Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational characterization of the binding mode between oncoprotein Ets‐1 and DNA‐repair enzymes

The Ets‐1 oncoprotein is a transcription factor that promotes target gene expression in specific biological processes. Typically, Ets‐1 activity is low in healthy cells, but elevated levels of expression have been found in cancerous cells, specifically related to tumor progression. Like the vast majority of the cellular effectors, Ets‐1 does not act alone but in association with partners. Given the important role that is attributed to Ets‐1 in major human diseases, it is crucial to identify its partners and characterize their interactions. In this context, two DNA‐repair enzymes, PARP‐1 and DNA‐PK, have been identified recently as interaction partners of Ets‐1. We here identify their binding mode by means of protein docking. The results identify the interacting surface between Ets‐1 and the two DNA‐repair enzymes centered on the α‐helix H1 of the ETS domain, leaving α‐helix H3 available to bind DNA. The models highlight a hydrophobic patch on Ets‐1 at the center of the interaction interface that includes three tryptophans (Trp338, Trp356, and Trp361). We rationalize the binding mode using a series of computational analyses, including alanine scanning, molecular dynamics simulation, and residue centrality analysis. Our study constitutes a first but important step in the characterization, at the molecular level, of the interaction between an oncoprotein and DNA‐repair enzymes.
Asymmetric neural tracking of gain and loss magnitude during adolescence

Abstract Adolescence has been characterized as a developmental period of heightened reward seeking and attenuated aversive processing. However, it remains unclear how the neural bases of distinct outcome valuation processes shift during this stage of the lifespan. A total of 74 participants ranging in age from 13 to 20 years completed a value‐modulated functional magnetic resonance imaging (fMRI) task in which participants earn low and high magnitude monetary outcomes to test whether gain and loss magnitude tracking—the neural representation of relative value in context—change differentially over this age span. Results revealed that gain and loss magnitude tracking follow asymmetric developmental trajectories. Gain magnitude tracking is elevated in the striatum during early adolescence and then decreases with age. By contrast, loss magnitude tracking in the anterior insula follows a quadratic pattern, undergoing a temporary attenuation during mid‐late adolescence. A typical comparison of gain vs loss outcomes (collapsing over magnitude effects) showed robust activity across a suite of brain regions sensitive to value based on prior work including the ventral striatum, but they exhibited no changes with age. These findings suggest that value coding subprocesses follow divergent developmental paths across adolescence, which may contribute to normative shifts in adolescent motivated behavior.
An evaluation in vitro of the efficacy of nutlin-3 and topotecan in combination with 177Lu-DOTATATE for the treatment of neuroblastoma

Targeted radiotherapy of metastatic neuroblastoma using the somatostatin receptor (SSTR)-targeted octreotide analogue DOTATATE radiolabelled with lutetium-177 (177Lu-DOTATATE) is a promising strategy. This study evaluates whether its effectiveness may be enhanced by combination with radiosensitising drugs. The growth rate of multicellular tumour spheroids, derived from the neuroblastoma cell lines SK-N-BE(2c), CHLA-15 and CHLA-20, was evaluated following treatment with 177Lu-DOTATATE, nutlin-3 and topotecan alone or in combination. Immunoblotting, immunostaining and flow cytometric analyses were used to determine activation of p53 signalling and cell death. Exposure to 177Lu-DOTATATE resulted in a significant growth delay in CHLA-15 and CHLA-20 spheroids, but not in SK-N-BE(2c) spheroids. Nutlin-3 enhanced the spheroid growth delay induced by topotecan in CHLA-15 and CHLA-20 spheroids, but not in SK-N-BE(2c) spheroids. Importantly, the combination of nutlin-3 with topotecan enhanced the spheroid growth delay induced by X-irradiation or by exposure to 177Lu-DOTATATE. The efficacy of the combination treatments was p53-dependent. These results indicate that targeted radiotherapy of high risk neuroblastoma with 177Lu-DOTATATE may be improved by combination with the radiosensitising drugs nutlin-3 and topotecan.
Exercising in Air Pollution: The Cleanest versus Dirtiest Cities Challenge

