Miracle-dz/UniFAR-FTUs huggingface dataset:
Synaptic Scaling Enables Dynamically Distinct Short- and Long-Term Memory Formation

Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling – a slow process usually associated with the maintenance of activity homeostasis – combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.
Incidence, Risk Factors, Microbiology and Outcomes of Pre-engraftment Bloodstream Infection After Haploidentical Hematopoietic Stem Cell Transplantation and Comparison With HLA-identical Sibling Transplantation.

Background Bloodstream infection (BSI) is a common and serious complication after hematopoietic stem cell transplantation (HSCT). An investigation of the characteristics of pre-engraftment BSI after haploidentical HSCT compared with human leukocyte antigen (HLA)-identical sibling HSCT has not been conducted. Methods A single-center cohort representing 1847 consecutive patients undergoing haploidentical or HLA-identical sibling HSCT from 2013 to 2016 was selected. We investigated the characteristics of pre-engraftment BSI after haploidentical HSCT and its impact on patient outcome, and we compared it with HLA-identical sibling HSCT. Results After haploidentical HSCT, the cumulative incidence of pre-engraftment BSI was higher (30-day: 9.2% [7.6, 10.8] vs 1.7% [0.5, 2.9], P < .0001) and median onset of BSI was earlier (day +3 vs day +9, P = .001) than HLA-identical sibling HSCT. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci were the most common isolates after haploidentical HSCT. However, Enterococcus faecium was the most common isolate after HLA-identical sibling HSCT. A multivariate analysis suggested that variables associated with BSI after haploidentical HSCT included a diagnosis of myelodysplastic syndrome (MDS), an interval from diagnosis to HSCT ≥190 days, carbapenem therapy, and grade 3-4 intestinal mucositis. The same variables, except MDS, were also associated with BSI after HLA-identical sibling HSCT. The multivariate analysis also suggested that BSI was a risk factor for increased all-cause mortality at 3 months after haploidentical HSCT (hazard ratio = 2.281; 95% confidence interval: 1.334, 3.900; P = .003). Conclusions Pre-engraftment BSI was more common after haploidentical HSCT than HLA-identical sibling HSCT. It was an independent factor associated with increased all-cause mortality at 3 months after haploidentical HSCT.
Variables Influencing the Accuracy of 3D Modeling of Existing Roads Using Consumer Cameras in Aerial Photogrammetry

Point cloud (PC) generation from photogrammetry–remotely piloted aircraft systems (RPAS) at high spatial and temporal resolution and accuracy is of increasing importance for many applications. For several years, photogrammetry–RPAS has been used to recover civil engineering works such as digital elevation models (DEMs), triangle irregular networks (TINs), contour levels, orthophotographs, etc. This study analyzes the influence of variables involved in the accuracy of PC generation over asphalt shapes and determines the most influential variable based on the development of an artificial neural network (ANN) with patterns identified in the test flights. The input variables were those involved, and output was the three-dimension root mean square error (3D-RMSE) of the PC in each ground control point (GCP). The result of the study shows that the most influential variable over PC accuracy is the modulation transfer function 50 (MTF50). In addition, the study obtained an average 3D-RMSE of 1 cm. The results can be used by the scientific and civil engineering communities to consider MTF50 variables in obtaining images from RPAS cameras and to predict the accuracy of a PC over asphalt based on the ANN developed. Also, this ANN could be the beginning of a large database containing patterns from several cameras and lenses in the world market.
Visitors’ Perceived Place Value and the Willingness to Pay in an Urban Lake Park

