Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function

Background Epicardial adipose tissue (EAT) is in immediate apposition to the underlying myocardium and, therefore, has the potential to influence myocardial systolic and diastolic function or myocardial geometry, through paracrine or compressive mechanical effects. We aimed to review the association between volumetric EAT and markers of myocardial function and geometry. Methods and Results PubMed, Medline, and Embase were searched from inception to May 2018. Studies were included only if complete EAT volume or mass was reported and related to a measure of myocardial function and/or geometry. Meta‐analysis and meta‐regression were used to evaluate the weighted mean difference of EAT in patients with and without diastolic dysfunction. Heterogeneity of data reporting precluded meta‐analysis for systolic and geometric associations. In the 22 studies included in the analysis, there was a significant correlation with increasing EAT and presence of diastolic dysfunction and mean e′ (average mitral annular tissue Doppler velocity) and E/e′ (early inflow / annular velocity ratio) but not E/A (ratio of peak early (E) and late (A) transmitral inflow velocities), independent of adiposity measures. There was a greater EAT in patients with diastolic dysfunction (weighted mean difference, 24.43 mL; 95% confidence interval, 18.5–30.4 mL; P<0.001), and meta‐regression confirmed the association of increasing EAT with diastolic dysfunction (P=0.001). Reported associations of increasing EAT with increasing left ventricular mass and the inverse correlation of EAT with left ventricular ejection fraction were inconsistent, and not independent from other adiposity measures. Conclusions EAT is associated with diastolic function, independent of other influential variables. EAT is an effect modifier for chamber size but not systolic function.
Energetic Fingerprinting of Ligand Binding to Paralogous Proteins: The Case of the Apoptotic Pathway

Networks of biological molecules are key to cellular function, governing processes ranging from signal cascade propagation to metabolic pathway regulation. Genetic duplication processes give rise to sets of regulatory proteins that have evolved from a common ancestor, leading to interactomes whose dysregulation is often associated with disease. A better understanding of the determinants of specificity at interfaces shared by functionally related proteins is crucial to the rational design of novel pharmacotherapeutic agents. To this end, a comprehensive data set of drug and drug-like binders was assembled for the Bcl-xL and Bcl-2 antiapoptotic proteins-archetypal examples of regulatory systems governed by evolutionarily conserved protein-protein interactions. These were first used to derive a two-dimensional quantitative structure-activity relationship (2D QSAR) model, predicting ligand specificity for these homologous proteins. The strengths and weaknesses of high-throughput 2D QSAR were then compared and contrasted to those of theoretically rigorous thermodynamic integration calculations performed on 14 complexes of Bcl-xL-specific, Bcl-2-specific, and potent dual binders bound to the Bcl-xL and Bcl-2 proteins. We demonstrate that free energy calculations provide an added layer of essential information, which traditional QSAR cannot capture. Moreover, we show that protein energetic responses to different ligands, expressed as per-residue energy values, can be used to fingerprint the protein-ligand interaction, extending the framework of four-dimensional molecular dynamics/quantitative structure-activity relationships (4D-MD/QSAR) toward the facilitation of future drug design strategies.
Cost-Effective Edge Server Placement in Wireless Metropolitan Area Networks

Remote clouds are gradually unable to achieve ultra-low latency to meet the requirements of mobile users because of the intolerable long distance between remote clouds and mobile users and the network congestion caused by the tremendous number of users. Mobile edge computing, a new paradigm, has been proposed to mitigate aforementioned effects. Existing studies mostly assume the edge servers have been deployed properly and they just pay attention to how to minimize the delay between edge servers and mobile users. In this paper, considering the practical environment, we investigate how to deploy edge servers effectively and economically in wireless metropolitan area networks. Thus, we address the problem of minimizing the number of edge servers while ensuring some QoS requirements. Aiming at more consistence with a generalized condition, we extend the definition of the dominating set, and transform the addressed problem into the minimum dominating set problem in graph theory. In addition, two conditions are considered for the capacities of edge servers: one is that the capacities of edge servers can be configured on demand, and the other is that all the edge servers have the same capacities. For the on-demand condition, a greedy based algorithm is proposed to find the solution, and the key idea is to iteratively choose nodes that can connect as many other nodes as possible under the delay, degree and cluster size constraints. Furthermore, a simulated annealing based approach is given for global optimization. For the second condition, a greedy based algorithm is also proposed to satisfy the capacity constraint of edge servers and minimize the number of edge servers simultaneously. The simulation results show that the proposed algorithms are feasible.
Comparative Judgment of Familiar Objects Is Modulated by Their Size

