Miracle-dz/UniFAR-FTUs huggingface dataset:
Mediator Tail Module Is Required for Tac1-Activated CDR1 Expression and Azole Resistance in Candida albicans

ABSTRACT The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1 and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C terminus of Tac1. GOF mutations within the Tac1 TAD, outside the context of full-length Tac1, generally do not enhance its absolute potential as a transcriptional activator. Negative regulation of the Tac1 TAD by the Tac1 middle region is necessary for the activating effect of GOF mutations or fluphenazine to be realized. We have found that full-length Tac1, when hyperactivated by xenobiotics or GOF mutations, facilitates the recruitment of the Mediator coactivator complex to the CDR1 promoter. Azole resistance and the activation of Tac1 target genes, such as CDR1, are dependent on the Tac1 TAD and subunits of the Mediator tail module. The dependence of different Tac1 target promoters on the Mediator tail module, however, varies widely. Lastly, we show that hyperactivation of Tac1 is correlated with its Mediator-dependent phosphorylation, a potentially useful biomarker for Tac1 hyperactivation. The role of Mediator in events downstream of Tac1 hyperactivation in fluconazole-resistant clinical isolates is complex and provides opportunities and challenges for therapeutic intervention.
Normative aspects of the pediatric auditory brainstem response.

: The success of any test procedure that involves decision analysis must be based on sound principles, reasonably obtainable data, and a knowledge of response variability. The use of brainstem electric response audiometry (BERA) has gained a prominent role in the clinical assessment of auditory, otoneurologic, and neurologic deficits. However, the road to clinical utility has not been without obstacles. The brainstem response has been besieged with numerous variables which have curtailed universal acceptance and contributed to a lack of established standards. Before BERA is used with any degree of confidence, response variability must be defined and controlled. The purpose of this paper is to review those technical, physiologic, and pathologic conditions which affect response measurement.
CT grading of lung disease in lymphangioleiomyomatosis.

OBJECTIVE The aim of this study was to determine whether a CT-based method shows lung lesions, grades disease severity, and evaluates lung tissue in areas adjacent to or remote from cysts in patients with lymphangioleiomyomatosis (LAM), a cystic lung disease that may cause respiratory failure and death. MATERIALS AND METHODS Three hundred twenty-six CT examinations of 52 patients with LAM were studied. After the lungs had been divided into segments and images had been subdivided into texture blocks, a multidimensional feature vector was used to differentiate and group each texture block. Cysts were outlined, and texture around and away from cysts was analyzed. Sequential CT scans and pulmonary function test results were evaluated to assess the trend of change. Histopathologic examinations were performed of biopsy specimens from 45 patients. RESULTS Differences in texture features between areas adjacent to and areas remote from the cysts were observed. The cyst score and sum entropy in areas around the cysts correlated with lung function (p<0.0001). Emphysematouslike changes in noncystic areas were identified in lung tissue of 31 of 45 patients. CONCLUSION A computational method that uses texture analysis and feature correlation can identify and quantify cystic areas where LAM exists and can detect abnormalities in areas near cysts. Pathologic data also show lung damage in areas adjacent to cysts. Several texture features correlate with lung function. Declines in lung function paralleled changes in texture features. In LAM, cystic changes alone may not define the extent of lung destruction.
Neighbour Origin and Ploidy Level Drive Impact of an Alien Invasive Plant Species in a Competitive Environment

