Miracle-dz/UniFAR-FTUs huggingface dataset:
Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital

Introduction To analyse the clinical and epidemiological characteristics and mortality-related factors of patients admitted to a secondary hospital with Infective Endocarditis (IE). Methods Observational study of a cohort of patients who have been diagnosed with IE in a secondary hospital and evaluated in accordance with a pre-established protocol. Results A total of 101 cases were evaluated (years 2000-2017), with an average age of 64 years and a male-to-female ratio of 2:1. 76% of the cases had an age-adjusted Charlson comorbidity index of >6, with 21% having had a dental procedure and 36% with a history of heart valve disease. The most common microorganism was methicillin-susceptible S. aureus (36%), with bacterial focus of unknown origin in 54%. The diagnostic delay time was 12 days in patients who were transferred, compared to 8 days in patients who were not transferred (p=0.07); the median surgery indication delay time was 5 days (IQR 13.5). The in-hospital mortality rate was 34.6% and the prognostic factors independently associated with mortality were: cerebrovascular events (OR 98.7%, 95% CI, 70.9–164.4); heart failure (OR 27.3, 95% CI, 10.2–149.1); and unsuitable antibiotic treatment (OR 7.2, 95% CI, 1.5–10.5). The mortality rate of the patients who were transferred and who therefore underwent surgery was 20% (5/25). Conclusions The onset of cerebrovascular events, heart failure and unsuitable antibiotic treatment are independently and significantly associated with in-hospital mortality. The mortality rate was higher than the published average (35%); the diagnostic delay was greater in patients for whom surgery was indicated.
Robust validation and performance comparison of immunogenicity assays assessing IgG and neutralizing antibodies to SARS-CoV-2

To enable benchmarking of immunogenicity between candidate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there is a need for standardized, validated immunogenicity assays. In this article, we report the design and criteria used to validate immunogenicity assays and the outcome of the validation of serologic and functional assays for the evaluation of functional immune response and antibody titers in human serum. A quantitative cell-based microneutralization (MNT) assay, utilizing a reference standard, for detecting anti-SARS-CoV-2 spike protein-neutralizing antibodies in human serum and Meso Scale Discovery’s multiplex electrochemiluminescence (MSD ECL) assay for immunoglobulin G (IgG) antibodies to SARS-CoV-2 spike, nucleocapsid, and receptor-binding domain (RBD) proteins were assessed for precision, accuracy, dilutional linearity, selectivity, and specificity using pooled human serum from coronavirus disease 2019 (COVID-19)-confirmed recovered donors. Both assays met prespecified acceptance criteria for precision, relative accuracy, dilutional linearity, selectivity, and specificity. Both assays demonstrated high specificity for the different SARS-CoV-2 antigens or virus tested, and no significant cross-reactivity with seasonal coronaviruses. An evaluation to compare the neutralizing activity in the MNT assay to the IgG measured using the MSD ECL assay showed a strong correlation between the presence of neutralizing activity and amount of antibodies against the spike and RBD proteins in sera from both convalescent and vaccinated individuals. Finally, the MNT assay was calibrated to the WHO reference standard to enable reporting of results in international units, thus facilitating comparison of immunogenicity data generated by different assays and/or laboratories. The MSD ECL assay has previously been calibrated. In conclusion, these validated assays for the evaluation of functional immune response and antibody titers following SARS-CoV-2 vaccination could provide a relatively simple standardized approach for accurately comparing immune responses to different vaccines and/or vaccination regimens.
Person- and Situation-Specific Factors in Discounting Science via Scientific Impotence Excuses

Munro (2010, https://doi.org/10.1111/j.1559-1816.2010.00588.x) found that individuals, when confronted with belief-disconfirming scientific evidence, resist this information by concluding that the topic at hand is not amenable to scientific investigation—a scientific impotence excuse. We strived to replicate this finding and to extend this work by analyzing other factors that might lead to scientific impotence excuses. As a person-specific factor, we analyzed the role of epistemic beliefs, and as a situational factor, we focused on the contradictoriness of the evidence at hand. Three sets of hypotheses were preregistered. In an experimental 2 × 3 online study drawing on a general population sample of N = 901 participants, we first assessed our participants’ prior beliefs on the effects of acupuncture versus massaging (pro acupuncture vs. no opinion). One experimental group then read fictitious empirical evidence claiming superiority of acupuncture, another group read evidence speaking against acupuncture, and a third group read conflicting evidence (i.e., a mix of pro- and contra-findings). Scientific impotence excuses were measured by a newly developed questionnaire. Our first hypothesis, which suggested that participants believing in the superiority of acupuncture would make stronger scientific impotence excuses when confronted with belief-disconfirming findings, was confirmed. A second hypothesis suggested that scientific impotence excuses would be stronger when individuals were confronted with evidence exhibiting a “nature” that contradicts their topic-specific epistemic beliefs. This hypothesis was partially supported. A third hypothesis suggested that individuals confronted with conflicting evidence would make stronger scientific impotence excuses, and this was again confirmed. Implications for theory and practice are discussed.
Genetic and environmental risk factors for reticular pseudodrusen in the EUGENDA study

