julilili42/papers huggingface dataset:
Effect of 12 weeks of once-daily tiotropium/olodaterol on exercise endurance during constant work-rate cycling and endurance shuttle walking in chronic obstructive pulmonary disease
2018-01-01

Background: The TORRACTO ® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. Methods: The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients. Results: A total of 404 patients received treatment, with 165 participating in the ESWT substudy. A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 μg [14% ( p = 0.02)] but not with tiotropium/olodaterol 2.5/5 μg [9% ( p = 0.14)] versus placebo. In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 μg [21% ( p = 0.055)] and tiotropium/olodaterol 2.5/5 μg [21% ( p = 0.056)] versus placebo. Conclusion: Tiotropium/olodaterol 5/5 μg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time. [ ClinicalTrials.gov identifier: NCT01525615.]
Tacrolimus Suppositories in Therapy-Resistant Ulcerative Proctitis
2018-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Ulcerative proctitis may often be managed with topical salicylates or steroids alone, but in some patients, symptoms are persistent and severe. We analyzed the efficacy of tacrolimus suppositories in patients who had proven refractory to combined topical and systemic treatment. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this retrospective analysis, ulcerative colitis activity index (CAI), side effects, co-medication and drug levels were assessed in 43 patients with distal ulcerative colitis who received suppositories containing 2 mg of tacrolimus b.i.d. as add-on medication. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 23 patients with ulcerative proctitis presented to follow-up within ≤50 days (mean 27.0 days) after suppositories were started. A decrease in CAI (from 8.0 to 5.5 points) was observed and 52.3% reached clinical remission (CAI ≤4). In total, 43 patients were available for analysis, of whom 9 had inflammation of the sigmoid colon as well. For the entire cohort, the median treatment duration was 76 days; 60% were in remission on the last documented visit. Serum measurements revealed a substantial tacrolimus level with a mean of 5.5 ng/mL. We observed one case of mild reversible acute kidney injury. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In ulcerative proctitis, adding tacrolimus suppositories can be an effective and safe option when topical mesalazine, corticoid formulations and concomitant oral or parenteral medications have failed.
Organ transplantation and gut microbiota: current reviews and future challenges.
2018-01-01

Organ transplantation is often the only effective treatment for patients with end-stage diseases, such as heart, liver, kidney and small bowel failure and is carried out frequently worldwide. Still the post-transplantation complications remain health- and life-threatening outcome that needed to be resolved. With the rapid development of molecular technologies in recent years, more and more researchers realize that the gut microbiota may play a critical role in human diseases. The intestinal microbiome has been proved to provide a lot of functions to the host, such as digesting food, modulating metabolism, promoting angiogenesis and regulating the immune system. Several studies have investigated the alteration of intestinal microbiota in post-transplantation patients and observed significant changes in the intestinal microbiome compared to the pre-transplant condition. Due to the abovementioned features that the gut microbiota may be used in the prognosis of clinical outcome of organ transplantation. In addition, the FMT (fecal microbiota transplantation), probiotics and prebiotics as the newest therapy methods, effectiveness of which has been verified in some diseases, such as Clostridium difficile infection, inflammatory bowel disease and other chronic disorders, might be used as the prognosis tool in organ transplantation as well. The purpose of this present review is to elucidate the relationship between gut microbiota and organ transplantation as well as the potential use of new therapies like fecal microbiota transplantation, probiotic and prebiotic administration after the transplantation, and provide some ideas for future researches in field of organ transplantation.
6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells
2018-01-01

Background/Aims: Prenylnaringenins are natural prenylflavonoids with anticancer properties. However, the underlying mechanisms have not been elucidated yet. Here we report a novel mode of action of 6- and 8-prenylnaringenin (PN) on human melanoma cells: Inhibition of cellular histone deacetylases (HDACs). Methods: We performed in silico and in vitro analyses using 6-PN or 8-PN to study a possible interaction of 6-PN or 8-PN with HDAC as well as Western blot and FACS analyses, real-time cell proliferation and cell viability assays to assess the impact of 6-PN and 8-PN on human metastatic melanoma cells. Results: In silico, 6-PN and 8-PN fit into the binding pocket of HDAC2, 4, 7 and 8, binding to the zinc ion of their catalytic center that is essential for enzymatic activity. In vitro, 100 μmol/L of 6-PN or 8-PN inhibited all 11 conserved human HDAC of class I, II and IV. In clinical oncology HDAC inhibitors are currently investigated as new anticancer compounds. In line, treatment of SK-MEL-28 cells with 6-PN or 8-PN induced a hyperacetylation of histone complex H3 within 2 h. Further, 6-PN or 8-PN mediated a prominent, dose-dependent reduction of cellular proliferation and viability of SK-MEL-28 and BLM melanoma cells. This effect was apoptosis-independent and accompanied by down-regulation of mTOR-specific pS6 protein via pERK/pP90 in SK-MEL-28 cells. Conclusion: The identification of a broad inhibitory capacity of 6-PN and 8-PN for HDAC enzymes with antiproliferative effects on melanoma cells opens the perspective for clinical application as novel anti-melanoma drugs and the usage as innovative lead structures for chemical modification to enhance pharmacology or inhibitory activities.
Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?
2018-01-01

