Miracle-dz/UniFAR-FTUs huggingface dataset:
Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain.

BACKGROUND We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain. METHODS A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential. RESULTS Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain. CONCLUSIONS Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains.
Emergency department boarding: a descriptive analysis and measurement of impact on outcomes.

OBJECTIVES Delays in transfer of admitted patients boarded in the emergency department (ED) to an inpatient bed is a major driver of ED overcrowding. We sought to identify explanatory factors behind ED boarding as well as the impact of boarding on total inpatient length of stay (IP LOS) and inpatient mortality. METHODS We conducted a retrospective single-centre observational study during the period between January 1 and December 31, 2015 at a very high volume community hospital. All patients admitted from the ED to Medicine, Pediatrics, Surgery, and Critical Care were identified. The mean ED LOS and boarding time as well as patient-specific and institutional factors that were independently associated with prolonged ED LOS (≥24 hours) and prolonged boarding time (≥12 hours) were identified. Mean inpatient length of stay (IP LOS) and the odds of inpatient mortality were calculated for those patients with prolonged ED wait times. RESULTS There were 13,872 unique admissions during the study period. Patients admitted to the Medicine service exhibited significantly higher ED wait times than other services. Within Medicine patients, there was a statistically significant greater odds of prolonged ED wait times for patients who were older, had a greater comorbidity burden, and required more specialized inpatient care. Medicine patients with prolonged boarding times also experienced a mean of 0.9 days longer IP LOS even after adjusting for confounders. CONCLUSION Within our cohort, older, sicker patients and those patients requiring more resource-intensive inpatient care had the longest ED wait times. These prolonged wait times are associated with significantly increased IP LOS.
Secular Trends in the Incidence of Dementia in a Multi-Ethnic Community.

BACKGROUND Determination of secular trends in cognitive aging is important for prioritization of resources, services, and research in aging populations. Prior studies have identified declining dementia incidence associated with changes in cardiovascular risk factors and increased educational attainment. However, few studies have examined these factors in multi-ethnic cohorts. OBJECTIVE To identify secular trends in the incidence rate of dementia in an elderly population. METHODS Participants in this study were drawn from the Washington Heights-Inwood Columbia Aging Project, a multi-ethnic cohort study of northern Manhattan residents aged 65 years and older. Cox proportional hazards models were used to examine differences in the incidence of dementia in cohorts recruited in 1992 and 1999, with age at dementia or age at last follow-up visit as the "time-to-event" variable. RESULTS Overall, there was a 41% reduction in the hazard ratio for dementia among participants in the 1999 cohort compared with those in the 1992 cohort, adjusting for age, sex, race, and baseline memory complaints (HR = 0.59). The reduction in incidence was greatest among non-Hispanic Whites and African-Americans and lowest among Hispanic participants (HRs = 0.60, 0.52 and 0.64, respectively), and was associated with increases in level of educational attainment, especially among African-Americans. Reduction in incidence of dementia was also greater among persons 75 years or older than among younger participants (HR = 0.52 versus HR = 0.69). CONCLUSIONS Our results support previous findings that secular trends in dementia incidence are changing, including in aging minority populations.
Happy ending: a randomized controlled trial of a digital multi-media smoking cessation intervention.

AIMS To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention. DESIGN Two-arm randomized control trial (RCT). Setting World Wide Web (WWW) study based in Norway. PARTICIPANTS Subjects (n = 396) were recruited via internet advertisements and assigned randomly to conditions. Inclusion criteria were willingness to quit smoking and being aged 18 years or older. INTERVENTION The treatment group received the internet- and cell-phone-based Happy Ending intervention. The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail, web-pages, interactive voice response (IVR) and short message service (SMS) technology. The control group received a self-help booklet. Additionally, both groups were offered free nicotine replacement therapy (NRT). MEASUREMENTS Abstinence was defined as 'not even a puff of smoke, for the last 7 days', and assessed by means of internet surveys or telephone interviews. The main outcome was repeated point abstinence at 1, 3, 6 and 12 months following cessation. FINDINGS Participants in the treatment group reported clinically and statistically significantly higher repeated point abstinence rates than control participants [22.3% versus 13.1%; odds ratio (OR) = 1.91, 95% confidence interval (CI): 1.12-3.26, P = 0.02; intent-to-treat). Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group. CONCLUSIONS As the first RCT documenting the long-term treatment effects of such an intervention, this study adds to the promise of digital media in supporting behaviour change.
Risk Assessment of Potentially Toxic Elements (PTEs) Pollution at a Rural Industrial Wasteland in an Abandoned Metallurgy Factory in North China

