Miracle-dz/UniFAR-FTUs huggingface dataset:
Sepsis is an important healthcare burden in Latin America: a call to action!

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The precise incidence of sepsis is unknown and there is a lack of populational studies on the disease, especially from low and middle-income countries. However, extrapolations of populational data from high-income countries suggest a number of 30 million sepsis cases annually worldwide with approximately 6 million deaths. (1) In Latin-American (LATAM) countries, the few available studies also suggest that sepsis represents a significant healthcare issue. A previous study from Brazil demonstrated that infection-associated organ dysfunction was related to up to 22% of all deaths in the country in 2010. (2) In Brazilian intensive care units (ICUs), sepsis prevalence is 30% and hospital mortality rate for ICU patients is 55%. (3) Studies from Colombia and Argentina also reported mortality rates for septic shock ranging from 45.6% to 51%. (4,5) Reasons for this significant burden of sepsis may include areas with inadequate provision of clean water, sanitation and nutrition, inadequate vaccination, as well as reduced awareness of sepsis among lay people and healthcare personnel, low access to intensive care services and an increased incidence of healthcare-associated infections. (6) In order to tackle the burden of sepsis worldwide, in 2012 the Global Sepsis Alliance (GSA) created the first World Sepsis Day (WSD) as a launch platform for the World Sepsis Declaration. The purposes of WSD are to increase the perception of sepsis importance among lay public, healthcare workers and policy makers and to encourage quality improvement programs for sepsis early identification and treatment. Since then, initiatives to improve sepsis awareness have increased worldwide with events for lay public, healthcare staff and policy makers. These initiatives have culminated with the approval on May 26th, 2017 of a sepsis resolution (WHA70.7) by the World Health Organization (WHO). (7) The WHO resolution recognizes sepsis as a major threat to patient safety and global health and urges the member states to start initiatives to improve sepsis prevention, recognition and treatment. This resolution has the potential to save millions of lives, however for that happening it requires coordinated efforts by politicians, policymakers, health care administrators, researchers, and clinicians working in all health care settings. (8) Also, regional alliances may be important in the sepsis agenda in order to foster collaboration between countries with similarities and improve coordinated regional advocacy as compared to single countries alone. As such, in May 30th 2018, the Instituto Latino Americano de Sepse (ILAS) organized a meeting for representatives of LATAM countries. This meeting was supported by the Instituto Latino Americano de Sepse Board1 (Collaborators: Luciano Cesar Pontes Azevedo, Alexandre Biasi Cavalcanti, Thiago Lisboa, Felipe Dal Pizzol, Flavia Ribeiro Machado).
IL-6 Signaling Blockade during CD40-Mediated Immune Activation Favors Antitumor Factors by Reducing TGF-β, Collagen Type I, and PD-L1/PD-1

IL-6 plays a role in cancer pathogenesis via its connection to proteins involved in the formation of desmoplastic stroma and to immunosuppression by driving differentiation of myeloid suppressor cells together with TGF-β. Inhibition of IL-6 signaling in the tumor microenvironment may, thus, limit desmoplasia and myeloid suppressor cell differentiation. CD40 signaling can further revert myeloid cell differentiation toward antitumor active phenotypes. Hence, the simultaneous use of IL-6 blockade with CD40 stimuli may tilt the tumor microenvironment to promote antitumor immune responses. In this paper, we evaluated the mechanisms of LOAd713, an oncolytic adenovirus designed to block IL-6R signaling and to provide myeloid cell activation via a trimerized membrane-bound isoleucine zipper (TMZ) CD40L. LOAd713-infected pancreatic cancer cells were killed by oncolysis, whereas infection of stellate cells reduced factors involved in stroma formation, including TGF-β-1 and collagen type I. Virus infection prevented IL-6/GM-CSF–mediated differentiation of myeloid suppressors, but not CD163 macrophages, whereas infection of dendritic cells led to upregulation of maturation markers, including CD83, CD86, IL-12p70, and IFN-γ. Further, IL-6R blockade prevented upregulation of programed death ligand 1 (PD-L1) and PD-1 on the stimulated dendritic cells. These results suggest that LOAd713 can kill infected tumor cells and has the capacity to affect the tumor microenvironment by stimulating stellate cells and myeloid suppressors with TMZ-CD40L and IL-6R blockade. Gene transfer of murine TMZ-CD40L prolonged survival in an animal model. LOAd713 may be an interesting therapeutic option for cancers connected to IL-6 signaling, such as pancreatic cancer.
SHNN-CAD+: An Improvement on SHNN-CAD for Adaptive Online Trajectory Anomaly Detection