Our understanding of the potential mechanisms driving the spread and naturalization of alien plant species has increased over the past decades, but specific knowledge on the factors contributing to their increased impact in the introduced range is still urgently needed. The native European plant Centaurea stoebe occurs as two cytotypes with different life histories (monocarpic diploids, allo-polycarpic tetraploids). However, only tetraploids have been found in its introduced range in North America, where C. stoebe has become a most prominent plant invader. Here, we focus on the ploidy level of C. stoebe and origin of neighbouring community in explaining the high impact during the invasion of new sites in the introduced range. We conducted a mesocosm experiment under open-field conditions with the diploid (EU2x) and tetraploid (EU4x) cytotype of Centaurea stoebe from its native European (EU) range, and with the invasive tetraploid (NA4x) cytotype from the introduced North American (NA) range in competition with EU (old) or NA (new) neighbouring plant communities. In the presence of competition, the biomass of EU neighbouring community was reduced to a comparable level by all three geo-cytotypes of C. stoebe. In contrast, the biomass of the NA neighbouring community was reduced beyond when competing with tetraploid, but not with diploid C. stoebe. The fact that the biomass of all three geo-cytotypes of C. stoebe was correlated with the biomass of the EU neighbouring community, but not with that of the NA neighbouring community suggests that different mechanisms underlie the competitive interactions between C. stoebe and its old vs. new neighbouring communities, such as competition for the same limiting resources at home vs competition through novel allelo-chemicals or differential resource uptake strategies in the introduced range. We therefore caution to simply use the ecosystem impact assessed at home to predict impact in the introduced range.
The difference of predictors for recurrence after catheter ablation of non-paroxysmal atrial fibrillation according to follow-up period.

The aim of this study was to assess the clinical and echocardiographic predictors for the recurrence of persistent atrial fibrillation (AF) after ablation during a long-term period.A total of 130 patients with persistent AF who had undergone radiofrequency catheter ablation (RFCA) were enrolled. We analyzed the relation between clinical parameters, echocardiographic parameters, and AF recurrences at 6 months, 1 year, and 2 years after ablation.During the 2-year follow-up, AF recurred in 61 patients (46.6%). In the 6 month follow-up, AF recurrence was associated only with total ablation time only. However, during the 1-year and 2-year follow-up periods, the presence of hypertension, impaired left atrial (LA) emptying fraction (eF) (≤ 20%), decreased LA appendage (LAA) emptying velocity (≤ 20 cm/sec), and LAAeF (≤ 20%) were correlated with AF recurrence (odds ratio [OR] = 1.87, 2.45, 1.93, and 2.15 respectively, P = 0.016, 0.004, 0.029, and 0.004 respectively). Among these factors, impaired LAeF was the only independent predictor of AF recurrence in multivariate analysis (OR = 2.81, P = 0.012). In patients with persistent AF who had undergone RFCA, the best predictor of AF recurrence after ablation varied according to the follow-up period. Diminished LA function was the only predictor of recurrence in the 2-year follow-up. Pre-procedural assessment of LA function might be helpful in selecting those patients who would benefit from RFCA.
Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in the rat brain are consistent with the tissue‐clearance rates of elemental manganese

Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in rat olfactory bulb (OB) and cortex were compared with the absolute manganese (Mn) concentrations from the corresponding excised tissue samples. In vivo T1 and T2 relaxation times were measured before, and at 1, 7, 28, and 35 d after intravenous infusion of 176 mg/kg MnCl2. The values of ΔR1, ΔR2, and absolute Mn concentration peaked at day 1 and then declined to near control levels after 28 to 35 d. The Mn bioelimination rate from the rat brain was significantly faster than that reported using radioisotope techniques. The R1 and R2 relaxation rates were linearly proportional to the underlying tissue Mn concentration and reflect the total absolute amount of Mn present in the tissue. The in vivo Mn r1 and r2 tissue relaxivities were comparable to the in vitro values for aqueous Mn2+. These results demonstrate that loss of manganese‐enhanced MRI (MEMRI) contrast after systemic Mn2+ administration is due to elimination of Mn2+ from the brain. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Impact of Chlamydia trachomatis in the reproductive setting: British Fertility Society Guidelines for practice

Chlamydia trachomatis infection of the genital tract is the most common sexually transmitted infection and has a world-wide distribution. The consequences of infection have an adverse effect on the reproductive health of women and are a common cause of infertility. Recent evidence also suggests an adverse effect on male reproduction. There is a need to standardise the approach in managing the impact of C. trachomatis infection on reproductive health. We have surveyed current UK practice towards screening and management of Chlamydia infections in the fertility setting. We found that at least 90% of clinicians surveyed offered screening. The literature on this topic was examined and revealed a paucity of solid evidence for estimating the risks of long-term reproductive sequelae following lower genital tract infection with C. trachomatis. The mechanism for the damage that occurs after Chlamydial infections is uncertain. However, instrumentation of the uterus in women with C. trachomatis infection is associated with a high risk of pelvic inflammatory disease, which can be prevented by appropriate antibiotic treatment and may prevent infected women from being at increased risk of the adverse sequelae, such as ectopic pregnancy and tubal factor infertility. Recommendations for practice have been proposed and the need for further studies is identified.
Effect of A549 neuroendocrine differentiation on cytotoxic immune response