Perceptual decisions such as that we have more strawberries than apples left in our fruit basket seem to be made effortlessly. However, it is not examined yet whether such decisions are also biased by the size of the objects, just like numerosity comparisons with meaningless dot arrays. We presented two homogeneous sets of larger and smaller fruits (e.g., three apples and four strawberries), and participants had to indicate which set was more numerous. Although accuracy was nearly perfect, a strong congruency effect was found in reaction times, showing it is more difficult to compare the numerosities of sets of 2 apples and 3 strawberries than the opposite, that is, 3 apples and 2 strawberries. Because the stimuli were selected to simulate everyday conditions as much as possible, the present results suggest that most likely also comparative numerosity judgment in daily life is biased by nonnumerical cues such as size of the objects.
Differential ratio amplicons (R amp) for the evaluation of RNA integrity extracted from complex environmental samples

Summary Reliability and reproducibility of transcriptomics‐based studies are dependent on RNA integrity. In microbial ecology, microfluidics‐based techniques, such as the Ribosomal Integrity Number (RIN), targeting rRNA are currently the only approaches to evaluate RNA integrity. However, the relationship between rRNA and mRNA integrity is unknown. Here, we present an integrity index, the Ratio Amplicon, R amp, adapted from human clinical studies, to directly monitor mRNA integrity from complex environmental samples. We show, in a suite of experimental degradations of RNA extracted from sediment, that while the RIN generally reflected the degradation status of RNA the R amp mapped mRNA degradation better. Furthermore, we examined the effect of degradation on transcript community structure by amplicon sequencing of 16S rRNA, amoA and glnA transcripts. We successfully sequenced transcripts for all three targets even from highly‐degraded RNA samples. While RNA degradation changed the community structure of the mRNA profiles, no changes were observed for the 16S rRNA transcript profiles. Since both RT‐Q‐PCR and sequencing results were obtained, even from highly degraded samples, we strongly recommend evaluating RNA integrity prior to downstream processing to ensure meaningful results. For this, both the RIN and R amp are useful, with the R amp better evaluating mRNA integrity in this study.
OBJECT BASED IMAGE ANALYSIS FOR AUTOMATED INFORMATION EXTRACTION - A SYNTHESIS

Over the last years, advances in computer technology, earth observation sensors and GIScience have led to the emerging field of "Object-based Image Analysis” (OBIA). The need for timely and accurate geo-spatial information is steadily increasing. It is necessary to synchronize technologies and harmonize approaches related to the acquisition, processing, and retrieval of multi-sensor, multi-spectral, multi-resolution data from various sensors. Moreover, the advancement of feature recognition and advanced image analysis techniques facilitate the extraction of thematic information, for policy making support and informed decisions. The availability of such data and the increasing worldwide use of geo-information have catalyzed the development of new methods to exploit image information more ‘intelligently’. In this paper we investigate the technical and methodological status quo in OBIA. We provide an overview on applications bridging remote sensing, mapping, and GIS with a focus on automated operations and repeatable and transferable solutions. We analyse the outcomes of the first conference on objectbased image analysis (OBIA’06) and draw conclusions in regard a) to the scientific progress in algorithms and methodologies, b) to the software situation and the commercial exploitation, and c) in particular to the conference topic ‘Automated Feature Extraction’.
3‐(4‐methoxyl)‐1‐(2‐(4‐coumarin)prop)‐2‐en‐1‐one inhibits the differentiation of Gaoyou duck embryonic osteoclasts in vitro