As highly developed nature, an urban lake park will be a place required to integrate various functions such as health promotion, recreation, and cultural exchange by focusing on ecological aspects. We applied latent profile analysis (LPA) to identify latent classes based on visitors’ perceived place value, and to estimate the willingness to pay (WTP) by these classifications. Park visitors were classified according to place value into three groups: Local Seekers (LS), Ecology Seekers (ES), and Recreation Seekers (RS). To compare the WTP of the three groups and examine differences in attributes between the groups, we used a choice experiment (CE). The results from the CE revealed that the WTP for attributes was ranked in the order of basic infrastructure, advanced services, and ecological activities. These differences in the WTP of visitors in an urban lake park may be useful for park management, such as providing strategies for zoning and ecotourism, which is specialized by visitor type.
Developmental effects of neonatal fractionated co‐exposure to low‐dose gamma radiation and paraquat on behaviour in adult mice

Radiological methods for screening, diagnostics and therapy are often used in healthcare; however, it has recently been reported that developmental exposure to low‐dose ionizing radiation (IR) causes neurotoxicity. Environmental chemicals also have the potential to affect the developing brain and the concomitant effects caused by IR and chemicals are of high interest today. We therefore aim to investigate if low‐dose IR can interact with the known neurotoxicant paraquat to induce neurotoxicity in the neonatal mouse model. Using the same model, we also aim to investigate if fractionated low‐dose IR can be as neurotoxic as higher acute doses. Male mice were exposed to a single dose of paraquat (0.2 or 0.02 mg/kg) on postnatal day 10 and 11. Two hours following paraquat exposure, mice were whole body irradiated with 100 or 300 mGy gamma radiation (137Cs). Behavioural observations were performed at 2 and 3 months of age. Following behavioural testing, we evaluated striatal dopaminergic gene transcription. Animals co‐exposed to IR and paraquat generally displayed altered spontaneous behaviour compared to controls and single agent exposed mice. Stronger effects by combined exposure were also observed on adult memory and learning. However, dopaminergic gene transcript levels remained unchanged by treatment. Co‐exposure to low‐dose IR and paraquat can interact to exacerbate neurotoxic effects and to impair cognitive function. Furthermore, fractionation of the radiation dose was observed to be as potent as higher acute exposure for induction of developmental neurotoxicity.
Factors Associated with Cervical Cancer Screening among Married Female Immigrants with Korean Husbands in South Korea

Background. The purpose of this study was to identify factors associated with the national cervical cancer screening behaviors of married female immigrants living in South Korea. Methods. The present study dataset was collected by the National Health Insurance Services in 2014–2015. A final study population of 15,935 was considered eligible for inclusion in this study if they met the criteria for participation in the national cervical cancer screening program in 2014–2015. Results. Of the 15,935 subjects, 7837 (49%) participated in cervical cancer screening. Based on the results of the logistic regression analysis of the association between cervical cancer screening behaviors and related factors, the odds ratio (OR) for participation in cervical cancer screening among individuals older than 50 years was the highest (OR: 2.13; 95% confidence interval (CI): 1.82–2.51), and the OR increased as their duration of stay in South Korea decreased. The OR of Chinese women for cervical cancer screening participation was higher than that of non-Chinese women (OR: 1.83; 95% CI: 1.69–1.99). The OR value was 29.4 (95% CI: 25.9–33.3) among those who participated in the general health screening compared with those who did not participate. Conclusions. To improve awareness about cervical cancer screening and reduce disparities in access to healthcare, appropriate programs should be developed to promote cervical cancer screening participation to socially vulnerable classes. Continuous social attention is needed to address these issues and encourage participation in general health screening to improve the rate of cervical cancer screening.
A Prospective Multicenter Clinical Observational Study on Vancomycin Efficiency and Safety With Therapeutic Drug Monitoring.

