the entorhinal cortex and hippocampus and then to propagate in a stereotypical fashion. Using diffusion‐weighted imaging, we test whether disruption of structural connectivity in AD is centered on these “epicenters of disease”.
Structure of the Monomeric 8-kDa Dynein Light Chain and Mechanism of the Domain-swapped Dimer Assembly*

The 8-kDa light chain of dynein (DLC8) is ubiquitously expressed in various cell types. Other than serving as a light chain of the dynein complexes, this highly conserved protein has been shown to bind a larger number of proteins with diverse biological functions. DLC8 forms a homodimer via three-dimensional domain swapping of an internal β-strand (the β2-strand) at neutral pH. The protein undergoes non-reversible dimer-to-monomer dissociation when the pH value of the protein solution decreases. The three-dimensional structure of the DLC8 monomer determined by NMR spectroscopy at pH 3.0 showed that the protein is well folded. The major conformational change accompanied by dimer dissociation is in the β2-strand of the protein, which undergoes transition from a β-strand to a nascent α-helix. The monomer form of DLC8 is not capable of binding to target proteins. Insertion of two flexible amino acid residues in the tight β1/β2-loop dramatically stabilized the monomer conformation of the protein. NMR studies showed that the mutation altered the conformation as well as the three-dimensional domain swapping-mediated assembly of the DLC8 dimer. The mutant DLC8 was unable to bind to its targets even at physiological pH. The three-dimensional structure of the mutant protein in its monomeric form provides the structural basis of the mutation-induced stabilization of the monomer conformation. Based on the experimental data, we conclude that the formation of the β2-strand swapping-mediated dimer is mandatory for the structure and function of DLC8. We further note that the DLC8 dimer represents a novel mode of three-dimensional domain swapping.
Health technology assessment in England: assessment and appraisal

The Health Technology Assessment (HTA) Programme in England is a government‐funded but independent research program. It is “needs‐led”, identifying technologies of most importance to the National Health Service and commissioning research to provide answers on these technologies useful to policymakers, clinicians and patients. It is “science‐added”, refining problems to researchable questions and working with researchers to ensure that the question is addressed, and disseminating the findings to key audiences. There is a clear distinction in England between assessment (a scientific process and the role of the HTA Programme) and appraisal (the role of policymakers, like the National Institute for Health and Clinical Excellence). There are many features common to HTA in Australia and England, but also differences, as HTA in each country has to adapt to its own environment.
Bose-Einstein condensation and spin mixtures of optically trapped metastable helium

We report the realization of a Bose-Einstein condensate of metastable helium-4 atoms ({sup 4}He*) in an all-optical potential. Up to 10{sup 5} spin-polarized {sup 4}He* atoms are condensed in an optical dipole trap formed from a single, focused, vertically propagating far-off-resonance laser beam. The vertical trap geometry is chosen to best match the resolution characteristics of a delay-line anode microchannel plate detector capable of registering single He* atoms. We also confirm the instability of certain spin-state combinations of {sup 4}He* to two-body inelastic processes, which necessarily affects the scope of future experiments using optically trapped spin mixtures. In order to better quantify this constraint, we measure spin-state-resolved two-body inelastic loss rate coefficients in the optical trap.
Plasmid Diversity in Neisseriae

ABSTRACT Horizontal gene transfer constitutes an important force in prokaryotic genome evolution, and it is well-known that plasmids are vehicles for DNA transfer. Chromosomal DNA is frequently exchanged between pathogenic and commensal neisseriae, but relatively little is known about plasmid diversity and prevalence among these nasopharyngeal inhabitants. We investigated the plasmid contents of 18 Neisseria lactamica isolates and 20 nasopharyngeal Neisseria meningitidis isolates. Of 18 N. lactamica strains, 9 harbored one or more plasmids, whereas only one N. meningitidis isolate contained a plasmid. Twelve plasmids were completely sequenced, while five plasmid sequences from the public databases were also included in the analyses. On the basis of nucleic acid sequences, mobilization, and replicase protein alignments, we distinguish six different plasmid groups (I to VI). Three plasmids from N. lactamica appeared to be highly similar on the nucleotide level to the meningococcal plasmids pJS-A (>99%) and pJS-B (>75%). The genetic organizations of two plasmids show a striking resemblance with that of the recently identified meningococcal disease-associated (MDA) phage, while four putative proteins encoded by these plasmids show 25% to 39% protein identity to those encoded by the MDA phage. The putative promoter of the gene encoding the replicase on these plasmids contains a polycytidine tract, suggesting that replication is subjected to phase variation. In conclusion, extensive plasmid diversity is encountered among commensal neisseriae. Members of three plasmid groups are found in both pathogenic and commensal neisseriae, indicating plasmid exchange between these species. Resemblance between plasmids and MDA phage may be indicative of dissemination of phage-related sequences among pathogenic and commensal neisseriae.
Retrospective Identification and Characterization of Candida dubliniensis Isolates among Candida albicans Clinical Laboratory Isolates from Human Immunodeficiency Virus (HIV)-Infected and Non-HIV-Infected Individuals

