Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhigh and ALDHlow-derived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma.
Diabetes mellitus prevalence in tuberculosis patients and the background population in Guinea-Bissau: a disease burden study from the capital Bissau.

BACKGROUND Data regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scare. We did a DM screening survey among TB patients and non-TB controls in Guinea-Bissau. METHODS The study was conducted at the Bandim Health Project (BHP) in the capital Bissau. From July 2010 to July 2011, newly diagnosed TB cases were identified through a TB notification system. Concurrently, non-TB controls were selected randomly from the BHP's demographic surveillance database and visited at home. Participants were tested using fasting blood glucose (FBG) measurements. DM was diagnosed as FBG ≥ 7 mmol/l. Our survey was linked to the patient database at the only existing Diabetes Clinic in Bissau. RESULTS TB patients (n=110) were older than the controls (n=572) (35 vs 31 years; p=0.02), more often male (55% vs 37%; p<0.001) and had a lower body mass index (18.7 vs 24.2 kg/m(2); p<0.001). The prevalence of DM was 2.8% (3/107) for TB patients and 2.1% (11/531) for controls (p=0.64). Excluding two controls already receiving anti-diabetic treatment, the prevalence of DM was 2.8% (3/107) vs 1.7% (9/529) (p=0.44). CONCLUSIONS The prevalence of DM was low, also among TB patients. No association between DM and TB was found.
Retinal Vascular Caliber and the Long‐Term Risk of Diabetes and Impaired Fasting Glucose: The Blue Mountains Eye Study

Objective: To assess the associations of retinal vessel caliber with the 10‐year incidence of diabetes and impaired fasting glucose (IFG). Methods: The Blue Mountains Eye Study is a population based cohort study of Australian residents aged at least 49 years, with baseline examinations conducted during 1992–4. Retinal arteriolar and venular calibers were measured and summarized from baseline digitized images in 3368 participants. Diabetes was defined as a physician‐diagnosis of diabetes or fasting blood glucose ≥ 126 mg/dL and IFG as fasting blood glucose 109 to 125 mg/dL. Ten year incidence of diabetes and IFG was defined from 5‐ and 10‐year follow up data. Results: After adjusting for age and gender, wider retinal venular caliber was associated with an increased incidence of diabetes and IFG. These associations were not significant after controlling for baseline glucose, body mass index and other factors. In persons 49–70 years of age at baseline, however, the association of wider retinal venular caliber and incident IFG persisted after further controlling for other factors (OR, 1.53, 95% CI, 1.11–2.12). Retinal arteriolar caliber was not associated with incident diabetes or IFG. Conclusions: This study suggests that wider retinal venular caliber was associated with higher risk of IFG in middle‐aged persons.
Misdiagnosis of florid cemento-osseous dysplasia leading to unnecessary root canal treatment: a case report

This case report demonstrates an unnecessary endodontic treatment of teeth with florid cemento-osseous dysplasia (FCOD) due to a misdiagnosis as periapical pathosis and emphasizes the importance of correct diagnosis to avoid unnecessary treatment. A 30-year-old woman was referred to our institution for apicoectomies of the mandibular left canine and both the lateral incisors. The periapical lesions associated with these teeth had failed to resolve after root canal treatment over a 3-year period. Radiographic examinations revealed multiple lesions on the right canine, the second premolar, and both first molars as well as the anterior region of the mandible. Based on clinical, radiographic and histological evaluations, the patient condition was diagnosed as FCOD. The patient has been monitored for 2 years. To avoid unnecessary invasive treatment, accurate diagnosis is essential before treatment is carried out in managing FCOD.
Induction of dnaN and dnaQ gene expression in Escherichia coli by alkylation damage to DNA.

