Miracle-dz/UniFAR-FTUs huggingface dataset:
Conserved Protective Mechanisms in Radiation and Genetically Attenuated uis3(-) and uis4(-) Plasmodium Sporozoites

Immunization with radiation attenuated Plasmodium sporozoites (RAS) elicits sterile protective immunity against sporozoite challenge in murine models and in humans. Similarly to RAS, the genetically attenuated sporozoites (GAPs) named uis3(-), uis4(-) and P36p(-) have arrested growth during the liver stage development, and generate a powerful protective immune response in mice. We compared the protective mechanisms in P. yoelii RAS, uis3(-) and uis4(-) in BALB/c mice. In RAS and GAPs, sterile immunity is only achieved after one or more booster injections. There were no differences in the immune responses to the circumsporozoite protein (CSP) generated by RAS and GAPs. To evaluate the role of non-CSP T-cell antigens we immunized antibody deficient, CSP-transgenic BALB/c mice, that are T cell tolerant to CSP, with P. yoelii RAS or with uis3(-) or uis4(-) GAPs, and challenged them with wild type sporozoites. In every instance the parasite liver stage burden was approximately 3 logs higher in antibody deficient CSP transgenic mice as compared to antibody deficient mice alone. We conclude that CSP is a powerful protective antigen in both RAS and GAPs viz., uis3(-) and uis4(-) and that the protective mechanisms are similar independently of the method of sporozoite attenuation.
Cost Analysis of Operating an Anatomic Pathology Laboratory in a Middle-Income Country

Objective To examine the cost of operating an anatomic pathology laboratory in a teaching hospital in Malaysia. Once the cost is determined, compare it with the costs of operating other laboratories in the same hospital, and operating anatomic pathology laboratories in other countries. Methods Cost and workload data were obtained from hospital records for 2015. Time allocation of staff between laboratory testing and other activities was determined using assumptions from published workload studies. Results The laboratory received 20,093 cases for testing in 2015, and total expenditures were US $1.20 million, ie, $61.97 per case. The anatomic pathology laboratory accounted for 5.2% of the laboratory budget at the hospital, compared to 64.3% for the clinical laboratory and 30.5% for the microbiology laboratory. We provide comparisons to a similar laboratory in the United States. Conclusions Anatomic pathology is more costly than other hospital laboratories due to the labor-intensive work, but is essential, particularly for cancer diagnoses and treatment.
Potentially Traumatic Events and Job Satisfaction: A Prospective Population-Based Comparative Study

Objective: The aim of this study was to examine the effects of potentially traumatic events (PTEs), posttraumatic stress symptoms (PTSS), and coping self-efficacy (CSE) on post-event job satisfaction. Methods: Repeated analysis of variance (ANOVA) was used to assess differences in the course of job satisfaction during 1 year between population-based samples of affected and nonaffected workers. Multivariate regression analyses were conducted with pre-event health, job satisfaction and insecurity, and postevent PTSS and CSE as predictors. Results: About 16% of the affected workers had probable PTSD. The course of job satisfaction between affected (n = 123) and nonaffected workers (n = 644) did not differ significantly. PTSS and CSE did not independently predict post-event satisfaction, in contrast to pre-event job satisfaction. Conclusion: Findings suggest that when needed social support is provided, concerns about the negative effects of potentially traumatic events on job satisfaction could be somewhat relaxed.
Media Reporting of Health Interventions: Signs of Improvement, but Major Problems Persist

Background Studies have persistently shown deficiencies in medical reporting by the mainstream media. We have been monitoring the accuracy and comprehensiveness of medical news reporting in Australia since mid 2004. This analysis of more than 1200 stories in the Australian media compares different types of media outlets and examines reporting trends over time. Methods and Findings Between March 2004 and June 2008 1230 news stories were rated on a national medical news monitoring web site, Media Doctor Australia. These covered a variety of health interventions ranging from drugs, diagnostic tests and surgery to dietary and complementary therapies. Each story was independently assessed by two reviewers using ten criteria. Scores were expressed as percentages of total assessable items deemed satisfactory according to a coding guide. Analysis of variance was used to compare mean scores and Fishers exact test to compare proportions. Trends over time were analysed using un-weighted linear regression analysis. Broadsheet newspapers had the highest average satisfactory scores: 58% (95% CI 56–60%), compared with tabloid newspapers and online news outlets, 48% (95% CI 44–52) and 48% (95% CI 46–50) respectively. The lowest scores were assigned to stories broadcast by human interest/current affairs television programmes (average score 33% (95% CI 28–38)). While there was a non- significant increase in average scores for all outlets, a significant improvement was seen in the online news media: a rise of 5.1% (95%CI 1.32, 8.97; P 0.009). Statistically significant improvements were seen in coverage of the potential harms of interventions, the availability of treatment or diagnostic options, and accurate quantification of benefits. Conclusion Although the overall quality of medical reporting in the general media remains poor, this study showed modest improvements in some areas. However, the most striking finding was the continuing very poor coverage of health news by commercial current affairs television programs.
Sex differences in post-traumatic stress disorder in cardiovascular patients after the Great East Japan Earthquake: a report from the CHART-2 Study