Purpose The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD). Methods This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined. Results RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886. Conclusions RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.
Evaluation of tourism competitiveness and mechanisms of spatial differentiation in Xinjiang, China

Evaluation of tourism competitiveness is useful for measuring the level of regional tourism development. It is of great importance to understand the advantages and disadvantages of tourism development correctly and formulate corresponding development strategies. To investigate tourism competitiveness, this paper established an evaluation index system, including tourism development competitiveness, tourism resource competitiveness, and tourism-support competitiveness, for 14 prefectures and cities in Xinjiang in China. The characteristics and laws of spatial differentiation were analyzed. Factor analysis was applied to examine the spatial differentiation of regional tourism competitiveness. The results showed an obvious spatial differentiation in tourism competitiveness among the 14 prefectures and cities. In terms of development competitiveness, Yili and Urumqi constituted the spatial center, followed by Changji, Altay, and Ba Prefecture. As the provincial capital, Urumqi has political, economic, cultural, transportation, and geographic advantages, but its competitiveness is not prominent in terms of monopoly and efficiency. In terms of resource competitiveness, Yili is the core attraction, while Urumqi, Kashgar, Altay, and Ba Prefecture are dominant attractions. With respect to supporting competitiveness, Bo Prefecture has high value, followed by Urumqi City and Aksu. Hetian and Ke Prefecture have the lowest values. The comprehensive competitiveness of tourism is centered on Yili. Urumqi and Bo Prefecture are subcenters, and Changji, Altay, Ba Prefecture, Aksu, and Kashgar are characterized as multi-polar competition areas. Using the KMO and Bartlett’s sphericity tests, the cumulative contribution variance of the eigenvalues of the eight factors extracted by the maximum variance rotation method was found to be 92.714%. Socio-economic conditions, tourism resources, infrastructure construction, regional cultural influence, ecological environment carrying capacity, tertiary industry development, tourism service level, and living security system are the main driving factors affecting the spatial differentiation of tourism competitiveness in Xinjiang. Analyzing the spatial evolution characteristics and the driving factors of the regional tourism competitiveness in Xinjiang, this paper seeks to promote the optimal allocation of tourism production factors in the macro regional system, and provide theoretical guidance and an empirical basis for the comprehensive and harmonic development of regional tourism.
Evaluation of MYRF as a candidate gene for primary angle closure glaucoma

Purpose Primary angle-closure glaucoma (PACG) is a leading cause of blindness. Despite tremendous human effort and financial input, no definitive causative gene has been identified either through genome-wide association or Mendelian family studies. In the current study, novel candidate genes for PACG were investigated by studying the variants of nanophthalmos-associated genes. Methods A case-control study was conducted that included 45 PACG patients and 12 normal controls with short axial length (AL, less than 23.5 mm but more than 20.5 mm). Whole-exome sequencing (WES) was performed to screen the variants in previously identified nanophthalmos-associated genes, as well as other risk genes. Results The age range of the 45 PACG patients was 24 to 80 years, with an average AL of 21.87±0.65 mm (range: 20.54–23.45 mm) in the right eye and 21.89±0.64 mm (range 20.60–23.23 mm) in the left eye. Four novel myelin regulatory factor (MYRF) gene missense variants (p.G117S, p.H1057R, p.H230R, and p.R316C) were identified in four out of the 45 enrolled PACG patients, respectively. No MYRF or other nanophthalmos-associated gene variants were detected in the 12 normal controls. Conclusions An appropriate approach was adopted to investigate the genetics of PACG through nanophthalmos-associated genes. A genetic variant, MYRF, was identified in four out of 45 PACG patients, which might be a novel candidate gene for PACG.
Specific patterns of vital sign fluctuations predict infection and enable sepsis diagnosis in pediatric burn patients