The dnaN and dnaQ genes encode the beta‐subunit and the epsilon‐subunit of the DNA polymerase III holoenzyme. By transcriptional fusions to the galK gene, translational fusions to lacZ and comparative S1 mapping analysis, we investigated the in‐vivo regulation of dnaN and dnaQ. We found that DNA damage caused by the alkylating agent methyl methanesulphonate (MMS) leads to a significant induction in dnaN and dnaQ gene expression suggesting a requirement of increased amounts of at least some DNA polymerase III holoenzyme subunits for recovery from DNA damage caused by MMS. These results are first evidences that subunits of the DNA polymerase III holoenzyme are DNA damage inducible. This MMS induction of dnaN and dnaQ gene expression is unrelated to the adaptive response. It was not observed in lexA and recA mutants which abolish the induction of the SOS response.
Expenditures for the treatment of major depression.

OBJECTIVE Health policy makers lack accurate information about per capita spending for the treatment of major depression, the distribution of those expenditures, and the proportion of the health care dollar consumed by depression treatment. METHOD The authors recruited and followed a community cohort of individuals with major depression; the 298 subjects were either enrolled in fee-for-service insurance plans or self-insured. Charges for all health care services received during the year following baseline were abstracted from medical and insurance records. RESULTS Over the course of 1 year, 48.1% of the subjects received depression treatment. The per capita total expenditure for inpatient and outpatient depression treatment averaged $631, with a median of $152, for the treated subjects. Just 4.9% of the treated subjects consumed 45.0% of the outpatient expenditures. Depression treatment consumed only 8 cents of every health care dollar spent on the patients treated for depression. CONCLUSIONS Studies are needed to examine how the level and distribution of expenditures for depression treatment change under managed care and to determine whether and how any differences affect outcomes in the afflicted population. Managed care attempts to contain costs by limiting outpatient care may not affect total health care expenditures dramatically, since depression treatment consumes such a minuscule portion of the health care dollar spent on this population.
Congenital plasminogen deficiency associated with venous thromboembolism: therapeutic trial with stanozolol

We describe the case of a 34‐year‐old man with a history of venous thrombotic disease and demonstrate that his plasma plasminogen was reduced to about half‐normal levels but was functionally intact. The deficiency was inherited as an autosomal trait and the propositus and his sister are heterozygotes. The propositus, but no other family member, had an associated deficiency of plasminogen activator activity, probably due to heightened plasminogen activator inhibition in his plasma. A therapeutic trial with the anabolic steroid stanozolol transiently normalized plasminogen and plasminogen activator levels.
Max-Violation Perceptron and Forced Decoding for Scalable MT Training

While large-scale discriminative training has triumphed in many NLP problems, its definite success on machine translation has been largely elusive. Most recent efforts along this line are not scalable (training on the small dev set with features from top 100 most frequent words) and overly complicated. We instead present a very simple yet theoretically motivated approach by extending the recent framework of “violation-fixing perceptron”, using forced decoding to compute the target derivations. Extensive phrase-based translation experiments on both Chinese-to-English and Spanish-to-English tasks show substantial gains in BLEU by up to +2.3/+2.0 on dev/test over MERT, thanks to 20M+ sparse features. This is the first successful effort of large-scale online discriminative training for MT.
A functional network involved in the recycling of nucleocytoplasmic pre-60S factors

Eukaryotic pre-ribosomes go through cytoplasmic maturation steps before entering translation. The nucleocytoplasmic proteins participating in these late stages of maturation are reimported to the nucleus. In this study, we describe a functional network focused on Rei1/Ybr267w, a strictly cytoplasmic pre-60S factor indirectly involved in nuclear 27S pre-ribosomal RNA processing. In the absence of Rei1, the nuclear import of at least three other pre-60S factors is impaired. The accumulation in the cytoplasm of a small complex formed by the association of Arx1 with a novel factor, Alb1/Yjl122w, inhibits the release of the putative antiassociation factor Tif6 from the premature large ribosomal subunits and its recycling to the nucleus. We propose a model in which Rei1 is a key factor for the coordinated dissociation and recycling of the last pre-60S factors before newly synthesized large ribosomal subunits enter translation.
Monitoring bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR

