Miracle-dz/UniFAR-FTUs huggingface dataset:
Methionine is required for cAMP‐PKA‐mediated morphogenesis and virulence of Candida albicans

Candida albicans is a major human fungal pathogen, causing superficial, as well as life‐threatening invasive infections. Therefore, it has to adequately sense and respond to the host defense by expressing appropriate virulence attributes. The most important virulence factor of C. albicans is the yeast‐to‐hyphae morphogenetic switch, which can be induced by numerous environmental cues, including the amino acid methionine. Here, we show an essential role for methionine permease Mup1 in methionine‐induced morphogenesis, biofilm formation, survival inside macrophages and virulence. Furthermore, we demonstrate that this process requires conversion of methionine into S‐adenosyl methionine (SAM) and its decarboxylation by Spe2. The resulting amino‐propyl group is then used for biosynthesis of polyamines, which have been shown to activate adenylate cyclase. Inhibition of the SPE2 SAM decarboxylase gene strongly impairs methionine‐induced morphogenesis on specific media and significantly delays virulence in the mouse systemic infection model system. Further proof of the connection between methionine uptake and initial metabolism and the cAMP‐PKA pathway was obtained by showing that both Mup1 and Spe2 are required for cAMP production in response to methionine. Our results suggest that amino acid transport and further metabolism are interesting therapeutic targets as inhibitors of this may prevent the morphogenetic switch, thereby preventing virulence.
Indirect Factors Affecting Personal Solvency: Empirical Analysis Of Lithuanian Consumer Credit Market

The aim of this article is to analyze the interrelationship between solvencies of consumer credits customers and indirect factors such as borrowing motivation as well as demographical and socioeconomic factors characterizing the borrowers’ personality. The results of this research were obtained using statistical software SPSS. Systemic scientific literature analysis, correlation analysis of randomly selected records from consumer credit contracts, Student t-test criteria application for testing hypothesis, analysis of Levine's and Pearson’s correlation criteria are used in the article. In addition, previously carried out expert evaluation research results were compared with actual consumer credit contracts data. The novelty of this research is classification of factors influencing personal solvency into direct and indirect. The influence of indirect factors (demographic, socioeconomic and borrowing motives) has been investigated in risky consumer credit market of Lithuania. The results show that the most influencing indirect factor is the purpose of consumer credit.
Theory on resistance of m × n cobweb network and its application

A basic theorem of equivalent resistance between two arbitrary nodes in an m × n cobweb network in both finite and infinite conditions is discovered, and two conjectures on the equivalent resistance are proved in terms of the basic theorem. We built a tridiagonal matrix equation by means of network analysis and made a diagonalization method of matrix transformation and work out its explicit expressions. The new formulae obtained here can be effectively applied in complex impedance network, especially the formulation leads to the occurrence of resonances and a series of novel results in RLC (denote resistor, inductance and capacitance) network. These curious results suggest the possibility of practical applications to resonant circuits. Copyright © 2014 John Wiley & Sons, Ltd.
Investigating Novel Resistance Mechanisms to Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib in Non–Small Cell Lung Cancer Patients

