Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating direct healthcare costs attributable to laboratory‐confirmed Lyme disease in Ontario, Canada: A population‐based matched cohort study using health administrative data

The objective of this study was to determine healthcare costs attributable to laboratory‐confirmed Lyme disease (LD) from the healthcare payer perspective in Ontario, Canada. A cost‐of‐illness study was conducted for incident LD subjects from 1 January 2006 through 31 December 2013 ascertained from provincial laboratory and reportable disease databases, linked to health administrative data. All LD subjects included were laboratory‐confirmed, according to provincial case definitions. Incident LD subjects were propensity‐score matched to uninfected subjects on age, sex, comorbidities and urban/rural status. We used phase‐of‐care methods to calculate attributable costs for two phases of illness: initial care (≤30 days following “index date”) and continuing care (>30 days after index date to the end of the follow‐up period). A total of 663 incident, confirmed LD subjects were identified from 2006 through 2013. Mean age was 44.2 ± 20.1 years; 339 (51.1%) were female; and 31 (4.7%) were hospitalized ≤30 days after index date. Six hundred fifty‐eight (99.2%) LD subjects were matched to uninfected subjects; mean follow‐up time was 3.3 years. Mean attributable costs per case during the initial care phase and continuing care were $277 (95% CI: $197, $357) and −$5 (−$27, $17), respectively. Attributable costs per LD subject aged 5–14 years were $440 ($132, $747), greater than the costs observed for other age strata. Expected 1‐year attributable costs were $832, given continuing care costs were negligible. Limitations to our study include estimating costs using a cohort of only laboratory‐confirmed LD cases, introducing selection bias for diagnosed and treated patients who may have a lower risk of developing sequelae. In conclusion, the initial care phase of LD is associated with increased healthcare costs, but without significant costs attributable to LD infection after 30 days. Estimates of costs attributable to LD are important for healthcare resource prioritization and the evaluation of novel interventions.
Effects of abusive supervision on employees' innovative behavior: The role of job insecurity and locus of control.

Drawing on the Conservation of Resources Theory by Hobfoll, we examined the relationships between abusive supervision, job insecurity, locus of control, and employees' innovative behavior. Using self-reported data collected from employees among four enterprises in China (N = 641), we found that abusive supervision was positively correlated with job insecurity. In contrast, both job insecurity and abusive supervision were negatively correlated with employees' innovative behavior, with the impact of abusive supervision on innovative behavior being mediated by its effect on job insecurity. Having an external locus of control that served as a buffering factor for employees, mitigating the relationship between abusive supervision and job insecurity. These findings complement the existing research on the impacts of abusive leadership, providing practical information for enterprises on how to enhance levels of innovation and vitality among employees.
Gut microbiota density influences host physiology and is shaped by host and microbial factors

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.
Contribution of synovial macrophages to rat advanced osteoarthritis pain resistant to cyclooxygenase inhibitors

Abstract Most advanced knee osteoarthritis (OA) patients experience chronic pain resistant to cyclooxygenase (COX) inhibitors. However, the cells and molecules involved in this advanced OA pain remain poorly understood. In this study, we developed a rat model of advanced knee OA by modification of the monoiodoacetate-induced OA pain model and examined involvement of synovial macrophages in advanced OA pain. Cyclooxygenase inhibitors, such as celecoxib and naproxen, and a steroid were ineffective, but an opioid and anti–nerve growth factor (NGF) antibody was effective for pain management in the advanced OA model. Similar to advanced OA patients, histological analysis indicated severe bone marrow damages, synovitis, and cartilage damage and an increase of macrophages with high expression of interleukin-1&bgr;, NGF, nitric oxide synthase (NOS) 1, NOS2, and COX-2 in the knee joint of the advanced OA model. Intravenous injection of clodronate liposomes depleted synovial macrophages, which decreased the level of not only proinflammatory mediator interleukin-1&bgr; but also NGF in the knee joint, leading to pain suppression in the advanced OA model. These data suggest the involvement of synovial macrophages in advanced knee OA pain resistant to COX inhibitors by increasing proinflammatory mediators, and that drugs targeting synovial macrophages might have potent analgesic effects.
Demographic Variation in the Frequency of Gliomas in Florida

