Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients

TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC) patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS), overall survival (OS), and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype) to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10-4). It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023). In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002). The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.
Total and tropospheric BrO derived from GOME and SCIAMACHY as part of the temis project

Bromine monoxide plays an important role in the chemistry of the polar atmosphere because of its high efficiency as a catalyst of the ozone destruction in both the stratosphere and the troposphere. In the polar boundary layer, large cyclic emissions are observed every year at spring (the so-called "bromine explosion" phenomenon), which are responsible for the occurrence of fast and efficient tropospheric ozone destruction events. Total columns of BrO have been monitored by the GOME instrument onboard the ESA ERS-2 satellite since 1995. Since July 2002, similar observations can be obtained with SCIAMACHY on the ENVISAT platform. In the present contribution, analyses for total and tropospheric BrO columns derived from both instruments are described, with a focus on the assessment of their mutual consistency. Attempts to extract quantitative estimates of the tropospheric BrO contents over polar and mid-latitude regions are presented, using an algorithm that combines GOME measurements with SLIMCAT 3D chemical transport calculations. Key aspects of the tropospheric BrO retrieval and current sources of uncertainties are discussed.
Antioxidant Activity and Phenolic Content of Paederia foetida and Syzygium aqueum

The antioxidant activity of fresh and dried plant extracts of Paederia foetida and Syzygium aqueum were studied using β-carotene bleaching and the 2,2’-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) radical cation assay. The percentage of antioxidant activity for all extract samples using both assays was between 58 and 80%. The fresh samples of both plants had higher antioxidant activity than the dried samples. The results of the β-carotene bleaching assay were correlated (R2 = 0.9849) with those of the ABTS assay.
Fact-Checking Polarized Politics: Does The Fact-Check Industry Provide Consistent Guidance on Disputed Realities?

Abstract In the contemporary political environment of polarized claims about disputed realities, the online fact-check industry was born. These enterprises have received awards and praise but also accusations of bias and error, bringing their methods and conclusions into question. This paper examines the comparative epistemology of the three major fact-check sites: do they examine the same questions and reach the same conclusions? A content analysis of the published fact-checks addressing three disputed realties – the existence of climate change, the influence of racism, and the consequences of the national debt – suggests substantial differences in the questions asked and the answers offered, limiting the usefulness of fact-checking for citizens trying to decide which version of disputed realities to believe.
Upper esophageal sphincter mechanical states analysis: a novel methodology to describe UES relaxation and opening

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation of neural inputs to these muscles, the intrinsic cricopharyngeus muscle and extrinsic suprahyoid muscles, results in their contraction or relaxation, which changes the diameter of the lumen, alters the intraluminal pressure and ultimately inhibits or promotes flow of content. This relationship that exists between the changes in diameter and concurrent changes in intraluminal pressure has been used previously to calculate the “mechanical states” of the muscle; that is when the muscles are passively or actively, relaxing or contracting. Diseases that alter the neural pathways to these muscles can result in weakening the muscle contractility and/or decreasing the muscle compliance, all of which can cause dysphagia. Detecting these changes in the mechanical state of the muscle is difficult and as the current interpretation of UES motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during swallow can be missed. We hypothesized that quantification of mechanical states of the UES and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern the timing and extent of UES opening during swallowing. To achieve this we initially analyzed swallows captured by simultaneous videofluoroscopy and UES pressure with impedance recording. From these data we demonstrated that intraluminal impedance measurements could be used to determine changes in the internal diameter of the lumen when compared to videofluoroscopy. Then using a database of pressure-impedance studies, recorded from young and aged healthy controls and patients with motor neuron disease, we calculated the UES mechanical states in relation to a standardized swallowed bolus volume, normal aging and dysphagia pathology. Our results indicated that eight different mechanical states were almost always seen during healthy swallowing and some of these calculated changes in muscle function were consistent with the known neurally dependent phasic discharge patterns of cricopharyngeus muscle activity during swallowing. Clearly defined changes in the mechanical states were observed in motor neuron disease when compared to age matched healthy controls. Our data indicate that mechanical state predictions were simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.
An Analysis of Multiple Social Media Consultations in the European Parliament from a Public Policy Perspective