Purpose: The third-generation EGFR tyrosine kinase inhibitor osimertinib is approved to treat patients with EGFR T790M-positive non–small cell lung cancer (NSCLC) who have developed resistance to earlier-generation drugs. Acquired EGFR C797S mutation has been reported to mediate osimertinib resistance in some patients. However, the remaining resistance mechanisms are largely unknown. Experimental Design: We performed mutation profiling using targeted next-generation sequencing (NGS) for 416 cancer-relevant genes on 93 osimertinib-resistant lung cancer patients' samples, mainly cell-free DNAs (cfDNAs), and matched pretreatment samples of 12 patients. In vitro experiments were conducted to functionally study the secondary EGFR mutations identified. Results: EGFR G796/C797, L792, and L718/G719 mutations were identified in 24.7%, 10.8%, and 9.7% of the cases, respectively, with certain mutations coexisting in one patient with different prevalence. L792 and L718 mutants markedly increased the half inhibitory concentration (IC50) of osimertinib in vitro, among which the L718Q mutation conferred the greatest resistance to osimertinib, as well as gefitinib resistance when not coexisting with T790M. Further analysis of the 12 matched pretreatment samples confirmed that these EGFR mutations were acquired during osimertinib treatment. Alterations in parallel or downstream oncogenes such as MET, KRAS, and PIK3CA were also discovered, potentially contributing to the osimertinib-resistance in patients without EGFR secondary mutations. Conclusions: We present comprehensive mutation profiles of a large cohort of osimertinib-resistance lung cancer patients using mainly cfDNA. Besides C797 mutations, novel secondary mutations of EGFR L718 and L792 residues confer osimertinib resistance, both in vitro and in vivo, and are of great clinical and pharmaceutical relevance. Clin Cancer Res; 24(13); 3097–107. ©2018 AACR.
Lean Mass and Fat Mass as Mediators of the Relationship Between Physical Activity and Bone Mineral Density in Postmenopausal Women

Background: The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women. Materials and Methods: This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD. Results: In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively. Conclusion: LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.
Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3

In human trophoblast cells, cyclic AMP or its inducer forskolin (FSK) activates two downstream signaling molecules, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), both of which induce syncytialization, cell fusion, and the production of human chorionic gonadotropin (hCG) and progesterone. However, a transcription factor other than GCM1 and molecular mechanisms associated with these events have not been well characterized. To identify novel transcription factors involved in syncytialization of cAMP‐stimulated human choriocarcinoma BeWo cells, the microarray analysis was performed with RNAs extracted from PKA‐ or EPAC‐selective cAMP analog‐stimulated BeWo cells, from which two up‐regulated transcription factors, STAT5 and NR4A3, were found. The knockdown of STAT5B decreased FSK‐induced cell fusion and the expression of syncytialization markers, CGB, syncytin1, syncytin2, GCM1, and OVOL1, but NR4A3 knockdown increased FSK‐induced cell fusion and the expression of CGB and syncytin2. These findings indicated that cAMP‐PKA up‐regulated STAT5B, followed by increase in syncytin2 expression through GCM1 and OVOL1, resulting in cell fusion and hCG production, while cAMP‐PKA‐up‐regulated NR4A3 could decrease syncytin2 expression, and suggested that both positive and negative effects of STAT5B and NR4A3, respectively, are required to control the degree of syncytialization in human trophoblast cells.
Investigation of the Relationship between Anterior Knee Pain and Chondromalacia Patellae and Patellofemoral Malalignment.

Objective The study aimed to investigate whether there is any association of anterior knee pain and knee function with chondromalacia stage and patellofemoral alignment in patients with anterior knee pain for over a month and with chondromalacia patellae (CMP) detected by magnetic resonance imaging (MRI). Materials and Methods We reviewed the medical records of 38 patients who underwent a knee MRI examination and were diagnosed with chondromalacia based on the MRI. Knee MRI images were evaluated by a radiologist for chondromalacia staging. Patients were divided into two groups as early stage (stage 1-2) and advanced stage (stage 3-4) chondromalacia. Patients' demographical data (age, sex, and occupation), clinical features, physical examination findings and patellofemoral pain severity scale, kujala patellofemoral scoring system, and functional index questionnaire scores were obtained from their medical records. Trochlear sulcus angle, sulcus depth, lateral patellofemoral angle, patellar translation, and Insall-Salvati index were measured using the MRI images. Results The mean patient age was higher in the advanced stage CMP group compared to the early stage CMP group (p=0.038). There was no statistically significant difference regarding other demographical data (p>0.05). MRI measurement parameters did not show difference between the groups (p>0.05). Patients in the advanced stage CMP group had higher patellofemoral pain severity score, lower kujala patellofemoral score, and lower functional index questionnaire score compared to the early stage CMP group. The differences were statistically significant (p=0.008, p=0.012, and p=0.026, respectively). Conclusion As chondromalacia stage advances, the symptom severity worsens and knee functions decline; however, MRI measurements do not show difference between early and advanced stage CMP patients.
A synthesis of genetic connectivity in deep‐sea fauna and implications for marine reserve design