Both veterinarians caring for dolphins in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin (Tursiops truncatus) health. Quantitative PCR (qPCR) can be used to assess cytokine transcription patterns of peripheral blood mononuclear cells (PBMC). This can supplement currently available blood tests with information on immune status. Full realization of this potential requires establishment of normal ranges of cytokine gene transcription levels in bottlenose dolphins. We surveyed four dolphins over the span of seven months by serial bleeds. PBMC were stimulated with phytohaemagglutinin (1, 5, and 10 μg/mL) and concanavalin A (1 μg/mL) for 48 H in vitro. RNA from these cultures was probed by qPCR using Tursiops truncatus-specific primers (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-13, IL-18, IFN-γ and TNF-α). Two blood samples from an additional bottlenose dolphin diagnosed with acute pulmonary disease add further perspective to the data. We observed that mitogen choice made a significant difference in the magnitude of gene transcription observed. On the other hand, most cytokines tested exhibited limited intra-animal variation. However, IL-6 and IL-12p40 differed between older and younger dolphins. Furthermore, the magnitude of mitogenic response clusters the tested cytokines into three groups. The data provide a reference for the selection of target cytokine mRNAs and their expected range of mitogen-stimulated cytokine gene transcription for future studies.
Relative risk and odds ratio: a data mining perspective

We are often interested to test whether a given cause has a given effect. If we cannot specify the nature of the factors involved, such tests are called model-free studies. There are two major strategies to demonstrate associations between risk factors (ie. patterns) and outcome phenotypes (ie. class labels). The first is that of prospective study designs, and the analysis is based on the concept of "relative risk": What fraction of the exposed (ie. has the pattern) or unexposed (ie. lacks the pattern) individuals have the phenotype (ie. the class label)? The second is that of retrospective designs, and the analysis is based on the concept of "odds ratio": The odds that a case has been exposed to a risk factor is compared to the odds for a case that has not been exposed. The efficient extraction of patterns that have good relative risk and/or odds ratio has not been previously studied in the data mining context. In this paper, we investigate such patterns. We show that this pattern space can be systematically stratified into plateaus of convex spaces based on their support levels. Exploiting convexity, we formulate a number of sound and complete algorithms to extract the most general and the most specific of such patterns at each support level. We compare these algorithms. We further demonstrate that the most efficient among these algorithms is able to mine these sophisticated patterns at a speed comparable to that of mining frequent closed patterns, which are patterns that satisfy considerably simpler conditions.
Effect of panretinal photocoagulation on macular morphology and thickness in eyes with proliferative diabetic retinopathy without clinically significant macular edema

Background The purpose of this study was to investigate the effect of panretinal photocoagulation (PRP) on macular morphology and thickness in eyes with proliferative diabetic retinopathy (PDR) and without clinically significant macular edema. Methods This was a prospective study of 76 eyes from 68 patients diagnosed to have PDR without clinically significant macular edema. Baseline and post PRP visual acuity, morphological changes on optical coherence tomography (OCT), and central foveal thickness were evaluated at one week, one month, and 3 months. Results The mean patient age was 56.47 ± 6.55 years. Sixty-two eyes (81.58%) had stable or improved vision, while 14 eyes (18.42%) had worsened visual acuity at 3 months. Compared with baseline, mean visual acuity dropped as early as one week but was regained by 3 months. Mean preoperative central foveal thickness was 222.05 ± 59.11 μm, which increased significantly to 266.84 ± 84.67 μm at one week (P = 0.001), and remained higher at 264.05 ± 102.56 μm by one month (P = 0.01) and 256 ± 101.38 μm by 3 months (P = 0.04). Thirty-four percent of eyes with a normal macula showed morphological changes following PRP. The most common morphological change on OCT after PRP was spongy edema, seen in 48 eyes (31.6%), followed by cystoid macular edema in 36 eyes (23.7%), vitreomacular traction in 28 eyes (18.4%), epiretinal membrane in 24 eyes (15.8%), and subfoveal serous detachment in 16 eyes (10.5%). Conclusion PRP may cause a temporary drop in vision in the early post laser phase, and causes macular morphology/thickness changes in eyes with PDR and without clinically significant macular edema. In this study, the change in central foveal thickness did not correlate with a change in visual acuity, and the type of diabetic macular edema on OCT appeared more relevant and correlated better with the visual outcome.
The Drosophila cytokine receptor Domeless controls border cell migration and epithelial polarization during oogenesis