The potential toxic elements (PTEs) pollution problems in many rural industrial wastelands have been observed to be conspicuous. Therefore, 40 top soil samples were collected from the wasteland of a typical rural metallurgy factory in Baoding, China. The total concentrations of six key PTEs were measured. The soil properties and speciation of the PTEs were also identified. Extremely high concentrations of As, Cd, Pb, and Zn were observed in the surface soils. Using the PTEs concentration in the top soils of the rural industrial wasteland, the following indices of pollution were calculated: the pollution load index (PLI), the geo-accumulation Index (Igeo), the risk assessment code (RAC), and the health risk assessment (HRA). The analysis of the PLI and Igeo indicated that site #1 was relatively clean, while sites #2 and #3 were heavily polluted. The results of the RAC showed that PTEs in top soils at sites #2 and #3 were significantly increased (p < 0.05) for Cd and Zn. The HRA indicated that both As and Pb presented non-carcinogenic risks to children and adults at sites #2 and #3. Our findings can be a reference for risk prevention of industrially abandoned land in rural China.
Thermal analysis of ice and glass transitions in insects that do and do not survive freezing

ABSTRACT Some insects rely on the strategy of freeze tolerance for winter survival. During freezing, extracellular body water transitions from the liquid to the solid phase and cells undergo freeze-induced dehydration. Here, we present results of a thermal analysis (from differential scanning calorimetry) of ice fraction dynamics during gradual cooling after inoculative freezing in variously acclimated larvae of two drosophilid flies, Drosophila melanogaster and Chymomyza costata. Although the species and variants ranged broadly between 0 and close to 100% survival of freezing, there were relatively small differences in ice fraction dynamics. For instance, the maximum ice fraction (IFmax) ranged between 67.9% and 77.7% total body water (TBW). Chymomyza costata larvae showed statistically significant phenotypic shifts in parameters of ice fraction dynamics (melting point and IFmax) upon entry into diapause, cold acclimation and feeding on a proline-augmented diet. These differences were mostly driven by colligative effects of accumulated proline (ranging between 6 and 487 mmol kg−1 TBW) and other metabolites. Our data suggest that these colligative effects per se do not represent a sufficient mechanistic explanation for high freeze tolerance observed in diapausing, cold-acclimated C. costata larvae. Instead, we hypothesize that accumulated proline exerts its protective role via a combination of mechanisms. Specifically, we found a tight association between proline-induced stimulation of glass transition in partially frozen body liquids (vitrification) and survival of cryopreservation in liquid nitrogen. Highlighted Article: Differential scanning calorimetry analysis of ice fraction dynamics in two drosophilid flies indicates a tight association between proline-induced vitrification and survival of cryopreservation in Chymomyza costata larvae.
Clinical impact of recent genetic discoveries in osteoporosis

Osteoporotic fracture carries an enormous public health burden in terms of mortality and morbidity. Current approaches to identify individuals at high risk for fracture are based on assessment of bone mineral density and presence of other osteoporosis risk factors. Bone mineral density and susceptibility to osteoporotic fractures are highly heritable, and over 60 loci have been robustly associated with one or both traits through genome-wide association studies carried out over the past 7 years. In this review, we discuss opportunities and challenges for incorporating these genetic discoveries into strategies to prevent osteoporotic fracture and translating new insights obtained from these discoveries into development of new therapeutic targets.
The Impact of Selective-Logging and Forest Clearance for Oil Palm on Fungal Communities in Borneo

Tropical forests are being rapidly altered by logging, and cleared for agriculture. Understanding the effects of these land use changes on soil fungi, which play vital roles in the soil ecosystem functioning and services, is a major conservation frontier. Using 454-pyrosequencing of the ITS1 region of extracted soil DNA, we compared communities of soil fungi between unlogged, once-logged, and twice-logged rainforest, and areas cleared for oil palm, in Sabah, Malaysia. Overall fungal community composition differed significantly between forest and oil palm plantation. The OTU richness and Chao 1 were higher in forest, compared to oil palm plantation. As a proportion of total reads, Basidiomycota were more abundant in forest soil, compared to oil palm plantation soil. The turnover of fungal OTUs across space, true β-diversity, was also higher in forest than oil palm plantation. Ectomycorrhizal (EcM) fungal abundance was significantly different between land uses, with highest relative abundance (out of total fungal reads) observed in unlogged forest soil, lower abundance in logged forest, and lowest in oil palm. In their entirety, these results indicate a pervasive effect of conversion to oil palm on fungal community structure. Such wholesale changes in fungal communities might impact the long-term sustainability of oil palm agriculture. Logging also has more subtle long term effects, on relative abundance of EcM fungi, which might affect tree recruitment and nutrient cycling. However, in general the logged forest retains most of the diversity and community composition of unlogged forest.
Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort

Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; NRecurrence=109; NMLprogression=27). The expression signature included transcripts representing 49 genes. In the FH cohort, a 25% increase in the signature was associated with a hazard ratio (HR) of 1.51 (P=2.7×10−5) for recurrence. The signature's area under the curve (AUC) for predicting recurrence and ML progression was 0.68 and 0.76, respectively. Compared to a model with age at diagnosis, pathological stage and GS, the gene expression signature improved the AUC for recurrence (3%) and ML progression (6%). Higher levels of the signature were associated with increased expression of genes in cell cycle-related pathways and decreased expression of genes in androgen response, estrogen response, oxidative phosphorylation, and apoptosis. This gene expression signature based on GS may improve the prediction of recurrence as well as ML progression in PCa patients after radical prostatectomy.
Postnatal Weight Gain Patterns in Preterm Very-Low-Birth-Weight Infants Born in a Tertiary Care Center in South India

Background Extrauterine growth retardation is a common problem in preterm, very-low-birth-weight (VLBW) babies, as well as paucity of growth charts that follow their postnatal growth. Aim To evaluate and plot postnatal weight gain patterns of preterm VLBW babies of <34 weeks' gestation born at a tertiary care neonatal unit in South India. Methods Weight gain patterns of all preterm (27 to < 34 weeks' gestation) and VLBW (<1500 g) neonates were used for plotting the centile curves by retrospective review of electronic medical records. The growth velocity was calculated from birth and from the time baby regained their birth weight. Results Mean growth rate (±SD) of these babies was 16.2 ± 2.4 g/kg/day and average time to regain birth weight was 14.2 days (range 12.0-17.6). Conclusion The recommended growth velocity of 10-15 g/kg/day can be achieved using unfortified expressed breast milk, though at higher feeding volumes of 200 ml/kg/day. These centile curves can be useful for monitoring postnatal growth.
Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (p<0.001). Completeness varied in-between categories, and was lowest in the category “pharmacokinetics” (68.0%±4.2%; p<0.001) and highest in the category “indication” (91.3%±2.0%) when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.
Amyloid Burden in Obstructive Sleep Apnea.

To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.
Association Between Natural Killer Cell Activity and Colorectal Cancer in High-Risk Subjects Undergoing Colonoscopy.

BACKGROUND & AIMS Low activity of natural killer (NK) cells has been associated with increased risk of cancer and has been reported in patients with colorectal cancer (CRC). Activity of NK cells can be measured in a small volume of whole blood by a commercially available test. We investigated whether this test could be used to identify patients with CRC, using findings from colonoscopy as a reference standard. METHODS We performed an open-label, prospective, cross-sectional study of 872 high-risk subjects (more than 40 years old) screened for CRC by colonoscopy at a university hospital in Montreal, Canada from October 2014 through January 2016. Blood samples were collected on the day of colonoscopy, prior to the procedure. The test involves stimulation of whole blood with cytokine that induces NK cells to secrete interferon gamma (IFNG), which is quantified by an ELISA. Tissue samples were taken from lesions during the colonoscopy and analyzed histologically; subjects were classified as having no evidence of disease, adenomatous polyps of less than 10 mm, of 10 mm or more, or CRC. We used the non-parametric Mann-Whitney test to compare NK cell activity between subjects with no evidence of CRC and subjects found to have CRC. Receiver operating characteristic curve analysis was used to assess the ability of the test to identify individuals with CRC. The primary objective was to determine the difference in NK cell activity between subjects with vs without CRC. The secondary objective was the test performance, based on receiver operating characteristic analysis, and cut-off value that most accurately identified individuals with CRC. RESULTS We found a significant difference in NK cell activity between the 23 subjects with CRC (based on pathology analysis) and the 849 subjects without CRC: subjects found to have CRC by colonoscopy had a median level of 86.0 pg IFNG/mL (inter-quartile range, 43.3-151.0 pg IFNG/mL), whereas subjects without CRC had a median level of 298.1 pg IFNG/mL (inter-quartile range, 100.4-920.2 pg IFNG/mL) (P = .0002). The cut-off value that most accurately identified subjects with CRC was 181 pg/mL. The NK cell activity test identified subjects with CRC with 87.0% sensitivity, 60.8% specificity, a positive predictive value of 5.7%, and a negative predictive value of 99.4%. The odds ratio for detection of CRC in subjects with low NK cell activity vs subjects with higher NK cell activity was 10.3 (95% CI, 3.03-34.9). CONCLUSIONS Using colonoscopy as the reference standard, a test for NK cell activity in whole blood samples identified patients with CRC with 87.0% sensitivity and a negative predictive value of 99.4%. Subjects with low NK cell activity had a 10-fold higher risk of CRC compared with subjects with high NK cell activity. This test might be used in clinical practice to assess patients for risk of CRC. Clinicaltrials.gov number: NCT02291198.