Aims The temporal changes and sex differences in post-traumatic stress disorder (PTSD) after natural disasters remain unclear. Therefore, we examined the prevalence, prognostic impacts, and determinant factors of PTSD after the Great East Japan Earthquake (GEJE) of 11 March 2011 in cardiovascular (CV) patients registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-2 Study (n = 10 219), with a special reference to sex. Methods and results By self-completion questionnaires of the Japanese-language version of the Impact of Event Scale-Revised (IES-R-J), the prevalence of PTSD, defined as IES-R-J score ≥25, was 14.8, 15.7, 7.4, and 7.5% in 2011, 2012, 2013, and 2014, respectively. The PTSD rate was higher in women than in men in all years (all P < 0.01). During a median 3.5-year follow-up period, the patients with PTSD in 2011 more frequently experienced a composite of all-cause death and hospitalization for acute myocardial infarction, stroke, and heart failure than those without PTSD [adjusted hazard ratio (aHR) 1.27, P < 0.01]. Importantly, the prognostic impacts of PTSD on all-cause death (aHR 2.10 vs. 0.87, P for interaction = 0.03) and CV death (aHR 3.43 vs. 0.90, P for interaction = 0.02) were significant in women but not in men. While insomnia medication was a prominent determinant factor of PTSD in both sexes during 2011-14, economic poverty was significantly associated with PTSD only in men. Conclusion After the GEJE, marked sex differences existed in the prevalence, prognostic impacts, and determinant factors of PTSD, suggesting the importance of sex-sepcific mental stress care in disaster medicine.
Examining the visual processing patterns of lonely adults.

Prior research has shown that loneliness is associated with hypervigilance to social threats, with eye-tracking research showing lonely people display a specific attentional bias when viewing social rejection and social exclusion video footage (Bangee, Harris, Bridges, Rotenberg & Qualter, 2014; Qualter, Rotenberg, Barrett et al., 2013). The current study uses eye-tracker methodology to examine whether that attentional bias extends to negative emotional faces and negative social non-rejecting stimuli, or whether it could be explained only as a specific bias to social rejection/exclusion. It is important to establish whether loneliness relates to a specific or general attention bias because it may explain the maintenance of loneliness. Participants (N = 43, F = 35, Mage = 20 years and 2 months, SD = 3 months) took part in three tasks, where they viewed different social information: Task 1 - slides displaying four faces each with different emotions (anger, afraid, happy and neutral), Task 2 - slides displaying sixteen faces with varying ratios expressing happiness and anger, and Task 3 - slides displaying four visual scenes (socially rejecting, physically threatening, socially positive, neutral). For all three tasks, eye movements were recorded in real time with an eye-tracker. Results showed no association between loneliness and viewing patterns of facial expressions, but an association between loneliness and hypervigilant viewing of social rejecting stimuli. The findings indicate that lonely adults do not have a generalised hypervigilance to social threat, but have, instead, a specific attentional bias to rejection information in social contexts. Implications of the findings for interventions are discussed.
Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet

[Purpose] This study aimed to investigate the effects of treadmill exercise on body weight, blood biochemistry, and autophagy. [Methods] Triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, and glucose levels were measured, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated, and the soleus muscle was analyzed for autophagy-related factors (Beclin-1, p62, LC3, Lamp-2) in rats with obesity induced by a high-fat diet. Eight-week-old Sprague Dawley rats were fed a high-fat diet for 35 weeks and then subjected to 10 weeks of treadmill exercise. The experimental group was divided into a Normal Diet-Sedentary (ND-SED, n=8) group, an (High-Fat Diet-Sedentary (HF-SED, n=8) group, and an High-Fat Diet + Treadmill Exercise (HF-TE, n=8) group. The intensity of treadmill exercise was set as 8 m/min for 5 min, 11 m/min for 5 min, 15 m/min for 20 min, and 11 m/min for the last 5 minutes. A glucose tolerance test was performed at the 2nd and 8th week of exercise by sampling of tail blood. [Results] With endurance exercise, the HFTE group showed a significant decrease in body weight, with improved blood biochemical indices and HOMA-IR scores, in comparison with the HF-SED group. However, there was no significant difference in Beclin-1, p62, LC3, and Lamp-2 proteins as measured by autophagic flux in the soleus muscle. [Conclusion] Treadmill exercise induced improvements in body weight, body fat, and biochemical indicators of obesity and Type 2 diabetes, but had no effect on autophagy in soleus muscle.
Grassland responses to three years of elevated temperature, CO2, precipitation, and N deposition