Government institutions of various levels have started experimenting with the use of social media for increasing citizens‟ involvement in their public policy making processes. It is necessary to evaluate systematically these initiatives from various perspectives, in order to develop new knowledge in this recently emerged area, concerning methods of social media exploitation in government, the value they can generate, and also the challenges they pose and their limitations. This paper contributes in this direction, by analysing three centrally managed multiple social media consulations conducted by Members of the European Parliament, from a public policy perspective, based on the wicked problems theory. It has been concluded that the above method of social media exploitation has a good potential for disseminating highly informative multimedia content on a policy under formulation to a much wider audience than the usual participants in the „traditional‟ European Parliament consultations, and also involving and stimulating them to think about the policy, leading to the collection of useful relevant ideas, knowledge and opinions, in a cost efficient manner. However, in order to go into more discussion depth it will be necessary to conduct further consultations, more focused on particular subtopics and participants. Furthermore,their outcomes should be combined and integrated with the ones of the „traditional‟ consultations and experts‟ studies. Finally, a critical success factor is to build wide, knowledgeable, diverse and pluralistic communities for these social media consultations, including various social actors with strong interest and good knowledge of the particular problem, and extending beyond the networks of the initiator.
Costs in inflammatory bowel diseases

Variables influencing total direct medical costs in inflammatory bowel diseases include country, diagnosis (generally, patients with Crohn's disease generated higher costs compared with patients with ulcerative colitis), and year since diagnosis. In all studies the mean costs were higher than the median costs, which indicates that a relatively small group of the most severely ill patients significantly affect the total cost of treatment of these diseases. A major component of direct medical costs was attributed to hospitalisation, ranging from 49% to 80% of the total. The costs of surgery constituted 40–61% of inpatient costs. Indirect costs in inflammatory bowel diseases, unappreciated and often underestimated (considered by few authors and as a loss of work), are in fact important and may even exceed direct medical costs.
The Association Between Childhood Maltreatment and Coping Strategies: The Indirect Effect Through Attachment

ABSTRACT Maladaptive coping strategies represent a potentially treatable component of psychopathologies associated with childhood abuse and neglect. Coping strategies are relatively stable constructs that may be viewed as trait-like behavioral manifestations of larger, albeit less accessible, intra- and interpersonal processes, such as activation of the attachment system. The authors investigated a potential mediational pathway from childhood maltreatment (in the form of physical and emotional abuse experiences) to coping strategies developed in emerging adulthood through attachment organization in a sample of undergraduate psychology research participants at a public Midwestern university (N = 225). Avoidant attachment patterns helped to explain the relationship between increased instances of childhood maltreatment and a decreased use of adaptive coping strategies. Further, both anxious and avoidant attachment mediated the relationship between childhood maltreatment and an increased use of maladaptive coping. By utilizing an attachment theory–informed approach as an explanatory guide, researchers and clinicians may be better able to conceptualize, study, and treat complex cases by understanding the underlying relationships between childhood maltreatment, attachment, and coping.
Fully reversible pulmonary arterial hypertension associated with dasatinib treatment for chronic myeloid leukaemia