In mammals, the JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) signaling pathway is activated in response to cytokines and growth factors to control blood cell development, proliferation and cell determination. In Drosophila, a conserved JAK/STAT signaling pathway controls segmentation in embryos, as well as blood cell development and other processes in larvae and adults. During embryogenesis, transduction of the Unpaired [Upd; also known as Outstretched (Os)] ligand through the JAK/STAT pathway requires Domeless, a putative membrane protein with distant homology to vertebrate type I cytokine receptors. We have isolated domeless (dome) in a screen to identify genes essential in epithelial morphogenesis during oogenesis. The level of dome activity is critical for proper border cell migration and is controlled in part through a negative feedback loop. In addition to its essential role in border cells, we show that dome is required in the germarium for the polarization of follicle cells during encapsulation of germline cells. In this process, dome controls the expression of the apical determinant Crumbs. In contrast to the ligand Upd, whose expression is limited to a pair of polar cells at both ends of the egg chamber, dome is expressed in all germline and follicle cells. However, the Dome protein is specifically localized at apicolateral membranes and undergoes ligand-dependent internalization in the follicle cells. dome mutations interact genetically with JAK/STAT pathway genes in border cell migration and abolish the nuclear translocation of Stat92E in vivo. We also show that dome functions downstream of upd and that both the extracellular and intracellular domains of Dome are required for JAK/STAT signaling. Altogether, our data indicate that Dome is an essential receptor molecule for Upd and JAK/STAT signaling during oogenesis.
Context-aware Argumentative Relation Mining

Context is crucial for identifying argumen-tative relations in text, but many argument mining methods make little use of contextual features. This paper presents context-aware argumentative relation mining that uses features extracted from writing topics as well as from windows of context sentences. Experiments on student essays demonstrate that the proposed features improve predictive performance in two argu-mentative relation classiﬁcation tasks
Transcriptomic Analysis of Phenotypic Changes in Birch (Betula platyphylla) Autotetraploids

Plant breeders have focused much attention on polyploid trees because of their importance to forestry. To evaluate the impact of intraspecies genome duplication on the transcriptome, a series of Betula platyphylla autotetraploids and diploids were generated from four full-sib families. The phenotypes and transcriptomes of these autotetraploid individuals were compared with those of diploid trees. Autotetraploids were generally superior in breast-height diameter, volume, leaf, fruit and stoma and were generally inferior in height compared to diploids. Transcriptome data revealed numerous changes in gene expression attributable to autotetraploidization, which resulted in the upregulation of 7052 unigenes and the downregulation of 3658 unigenes. Pathway analysis revealed that the biosynthesis and signal transduction of indoleacetate (IAA) and ethylene were altered after genome duplication, which may have contributed to phenotypic changes. These results shed light on variations in birch autotetraploidization and help identify important genes for the genetic engineering of birch trees.
The Desirability Paradox in the Effects of Media Literacy Training