To perform anomaly detection for trajectory data, we study the Sequential Hausdorff Nearest-Neighbor Conformal Anomaly Detector (SHNN-CAD) approach, and propose an enhanced version called SHNN-CAD+. SHNN-CAD was introduced based on the theory of conformal prediction dealing with the problem of online detection. Unlike most related approaches requiring several not intuitive parameters, SHNN-CAD has the advantage of being parameter-light which enables the easy reproduction of experiments. We propose to adaptively determine the anomaly threshold during the online detection procedure instead of predefining it without any prior knowledge, which makes the algorithm more usable in practical applications. We present a modified Hausdorff distance measure that takes into account the direction difference and also reduces the computational complexity. In addition, the anomaly detection is more flexible and accurate via a re-do strategy. Extensive experiments on both real-world and synthetic data show that SHNN-CAD+ outperforms SHNN-CAD with regard to accuracy and running time.
Voltage-Dependent Membrane Properties Shape the Size But Not the Frequency Content of Spontaneous Voltage Fluctuations in Layer 2/3 Somatosensory Cortex

Under awake and idling conditions, spontaneous intracellular membrane voltage is characterized by large, synchronous, low-frequency fluctuations. Although these properties reflect correlations in synaptic inputs, intrinsic membrane properties often indicate voltage-dependent changes in membrane resistance and time constant values that can amplify and help to generate low-frequency voltage fluctuations. The specific contribution of intrinsic and synaptic factors to the generation of spontaneous fluctuations, however, remains poorly understood. Using visually guided intracellular recordings of somatosensory layer 2/3 pyramidal cells and interneurons in awake male and female mice, we measured the spectrum and size of voltage fluctuation and intrinsic cellular properties at different voltages. In both cell types, depolarizing neurons increased the size of voltage fluctuations. Amplitude changes scaled with voltage-dependent changes in membrane input resistance. Because of the small membrane time constants observed in both pyramidal cells and interneuron cell bodies, the low-frequency content of membrane fluctuations reflects correlations in the synaptic current inputs rather than significant filtering associated with membrane capacitance. Further, blocking synaptic inputs minimally altered somatic membrane resistance and time constant values. Overall, these results indicate that spontaneous synaptic inputs generate a low-conductance state in which the amplitude, but not frequency structure, is influenced by intrinsic membrane properties. SIGNIFICANCE STATEMENT In the absence of sensory drive, cortical activity in awake animals is associated with self-generated and seemingly random membrane voltage fluctuations characterized by large amplitude and low frequency. Partially, these properties reflect correlations in synaptic input. Nonetheless, neurons express voltage-dependent intrinsic properties that can potentially influence the amplitude and frequency of spontaneous activity. Using visually guided intracellular recordings of cortical neurons in awake mice, we measured the voltage dependence of spontaneous voltage fluctuations and intrinsic membrane properties. We show that voltage-dependent changes in membrane resistance amplify synaptic activity, whereas the frequency of voltage fluctuations reflects correlations in synaptic inputs. Last, synaptic activity has a small impact on intrinsic membrane properties in both pyramidal cells and interneurons.
Socioeconomic Inequalities in Adolescent Substance Use: Evidence From Twenty-Four European Countries