Background and objectives: Glial brain cancers affect nearly 20,000 individuals in the United States (USA) annually. SEER database data exploring the relationship between race and gliomas is now available and have shown that cerebral gliomas occur at a higher frequency in Caucasian men. However, such analyses did not include demographic data specific to the state of Florida. This study assessed the association between race and glial vs. non-glial Central Nervous System (CNS) cancers in Florida, USA. Materials and Methods: This case-control study utilized the Florida Cancer Data Registry (FCDS), in which race was considered the exposure and development of glioma as the measured outcome. The sample was comprised of patients in Florida diagnosed with brain tumors from 1981 to 2013. Relative racial frequencies were compared between patients with glial brain tumors and those with other CNS tumors. Data was analyzed using logistic regression in order to determine any associations between race and frequency of diagnosis adjusting for several confounders (age, sex, smoking status, year of diagnosis, and insurance status). Results: Between 1981 and 2013 a total of 14,092 patients meeting the inclusion and exclusion criteria were diagnosed in Florida with a primary brain tumor. Being of non-white race was associated with 60% decreased odds of glioma diagnosis compared to the reference white population (adjusted OR 0.4, 95% CI 0.34–0.47). Secondary findings include associations between increasing age and male sex with increased odds of glioma diagnosis. Decreased adjusted odds of glioma diagnosis were found with former smoking status (reference non-smokers), diagnosis between 2001 and 2010 (reference 1981–1990), and Medicaid or Medicare insurance (reference private insurance). Hispanic ethnicity, current smoking status, no insurance/self-pay, and geographical location (urban vs. rural) all had no association with glioma diagnosis. Conclusions: These findings are consistent with and help reinforce previous studies utilizing national databases (SEER) which also showed increasing odds of glioma diagnosis in older white males. Various potential explanations for these findings include genetic predisposition, lifestyle and behavioral factors, and socioeconomic status, including access to healthcare. Future research aims at identifying potential genetic etiologies.
Bacterial killing by complement requires membrane attack complex formation via surface‐bound C5 convertases

The immune system kills bacteria by the formation of lytic membrane attack complexes (MACs), triggered when complement enzymes cleave C5. At present, it is not understood how the MAC perturbs the composite cell envelope of Gram‐negative bacteria. Here, we show that the role of C5 convertase enzymes in MAC assembly extends beyond the cleavage of C5 into the MAC precursor C5b. Although purified MAC complexes generated from preassembled C5b6 perforate artificial lipid membranes and mammalian cells, these components lack bactericidal activity. In order to permeabilize both the bacterial outer and inner membrane and thus kill a bacterium, MACs need to be assembled locally by the C5 convertase enzymes. Our data indicate that C5b6 rapidly loses the capacity to form bactericidal pores; therefore, bacterial killing requires both in situ conversion of C5 and immediate insertion of C5b67 into the membrane. Using flow cytometry and atomic force microscopy, we show that local assembly of C5b6 at the bacterial surface is required for the efficient insertion of MAC pores into bacterial membranes. These studies provide basic molecular insights into MAC assembly and bacterial killing by the immune system.
Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo

Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. ABSTRACT Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.
The pleiotropic Legionella transcription factor LvbR links the Lqs and c‐di‐GMP regulatory networks to control biofilm architecture and virulence

The causative agent of Legionnaires' disease, Legionella pneumophila, colonizes amoebae and biofilms in the environment. The opportunistic pathogen employs the Lqs (Legionella quorum sensing) system and the signalling molecule LAI-1 (Legionella autoinducer-1) to regulate virulence, motility, natural competence and expression of a 133 kb genomic "fitness island", including a putative novel regulator. Here, we show that the regulator termed LvbR is an LqsS-regulated transcription factor that binds to the promoter of lpg1056/hnox1 (encoding an inhibitor of the diguanylate cyclase Lpg1057), and thus, regulates proteins involved in c-di-GMP metabolism. LvbR determines biofilm architecture, since L. pneumophila lacking lvbR accumulates less sessile biomass and forms homogeneous mat-like structures, while the parental strain develops more compact bacterial aggregates. Comparative transcriptomics of sessile and planktonic ΔlvbR or ΔlqsR mutant strains revealed concerted (virulence, fitness island, metabolism) and reciprocally (motility) regulated genes in biofilm and broth respectively. Moreover, ΔlvbR is hyper-competent for DNA uptake, defective for phagocyte infection, outcompeted by the parental strain in amoebae co-infections and impaired for cell migration inhibition. Taken together, our results indicate that L. pneumophila LvbR is a novel pleiotropic transcription factor, which links the Lqs and c-di-GMP regulatory networks to control biofilm architecture and pathogen-host cell interactions.
Biological Activities and Chemical Composition of Santolina africana Jord. et Fourr. Aerial Part Essential Oil from Algeria: Occurrence of Polyacetylene Derivatives