Background: Aerobic exercise is recommended to improve health. However, the increased ventilation might increase the doses of inhaled air pollutants, negating the health benefits in highly polluted areas. Our objective was to estimate the inhaled dose of air pollutants during two simulated exercise sessions at cleanest and dirtiest cities reported by World Health Organization (WHO) considering air quality. Methods: Minute ventilation data were extracted from laboratory-based exercise of 116 incremental running tests and used to calculate total ventilation of a hypothetical 30-min moderate continuous exercise routine. Afterwards, total ventilation values were combined with particulate matter (PM) data reported by the WHO for the 10 cleanest and 10 dirtiest cities, to calculate inhaled doses and the relative risk of all-cause mortality by exercising in different air pollution concentrations. Findings: The dirtiest cities are located at less developed countries compared to cleanest cities. The inhaled dose of PM2.5 and PM10 were significantly higher in the dirtiest cities compared to the cleanest cities at rest and exercise, and significantly higher during exercise compared to the rest at dirtiest cities. The relative risk of all-cause mortality analysis showed that, while exercise in the cleanest cities improved health benefits throughout up to 90 min, there were no further health benefits after 15 min of exercise in the dirtiest cities, and the air pollution health risks surpassed the exercise benefits after 75 min. Interpretation: Our findings suggest that a traditional 30-min of moderate aerobic exercise session might induce inhalation of high levels of pollutants when performed at dirtiest cities. Considering several adverse health effects from air pollutants inhalation, so the results suggest that the air pollution levels of the cities should be taken into account for physical exercise recommendations.
Correlation between Quantity of Transferred Lymph Nodes and Outcome in Vascularized Submental Lymph Node Flap Transfer for Lower Limb Lymphedema

Background: Vascularized lymph node transfer has shown promising results in the treatment of lower limb lymphedema, but little is known about the number of lymph nodes needed for the transfer to achieve optimal results. This study investigated the correlation between number of transferred lymph nodes in submental vascularized lymph node transfer and outcomes regarding limb circumference reduction and cellulitis incidence. Methods: Thirty-five patients who had received vascularized submental lymph node transfer to an ankle for lower limb lymphedema following gynecologic cancer treatment were included in the study. Limb circumference was determined by means of tape measurement preoperatively and postoperatively and was used to calculate the circumferential difference. Ultrasonography was performed postoperatively to determine the number of lymph nodes within the transferred flap. Patients were divided into groups A through C depending on the number of transferred lymph nodes: 1 or 2 (n = 10), 3 or 4 (n = 14), and 5 to 8 (n = 11), respectively. Results: The mean age of the patients was 60.0 ± 9.2 years. All flaps survived. The mean improvement of circumferential difference for the whole cohort was 19.8 ± 9.2 percent. Groups B and C both had significantly higher improvements in the circumferential difference than group A (p = 0.04 and p = 0.02, respectively), but when compared to each other, the difference was nonsignificant. All groups had significant reductions in the incidence of cellulitis postoperatively. Conclusions: Submental vascularized lymph node transfer for lower limb lymphedema reduced the incidence of cellulitis, regardless of the number of transferred lymph nodes. The transfer of three or more lymph nodes provided significantly better outcome regarding limb circumference reduction than the transfer of two or fewer lymph nodes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
The Spatio-Temporal Disparities of Areas Benefitting from the Wind Erosion Prevention Service

Ecosystem services are closely linked to human welfare. The flow of ecosystem service can establish spatio-temporal relationships between ecosystem service provision areas (SPAs) and service beneficiary areas (SBAs). In this study, the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used to simulate the spatial flow path of the wind erosion prevention (WEP) service in Yanchi County. The frequency at which the simulated trajectories passed through each grid cell was used as a proxy for spatio-temporal disparities in SBAs, and the distribution of benefitting land cover, population, and gross domestic product (GDP) reflected the effects of the WEP flow. The flow paths of the Yanchi County WEP in 2010 mainly extended to eastern and central China, North Korea, South Korea, Japan, Mongolia, and eastern Russia, and were more intensive and longer in spring and winter than in autumn and winter. The SBAs covered an area of 1153.2 × 104 km2 in 2010, with dominant service beneficiary areas (DSBAs) comprising 185.1 × 104 km2 and accounting for 16.1% of the total beneficiary area of the year. The areas through which the flow paths passed with a high frequency (≥10%) were mainly located in Shaanxi, Shanxi, Henan, western Shandong, Hebei, Beijing, and northern Hubei, and the spatial scale of these areas varied, demonstrating obvious seasonal changes, and was the largest in spring. The benefitting land cover was mainly cropland across all of the SBAs, with one billion benefitting people (accounting for 77.11% of the total population of China) associated with a gross domestic product (GDP) of 26.8 trillion RMB (Chinese currency; as of 2018-06-22, 6.497 RMB = US $1, accounting for 87.90% of the total GDP of China). Furthermore, the population and socio-economic development in the DSBAs (21 million people and 0.53 trillion RMB GDP) were no longer affected by wind erosion from Yanchi County. This study revealed the spatio-temporal disparities of the SBAs of WEP in Yanchi County from an ecosystem services flow perspective and provides a scientific and effective basis for policymakers to perform standard ecological compensation accounting and to formulate ecological protection policies.
Liquid biopsy for infectious diseases: Sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

Diagnosis of life-threatening deep-seated infections currently requires invasive sampling of the infected tissue to provide a microbiologic diagnosis. These procedures can lead to high morbidity in patients and add to healthcare costs. Here we describe a novel next-generation sequencing assay that was used to detect pathogen-derived cell-free DNA in peripheral blood of patients with biopsy-proven invasive fungal infections. The non-invasive nature of this approach could provide rapid, actionable treatment information for invasive fungal infections when a biopsy is not possible.
An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy.