Abstract Background: While there is evidence for socioeconomic inequalities in some adolescent substance use behaviors, there is limited information on how socioeconomic inequalities compare across European countries and over time. Objectives: To compare socioeconomic inequalities in problematic adolescent substance use (regular smoking, heavy episodic drinking, and cannabis use) across 24 European countries at two time points. Methods: We use the European School Survey Project on Alcohol and Other Drugs (ESPAD) to examine socioeconomic inequalities in problematic adolescent substance use across 24 European countries in 2007 (n = 73,877) and 2011 (n = 71,060) using within country logistic regressions. Socioeconomic inequalities are measured using a relative index of inequality based on highest level of parental education relative to country of residence within survey year. Countries are ranked according to socioeconomic differentials. Results: In 2007, lower socioeconomic status (SES) adolescents had significantly higher odds of heavy episodic drinking in 10 countries, regular smoking in 12 countries, and recent cannabis use in 1 country. In 2011, the number of countries were 11, 15, and 0, respectively. In 2007, lower SES adolescents had a significantly lower odds of heavy episodic drinking in one country, regular smoking in one country, and cannabis use in four countries. In 2011, the number of countries were two, one, and six, respectively. There was little evidence for changes in socioeconomic inequalities over time. Conclusions: There are large country level differences in socioeconomic inequalities in adolescent substance use.
Does Emotional Intelligence Predict Athletes’ Motivation to Participate in Sports?

The relationship between emotional intelligence (EI) and successful athletic performance has been previously recognized, but there remains a need to investigate how EI impacts athletes’ sports motivation. This cross-sectional study investigated how different EI dimensions related to athletes’ motivation among 239 adult basketball players (129 females) aged 18-34 years. Our research participants completed questionnaires that included the self-reported Emotional Intelligence Scale and Sport Motivation Scale II. We found significant correlations between total EI and intrinsic, integrated, identified, and introjected regulation. Higher EI was negatively related to athletes’ amotivation. More specifically, the self-reported abilities to perceive emotion and manage others’ emotions were significantly related to intrinsic, integrated, and identified regulation, and only managing one’s own emotions negatively related to athletes’ amotivation.
The Use of the Exoscope in Lateral Skull Base Surgery: Advantages and Limitations.

OBJECTIVE We describe our experience using the extracorporeal video microscope, the "exoscope" for various applications within the field of lateral skull base surgery. STUDY DESIGN A retrospective case series was performed investigating patient demographics, indications for surgery, procedure type, operative time, approach to the skull base, complications, adequacy of visualization, and surgeon comfortability. PATIENTS Six cases were performed with a three dimensional surgical exoscope, obviating the use of a traditional binocular microscope. SETTING Academic, tertiary referral center. MAIN OUTCOME MEASURES Type of surgical approach, operative time, patient demographics, surgical complications, and surgeon comfortability. RESULTS The following procedures were performed; four vestibular schwannoma resections via suboccipital craniotomy and two combined transmastoid and transtemporal approaches for temporal lobe encephalocele repairs. The average operative time was 227 and 577 minutes for temporal lobe encephalocele repairs and vestibular schwannoma cases, respectively. No intraoperative complications were encountered during these cases. None of the procedures required abandonment of the exoscope in favor of the microscope during the procedure. Advantages include high-resolution three-dimensional visualization, increased degrees of freedom for exoscope adjustment, and reduced surgeon fatigue in a fixed, unnatural posture. Limitations include decreased depth perception and increased operative time. CONCLUSION The exoscope system is a safe and effective alternative or adjunct to the existing binocular operating microscope for lateral skull based procedures. The exoscope provides the surgeon with a comfortable, high-resolution visualization without compromising surgical exposure and patient safety. LEVEL OF EVIDENCE 4.
Fast Cross-Validation for Kernel-Based Algorithms

Cross-validation (CV) is a widely adopted approach for selecting the optimal model. However, the computation of empirical cross-validation error (CVE) has high complexity due to multiple times of learner training. In this paper, we develop a novel approximation theory of CVE and present an approximate approach to CV based on the Bouligand influence function (BIF) for kernel-based algorithms. We first represent the BIF and higher order BIFs in Taylor expansions, and approximate CV via the Taylor expansions. We then derive an upper bound of the discrepancy between the original and approximate CV. Furthermore, we provide a novel computing method to calculate the BIF for general distribution, and evaluate BIF criterion for sample distribution to approximate CV. The proposed approximate CV requires training on the full data set only once and is suitable for a wide variety of kernel-based algorithms. Experimental results demonstrate that the proposed approximate CV is sound and effective.
Partial Characterization, the Immune Modulation and Anticancer Activities of Sulfated Polysaccharides from Filamentous Microalgae Tribonema sp.