The chemical composition of 18 oil samples of Santolina africana isolated from aerial parts at full flowering, collected in three locations in eastern Algeria was determined by GC(RI), GC/MS and 13C-NMR analysis. The major components were: germacrene D, myrcene, spathulenol, α-bisabolol, β-pinene, 1,8-cineole, cis-chrysanthenol, capillene, santolina alcohol, camphor, terpinen-4-ol and lyratol. The chemical composition appeared homogeneous and characterized by the occurrence of four derivatives which exhibited a conjugated alkene dialkyne moiety. They were identified for the first time in an essential oil from S. africana. The collective oil sample exhibited moderate antimicrobial and antioxidant activities whereas the anti-inflammatory activity presented a real potential. IC50 value of Santolina africana essential oil (0.065 ± 0.004 mg/mL) is 5-fold higher than IC50 value of NDGA used as positive control.
Airway microenvironment alterations and pathogen growth in cystic fibrosis

Cystic Fibrosis Transmembrane Regulator (CFTR) dysfunction is associated with epithelial cell vulnerability and with dysregulation of the local inflammatory responses resulting in excessive airway neutrophilic inflammation and pathogen growth. In combination with impaired mucociliary clearance, and dysregulation of defense function, bacterial infection follows with eventual airway damage and remodeling. Because of these inherent vulnerabilities, viral infections are also more severe and prolonged and appear to render the airway even more prone to bacterial infection. Airway acidity, deficient nitric oxide production and increased iron concentrations, further enhance the airway milieu's susceptibility to infection. Novel diagnostic techniques of the airway microbiome elucidate the coexistence of an array of non‐virulent taxa beyond the recognized virulent organisms, predominantly Pseudomonas aeruginosa. The complex interplay between these two bacterial populations, including upregulation of virulence genes and utilization of mucin as a nutrient source, modulates the action of pathogens, modifies the CF airway milieu and contributes to the processes leading to airway derangement. The review provides an update on recent advances of the complex mechanisms that render the CF airway vulnerable to inflammation, infection and ultimately structural damage, the key pathogenetic elements of CF. The recent contributions on CF pathogenesis will hopefully help in identifying new prophylactic measures and therapeutic targets for this highly destructive disorder.
Cut to the Quick: The Consequences of Youth Violent Victimization for the Timing of Dating Debut and First Union Formation

Concentrated in adolescence, violent victimization is developmentally disruptive. It undermines physical, mental, and socioemotional well-being and compromises youths’ transitions into and progression through key life course tasks. Youth violent victimization (YVV) has been linked to precocious exits from adolescence and premature entries into adulthood. This includes early entry into coresidential romantic unions, which is but one stage of a relationship sequence generally beginning via dating debut. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) and Cox regression, we examine the effects of YVV on the timing of dating debut and progression to first coresidential unions during adolescence and the transition to adulthood. We pay particular attention to how these effects may be structured by age and gender. Overall, we find that victims begin dating sooner and progress more quickly from dating to first unions than do non-victims. However, youths victimized in early adolescence withdraw from dating and union formation, whereas late adolescent victims appear to overinvest in relationships—at least temporarily—displaying accelerated entry into dating and rapid progression to first unions. We conclude by discussing the implication of these age-graded patterns for intervention efforts and youth well-being more broadly.
Calcium Pyruvate Exerts Beneficial Effects in an Experimental Model of Irritable Bowel Disease Induced by DCA in Rats