This study examines a paradox in findings regarding the effects of media literacy training on adolescents' decision making about tobacco use. Recent experiments have found that media literacy training successfully reduced participants' beliefs associated with risky behavior, whereas at the same time, their positive affect toward individuals portrayed in advertising increased. Study results confirm the hypothesis that media literacy training changes the way individuals think about the desirability of portrayals in the media. Although desirability usually represents individuals' affect toward portrayals, reports gathered after media literacy training also appear to reflect participants' increased awareness of the efforts made by advertisers to produce attractive portrayals designed to sell products and services. This awareness reduces or eliminates the impact that positive affect otherwise would have on decision making. Because this analysis suggests that individuals may respond to survey questions differently depending on their level of skill or involvement, the results raise important issues regarding issues of reliability and validity that may extend well beyond tests of this theoretical model or particular evaluation.
High-resolution forest carbon stocks and emissions in the Amazon

Efforts to mitigate climate change through the Reduced Emissions from Deforestation and Degradation (REDD) depend on mapping and monitoring of tropical forest carbon stocks and emissions over large geographic areas. With a new integrated use of satellite imaging, airborne light detection and ranging, and field plots, we mapped aboveground carbon stocks and emissions at 0.1-ha resolution over 4.3 million ha of the Peruvian Amazon, an area twice that of all forests in Costa Rica, to reveal the determinants of forest carbon density and to demonstrate the feasibility of mapping carbon emissions for REDD. We discovered previously unknown variation in carbon storage at multiple scales based on geologic substrate and forest type. From 1999 to 2009, emissions from land use totaled 1.1% of the standing carbon throughout the region. Forest degradation, such as from selective logging, increased regional carbon emissions by 47% over deforestation alone, and secondary regrowth provided an 18% offset against total gross emissions. Very high-resolution monitoring reduces uncertainty in carbon emissions for REDD programs while uncovering fundamental environmental controls on forest carbon storage and their interactions with land-use change.
Peroxisomal Ubiquitin-Protein Ligases Peroxin2 and Peroxin10 Have Distinct But Synergistic Roles in Matrix Protein Import and Peroxin5 Retrotranslocation in Arabidopsis1[W][OPEN]

Two Arabidopsis membrane peroxins contribute to peroxisomal matrix protein import via distinct roles in recycling and degrading a matrix receptor protein. Peroxisomal matrix proteins carry peroxisomal targeting signals (PTSs), PTS1 or PTS2, and are imported into the organelle with the assistance of peroxin (PEX) proteins. From a microscopy-based screen to identify Arabidopsis (Arabidopsis thaliana) mutants defective in matrix protein degradation, we isolated unique mutations in PEX2 and PEX10, which encode ubiquitin-protein ligases anchored in the peroxisomal membrane. In yeast (Saccharomyces cerevisiae), PEX2, PEX10, and a third ligase, PEX12, ubiquitinate a peroxisome matrix protein receptor, PEX5, allowing the PEX1 and PEX6 ATP-hydrolyzing enzymes to retrotranslocate PEX5 out of the membrane after cargo delivery. We found that the pex2-1 and pex10-2 Arabidopsis mutants exhibited defects in peroxisomal physiology and matrix protein import. Moreover, the pex2-1 pex10-2 double mutant exhibited severely impaired growth and synergistic physiological defects, suggesting that PEX2 and PEX10 function cooperatively in the wild type. The pex2-1 lesion restored the unusually low PEX5 levels in the pex6-1 mutant, implicating PEX2 in PEX5 degradation when retrotranslocation is impaired. PEX5 overexpression altered pex10-2 but not pex2-1 defects, suggesting that PEX10 facilitates PEX5 retrotranslocation from the peroxisomal membrane. Although the pex2-1 pex10-2 double mutant displayed severe import defects of both PTS1 and PTS2 proteins into peroxisomes, both pex2-1 and pex10-2 single mutants exhibited clear import defects of PTS1 proteins but apparently normal PTS2 import. A similar PTS1-specific pattern was observed in the pex4-1 ubiquitin-conjugating enzyme mutant. Our results indicate that Arabidopsis PEX2 and PEX10 cooperate to support import of matrix proteins into plant peroxisomes and suggest that some PTS2 import can still occur when PEX5 retrotranslocation is slowed.