To the Editors: Pulmonary arterial hypertension (PAH) is a devastating disease that is characterised by a progressive increase in pulmonary vascular resistance (PVR), chronic right heart failure and premature death. Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ( P pa) ≥25 mmHg at rest, and the haemodynamic definition discerns pre- and post-capillary PH [1]. Furthermore, PAH is distinguished from other forms of PH that may occur secondary to various underlying causes, including left heart disease, chronic lung disorders and thromboembolic disease [1]. Although the development of targeted PAH therapies, such as endothelin receptor antagonists, phosphodiesterase type-5 inhibitors (PDE5i) and prostanoids, has markedly improved the clinical situation and outcome of affected patients, the current medical treatment of PAH is not satisfactory. Recently, tyrosine kinase inhibitors (TKIs), particularly imatinib, have been proposed as a potential novel treatment option in PAH [2–7]. Imatinib was the first TKI that achieved regulatory approval for the treatment of chronic myeloid leukaemia (CML) and has become the standard of care for patients with this disease, as it inhibits the hybrid BCR–ABL oncogene that is pathogenic in the development of CML. Imatinib inhibits several tyrosine kinases, including BCR–ABL, the platelet-derived growth factor receptor (PDGFR) and c-Kit. More recently, additional TKIs, including dasatinib and nilotinib, have been introduced for the treatment of CML in patients who are intolerant or unresponsive to imatinib. The potential efficacy of imatinib in PAH is attributable to its inhibitory effect on the PDGFR. Platelet-derived growth factor (PDGF) is thought to play a pivotal role in the pathobiology of PAH by initiating and maintaining the underlying pulmonary vascular remodelling [7, 8]. Consistent with this, inhibition of PDGFR signalling by imatinib was recently shown to reverse PAH in animal models, and to …
First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy.

UNLABELLED Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as "undruggable. " We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development. SIGNIFICANCE This is the fi rst study of a STAT3-selective inhibitor in humans and the fi rst evidence that a transcription factor decoy can be modifi ed to enable systemic delivery. These findings have therapeutic implications beyond STAT3 to other “undruggable” targets in human cancers.
Mode of action of dysgalacticin: a large heat-labile bacteriocin.

OBJECTIVES The mode of action of dysgalacticin, a large (21.5 kDa), heat-labile bacteriocin that is active against the human pathogen Streptococcus pyogenes, was investigated. METHODS We used recombinant dysgalacticin to determine its mode of action against S. pyogenes. Antimicrobial activity of dysgalacticin was determined by MIC assays and viability counts. The extracellular pH of glucose-energized S. pyogenes cell suspensions was measured to determine the influence of dysgalacticin on glucose fermentation. To examine the effect of dysgalacticin on glucose transport, uptake of [14C]glucose and the non-metabolizable analogue [3H]2-deoxyglucose (2DG) was measured. Furthermore, the effect of dysgalacticin on membrane integrity, intracellular potassium concentration, membrane potential and [14C]serine uptake was determined. RESULTS Dysgalacticin was bactericidal towards S. pyogenes and inhibited glucose fermentation by non-growing cell suspensions. Dysgalacticin blocked transport of both glucose and 2DG, indicating that dysgalacticin targets the phosphoenolpyruvate-dependent glucose- and mannose-phosphotransferase system (PTS) of S. pyogenes. This inhibitory activity was voltage-independent, and in addition to the inhibition of glucose transport, dysgalacticin increased the permeability of the cytoplasmic membrane mediating leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [14C]serine uptake, a membrane potential-dependent process in S. pyogenes. CONCLUSIONS Taken together, these data indicate that dysgalacticin targets the glucose- and/or mannose-PTS as a receptor leading to inhibition of sugar uptake. As a result of this interaction, dysgalacticin perturbs membrane integrity leading to loss of intracellular K+ ions and dissipation of the membrane potential, ultimately leading to cell death.
A Framework for Evaluating Speech Representations

Listeners track distributions of speech sounds along perceptual dimensions. We introduce a method for evaluating hypotheses about what those dimensions are, using a cognitive model whose prior distribution is estimated directly from speech recordings. We use this method to evaluate two speaker normalization algorithms against human data. Simulations show that representations that are normalized across speakers predict human discrimination data better than unnormalized representations, consistent with previous research. Results further reveal differences across normalization methods in how well each predicts human data. This work provides a framework for evaluating hypothesized representations of speech and lays the groundwork for testing models of speech perception on natural speech recordings from ecologically valid settings.
ThinkHome Energy Efficiency in Future Smart Homes