ABSTRACT This study determined the influence of 3‐(4‐methoxyl)‐1‐(2‐(4‐coumarin)prop)‐2‐en‐1‐one (MCPEO) on the differentiation of Gaoyou duck embryo osteoclasts cultured in vitro. Bone marrow mononuclear cells (BM‐MNCs) were harvested from 23‐day‐old Gaoyou duck embryos and induced by receptor activator of nuclear factor &kgr;B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF) in the presence of MCPEO at different concentrations (i.e., 1, 5, 10, 20, and 40 &mgr;M). Cell viability measurement, tartrate‐resistant acid phosphatase (TRAP) staining, resorption activity assay, and co‐staining with Tetramethylrhodamine (TRITC)‐conjugated phalloidin and Hoechst 33,258 were conducted. Results indicated that MCPEO influenced the cell viability of the M‐CSF + RANKL‐induced BM‐MNCs in a concentration‐dependent manner, reduced the formation of positive multinucleated cells, and restrained the resorption capability of osteoclasts. Microfilament and nuclear staining indicated that MCPEO restricted the differentiation of BM‐MNCs into large multinucleated osteoclasts. In short, MCPEO can inhibit the differentiation of BM‐MNCs into mature osteoclasts in duck embryos. Therefore, MCPEO is a promising agent for the treatment of poultry osteoporosis.
Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C

Abstract Epstein–Barr virus proteins EBNA3A, EBNA3B and EBNA3C control hundreds of host genes after infection. Changes in epigenetic marks around EBNA3-regulated genes suggest that they exert transcriptional control in collaboration with epigenetic factors. The roles of polycomb repressive complex (PRC)2 subunit SUZ12 and of PRC1 subunit BMI1 were assessed for their importance in EBNA3-mediated repression and activation. ChIP-seq experiments for SUZ12 and BMI1 were performed to determine their global localization on chromatin and analysis offered further insight into polycomb protein distribution in differentiated cells. Their localization was compared to that of each EBNA3 to resolve longstanding questions about the EBNA3–polycomb relationship. SUZ12 did not co-localize with any EBNA3, whereas EBNA3C co-localized significantly and co-immunoprecipitated with BMI1. In cells expressing a conditional EBNA3C, BMI1 was sequestered to EBNA3C-binding sites after EBNA3C activation. When SUZ12 or BMI1 was knocked down in the same cells, SUZ12 did not contribute to EBNA3C-mediated regulation. Surprisingly, after BMI1 knockdown, EBNA3C repressed equally efficiently but host gene activation by EBNA3C was impaired. This overturns previous assumptions about BMI1/PRC1 functions during EBNA3C-mediated regulation, for the first time identifies directly a host factor involved in EBNA3-mediated activation and provides a new insight into how PRC1 can be involved in gene activation.
Standards for the diagnosis and management of complex regional pain syndrome: Results of a European Pain Federation task force

Complex regional pain syndrome is a painful and disabling post‐traumatic primary pain disorder. Acute and chronic complex regional pain syndrome (CRPS) are major clinical challenges. In Europe, progress is hampered by significant heterogeneity in clinical practice. We sought to establish standards for the diagnosis and management of CRPS.
Prevalence of peri‐implant disease and risk indicators in a Japanese population with at least 3 years in function—A multicentre retrospective study

OBJECTIVES The aim of this study was to evaluate the prevalence of peri-implant disease and analyze risk indicators in Japanese subjects with ≥3 years of implant function. MATERIAL AND METHODS Five hundred and forty-three subjects treated with 1,613 implants were evaluated. Information was collected about the patients' physical and dental history, as well as implant details. Peri-implant evaluation included probing depth, bleeding on probing (BoP), suppuration (Sup), and keratinized tissue width. Bone loss was calculated from intra-oral radiographs taken after 1 year and more than 3 years of function. Implants were classified into three groups: healthy, peri-implant mucositis (BoP without bone loss), and peri-implantitis (BoP and/or Sup with bone loss >1 mm). These data were analyzed by multivariable multinomial logistic regression. RESULTS The prevalence of peri-implant mucositis and peri-implantitis at the subject level was 23.9% and 15.8%, respectively. An association was found between peri-implant mucositis and plaque control record (PCR) >20% and keratinized tissue width <2 mm. Peri-implantitis was associated with PCR >20%, smoking, insertion in the maxilla, and keratinized tissue width <2 mm. CONCLUSIONS Within the limitations of this study, the prevalence of peri-implant diseases was elucidated in a Japanese population. Peri-implant mucositis was associated with poor oral hygiene and less keratinized tissue. Poor oral hygiene, smoking, insertion in the maxilla, and less keratinized tissue were risk indicators for peri-implantitis.
Identification of amniotic fluid metabolomic and placental transcriptomic changes associated with abnormal development of cloned pig fetuses