Objectives . To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). Patients and Methods . The study comprised 758 urine samples either collected from the bladder (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>373</mml:mn></mml:math>) or UUT (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>385</mml:mn></mml:math>). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. Results . UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions . Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.
Generating Feedback for English Foreign Language Exercises
2018-01-01

Björn Rudzewitz, Ramon Ziai, Kordula De Kuthy, Verena Möller, Florian Nuxoll, Detmar Meurers. Proceedings of the Thirteenth Workshop on Innovative Use of NLP for Building Educational Applications. 2018.
Structure-based protein engineering enables prenyl donor switching of a fungal aromatic prenyltransferase
2018-01-01

Structure-guided molecular modelling and site-directed mutagenesis of the tryptophan dimethylallyl transferase FgaPT2 led to creation of mutants with strongly enhanced activities towards geranyl and farnesyl diphosphates.
A Dilemma for ‘Selection-for-Action’
2018-01-01

One of the most influential recent accounts of attention is Wayne Wu’s. According to Wu, attention is selection-for-action. I argue that this proposal faces a dilemma: either it denies clear cases of attention capture, or it acknowledges these cases but classifies many inattentive episodes as attentive.
Quantitative Measurements of Motor Function in Alzheimer’s Disease, Frontotemporal Dementia, and Dementia with Lewy Bodies: A Proof-of-Concept Study
2018-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; This study examines the efficacy of using quantitative measurements of motor dysfunction, compared to clinical ratings, in Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this cross-sectional study, 49 patients with a diagnosis of AD (&lt;i&gt;n&lt;/i&gt; = 17), FTD (&lt;i&gt;n&lt;/i&gt; = 19), or DLB (&lt;i&gt;n&lt;/i&gt; = 13) were included and underwent cognitive testing, clinical motor evaluation, and quantitative motor tests: pronation/supination hand tapping, grasping and lifting, and finger and foot tapping. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Our results revealed significantly higher Q-Motor values in pronation/supination and in grip lift force assessment in AD, FTD, and DLB compared to healthy controls (HC). Q-Motor values detected significant differences between AD and HC, while clinical ratings did not. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Our results suggest that quantitative measurements provide more objective and sensitive measurements of motor dysfunction in dementia.
Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification
2018-01-01