With anthropogenic impacts rapidly advancing into deeper waters, there is growing interest in establishing deep‐sea marine protected areas (MPAs) or reserves. Reserve design depends on estimates of connectivity and scales of dispersal for the taxa of interest. Deep‐sea taxa are hypothesized to disperse greater distances than shallow‐water taxa, which implies that reserves would need to be larger in size and networks could be more widely spaced; however, this paradigm has not been tested. We compiled population genetic studies of deep‐sea fauna and estimated dispersal distances for 51 studies using a method based on isolation‐by‐distance slopes. Estimates of dispersal distance ranged from 0.24 km to 2028 km with a geometric mean of 33.2 km and differed in relation to taxonomic and life‐history factors as well as several study parameters. Dispersal distances were generally greater for fishes than invertebrates with the Mollusca being the least dispersive sampled phylum. Species that are pelagic as adults were more dispersive than those with sessile or sedentary lifestyles. Benthic species from soft‐substrate habitats were generally less dispersive than species from hard substrate, demersal or pelagic habitats. As expected, species with pelagic and/or feeding (planktotrophic) larvae were more dispersive than other larval types. Many of these comparisons were confounded by taxonomic or other life‐history differences (e.g. fishes being more dispersive than invertebrates) making any simple interpretation difficult. Our results provide the first rough estimate of the range of dispersal distances in the deep sea and allow comparisons to shallow‐water assemblages. Overall, dispersal distances were greater for deeper taxa, although the differences were not large (0.3–0.6 orders of magnitude between means), and imbalanced sampling of shallow and deep taxa complicates any simple interpretation. Our analyses suggest the scales of dispersal and connectivity for reserve design in the deep sea might be comparable to or slightly larger than those in shallow water. Deep‐sea reserve design will need to consider the enormous variety of taxa, life histories, hydrodynamics, spatial configuration of habitats and patterns of species distributions. The many caveats of our analyses provide a strong impetus for substantial future efforts to assess connectivity of deep‐sea species from a variety of habitats, taxonomic groups and depth zones.
Sprint interval training on the vertical treadmill improves aerobic and anaerobic running performance

The vertical treadmill (VertiRun) is an unresearched mode of exercise where users engage in a “running-like” action whilst body weight is supported by a recumbent bench and overhanging resistance cables are tethered to the user’s ankles. The purpose of this study was to determine the effects of training on a VertiRun and any cross-training effect on running performance. Thirty active males (age, 22±4 years; stature, 1.79±0.08 m; body mass, 78.5±12.6 kg) volunteered for this study. Participants’ aerobic and anaerobic running performance were determined by incremental maximum rate of oxygen consumption (VO2max) treadmill test and a maximum anaerobic running test (MART), respectively. Participants were matched and then randomly assigned to either a VertiRun group, 20-m shuttle sprint group or control group. The intervention consisted of 4–6, 30-sec all-out efforts with 4-min recovery between bouts, 3 days a week for 6 weeks. The pre- and postintervention VO2max and MART were analysed using a mixed repeated measures analysis of variance. MART increased by 4.5% in the VertiRun group (P=0.006) and 4% in the sprint group (P<0.001). VO2max increased by 6.2% in the VertiRun group (P=0.009) and 5.5% in the sprint group (P=0.020). The MART and VO2max of the control group were unchanged (P=0.910 and P=0.915, respectively). These data suggest that the VertiRun could be an effective cross-training mode for running and could supplement training programmes. Also, as VertiRun is a low-impact exercise it might be useful in the physical preparation of athletes returning to sport following lower limb injury.
Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst.