PURPOSE To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. METHODS Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. RESULTS Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. CONCLUSION The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.
Characterization of septin expression in normal and fibrotic kidneys

Chronic kidney disease (CKD) is characterized by the loss of nephrons and worsening organ‐fibrosis that leads to deterioration and ultimately the total breakdown of kidney function. Renal fibrosis has become a major public health problem worldwide and necessitates hemodialysis and kidney transplantation in affected patients. CKD is mainly characterized by the activation and proliferation of interstitial fibroblasts and by excessive synthesis and accumulation of extracellular matrix components, causing the disruption of the normal tissue architecture of the kidney. Septins are GTPase proteins associated with membranes, actin filaments, and microtubules and are undoubtedly crucial for cytoskeleton organization. Although some septins are involved in liver fibrosis, they have not been investigated in the context of renal fibrosis. Here, we show that numerous septins are expressed in the healthy kidney and demonstrate in fibrotic mouse kidneys that various septins are remarkably up‐regulated in the tubulointerstitium compared to contralateral control kidneys. We observed the same findings in human fibrotic kidneys. In both healthy and fibrotic kidneys, septins are coexpressed with extracellular matrix components, reinforcing the structural function of septins as cytoskeletal components. Furthermore, we could show in septin 8‐deficient mice that septin 8 is dispensable for the formation of renal fibrosis, and that no other septin was compensatory changed in kidneys compared to wild‐type mice.
Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake

Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity. Herein, we also demonstrated that this body weight decrease was more likely associated with an increased BAT thermogenesis and browning of white adipose tissue (WAT) than to anorexia. Overall, these results indicate that the modulation of GRP78 in the VMH may be a target against obesity.
Levenberg-Marquardt Neural Network Algorithm for Degree of Arteriovenous Fistula Stenosis Classification Using a Dual Optical Photoplethysmography Sensor

This paper proposes a noninvasive dual optical photoplethysmography (PPG) sensor to classify the degree of arteriovenous fistula (AVF) stenosis in hemodialysis (HD) patients. Dual PPG measurement node (DPMN) becomes the primary tool in this work for detecting abnormal narrowing vessel simultaneously in multi-beds monitoring patients. The mean and variance of Rising Slope (RS) and Falling Slope (FS) values between before and after HD treatment was used as the major features to classify AVF stenosis. Multilayer perceptron neural networks (MLPN) training algorithms are implemented for this analysis, which are the Levenberg-Marquardt, Scaled Conjugate Gradient, and Resilient Back-propagation, to identify the degree of HD patient stenosis. Eleven patients were recruited with mean age of 77 ± 10.8 years for analysis. The experimental results indicated that the variance of RS in the HD hand between before and after treatment was significant difference statistically to stenosis (p < 0.05). Levenberg-Marquardt algorithm (LMA) was significantly outperforms the other training algorithm. The classification accuracy and precision reached 94.82% and 92.22% respectively, thus this technique has a potential contribution to the early identification of stenosis for a medical diagnostic support system.
Multi-hydrolytic enzyme accumulation and microbial community structure of anaerobic co-digestion of food waste and waste-activated sludge

ABSTRACT The accumulation of multi-hydrolytic enzyme through anaerobic co-digestion of waste-activated sludge (WAS) and food waste (FW) was studied by regulating temperature, pH and the mass ratio of FW to WAS (F/W). Experimental results showed that temperature had a profound effect on the activity of the enzyme and the most suitable temperatures for the accumulation of amylase and protease were 37°C and 50°C, respectively. The highest activity of amylase and protease accumulated reached 10.29 and 19.23 U/mL at an F/W ratio of 2:1. The addition of anaerobic co-digestion solution enriching protease and amylase had positive effects on the hydrolysis of WAS. In addition, the Illumina high-throughput sequencing demonstrated that the bacterial diversity decreased, but the bacterial abundance increased during the co-digestion process of WAS and FW. The predominant strains for secreting amylase were Lactobacillus and Clostridium-sensu-strito-1, and Aeromonas was the dominant strain for secreting protease. GRAPHICAL ABSTRACT
Proficiency testing for the detection of Middle East respiratory syndrome coronavirus demonstrates global capacity to detect Middle East respiratory syndrome coronavirus