Global climate and atmospheric changes may interact in their effects on the diversity and composition of natural communities. We followed responses of an annual grassland to three years of all possible combinations of experimentally elevated CO 2 (1300 mL/L), warming (180 W/m 2 , 1;18C), nitrogen deposition (17 g N·m 22 ·yr 21 ), and precip- itation (150%). Responses of the 10 most common plant species to global changes and to interannual variability were weak but sufficiently consistent within functional groups to drive clearer responses at the functional group level. The dominant functional groups (annual grasses and forbs) showed distinct production and abundance responses to individual global changes. After three years, N deposition suppressed plant diversity, forb production, and forb abundance in association with enhanced grass production. Elevated precipitation en- hanced plant diversity, forb production, and forb abundance but affected grasses little. Warming increased forb production and abundance but did not strongly affect diversity or grass response. Elevated CO2 reduced diversity with little effect on relative abundance or production of forbs and grasses. Realistic combinations of global changes had small di- versity effects but more marked effects on the relative dominance of forbs and grasses. The largest change in relative functional group abundance (150% forbs) occurred under the combination of elevated CO2 1 warming 1 precipitation, which will likely affect much of California in the future. Strong interannual variability in diversity, individual species abundances, and functional group abundances indicated that in our system, (1) responses after three years were not constrained by lags in community response, (2) individual species were more sensitive to interannual variability and extremes than to mean changes in en- vironmental and resource conditions, and (3) simulated global changes interacted with interannual variability to produce responses of varying magnitude and even direction among years. Relative abundance of forbs, the most speciose group in the community, ranged after three years from . 30% under elevated CO2 1 warming 1 precipitation to ,12% under N deposition. While opposing production responses at the ecosystem level by different func- tional groups may buffer responses such as net primary production (NPP) change, these shifts in relative dominance could influence ecosystem processes such as nutrient cycling and NPP via differences between grasses and forbs in tissue chemistry, allocation, phe- nology, and productivity.
Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Salmonella enterica serovars Typhi and Paratyphi

Objectives Surveillance of antimicrobial resistance (AMR) in Salmonella enterica serovars Typhi and Paratyphi is essential to provide an evidence base for empirical treatment protocols and to monitor emerging AMR. We sought to compare phenotypic and WGS-based genotypic methods for the detection of AMR in Salmonella Typhi and Salmonella Paratyphi. Methods WGS data from 603 isolates of Salmonella Typhi (n = 332) and Salmonella Paratyphi (n = 271) were mapped to genes or chromosomal mutations known to be associated with phenotypic AMR and compared with phenotypic susceptibility data interpreted using breakpoints recommended by EUCAST. Results There were two (0.03%) discordant interpretations out of a possible 6030 isolate/antimicrobial class combinations. MDR (resistant to three or more classes of antimicrobial) was detected in 83/332 (25.0%) Salmonella Typhi isolates, but was not detected in Salmonella Paratyphi. Thirty-six (10.8%) isolates of Salmonella Typhi were resistant to ciprofloxacin (MIC >0.5 mg/L), with 33 (9.9%) of 332 exhibiting mutations in gyrA and parC, and 244 (73.5%) isolates had reduced susceptibility to ciprofloxacin (MIC 0.06-0.25 mg/L). In comparison, 209/227 (92.1%) isolates of Salmonella Paratyphi A exhibited resistance to ciprofloxacin (MIC >0.5 mg/L). No resistance to azithromycin or the third-generation cephalosporins was detected. Conclusions WGS data provided a robust and informative approach for monitoring MDR and emerging resistance to ciprofloxacin in Salmonella Typhi and Salmonella Paratyphi. Phenotypic antimicrobial susceptibility testing continues to be performed to guide targeted individual patient treatment, but inferred AMR profiles from WGS data may be used for surveillance and to guide empirical therapy.
Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model

ABSTRACT Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16–21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38–59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.
Recognizing and Encoding Discorder Concepts in Clinical Text using Machine Learning and Vector Space Model

The ShARe/CLEF eHealth Evaluation Lab (SHEL) organized a chal- lenge on natural language processing (NLP) and information retrieval (IR) in the medical domain in 2013. The first task of the 2013 ShARe/CLEF challenge was to extract disorder mention spans and their associated UMLS (Unified Medical Language System) concept unique identifiers (CUIs). We participated in Task 1 and developed a clinical disorder recognition and encoding system. The proposed system consists of two components: a machine learning-based approach to recognize disorder entities and a vector space model-based method to encode disorders to UMLS CUIs. The challenge organizers manually anno- tated disorder entities and corresponding UMLS CUIs in 298 clinical notes, of which 199 notes were used for training and 99 were for testing. Evaluation on the test data set showed that our system achieved the best F-measure of 0.750 for entity recognition (ranked first) and the highest F-measure of 0.514 for UMLS CUI encoding (ranked third), indicating the promise of the proposed ap- proaches.
A Trimer Consisting of the Tubulin-specific Chaperone D (TBCD), Regulatory GTPase ARL2, and β-Tubulin Is Required for Maintaining the Microtubule Network*