Smart homes have been viewed with increasing interest by both home owners and the research community in the past few years. One reason for this development is that the use of modern automation technology in the home or building promises considerable savings of energy, therefore, simultaneously reducing the operational costs of the building over its whole lifecycle. However, the full potential of smart homes still lies fallow, due to the complexity and diversity of the systems, badly engineered and configured installations, as well as the frequent problem of suboptimal control strategies. Summarized, these problems converge to two undesirable conditions in the "not-so-smart" home: energy consumption is still higher than actually necessary and users are unable to yield full comfort in their automated homes. This work puts its focus on alleviating the current problems by proposing a comprehensive system concept, that shall ensure that smart homes can keep their promise in the future. The system operates on an extensive knowledge base that stores all information needed to fulfill the goals of energy efficiency and user comfort. Its intelligence is implemented as and within a multiagent system that also caters for the system's openness to the outside world. As a first evaluation, a profile-based control strategy for thermal comfort is developed and verified by means of simulation.
ANOMALOUS COURSE OF THE MEDIAL SURAL CUTANEOUS NERVE AND ITS CLINICAL IMPLICATIONS

The sural nerve is formed by the union of the medial sural cutaneous nerve, which is a branch of the main trunk (the tibial nerve), and the common fibular communicating branch of the lateral sural cutaneous nerve, which is a branch of the common fibular nerve. Anatomical variations in the formation of the sural nerve are common, although the topographical localization of this nerve is constant. In this report, we describe three cases of an anomalous course of the medial sural cutaneous nerve which descended through the gastrocnemius via a tunnel formed within the muscle. Such anatomical variations of the sural nerve are clinically important when evaluating sensory axonal loss in distal axonal neuropathies since sural nerve mononeuropathy is less likely to occur.
The moderating effects of protective and risk factors on outcomes for behavioral smoking cessation treatment

THE MODERATING EFFECTS OF PROTECTIVE AND RISK FACTORS ON OUTCOMES FOR BEHAVIORAL SMOKING CESSATION TREATMENT by HOLLY H. REID August 2016 Advisor: Paul A. Toro, Ph.D. Major: Clinical Psychology Degree: Doctor of Philosophy The rate of cigarette smoking is three-fold higher among adults living with Human Immunodeficiency Virus (HIV)/Autoimmune Deficiency Syndrome (AIDS) than in the general population (Centers for Disease Control and Prevention, 2015). Relative to nonsmoking HIV-positive adults, HIV-positive cigarette smokers have even higher mortality rates, more physical health problems, greater tobacco-related health disparities, lower quality of life, and more barriers to treatment. These barriers are often interrelated with the significantly higher rate of trauma and violence exposure reported in both cigarette smokers and persons living with HIV/AIDS (PLWHA; CDC). Violence exposure not only predicts emotional distress and substance use, but also mediates between victimization and cigarette use (e.g., Feldner, Babson, & Zvolensky, 2007). Psychological and physical trauma additionally impact both short and long-term substance use treatment outcomes, independent of treatment modality (e.g., Ford et al., 2007). Though social support is consistently linked to both smoking behaviors, and mental and behavioral outcomes for PLWHA, few studies have examined the role of social support in smoking treatment among this population. Additionally, no studies have explored social and
FUNZIONI METACOGNITIVE, STILI DI ATTACCAMENTO E DIMENSIONI PATOLOGICHE

There has been some researchs over the years investigating the correlation between metacognition and attachment styles and between metacognition and mental states. The present study aims to examine the themes of metacognition and attachment in depth, assessing the hypotesis that certain symptomatic aspects could be correlated to specific metacognitive functions and particular attachment styles. An analysis was also made of the correlation between the latter two variables. The research sample consisted of 30 Italian subjects, male and female, aged between 25 and 60 years old. The test battery includes: Symptom Checklist -90-Revised (SCL-90R); Attachment Scale Questionnaire (ASQ); MAS 4.0 Version for the metacognition evaluation; and Adult Attachment Interview (AAI). Our results showed greater level of insecurity in attachment relationships in those subjects with high scores in each of the scales concerning symptoms. An only one significant correlation was found between metacognitive functions and attachment styles. Moreover, subjects with anxious and depressive symptoms showed higher scores in only one of subscales concerning metacognitive functioning.