The first reported case of Middle East respiratory syndrome coronavirus (MERS‐CoV) infection was identified in Saudi Arabia in September 2012, since which time there have been over 2000 laboratory‐confirmed cases, including 750 deaths in 27 countries. Nucleic acid testing (NAT) is the preferred method for the detection of MERS‐CoV. A single round of a Proficiency Testing Program (PTP) was used to assess the capability of laboratories globally to accurately detect the presence of MERS‐CoV using NAT. A panel of eleven lyophilized specimens containing different viral loads of MERS‐CoV, common coronaviruses, and in vitro RNA transcripts was distributed to laboratories in all six World Health Organization regions. A total of 96 laboratories from 79 countries participating in the PTP, with 76 of 96 (79.2%) reporting correct MERS‐CoV results for all nine scored specimens. A further 10 laboratories (10.4%) scored correctly in eight of nine specimens of the PTP. The majority of laboratories demonstrated satisfactory performance in detecting the presence of MERS‐CoV using NAT. However, some laboratories require improved assay sensitivity, reduced cross contamination of samples, and improved speciation of coronavirus subtypes for potentially complex clinical specimens. Further PTP and enhanced links with expert laboratories globally may improve the laboratory performance.
Inference of cell type content from human brain transcriptomic datasets illuminates the effects of age, manner of death, dissection, and psychiatric diagnosis

Psychiatric illness is unlikely to arise from pathology occurring uniformly across all cell types in affected brain regions. Despite this, transcriptomic analyses of the human brain have typically been conducted using macro-dissected tissue due to the difficulty of performing single-cell type analyses with donated post-mortem brains. To address this issue statistically, we compiled a database of several thousand transcripts that were specifically-enriched in one of 10 primary cortical cell types in previous publications. Using this database, we predicted the relative cell type content for 833 human cortical samples using microarray or RNA-Seq data from the Pritzker Consortium (GSE92538) or publicly-available databases (GSE53987, GSE21935, GSE21138, CommonMind Consortium). These predictions were generated by averaging normalized expression levels across transcripts specific to each cell type using our R-package BrainInABlender (validated and publicly-released on github). Using this method, we found that the principal components of variation in the datasets strongly correlated with the predicted neuronal/glial content of the samples. This variability was not simply due to dissection–the relative balance of brain cell types appeared to be influenced by a variety of demographic, pre- and post-mortem variables. Prolonged hypoxia around the time of death predicted increased astrocytic and endothelial gene expression, illustrating vascular upregulation. Aging was associated with decreased neuronal gene expression. Red blood cell gene expression was reduced in individuals who died following systemic blood loss. Subjects with Major Depressive Disorder had decreased astrocytic gene expression, mirroring previous morphometric observations. Subjects with Schizophrenia had reduced red blood cell gene expression, resembling the hypofrontality detected in fMRI experiments. Finally, in datasets containing samples with especially variable cell content, we found that controlling for predicted sample cell content while evaluating differential expression improved the detection of previously-identified psychiatric effects. We conclude that accounting for cell type can greatly improve the interpretability of transcriptomic data.
Length of stimulus presentation and visual angle are critical for efficient visual PER conditioning in the restrained honey bee, Apis mellifera

ABSTRACT Learning visual cues is an essential capability of bees for vital behaviors such as orientation in space and recognition of nest sites, food sources and mating partners. To study learning and memory in bees under controlled conditions, the proboscis extension response (PER) provides a well-established behavioral paradigm. While many studies have used the PER paradigm to test olfactory learning in bees because of its robustness and reproducibility, studies on PER conditioning of visual stimuli are rare. In this study, we designed a new setup to test the learning performance of restrained honey bees and the impact of several parameters: stimulus presentation length, stimulus size (i.e. visual angle) and ambient illumination. Intact honey bee workers could successfully discriminate between two monochromatic lights when the color stimulus was presented for 4, 7 and 10 s before a sugar reward was offered, reaching similar performance levels to those for olfactory conditioning. However, bees did not learn at shorter presentation durations. Similar to free-flying honey bees, harnessed bees were able to associate a visual stimulus with a reward at small visual angles (5 deg) but failed to utilize the chromatic information to discriminate the learned stimulus from a novel color. Finally, ambient light had no effect on acquisition performance. We discuss possible reasons for the distinct differences between olfactory and visual PER conditioning. Summary: Visual PER conditioning in bees is difficult and less reliable than olfactory learning; stimulus length and visual angle limit the learning performance of bees during PER conditioning.