Background Vancomycin is a first-line antibiotic used for the treatment of severe gram-positive bacterial infections. Clinical guidelines recommend that the vancomycin trough concentration be 10-15 mg/L for regular infections and 15-20 mg/L for severe infections. We investigated whether increasing the vancomycin concentration would result in better clinical outcomes with sustainable adverse effects (AEs) in the Chinese population. Methods A prospective, open, multicenter clinical observational study was performed in patients with gram-positive bacterial infections from 13 teaching hospitals. Patients received vancomycin therapeutic drug monitoring. Clinical, microbiological, and laboratory data were collected. Results In total, 510 patients were enrolled, and 470 were evaluable, of whom 370 were adults and 100 were children; 35.53% had methicillin-resistant Staphylococcus aureus infections (vancomycin 50% minimum inhibitory concentration [MIC50] = 1, 90% minimum inhibitory concentration [MIC90] = 1), and 23.19% had Enterococcus species infections (vancomycin MIC50 = 1, MIC90 = 2). The average trough concentration was 10.54 ± 8.08 mg/L in adults and 6.74 ± 8.93 mg/L in children. The infection was eradicated in 86.22% of adults and 96% of children. Thirty-six vancomycin-related nephrotoxicity cases were reported in the enrolled population. No severe AEs or deaths were related to vancomycin therapy. Logistic regression analysis showed that trough concentration had no relationship with clinical outcomes (adults P = .75, children P = .68) but was correlated with adult nephrotoxicity (P < .0001). Vancomycin trough concentration had an applicable cut point at 13 mg/L. Conclusions Our study shows that vancomycin trough concentration has no statistical correlation with clinical outcomes, and is an indicator of nephrotoxicity in the observed population. We found no evidence that increasing vancomycin trough concentration to 15-20 mg/L can benefit Chinese patients with complicated infections. Clinical Trials Registration ChiCTR-OPC-16007920.
Effects of Moderate Ethanol Consumption on Lipid Metabolism and Inflammation Through Regulation of Gene Expression in Rats

Aims Epidemiological studies and experimental data from rodent models have reported a non-linear relationship between consumption of alcohol and cardiovascular disease (CVD) risk that suggests that light-to-moderate drinking as opposed to excessive consumption may provide some cardiovascular benefits. The present study examined potential mechanisms by which moderate alcohol consumption may provide a protective effect against CVD. Short summary Wistar rats exposed for 3 months to a 20% ethanol intermittent-access voluntary drinking paradigm displayed a reduction in epididymal fat, blood glucose and non-HDL and total cholesterol. These effects were accompanied by decreased expression of Hmgcr, Srebp-2, Cox-2 and RelA, indicating downregulation of genes involved in cholesterol synthesis and inflammation. Methods Twenty-four male Wistar rats voluntarily consumed a 20% v/v ethanol solution on alternate days for 13 weeks (ethanol-treated) or were given access to water alone (non-ethanol-exposed control). Results There was no difference in body weight gain between the two groups, however, epididymal fat weight was lower in ethanol-fed rats (P = 0.030). Blood glucose, total cholesterol, non-high-density lipoprotein (HDL) and oxidized low-density lipoprotein (LDL) levels were lower in the ethanol group compared to controls (P < 0.05). There was a significant reduction in the expression of hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 in ethanol-treated rats (P < 0.05), suggesting that ethanol may have lowered cholesterol levels via downregulation of genes involved in cholesterol synthesis. Paraoxonase-1, which is associated with inhibition of LDL cholesterol oxidation, was upregulated in the ethanol group (P = 0.029). Ethanol-treated rats exhibited significantly lower levels of high-mobility box group protein 1 (P ≤ 0.05). Cyclooxygenase-2 and RelA gene expression were significantly lower in ethanol-treated rats (P < 0.05), indicating possible anti-inflammatory effects. Conclusions These findings suggest that moderate ethanol consumption may potentially contribute to improved cardiovascular outcomes by reducing body fat, improving blood cholesterol and blood glucose, and modulation of gene expression involved in inflammation and/or cholesterol synthesis.
Effects of Neonatal Stress on Ovarian Follicular Reserve and Initial Follicular Waves in Rats