Piglets cloned by somatic cell nuclear transfer (SCNT) show a high incidence of malformations and a high death rate during the perinatal period. To investigate the underlying mechanisms for abnormal development of cloned pig fetuses, we compared body weight, amniotic fluid (AF) metabolome, and placental transcriptome between SCNT‐ and artificial insemination (AI)‐derived pig fetuses. Results showed that the body weight of SCNT pig fetuses was significantly lower than that of AI pig fetuses. The identified differential metabolites between the two groups of AF were mainly involved in bile acids and steroid hormones. The levels of all detected bile acids in SCNT AF were significantly higher than those in AI AF. The increase in the AF bile acid levels in SCNT fetuses was linked with the downregulation of placental bile acid transporter expression and the abnormal development of placental folds (PFs), both of which negatively affected the transfer of bile acids from AF across the placenta into the mother’s circulation. Alteration in the AF steroid hormone levels in cloned fetuses was associated with decreased expression of enzymes responsible for steroid hormone biosynthesis in the placenta. In conclusion, cloned pig fetuses undergo abnormal intrauterine development associated with alteration of bile acid and steroid hormone levels in AF, which may be due to the poor development of PFs and the erroneous expression of bile acid transporters and enzymes responsible for steroid hormone biosynthesis in the placentas.
Attenuated Replication of Lassa Virus Vaccine Candidate ML29 in STAT-1-/- Mice

Lassa virus (LASV), a highly prevalent mammalian arenavirus endemic in West Africa, can cause Lassa fever (LF), which is responsible for thousands of deaths annually. LASV is transmitted to humans from naturally infected rodents. At present, there is not an effective vaccine nor treatment. The genetic diversity of LASV is the greatest challenge for vaccine development. The reassortant ML29 carrying the L segment from the nonpathogenic Mopeia virus (MOPV) and the S segment from LASV is a vaccine candidate under current development. ML29 demonstrated complete protection in validated animal models against a Nigerian strain from clade II, which was responsible for the worst outbreak on record in 2018. This study demonstrated that ML29 was more attenuated than MOPV in STAT1-/- mice, a small animal model of human LF and its sequelae. ML29 infection of these mice resulted in more than a thousand-fold reduction in viremia and viral load in tissues and strong LASV-specific adaptive T cell responses compared to MOPV-infected mice. Persistent infection of Vero cells with ML29 resulted in generation of interfering particles (IPs), which strongly interfered with the replication of LASV, MOPV and LCMV, the prototype of the Arenaviridae. ML29 IPs induced potent cell-mediated immunity and were fully attenuated in STAT1-/- mice. Formulation of ML29 with IPs will improve the breadth of the host's immune responses and further contribute to development of a pan-LASV vaccine with full coverage meeting the WHO requirements.
Higher prevalence of permanent congenital hypothyroidism in the Southwest of Iran mostly caused by dyshormonogenesis: a five-year follow-up study