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Hyperphosphatemia promotes medial vascular calcification, at least partly, by induction of osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). The complex signaling pathways regulating this process are still incompletely understood. The present study investigated the role of cytosolic serine hydroxymethyl transferase 1 (SHMT1) in phosphate-induced vascular calcification. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Endogenous expression of SHMT1 was suppressed by silencing in primary human aortic smooth muscle cells (HAoSMCs) followed by treatment without and with phosphate or antioxidants. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In HAoSMCs, &lt;i&gt;SHMT1&lt;/i&gt; mRNA expression was up-regulated by phosphate. Silencing of SHMT1 alone was sufficient to induce osteo-/chondrogenic transdifferentiation of HAoSMCs, as shown by increased tissue-nonspecific alkaline phosphatase (ALPL) activity and osteogenic markers &lt;i&gt;MSX2&lt;/i&gt;, &lt;i&gt;CBFA1&lt;/i&gt; and &lt;i&gt;ALPL&lt;/i&gt; mRNA expression. Furthermore, phosphate-induced &lt;i&gt;ALPL&lt;/i&gt; mRNA expression and activity as well as calcification were augmented in SHMT1 silenced HAoSMCs as compared to negative control siRNA transfected HAoSMCs. Silencing of SHMT1 decreased total antioxidant capacity and up-regulated NADH/NADPH oxidase system components &lt;i&gt;NOX4&lt;/i&gt; and &lt;i&gt;CYBA&lt;/i&gt; mRNA expression in HAoSMCs, effects paralleled by increased mRNA expression of matrix metalloproteinase &lt;i&gt;MMP2&lt;/i&gt; as well as &lt;i&gt;BAX/BCL2&lt;/i&gt; ratio. More importantly, additional treatment with antioxidants TEMPOL or TIRON blunted the increased osteogenic markers mRNA expression in SHMT1 silenced HAoSMCs. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Silencing of SHMT1 promotes osteo-/chondrogenic signaling in VSMCs, at least in part, by inducing cellular oxidative stress. It thus aggravates phosphate-induced calcification of VSMCs. The present findings support a regulatory role of SHMT1 in vascular calcification during conditions of hyperphosphatemia such as chronic kidney disease.
Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease
2018-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Eight percent of the human genome consists of human endogenous retroviruses (HERV). These genetic elements are remnants of ancient retroviral germ-line infections. Altered HERV expression is associated with several chronic inflammatory diseases. A physiological role of the HERV-derived proteins syncytin-1 and -2 has been described for the integrity of the human placental cell layer in terms of maintaining feto-maternal tolerance. The aim of this project was to investigate HERV expression in Crohn’s disease (CD) with a further focus on syncytins in the gut. &lt;b&gt;&lt;i&gt;Material and Methods:&lt;/i&gt;&lt;/b&gt; Seventy-four ileal and colonic tissue samples of CD patients and healthy controls have been investigated for mRNA expression of major HERV groups by a comprehensive microarray screening. The most prominent differences have been validated by qRT-PCR. Immunohistochemistry (IHC), Western Blot (WB) and qRT-PCR were performed for syncytin-1 and -2. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; HERV microarray screening revealed a distinct expression profile in ileal and colonic tissue, as well as differential expression in CD compared to healthy controls. qRT-PCR validated differential expression of at least 3 HERV-groups in CD. qRT-PCR, IHC and WB showed a tissue-dependent diminished epithelial expression of syncytins in inflamed CD. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; For the first time, HERV expression has been comprehensively studied in the gut. Between CD and healthy controls we could show a tissue dependent differential HERV expression profile. Notably, we could show that syncytin-1 and -2 are expressed in the epithelial layer in ileal and colonic tissue samples, whereas their diminished tissue-dependent expression in inflamed CD might modulate inflammatory processes at the gut barrier.
The Politics of the Ancestors
2018-01-01

Der Band gibt wichtige Impulse zur politischen Interpretation der Erzelternerzählungen. Die Beiträge fragen nach der politischen Intention verschiedener Teilerzählungen oder literarischer Schichten. Behandelt wird auch die politische Bedeutung der Ahnfrauen. Zudem wird der politischen Rezeption der Erzelternerzählungen in der frühjüdischen Literatur sowie im Islam nachgegangen
Synthesis of homometallic divalent lanthanide organoimides from benzyl complexes
2018-01-01

Double protonolysis of [Ln(CH<sub>2</sub>Ph)<sub>2</sub>]<sub>n</sub> (Ln = Eu and Yb) with 2,6-diisopropylaniline gives efficient access to [(thf)Ln(μ<sub>3</sub>-NDipp)]<sub>4</sub> featuring a heterocubane structure.
<i>NuSTAR</i> and NICER reveal IGR J17591-2342 as a new accreting millisecond X-ray pulsar
2018-01-01

We report the discovery by the Nuclear Spectroscopic Telescope Array ( NuSTAR ) and the Neutron Star Interior Composition Explorer (NICER) of the accreting millisecond X-ray pulsar IGR J17591–2342. Coherent X-ray pulsations around 527.4 Hz (1.9 ms) with a clear Doppler modulation were detected. This implies an orbital period of ∼8.8 h and a projected semi-major axis of ∼1.23 lt-s. With the binary mass function, we estimate a minimum companion mass of 0.42 M ⊙ , obtained assuming a neutron star mass of 1.4 M ⊙ and an inclination angle lower than 60°, as suggested by the absence of eclipses or dips in the light curve of the source. The broad-band energy spectrum, obtained by combining NuSTAR , swift and INTEGRAL observations, is dominated by Comptonisation of soft thermal seed photons with a temperature of ∼0.7 keV by electrons heated to 21 keV. We also detect black-body-like thermal direct emission that is compatible with an emission region of a few kilometers and a temperature compatible with the seed source of Comptonisation. A weak Gaussian line centred on the iron K α complex can be interpreted as a signature of disc reflection. A similar spectrum characterises the NICER spectra, which was measured when the outburst faded.
Novel variants identified with next-generation sequencing in Polish patients with cone-rod dystrophy.
2018-01-01

This is the first report on the spectrum of disease genes and pathogenic variants causing CRD in the Polish population. The study presents five novel variants identified in four genes and therefore, broadens the spectrum of probable pathogenic variants associated with CRD.
Hamiltonian Approach to QCD in Coulomb Gauge: A Survey of Recent Results
2018-01-01