The study tested the hypothesis that stress experienced during neonatal life alters follicular reserve and onset of initial follicular waves. Rat pups immediately after their birth (postnatal day 1) were randomly segregated into three groups and the first group pups were autopsied on postnatal day 1, second group served as controls and those in third group were exposed to a stressor (maternal separation 6 hours/ day) from postnatal day 1 to 3. Five pups in control and stress group were autopsied on postnatal day 4, 6 and 8. There was a significant increase in blood corticosterone level in stressed rats on postnatal day 4. Neonatal stress did not delay the timing of folliculogenesis and onset of initial follicular waves. However, mean number of oocytes, primordial and primary follicles on postnatal day 4, 6 and 8 was significantly lower in stressed rats compared to controls. Reduction in follicular number was due to increased rate of atresia which was assessed by TUNEL and caspase-3 assay. The results, for the first time, reveal that neo-natal stress has dire consequence as it reduces the number of oocytes and primordial follicles (follicular reserve) which might curtail the reproductive lifespan of neo-natally stressed rats
Designed Elastic Networks: Models of Complex Protein Machinery

Recently, the design of mechanical networks with protein-inspired responses has become increasingly popular. Here, we review contributions which were motivated by studies of protein dynamics employing coarse-grained elastic network models. First, the concept of evolutionary optimization that we developed to design network structures which execute prescribed tasks is explained. We then review what presumably marks the origin of the idea to design complex functional networks which encode protein-inspired behavior, namely the design of an elastic network structure which emulates the cycles of ATP-powered conformational motion in protein machines. Two recent applications are reviewed. First, the construction of a model molecular motor, whose operation incorporates both the tight coupling power stroke as well as the loose coupling Brownian ratchet mechanism, is discussed. Second, the evolutionary design of network structures which encode optimal long-range communication between remote sites and represent mechanical models of allosteric proteins is presented. We discuss the prospects of designed protein-mimicking elastic networks as model systems to elucidate the design principles and functional signatures underlying the operation of complex protein machinery.
MRI bone marrow oedema precedes lumbar bone stress injury diagnosis in junior elite cricket fast bowlers

Objectives Lumbar bone stress injury (‘bone stress injury’) is common in junior fast bowlers. The repetitive loading of cricket fast bowling may cause bone marrow oedema (BMO), detectable on MRI, before the bowler suffers from symptomatic bone stress injury. We investigated the temporal relationship between BMO, bone stress injury, along with bowling workload correlates, in elite junior fast bowlers throughout a cricket season. Methods 65 junior fast bowlers were prospectively monitored for one 8-month cricket season. For research purposes, participants had up to six MRI scans at set times in the season; findings were withheld from them and their clinicians. Standard practices for bowling workload monitoring and injury diagnosis were followed. Results 15 (23%) participants developed bone stress injury during the study. All 15 of these participants had BMO detected on at least one of the preceding MRI scans, including the scan immediately prior to diagnosis. The risk of BMO progressing to bone stress injury during the season was greatest for participants with BMO present 2 weeks prior to the national championship tournament (period of high load) (RR=18.9, OR=44.8). Both bone stress injury and BMO were associated with bowling a higher percentage of days in training and having a shorter bowling break during the season. The number of balls bowled and acute-to-chronic workload were not associated with imaging abnormalities or injury. Conclusion The presence of BMO on MRI in asymptomatic junior cricket fast bowlers confers a very high risk for bone stress injury. The risk may be managed by MRI screening and monitoring bowling frequency.
Evaluating GANs via Duality