ABSTRACT Objective: The incidence of congenital hypothyroidism (CH) varies globally. This 5-year study aimed to determine the prevalence of permanent CH in the southwest of Iran. Materials and methods: Between January 2007 and December 2009, all newborns in Ahvaz, the biggest city in the southwest of Iran, were screened for CH using a heel-prick sample for thyrotropin (TSH) levels. Subjects with TSH ≥ 5 mU/L were evaluated for T4-TSH. Infants with T4 < 6.5 µg/dL, TSH > 10 mU/L, and normal T4 but persistent (> 60 days) high TSH were considered to have CH. After the third birthday, treatment was discontinued, and T4-TSH was reevaluated; subjects with TSH ≥ 10 mU/L were investigated using thyroid Tc99 scintigraphy (TS). Based on TS, they were classified as normal, dysgenetic, or athyretic (agenesis). Results: Screening was performed for 86,567 neonates, and 194 were confirmed to have CH (100 males; F/M = 0.94; overall incidence 1:446). After the third birthday, reevaluation was performed in all (except 18 that were not accessible). From 176 patients, 81 (46%) were diagnosed with permanent CH, and 95 were discharged as transient. Considering the same percentage in the lost cases, the prevalence of permanent CH was found to be 1:970. TS performed for 53 of the permanent subjects found agenesis/dysgenesis in 25 (F:M = 15:10) and a normal result in 28 (F:M = 11:17), indicating dyshormonogenesis as the cause in more than 50% of subjects. Conclusions: The incidence of CH in this area was found to be higher than that in other countries but less than the incidence rate reported in central Iran. The large number of transient cases of CH suggests environmental or maternal causes for the incidence rather than a genetic basis.
Hepatobiliary and Pancreatic: A procalcitonin‐secreting and calcitonin‐secreting pancreatic neuroendocrine carcinoma

A 71-year-old man was admitted to our hospital with a 3-month history of diarrhea. The patient’s abdomen was soft, and no palpable masses were detected. Levels of the circulating tumor markers carcinoembryonic antigen (6.3 ng/mL [normal range: 0–5.0 ng/mL]) and carbohydrate antigen 19–9 (40.5 U/mL [normal range: 0–37 U/mL]) were mildly elevated. Contrast-enhanced computed tomography showed a 30-mm hypovascular tumor at the head of the pancreas, accompanied by multiple liver metastases and stenosis of the portal vein (Fig. 1a,b). Magnetic resonance imaging revealed a hyperintensity on T2-weighted images and diffusion-weighted imaging on the head of the pancreas (Fig. 1c). Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct at the same site, as well as parenchymal atrophy and dilation of the main pancreatic duct from the pancreatic body to the tail (Fig. 1d). Pancreatic cancer and pancreatic neuroendocrine tumor were considered as differential diagnoses, and the patient underwent endoscopic ultrasoundguided fine-needle aspiration and liver biopsy. Histologically, the lesion was positive for chromogranin A, synaptophysin, and Ki67 (labeling index > 30%) but negative for insulin, glucagon, gastrin, vasoactive intestinal peptide, and somatostatin (Fig. 2a, b). Therefore, the patient was diagnosed with pancreatic neuroendocrine carcinoma (PNEC). Three weeks later, the patient suddenly experienced a high fever. Blood levels of procalcitonin (PCT)were 927.04 ng/mL (normal range: 0–0.5 ng/mL) and later increased to 3783.13 mg/mL. In addition, blood levels of calcitonin had increased to 68 670 pg/mL (normal range: 0–5.15 pg/mL). Further, immunohistochemical analyses revealed that tumor cells were secreting PCT (clone 44d9, NB120-14817, Novus Biologicals, Littleton, CO, USA) and weakly positive for calcitonin (Fig. 2c,d). Therefore, the patient was diagnosed with a PCT-secreting and calcitonin-secreting PNEC. To our knowledge, this is the second report to describe the immunohistochemical diagnosis of a PCT-secreting and calcitoninsecreting PNEC. The patient in the first case, an approximately 70-year-old man with multiple liver metastases, was similar to the patient in the present case. Under physiologic conditions, calcitonin promotes intestinal motility and the secretion of electrolytes and water from the jejunum. A previous report demonstrated that watery diarrhea occurred secondary to high calcitonin levels (> 30 000 pg/mL) in a case of medullary thyroid carcinoma with extensive metastases. Similarly, the patient in the present case presented with high serum levels of calcitonin (68 670 pg/mL) and experienced watery diarrhea (> 3000 mL/day). Measuring serum levels of PCT and calcitonin may facilitate early diagnoses of liver-metastatic PNEC, particularly in ~70-year-old men with refractory diarrhea.