The present study was designed to determine the effects of factors secreted by the lung adenocarcinoma cell line with the neuroendocrine phenotype, A549NED, on cytotoxic T lymphocytes (CTLs) activity in vitro. A perspective that integrates the nervous, endocrine and immune system in cancer research is essential to understand the complexity of dynamic interactions in tumours. Extensive clinical research suggests that neuroendocrine differentiation (NED) is correlated with worse patient outcomes; however, little is known regarding the effects of neuroendocrine factors on the communication between the immune system and neoplastic cells. The human lung cancer cell line A549 was induced to NED (A549NED) using cAMP-elevating agents. The A549NED cells showed changes in cell morphology, an inhibition of proliferation, an overexpression of chromogranin and a differential pattern of biogenic amine production (decreased dopamine and increased serotonin [5-HT] levels). Using co-cultures to determine the cytolytic CTLs activity on target cells, we showed that the acquisition of NED inhibits the decrease in the viability of the target cells and release of fluorescence. Additionally, the conditioned medium of A549NED and 5-HT considerably decreased the viability and proliferation of the Jurkat cells after 24 h. Thus, our study successfully generated a neuroendocrine phenotype from the A549 cell line. In co-cultures with CTLs, the pattern of secretion by A549NED impaired the proliferation and cytotoxic activity of CTLs, which might be partly explained by the increased release of 5-HT.
Innovative Medical Devices for Telemedicine Applications

Telemedicine is a term generally used to describe a type of patient care which involves monitoring of a patient's condition by a healthcare worker located at a healthcare facility which is remote with respect to the location of the patient. Demand for electronic patient monitoring systems will appreciably grow in next years, bolstered by technological advances. Wireless multi-parameter monitors and stations will place gains in equipment sales. Although telemedicine systems have been implemented for many years, Ethernet has just begun to be implemented in the last decade. A much more cost-effective solution would be to take advantage of the already existing Internet. Moreover, the spread of wireless technology allows the development of more telemedicine devices with a low or no cost connections, at short or long distance, and also wearable and easily portable. From this point of view, telemedicine is defined as the delivery of health care and sharing of medical knowledge over distance using telecommunication means. Thus, telemedicine aims to provide expert-based health care to understaffed remote sites and advanced emergency care through modern telecommunication and information technologies. This concept of telemedicine was introduced about 30 years ago through the use of nowadays-common technologies like telephone and facsimile machines. Nowadays, telemedicine integrates network and medical technology, generally comprising remote diagnosis, expert consultation, information service, online checkups, remote communication, etc. Based on computers and network communication, it implements remote transfer, storage, query, comparison, display, and sharing of video and audio information and medical data of a patient. The availability of prompt and expert medical care can meaningfully improve health care services at understaffed rural or remote areas. Then, telemedicine, if adequately employed, is capable of providing enormous benefits to society. One such benefit is that patients can be examined without having to travel to a healthcare facility. This feature is particularly important for patients who live in remote areas who may not be able to easily travel to the nearest healthcare facility, or who need to be examined by a healthcare worker located far away from the patient, in another State, for example. Another benefit of telemedicine is that it is capable of allowing a patient to be examined more often than would be possible if the patient were required to travel to a healthcare facility due to the ease with which it can be administered.
Effects of transdermal testosterone treatment on inflammatory markers in elderly males.