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine Il-1β and the inducible enzyme Cox-2, which was reduced by the treatments. DCA also decreased the gut expression of the mucins Muc-2 and Muc-3, which was normalized by CPM, whereas gabapentin only increased significantly Muc-3. Moreover, DCA increased the expression of Tlr3, which was decreased to basal levels by all the treatments. However, the serotonin receptor Htr-4, which was also elevated, was not affected by any of the treatments, indicating no effect through this signalling pathway. In conclusion, CPM ameliorated the visceral hypersensitivity and the referred pain caused by DCA, being as effective as the control drug. Furthermore, it improved the immune status of the animals, which could contribute to the visceral analgesia and the regeneration of the intestinal epithelial barrier integrity.
Metastases to the Breast from Adenocarcinoma of Lung: Incidentally Detected with Routine Computed Tomography of Chest

The authors report an unusual case of breast metastases incidentally disclosed with a routine contrast-enhanced chest CT scan. A 53-year-old female patient underwent chemotherapy for lung cancer and multiple metastases, and a follow-up CT scan of chest disclosed multiple well-defined small nodules with homogeneous enhancement in her left breast. The breast nodules were non-palpable. Metastatic adenocarcinoma of pulmonary origin was subsequently confirmed at sonographically guided biopsy.
Nutritional status and clinical outcomes in pediatric patients with solid tumors : A systematic review of the literature.

INTRODUCTION Nutritional status (NS), defined by undernutrition (body mass index [BMI] <5th percentile) or overnutrition (BMI ≥ 85th percentile), is a poor prognostic indicator in pediatric oncology patients. The impact of NS has been primarily studied in hematologic malignancies. This review is intended to summarize literature reporting on the association of NS and treatment-related outcomes in pediatric solid tumors. METHODS We searched four electronic databases from inception through August 2018 without language restriction, and included studies of children with cancers arising from renal, bone, liver, eye, muscle, vascular, germ cell, and neural crest tissues, reporting on NS as a predictor for toxicity, survival or relapse. Due to data heterogeneity and limited availability of studies, formal statistical analysis was not achievable. Descriptive statistics were summarized in table format. RESULTS Of 8,991 reports identified, 75 full-text articles were evaluated, 10 of which met inclusion criteria. Up to 62% of patients were over- or undernourished at diagnosis. Abnormal BMI was associated with worse overall survival in Ewing sarcoma (hazard ratio (HR): 3.46, P = . 022), osteosarcoma (HR: 1.6, P < .005), and a trend toward poorer overall survival in rhabdomyosarcoma (HR: 1.70, P = .0596). High BMI in osteosarcoma was associated with increased nephrotoxicity (odds ratio: 2.8, P = .01) and postoperative complications. NS was not a significant predictor of outcomes in other included disease categories. CONCLUSIONS Existing literature supports the prognostic significance of NS in pediatric solid tumor patients and underscores the need for prospective studies to better elucidate underlying physiological changes in this population.
Stable carbon and nitrogen isotope inter- and intra-individual dietary reconstruction from the late 14th to early 18th century site of Alytus, Lithuania.

OBJECTIVES The Baltic region, particularly Lithuania, was a politically vibrant area of Eastern Europe during the medieval and early modern period. To better understand the diet of Lithuanians during the late 14th to early 18th century, we examine stable carbon and nitrogen isotope ratios from bone and dentin samples from the site of Alytus. We investigate possible dietary differences based on sex, age, and religious practice, as well as dietary changes throughout an individual's lifetime, within the broader European milieu. MATERIALS AND METHODS Stable carbon and nitrogen isotope analysis was conducted on bone (n = 35) and dentin (n = 38) collagen samples from a total of 39 individuals buried in the cemetery at Alytus (late 14th to early 18th centuries). RESULTS Results indicate individuals at Alytus consumed a C3 terrestrial based diet. The δ13 C and δ15 N values are not significantly different between bone and dentin, and did not vary by sex. DISCUSSION The diet at Alytus was homogeneous between males and females and between tissue types. The lack of evidence indicating substantial consumption of fish is unexpected given widespread Catholic fasting practices and marine resource trade throughout Europe. Comparisons with other populations indicate that individuals from Alytus differ in diet from contemporaneous Polish-Lithuanian Commonwealth elites. Comparison of the diets of non-elite individuals in the Eastern Baltic region also reveals dietary variability.