We report on recent results obtained within the Hamiltonian approach to QCD in Coulomb gauge. Furthermore this approach is compared to recent lattice data, which were obtained by an alternative gauge-fixing method and which show an improved agreement with the continuum results. By relating the Gribov confinement scenario to the center vortex picture of confinement, it is shown that the Coulomb string tension is tied to the spatial string tension. For the quark sector, a vacuum wave functional is used which explicitly contains the coupling of the quarks to the transverse gluons and which results in variational equations which are free of ultraviolet divergences. The variational approach is extended to finite temperatures by compactifying a spatial dimension. The effective potential of the Polyakov loop is evaluated from the zero-temperature variational solution. For pure Yang–Mills theory, the deconfinement phase transition is found to be second order for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">U</mml:mi><mml:mo stretchy="false">(</mml:mo><mml:mn fontstyle="italic">2</mml:mn><mml:mo stretchy="false">)</mml:mo></mml:math> and first order for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">U</mml:mi><mml:mo stretchy="false">(</mml:mo><mml:mn mathvariant="normal">3</mml:mn><mml:mo stretchy="false">)</mml:mo></mml:math>, in agreement with the lattice results. The corresponding critical temperatures are found to be <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mn mathvariant="normal">275</mml:mn><mml:mo> </mml:mo><mml:mi mathvariant="normal">M</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">V</mml:mi></mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn mathvariant="normal">280</mml:mn><mml:mo> </mml:mo><mml:mi mathvariant="normal">M</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">V</mml:mi></mml:math>, respectively. When quarks are included, the deconfinement transition turns into a crossover. From the dual and chiral quark condensate, one finds pseudocritical temperatures of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mn mathvariant="normal">198</mml:mn><mml:mo> </mml:mo><mml:mi mathvariant="normal">M</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">V</mml:mi></mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mn mathvariant="normal">170</mml:mn><mml:mo> </mml:mo><mml:mi mathvariant="normal">M</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">V</mml:mi></mml:math>, respectively, for the deconfinement and chiral transition.
Redox-enhanced hemilability of a tris(tert-butoxy)siloxy ligand at cerium
2018-01-01

Combined structural/electrochemical/computational studies of ceric Ce[OSi(O<italic>t</italic>Bu)<sub>3</sub>]<sub>4</sub>and cerous [Ce{OSi(O<italic>t</italic>Bu)<sub>3</sub>}<sub>4</sub>][K(2.2.2-crypt)] suggest a redox-modulated coordination switch of a tris(<italic>tert</italic>-butoxy)siloxy ligand.
The Zone of Latent Solutions and Its Relation to the Classics: Vygotsky and Köhler
2018-01-01

In 2009, Tennie et al. proposed the theory of the Zone of Latent Solutions (ZLS), defined as the range of behaviors (solutions) an individual of a species can invent independently, i.e., which it can acquire without any form of social learning. By definition, species limited to their ZLS are unable to innovate and/or transmit behavioral traits outside their ZLS, i.e., they lack traits which go beyond the level of the individual—traits resulting from a gradual cultural evolution over successive transmission events ["cumulative culture", Boyd and Richerson (Proc Br Acad 88:73–93, 1996)]. However, this does not exclude an influence of social learning on the population frequency of these behaviors: social learning can facilitate the (ultimately individual) acquisition of latent solutions and thus speed up and consolidate their spread within a population. Cultures—defined as behaviors at least influenced by social learning—are therefore still possible (and often, even likely). Here, we elaborate on the ZLS account and relate it to the theories of Vygotsky (Mind in Society: Development of Higher Psychological Processes. Harvard University Press, 1978) who studied the role of social learning in human culture. We argue that the ZLS is a missing phylogenetic "baseline" of Vygotsky's Zone of Actual Development (ZAD). Vygotsky's neglect of a need for a human "baseline ZAD" (namely, a human ZLS) may have been due to his (mis-)interpretation of Köhler's (The Mentality of Apes. Liveright, 1925) work on great ape behaviors: Köhler used his observations on individual chimpanzees to draw conclusions about the chimpanzee species as a whole, stating that chimpanzees can only copy what they could have invented themselves, thus coming close to the ZLS concept. Vygotsky—studying the range of behaviors individuals could achieve independently—seemingly did not see that Köhler was suggesting a species "baseline" (ZLS), upon which Vygotsky's idea of an individual's ZAD could develop. As a result, Vygotsky also did not see the need for a ZLS for his own study subjects: humans. Yet, there is no reason to assume that humans lack a ZLS, and in fact we present evidence for a human ZLS for tool-use behaviors.