Recently, Tribonema sp. , a kind of filamentous microalgae, has been studied for biofuel production due to its accumulation of triacylglycerols. However, the polysaccharides of Tribonema sp. and their biological activities have rarely been reported. In this paper, we extracted sulfated polysaccharides from Tribonema sp. (TSP), characterized their chemical composition and structure, and determined their immunostimulation and anticancer activities on RAW264.7 macrophage cells and HepG2 cells. The results showed that TSP is a sulfated polysaccharide with a Mw of 197 kDa. TSP is a heteropolysaccharide that is composed mainly of galactose. It showed significant immune-modulatory activity by stimulating macrophage cells, such as upregulating interleukin 6 (IL-6), interleukin 10 (IL-10), and tumor necrosis factor α (TNF-α). In addition, TSP also showed significant dose-dependent anticancer activity (with an inhibition rate of up to 66.8% at 250 µg/mL) on HepG2 cells as determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cycle analysis indicated that the anticancer activity of TSP is mainly the result of induced cell apoptosis rather than affecting the cell cycle and mitosis of HepG2 cells. These findings suggest that TSP might have potential as an anticancer resource, but further research is needed, especially in vivo experiments, to explore the anticancer mechanism of TSP.
The Chang Gung Research Database—A multi‐institutional electronic medical records database for real‐world epidemiological studies in Taiwan

The Chang Gung Research Database (CGRD), the largest multi‐institutional electronic medical records (EMR) collection in Taiwan, provides good access for researchers to efficiently use the standardized patient‐level data. This study evaluates the capacity and representativeness of the CGRD to promote secondary use of EMR data for clinical research with more accurate estimates.
Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor–related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation.
Dissemination of Imidacloprid Through Dairy Cattle Manure and Its Effect on the Biological Control Agent, Spalangia endius (Hymenoptera: Pteromalidae), and a Filth Fly Host, Musca domestica (Diptera: Muscidae).

Filth flies, including house flies, Musca domestica L. , develop in animal manure. Adult house flies often are controlled with pesticides such as imidacloprid. How imidacloprid disseminates and persists after it contaminates manure was measured at a dairy farm. A week after application of imidacloprid via fly bait to cattle manure, a mean of approximately 4 ppm of imidacloprid, and as high as 15 ppm, was quantifiable up to 12 cm from the application site, but not farther. Laboratory experiments addressed the impact of 15 ppm of imidacloprid in manure on egg-to-adult development of house flies and on the biological control ability of a house fly pupal parasitoid, Spalangia endius Walker. In uncontaminated manure, 93% of eggs developed to adults, versus 7% in contaminated manure. In the parasitoid experiment, fly pupae were placed in contaminated or uncontaminated manure with or without S. endius. In the absence of S. endius, nearly 100% of flies emerged, with or without imidacloprid. In the presence of S. endius, only 11% of flies emerged from uncontaminated manure, versus 36% from contaminated manure; and parasitoids emerged from 82% of hosts in uncontaminated manure versus 53% in contaminated manure. These results suggest that realistic concentrations of imidacloprid in filth fly breeding habitat may interfere with house flies developing to the pupal stage, but also with parasitoids locating and utilizing house flies. However, after 1 wk, the effects on parasitoids will be low 12 cm beyond where bait was applied.
Effect of Scanning Routes on the Stress and Deformation of Overhang Structures Fabricated by SLM

Selective laser melting (SLM) is a promising manufacturing method for the construction of complicated precision parts. However, deformation of the overhang during the fabrication process and post treatment is still a common problem. In this paper, the effect of the scanning route on the residual stress and deformation of fabricated AlSi10Mg overhang specimens by SLM was investigated. Different scanning routes for the overhang including longitudinal direction, transverse direction, and the alternation between these two scanning routes in consecutive layers were studied by experiments within this study. Numerical simulation was utilized to measure the stress of the specimens while deformation prediction was used for the different scanning routes. Both the experimental and simulated results showed that the scanning route had a substantial influence on the residual stress and deformation of the specimens. The longitudinal scanning resulted in significant upward bending deformation of the overhang as it was cut from the baseplate. However, there was less deformation for the overhangs fabricated by transverse and alternating scanning routes. A transverse scanning route is helpful for the reduction of residual stress in the longitudinal direction and the corresponding deformation.
Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study

Introduction: Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid–femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. Methods: We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ± 7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by −1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. Results: Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: −0.04 (−0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (−0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. Conclusion: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.