Generative Adversarial Networks (GANs) have shown great results in accurately modeling complex distributions, but their training is known to be difficult due to instabilities caused by a challenging minimax optimization problem. This is especially troublesome given the lack of an evaluation metric that can reliably detect non-convergent behaviors. We leverage the notion of duality gap from game theory in order to propose a novel convergence metric for GANs that has low computational cost. We verify the validity of the proposed metric for various test scenarios commonly used in the literature.
The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most challenging lethal tumors and has a very poor prognosis. In addition to cancer cells, the tumor microenvironment created by a repertoire of resident and recruited cells and the extracellular matrix also contribute to the acquisition of hallmarks of cancer. Among these factors, cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. CAFs originate from the activation of resident fibroblasts and pancreatic stellate cells, the differentiation of bone marrow-derived mesenchymal stem cells and epithelial-to-mesenchymal transition. CAFs acquire an activated phenotype via various cytokines and promote tumor proliferation and growth, accelerate invasion and metastasis, induce angiogenesis, promote inflammation and immune destruction, regulate tumor metabolism, and induce chemoresistance; these factors contribute to the acquisition of major hallmarks of PDAC. Therefore, an improved understanding of the impact of CAFs on the major hallmarks of PDAC will highlight the diagnostic and therapeutic values of these targeted cells.
Immunization with plasmids encoding M2 acetylcholine muscarinic receptor epitopes impairs cardiac function in mice and induces autophagy in the myocardium

Abstract Autoantibodies against the M2 subtype of muscarinic acetylcholine receptors with functional activities have been found in the sera of patients with dilated cardiomyopathy (DCM), and the second extracellular loop has been established as the predominant epitope. However, it has been shown that the third intracellular loop is recognized by Chagas disease patients with severe cardiac dysfunction. In this work, BALB/c mice were immunized with plasmids encoding these two epitopes, and a control group received the empty plasmid (pcDNA3 vector). Serum from these DNA-immunized animals had elevated and persistent titres of antibodies against respective antigens. Heart echocardiography indicated diminished left ventricular wall thickness and reduced ejection fraction for both epitope-immunized groups, and ergospirometry tests showed a significant decrease in the exercise time and oxygen consumption. Transfer of serum from these immunized mice into naïve recipients induced the same alterations in cardiac structure and function. Furthermore, electron microscopy analysis of donor-immunized animals revealed several ultrastructural alterations suggestive of autophagy and mitophagy, suggesting novel roles for these autoantibodies. Overall, greater functional and structural impairment was observed in the donor and recipient epitope groups, implicating the third intracellular loop epitope in the pathological effects for the first-time. Therefore, the corresponding peptides could be useful for autoimmune DCM diagnosis and targeted therapy.
Delta albumin is a better prognostic marker for complications following laparoscopic intestinal resection for Crohn’s disease than albumin alone – A retrospective cohort study

Purpose Little is known about the perioperative dynamic of albumin and its effect on surgical outcome in Crohn’s disease. Thus, we aimed to assess postoperative changes of albumin levels and their potentially predictive role for complications after laparoscopic intestinal resections. Methods We identified 182 patients who underwent laparoscopic intestinal resection for symptomatic Crohn´s disease between 2000 and 2014 for this retrospective cohort study. Pre- and postoperative serum albumin levels (within 4 days) were recorded retrospectively and proportional postoperative reduction (delta (Δ) albumin) was calculated. Complications were defined according to the Clavien-Dindo classification. Univariate and multivariate analysis describing an eventful postoperative course were conducted. Results Complications were found in 22.5% (n = 41), 6% (n = 11) developed major complications defined as Clavien Dindo III-V and 16.5% (n = 30) had minor complications (Clavien Dindo I-II). The median Δ albumin was 22.75% (range: -18.46–47.14%). Delta albumin was found to be significantly higher in patients who developed complications after surgery (p = 0.03). Notably, neither preoperative (p = 0.28) nor postoperative albumin levels (p = 0.41) taken as absolute numerical values correlated with an eventful course following intestinal resection. In the multivariate analysis, based on a cut-off of 24.27%, Δ albumin remained an independent factor for surgical complications (p = 0.04, OR 2.232) next to conversion rate (p<0.001, OR 5.577) and the presence of an inflammatory mass (p = 0.003, OR 0.280). Conclusion Δ albumin is a better prognostic marker for an eventful postoperative course after laparoscopic surgery in patients with Crohn’s disease in comparison to albumin alone.