Early recognition of the clinical signs of bloodstream infection in pediatric burn patients is key to improving survival rates in the burn unit. The objective of this study was to propose a simple scoring criteria that used readily available temperature, heart rate (HR) and mean arterial pressure (MAP) data to accurately predict bloodstream infection in pediatric burn patients. A retrospective chart review included 100 patients admitted to the pediatric burn unit for >20% total body surface area (TBSA) burn injuries. Each patient had multiple blood culture tests, and each test was treated as a separate and independent “infection event” for analysis. The time at each blood culture draw was time 0 for that event, and temperature, HR and MAP data was collected for 24 hours after the blood culture was drawn. “Infection events” included in this study had at least six complete sets of temperature, HR and MAP data entries. Median temperature, HR and MAP, as well as mean fever spikes, HR spikes and MAP dips, were compared between infection group (positive blood cultures) and control group (negative blood cultures). These vital sign fluctuations were evaluated individually and as a combination of all three as timely predictors of bloodstream infection. In addition, we tested the prediction of Gram-negative bacteria versus Gram-positive or fungi present in blood cultures. Patients in the infection group had significantly higher median temperatures (p<0.001), mean fever spikes (p<0.001) and mean HR spikes (p<0.001), compared to the control group. Using the combination scoring criteria to predict bloodstream infection, the strongest predictive values in the 24-hour timeframe had high sensitivity (93%) and specificity (81%). The predictive test metric based on vital sign spikes predicted Gram-negative bacteria, but with limited sensitivity (57%) and specificity (44%). A simple scoring criteria using a combination of fever spikes, HR spikes and MAP dips predicted bloodstream infection in pediatric burn patients, and can be feasibly implemented in routine clinical care. There is also potential to use the predictive metric to detect a few select organisms based on vital signs, however further work is necessary to enhance accuracy to levels that would allow consideration for clinical use.
Plasma and Vitreous Metabolomics Profiling of Proliferative Diabetic Retinopathy

Purpose To determine the differences of metabolites and metabolic pathways between patients with proliferative diabetic retinopathy (PDR) and without diabetes (nondiabetic controls) in plasma and vitreous, respectively, and to characterize the relationship between plasma and vitreous metabolic profiles. Methods Liquid chromatography/tandem mass spectrometry technology was performed to distinct metabolite profiles of plasma and vitreous. A total of 139 plasma samples from 88 patients with PDR and 51 nondiabetic controls, as well as 74 vitreous samples from 51 patients with PDR and 23 nondiabetic controls, were screened. Pathway analysis was performed using MetaboAnalyst 5.0. Pearson correlation analysis was used to investigate the correlation of metabolites in vitreous and plasma. Results After adjusting for age, fasting blood glucose, and urea, in vitreous metabolomes, a total of 76 features distinguished patients with PDR from controls. Fifteen differential metabolites were found in plasma metabolites. Pantothenate and CoA biosynthesis was the common metabolic pathway altered in both plasma and vitreous. Aromatic amino acid metabolism pathways were dysregulated in vitreous of PDR. For four metabolic features, there were positive correlations between vitreous and plasma. Conclusions Despite great differences between the metabolic profiles of plasma and vitreous in PDR cases, there are also similarities in the change of metabolites and metabolic pathways. Exploring the relationship of metabolomics between vitreous and plasma may help provide new understanding of the mechanism of PDR.
Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy

ABSTRACT Objectives: Lycium barbarum polysaccharide (LBP) is a natural polysaccharide extracted from Lycium barbarum that has anti-inflammatory, anti-apoptotic and anti-aging effects, and plays a role in the prevention and treatment of various diseases. In this study, we investigated the therapeutic effect of LBP on particulate matter 2.5 (PM2.5)-induced skin damage. Methods: Cell viability was analyzed by MTT and LDH assays. Apoptosis was analyzed by Annexin V-FITC/PI staining. Oxidative stress/damage were assessed by intracellular ROS levels, MDA content and SOD activity. The intracellular protein expression was analyzed by Western blot. Mitochondrial damage was assayed by mitochondrial membrane potential with JC-1 probe. LC3-GFP adenovirus was transfected into HaCaT cells to analyze intracellular autophagosome levels. Results: In PM2.5-treated HaCaT cells, LBP pretreatment reduced PM2.5-induced cytotoxicity, ameliorated cell morphology and reduced cell apoptosis. LBP also inhibited the expression levels of GRP78 and CHOP, reduced the conversion of LC3I to LC3II, inhibited Bax protein and activated Bcl-2 protein. Furthermore, LBP inhibited PM2.5-induced mitochondrial autophagy (mitophagy) and mitochondrial damage. PM2.5-induced autophagy was regulated by endoplasmic reticulum (ER) stress. Conclusion: LBP protects skin cells from PM2.5-induced cytotoxicity by regulating the oxidative stress-ER stress-autophagy-apoptosis signaling axis, revealing that LBP has a great potential for the skin protection. GRAPHICAL ABSTRACT
Compensatory intestinal antibody response against pro-inflammatory microbiota after bariatric surgery