ABSTRACT We report the case of a 14-year-old girl with a wide non-compressive pineal cyst, associated with the inability to control her sleep-wake schedule. Actigraphic monitoring showed a 24-hour free-running disorder (tau 26.96 hours). A 24-hour serum melatonin curve assay, with concomitant video-polysomnographic and body-core temperature monitoring, was performed. Melatonin curve showed a blunted nocturnal peak, lower total quantity of melatonin, and prolonged melatonin secretion in the morning, with normal temperature profile and sleep parameters. Treatment with melatonin up to 14 mg at bedtime was initiated with complete realignment of the sleep-wake rhythm (tau 23.93 hours). The role of the pineal cyst in the aforementioned alteration of melatonin secretion and free-running disorder remains controversial, but our case supports the utility of monitoring sleep/wake, temperature, and melatonin rhythms in the diagnostic work-up of pineal cysts associated with free-running disorder.
Investigating cranial morphological variation of early human skeletal remains from Chile: A 3D geometric morphometric approach.

OBJECTIVES Archaeological and genetic research has demonstrated that the Pacific Coast was a key route in the early colonization of South America. Research examining South American skeletons >8000 cal BP has revealed differences in cranial morphology between early and late Holocene populations, which may reflect distinct migration events and/or populations. However, genetic, cultural, and some skeletal data contradict this model. Given these discrepancies, this study examines ∼9000 years of prehistory to test the hypothesis that Early skeletons have a distinct cranial morphology from later skeletons. MATERIALS AND METHODS Using 3D digital models, craniofacial landmarks, and geometric morphometric analyses, we compared Early Holocene crania (n = 4) to later Chilean samples (n = 90) frequently absent in continental assessments of craniofacial variation. PCA, Mahalanobis distances, posterior and typicality probabilities were used to examine variation. RESULTS Two of the earliest skeletons from northern Chile show clear affinities to individuals from later sites in the same region. However, the hypothesis cannot be rejected as one Early individual from northern Chile and one individual from inland Patagonia did not always show clear affinities to coastal populations. DISCUSSION Biological affinities among northern populations and other regions of Chile align with genetic and archaeological data, supporting cultural and biological continuity along the Pacific Coast. In Patagonia, archaeological data are in accordance with skeletal differences between the Early inland steppe individual and coastal populations. This study incorporates 3D methods and skeletal datasets not widely used in assessments of biological affinity, thus contributing to a critical body of research examining the ancient population history of western South America.
Outlining the influence of non‐conventional yeasts in wine ageing over lees

During the last decade, the use of innovative yeast cultures of both Saccharomyces cerevisiae and non‐Saccharomyces yeasts as alternative tools to manage the winemaking process have turned the oenology industry. Although the contribution of different yeast species to wine quality during fermentation is increasingly understood, information about their role in wine ageing over lees is really scarce. This work aims to analyse the incidence of three non‐Saccharomyces yeast species of oenological interest (Torulaspora delbrueckii, Lachancea thermotolerans and Metschnikowia pulcherrima) and of a commercial mannoprotein‐overproducer S. cerevisiae strain compared with a conventional industrial yeast strain during wine ageing over lees. To evaluate their incidence in mouthfeel properties of wine after 4 months of ageing, the mannoprotein content of wines was evaluated, together with other wine analytic parameters, such as colour and aroma, biogenic amines and amino acids profile. Some differences among the studied parameters were observed during the study, especially regarding the mannoprotein concentration of wines. Our results suggest that the use of T. delbrueckii lees in wine ageing is a useful tool for the improvement of overall wine quality by notably increasing mannoproteins, reaching values higher than obtained using a S. cerevisiae overproducer strain. Copyright © 2016 John Wiley & Sons, Ltd.
Phase retrieval using unitary 2-designs

We consider a variant of the phase retrieval problem, where vectors are replaced by unitary matrices, i.e., the unknown signal is a unitary matrix U, and the measurements consist of squared inner products |tr(C†U)|2 with unitary matrices C that are chosen by the observer. This problem has applications to quantum process tomography, when the unknown process is a unitary operation.
Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers

Endometriosis, although not malignant, has clinically demonstrated properties of invasiveness and metastasis. The pathogenesis of endometriosis, however, has not yet been elucidated. The immunological differences between endometriosis and malignant gynecologic tumors were analyzed by assessing C-type lectin receptors, which are associated with innate immunity, and immunoglobulin secretion, which is associated with B cell adaptive immunity, in the peritoneal fluid of these patients. Peritoneal fluid samples were obtained from 42 patients with benign masses (control group), 38 with endometriosis, and 43 with gynecologic (ovarian, uterine, and cervical) cancers. The levels of expression in these samples of mRNAs encoding the C-type lectin receptors Dectin-1, MR1, MR2, DC-SIGN, Syk, Card 9, Bcl 10, Malt 1, src, Dec 205, Galectin, Tim 3, Trem 1, and DAP 12, were measured by real-time reverse transcription polymerase chain reaction, and the concentrations of IgG, IgA and IgM were measured by enzyme-linked immunosorbent assays (ELISA). Findings in the three groups were compared. The level of galectin mRNA was significantly lower, and the levels of MR2 and DAP 12 mRNAs significantly higher, in the endometriosis than in the control group (p<0.05 each). Compared with the gynecologic cancer group, the level of Bcl 10 mRNA was significantly lower, and the levels of MR1, MR2, Syk, Card 9, Malt 1, Dec 205, Tim 3, and DAP 12 mRNAs significantly higher, in the endometriosis group (p<0.05 each). The levels of MR2 and DAP 12 mRNAs were significantly higher in the endometriosis than in the control group (p<0.05 each), whereas the level of galectin mRNA was similar in the endometriosis and gynecologic cancer groups. IgA and IgG concentrations in peritoneal fluid were significantly lower in the gynecologic cancer than in the control group (p<0.05 each). However, concentrations of all three immunoglobulins in the endometriosis group did not differ from those in the other two groups (p>0.05). C-type lectin receptors and immunoglobulins act cooperatively and are closely associated in the pathogenesis of endometriosis. The decreased expression of galectin mRNA in the peritoneal fluid of the endometriosis group suggests that endometriosis and gynecologic cancers have similar immunologic characteristics.
Contrast venography vs. microwire assisted axillary venipuncture for cardiovascular implantable electronic device implantation

Aims This study was conducted to compare the safety and efficacy of microwire assisted technique with contrast venography guided axillary venipuncture in patients undergoing cardiovascular implantable electronic device (CIED) implantation. Methods and results This prospective randomized study included 212 consecutive adult patients undergoing CIED implantation at our institute between 2013 and 2015. Patients were randomized to either venography guided technique (Group I; n = 105) or microwire assisted technique (Group II; n = 107) for axillary venipuncture. In Group I axillary venogram was used as a roadmap for guiding the puncture. In Group II, a 0.014 inch hydrophilic coronary guidewire ('microwire') was introduced through the ipsilateral antecubital vein and puncture needle was aimed to hit the microwire over the first or second rib. Outcome measures including technical success rates; number of attempts to successful puncture; puncture duration; fluoroscopy times and adverse events were compared in the two groups. Overall success rates were similar in both groups (97.4% in Group I and 100% in Group II, P = 0.061). We demonstrated significantly higher first attempt success rates; shorter puncture durations and fluoroscopy times; and lower number of attempts to successful puncture with microwire assisted technique (89.3% vs. 65.6%; 36.7 ± 23.1 s vs. 67.8 ± 44.9 s; 62.4 ± 35.3 s vs. 118.9 ± 63.2 s; and 1.21 ± 0.82 vs. 2.16 ± 1.54 respectively, P < 0.001). Adverse event rates were significantly lower with microwire assisted technique (0.9% vs. 8.6%, P = 0.009). Conclusion Microwire assisted technique is a simple, quicker, safer and more efficacious alternative to contrast venography guided axillary venipuncture.