Microtubule dynamics involves the polymerization and depolymerization of tubulin dimers and is an essential and highly regulated process required for cell viability, architecture, and division. The regulation of the microtubule network also depends on the maintenance of a pool of αβ-tubulin heterodimers. These dimers are the end result of complex folding and assembly events, requiring the TCP1 Ring Complex (TriC or CCT) chaperonin and five tubulin-specific chaperones, tubulin binding cofactors A–E (TBCA–TBCE). However, models of the actions of these chaperones are incomplete or inconsistent. We previously purified TBCD from bovine tissues and showed that it tightly binds the small GTPase ARL2 but appears to be inactive. Here, in an effort to identify the functional form of TBCD and using non-denaturing gels and immunoblotting, we analyzed lysates from a number of mouse tissues and cell lines to identify the quaternary state(s) of TBCD and ARL2. We found that both proteins co-migrated in native gels in a complex of ∼200 kDa that also contained β-tubulin. Using human embryonic kidney cells enabled the purification of the TBCD·ARL2·β-tubulin trimer found in cell and tissue lysates as well as two other novel TBCD complexes. Characterization of ARL2 point mutants that disrupt binding to TBCD suggested that the ARL2-TBCD interaction is critical for proper maintenance of microtubule densities in cells. We conclude that the TBCD·ARL2·β-tubulin trimer represents a functional complex whose activity is fundamental to microtubule dynamics.
TGF-β Isoform Specific Regulation of Airway Inflammation and Remodelling in a Murine Model of Asthma

The TGF-β family of mediators are thought to play important roles in the regulation of inflammation and airway remodelling in asthma. All three mammalian isoforms of TGF-β, TGF-β1–3, are expressed in the airways and TGF-β1 and -β2 are increased in asthma. However, there is little information on the specific roles of individual TGF-β isoforms. In this study we assess the roles of TGF-β1 and TGF-β2 in the regulation of allergen-induced airway inflammation and remodelling associated with asthma, using a validated murine model of ovalbumin sensitization and challenge, and isoform specific TGF-β neutralising antibodies. Antibodies to both isoforms inhibited TGF-β mediated Smad signalling. Anti-TGF-β1 and anti-TGF-β2 inhibited ovalbumin-induced sub-epithelial collagen deposition but anti-TGF-β1 also specifically regulated airway and fibroblast decorin deposition by TGF-β1. Neither antibody affected the allergen-induced increase in sub-epithelial fibroblast-like cells. Anti- TGF-β1 also specifically inhibited ovalbumin-induced increases in monocyte/macrophage recruitment. Whereas, both TGF-β1 and TGF-β2 were involved in regulating allergen-induced increases in eosinophil and lymphocyte numbers. These data show that TGF-β1 and TGF-β2 exhibit a combination of specific and shared roles in the regulation of allergen-induced airway inflammation and remodelling. They also provide evidence in support of the potential for therapeutic regulation of specific subsets of cells and extracellular matrix proteins associated with inflammation and remodelling in airway diseases such as asthma and COPD, as well as other fibroproliferative diseases.
Random Sampling over Joins Revisited

Joins are expensive, especially on large data and/or multiple relations. One promising approach in mitigating their high costs is to just return a simple random sample of the full join results, which is sufficient for many tasks. Indeed, in as early as 1999, Chaudhuri et al. posed the problem of sampling over joins as a fundamental challenge in large database systems. They also pointed out a fundamental barrier for this problem, that the sampling operator cannot be pushed through a join, i.e., sample( R bowtie S )≠ sample( R ) bowtie sample( S ). To overcome this barrier, they used precomputed statistics to guide the sampling process, but only showed how this works for two-relation joins. This paper revisits this classic problem for both acyclic and cyclic multi-way joins. We build upon the idea of Chaudhuri et al., but extend it in several nontrivial directions. First, we propose a general framework for random sampling over multi-way joins, which includes the algorithm of Chaudhuri et al. as a special case. Second, we explore several ways to instantiate this framework, depending on what prior information is available about the underlying data, and offer different tradeoffs between sample generation latency and throughput. We analyze the properties of different instantiations and evaluate them against the baseline methods; the results clearly demonstrate the superiority of our new techniques.