OBJECTIVE During the male aging process, testosterone (T) levels progressively fall and inflammatory biomarkers increase. Although a relationship between these 2 phenomena has been tested in previous clinical trials, there is inconclusive evidence about the potential anti-inflammatory action of T. METHODS A total of 108 healthy males >65 years with serum T concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University and randomized to 60-cm2 T or a placebo patch for 36 months. Ninety-six subjects completed the trial. Information and stored serum specimens from this trial were used to test the hypothesis of the inhibitory effect of T on inflammation. We evaluated 70 males (42 in the T group) who had banked specimens from multiple time points available for assays of T, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, soluble TNF-α receptor-1 (TNFR1), interleukin-6 (IL-6), and soluble IL-6 receptors (sIL6r and sgp130). RESULTS The mean age ± SD at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months did not induce significant decreases in inflammatory markers. A trend toward a significant increase was observed in the placebo group for TNF-α (P = .03) and sgp130 (P = .01). Significant differences in estimated means of TNFR1 (but not other inflammatory markers), with lower levels in the T group, were observed at the 36-month time point. In T-treated subjects we found an almost significant treatment x time interaction term TNFR1 (P = .02) independent of total body fat content as assessed by dual energy X-ray absorptiometry (DXA). No serious adverse effect was observed. CONCLUSIONS Transdermal T treatment of older males for 36 months is not associated with significant changes in inflammatory markers.
The effect of academic education on employers’ satisfaction and audit quality in Iran

Purpose – The purpose of this paper is to examine the effect of academic education of auditors on the satisfaction of employees and the quality of audit reports. Design/methodology/approach – In order to collecting data a questionnaire designed and developed among the auditors, managers, and professors in Iran during November 20, 2014. Findings – The results of the study reveal that the inability to fully understand the audit report is one of the major problems of customers. For the audit firm, issues such as observation of accounting standards in financial statements, preparation of sufficient documents for the auditor, strong internal control, and understanding the limitations and problems of auditors were considered important. Originality/value – To the best of the authors’ knowledge the current paper is the first study which deals with the topic of the study in developing countries, especially Iran.
Scientific significance: This is an inspiring paper which includes a dynamic pelagic food chain as well as benthic food chain

Scientific significance: This is an inspiring paper which includes a dynamic pelagic food chain as well as benthic food chain. This is seldom seen in radioecology and hopefully opens up a world of new ideas in radioecology. At the same time it needs to maintain its connections to marine ecology, where the benthic and pelagic food webs have been studied for a long time. Thus it needs to be understandable both for radioecologist and marine ecologist, which can be difficult to achieve. Below are some comments how this can be improved. The presentation quality of paper is good, well written and structured, even if the connection between the two sites seem to be only the model and Cs. I don’t see any discussion or comparison what the difference is between the sites, just examples. The scientific quality has a good appearance, but when looking closer to the supporting model and references the results are weak. There is simple to little data to support the modelling results (exemplified below) . Moreover the scientific nomenclature is not consistent with e.g. marine ecological nomenclature and exact description of e.g. species.
Preliminary investigation of respiratory self‐gating for free‐breathing segmented cine MRI

Segmented cine MRI generally requires breath‐holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free‐breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self‐gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self‐gating technique uses interleaved radial k‐space sampling to provide low‐resolution images in real time during the free‐breathing acquisition that are compared to target expiration images. Only the raw data‐producing images with high correlation to the target images are included in the final high‐resolution reconstruction. The self‐gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath‐held techniques. Because of the difficulties associated with breath‐holding, the respiratory self‐gating technique represents an important practical advance for cardiac MRI. Magn Reson Med 53:159–168, 2005. Published 2004 Wiley‐Liss, Inc.
Alterations in fatty acid metabolism and sirtuin signaling characterize early type‐2 diabetic hearts of fructose‐fed rats

Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.
Negative signaling by inhibitory receptors: the NK cell paradigm

Summary: Receptors carrying immunoreceptor tyrosine‐based inhibition motifs (ITIMs) in their cytoplasmic tail control a vast array of cellular responses, ranging from autoimmunity, allergy, phagocytosis of red blood cells, graft versus host disease, to even neuronal plasticity in the brain. The inhibitory function of many receptors has been deduced on the basis of cytoplasmic ITIM sequences. Tight regulation of natural killer (NK) cell cytotoxicity and cytokine production by inhibitory receptors specific for major histocompatibility complex class I molecules has served as a model system to study the negative signaling pathway triggered by an ITIM‐containing receptor in the physiological context of NK–target cell interactions. Advances in our understanding of the molecular details of inhibitory signaling in NK cells have provided a conceptual framework to address how ITIM‐mediated regulation controls cellular reactivity in diverse cell types.