ABSTRACT Obesity and type 2 diabetes (T2D) are growing burdens for individuals and the health-care system. Bariatric surgery is an efficient, but drastic treatment to reduce body weight, normalize glucose values, and reduce low-grade inflammation. The gut microbiome, which is in part controlled by intestinal antibodies, such as IgA, is involved in the development of both conditions. Knowledge of the effect of bariatric surgery on systemic and intestinal antibody response is limited. Here, we determined the fecal antibody and gut microbiome response in 40 T2D and non-diabetic (ND) obese individuals that underwent bariatric surgery (N = 40). Body weight, fasting glucose concentrations and inflammatory parameters decreased after bariatric surgery, whereas pro-inflammatory bacterial species such as lipopolysaccharide (LPS), and flagellin increased in the feces. Simultaneously, concentrations of LPS- and flagellin-specific intestinal IgA levels increased with the majority of pro-inflammatory bacteria coated with IgA after surgery. Finally, serum antibodies decreased in both groups, along with a lower inflammatory tone. We conclude that intestinal rearrangement by bariatric surgery leads to expansion of typical pro-inflammatory bacteria, which may be compensated by an improved antibody response. Although further evidence and mechanistic insights are needed, we postulate that this apparent compensatory antibody response might help to reduce systemic inflammation by neutralizing intestinal immunogenic components and thereby enhance intestinal barrier function after bariatric surgery.
Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis

Translesion DNA synthesis (TLS) is a fundamental damage bypass pathway that utilises specialised polymerases with relaxed template specificity to achieve replication through damaged DNA. Misinsertions by low fidelity TLS polymerases may introduce additional mutations on undamaged DNA near the original lesion site, which we termed collateral mutations. In this study, we used whole genome sequencing datasets of chicken DT40 and several human cell lines to obtain evidence for collateral mutagenesis in higher eukaryotes. We found that cisplatin and UVC radiation frequently induce close mutation pairs within 25 base pairs that consist of an adduct-associated primary and a downstream collateral mutation, and genetically linked their formation to TLS activity involving PCNA ubiquitylation and polymerase κ. PCNA ubiquitylation was also indispensable for close mutation pairs observed amongst spontaneously arising base substitutions in cell lines with disrupted homologous recombination. Collateral mutation pairs were also found in melanoma genomes with evidence of UV exposure. We showed that collateral mutations frequently copy the upstream base, and extracted a base substitution signature that describes collateral mutagenesis in the presented dataset regardless of the primary mutagenic process. Using this mutation signature, we showed that collateral mutagenesis creates approximately 10–20% of non-paired substitutions as well, underscoring the importance of the process.
Coat score. A possible explanation for the zebuine selective sweep located on bovine chromosome 5: 47,670,001–48,100,000 bp

Abstract Over 65% of the world's cattle population resides in warm areas where heat stress conditions limit the breed of European taurine cattle. Composite breeds were developed to retain the main traits of both parental breeds. The skin plays a central role in animal response to heat stress. Research on the genetic architecture of skin traits has identified genes and regions related to warm resistance skin features. The aim of this study was to determine whether the indicine proportion accounted for coat type or whether there were genes of large effect segregating in Brangus. Bulls (n = 108) were genotyped using microarrays and their coat score and hair length were evaluated. Indicine-taurine genome-wide composition was estimated and GWAS was performed. Although significant correlations between indicine proportion and traits were not observed, four windows of SNPs on BTA4 and BTA5 explained more than 2% of the trait variance. The GWAS for coat score in summer showed the main peak on BTA5:46,941,446–48,030,219 bp, accounting for 4.65% of the variance. Our results suggest that the variation in coat score and undercoat hair length in Argentinian Brangus bulls is associated with the presence of some particular gene variants, rather than with the whole indicine genetic content.