ABSTRACT Fungal opportunistic infections, and in particular those caused by the various Candida species, have gained considerable significance as a cause of morbidity and, often, mortality. The newly described species Candida dubliniensis phenotypically resembles Candida albicans so closely that it is easily misidentified as such. The present study was designed to determine the frequency at which this new species is not recognized in the clinical laboratory, to determine the patient populations with which C. dubliniensis is associated, to determine colonization versus infection frequency, and to assess fluconazole resistance. Over a 2-year period, 1,251 isolates that were initially identified asC. albicans by a hospital clinical laboratory were reevaluated for C. dubliniensis by inability to grow at 45°C, colony color on CHROMagar Candida medium, coaggregation assay with Fusobacterium nucleatum, and sugar assimilation profiles (API 20C AUX yeast identification system). A total of 15 (1.2%) isolates from 12 patients were identified as C. dubliniensis. Ten of the patients were found to be immunocompromised (these included patients with human immunodeficiency virus infection or AIDS, cancer patients receiving chemotherapy, and patients awaiting transplantation). Thirteen isolates were highly susceptible to fluconazole (MIC, <0.5 μg/ml). Three isolates from one patient, genotypically confirmed as the same strain, showed variable susceptibility to fluconazole. The first isolate was susceptible, whereas the other two isolates were dose-dependent susceptible (MIC, 16.0 μg/ml). These data confirm the close association of C. dubliniensis with immunocompromised states and that increased fluconazole MICs may develop in vivo. This study emphasizes the importance of screening germ-tube-positive yeasts for the inability to grow at 45°C followed by confirmatory tests in order to properly identify this species.
Bone Mass, External Loads, and Stress Fracture in Female Runners

Increased incidence of stress fracture has been reported for amenorrheic runners, while some studies have reported decreased spinal bone mass in amenorrheic runners. Based on results from these studies, one tends to associate decreased spinal bone mass with an increased risk of stress fracture. The present study compared regional bone mass and external loads during running between six female runners reporting a history of stress fracture (seven tibial and three femoral neck) and eight female runners with no history of stress fracture. Dual photon absorptiometry measures indicated significantly greater spinal (L2-L4) and femoral neck bone mineral density in stress fracture subjects (p<0.05) but no differences between groups for tibial bone density. Normalized forces recorded from Kistler force plates indicated significantly greater vertical propulsive, maximal medial, lateral, and posterior forces for stress fracture subjects during running (p<0.05).
Comparison of Social, Affective, Educational Adjustment and Academic Achievement between the Students with Learning Disability and Normal Students

The research purpose is to draw a comparison between social, affective, educational adjustment and academic achievement between the students suffering from learning disabilities and normal students. The research employed a casual-comparative method. The statistical population included all the students suffering from learning disability and normal students studying in 3 rd to 6 th grades of the elementary schools located in Qom Province in the school year ran from 2012 to 2013, out of which a sample of 120 was selected through the convenience sampling and matching method. The data gathering tools included Adjustment Inventory for School Students -AISS (Sinha & Singh, 1993) and the grade point average as an indicator of academic achievement. The results of t- test indicated that there exists significant between-group difference. Moreover, the results of Mann-Whitney U test indicated that normal students score significantly higher on academic achievement as compared to the students who have learning disability. With regard the crucial importance and the role of adjustment in disable students' academic achievement, the absolute necessity for educational and counseling intervention for the enhancement of adjustment skills can be highlighted.
Distraction Osteogenesis for Congenitally Short Lesser Metatarsals

Six lesser metatarsal lengthening procedures were performed in three patients using a miniature external fixator to perform distraction osteogenesis. The metatarsals were lengthened an average of 15.5 mm. The external fixator was left in place for an average of 15.5 weeks, with additional time in a cast or cast shoe. Complications included five occurrences of infection, two cases of premature healing of the osteotomy, one nondisplaced fracture through the new bone formation, and hypertrophic granulation at a pin site. While all metatarsals were successfully lengthened, two rays (one patient) had symptomatic stiffness at the metatarsophalangeal joint with continued metatarsalgia.
Effect of Digestion and Storage of Human Milk on Free Fatty Acid Concentration and Cytotoxicity

Objectives: Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC), but even infants exclusively fed breast milk may develop NEC. Our objective was to determine whether stored milk and milk from donor milk (DM) banks could also become cytotoxic, especially after digestion. Methods: We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4°C or −20°C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/mL pancreatic lipase and/or trypsin and chymotrypsin. Results: DM and milk stored 3 days (at 4°C or −20°C) and then digested were cytotoxic. Storage at −20°C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. Conclusions: Present storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC.