julilili42/papers huggingface dataset:
T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)
2018-02-22

BACKGROUND T‐cell–depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high‐risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full‐matched donor. METHODS To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]). RESULTS The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 ( P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [ P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [ P = .72] and 54% vs 38% [ P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen. CONCLUSIONS The outcome of patients with acute leukemia who underwent T‐cell–depleted haplo has improved over time. Cancer 2018;124:2142‐50 . © 2018 American Cancer Society .
Renal Lesion Characterization with Spectral CT: Determining the Optimal Energy for Virtual Monoenergetic Reconstruction
2018-02-22

Purpose To investigate the relationship between energy level of virtual monoenergetic (VM) imaging and sensitivity in the detection of minimally enhancing renal lesions. Materials and Methods Phantoms simulating unenhanced and contrast material-enhanced renal parenchyma were equipped with inserts containing different concentrations of iodine (range, 0-1.15 mg iodine per milliliter). A total of 180 patients (117 men; mean age, 65.2 years ± 13.0 [standard deviation]) with 194 (62 solid, 132 cystic) renal lesions larger than 10 mm in diameter underwent unenhanced single-energy CT and contrast-enhanced dual-energy CT. VM imaging data sets were created for 70, 80, 90, and 100 keV. Renal lesions were measured, and enhancement was calculated. Area under the receiver operating characteristic curve (AUC) for renal lesion characterization was determined by using the DeLong method. Results The AUC was highest at 70 keV and decreased as energy increased toward 100 keV. AUC in the phantom decreased from 98% (95% confidence interval [CI]: 95, 100) at 70 keV to 88% (95% CI: 79, 96) at 100 keV (P = .004). AUC in patients decreased from 96% (95% CI: 94, 98) at 70 keV to 79% (95% CI: 71, 86) at 100 keV (P = .001). In patients with an enhancement threshold of 15 HU, sensitivity in the detection of solid renal lesions decreased between from 91% (49 of 62 [95% CI: 78, 97]) at 70 keV to 48% (33 of 62 [95% CI: 25, 71]) at 100 keV (P < .05), with no change in specificity (93% [120 of 132 {95% CI: 87, 97}] at 70 keV, 97% [125 of 132 {95% CI: 92, 99}] at 100 keV). Conclusion There is a reduction in diagnostic accuracy for renal lesion characterization with increasing VM imaging energy. The 70-keV setting may provide an optimal trade-off between sensitivity and specificity. <sup>©</sup> RSNA, 2018 Online supplemental material is available for this article.
Nature of Large Temporal Fluctuations of Hydrogen Transfer Rates in Single Molecules
2018-02-22

Double hydrogen transfer was monitored in single molecules of parent porphycene and its tetra- t-butyl derivative using confocal fluorescence microscopy. The molecules have been embedded in a polymer matrix. Under such conditions, a significant fraction of the population reveals a huge decrease of the tautomerization rate with respect to the value obtained from ensemble studies in solution. This effect is explained by a model that assumes that the rate is determined by the reorganization coordinate that involves slow relaxation of the polymer matrix. The model provides indirect evidence for the dominant role of tunneling. It is proposed that tautomerization in single molecules of the porphycene family can be used to probe polymer relaxation dynamics on the time scale ranging from picoseconds to minutes.
Bernese motive and goal inventory in exercise and sport: Validation of an updated version of the questionnaire
2018-02-22

Target group-specific intervention strategies are often called for in order to effectively promote exercise and sport. Currently, motives and goals are rarely included systematically in the design of interventions, despite the key role they play in well-being and adherence to exercise. The Bernese motive and goal inventory (BMZI) allows an individual diagnosis of motives and goals in exercise and sport in people in middle adulthood. The purpose of the present study was to elaborate on the original BMZI and to modify the questionnaire in order to improve its psychometric properties. The study is based on data from two samples (sample A: 448 employees of companies and authorities; sample B: 853 patients of a medical rehabilitation programme). We applied confirmatory factor analysis and exploratory structural equation modelling. Overall, both the original and the updated BMZI had an acceptable to good validity and a good reliability. However, the revised questionnaire had slightly better reliability. The updated BMZI consists of 23 items and covers the following motives and goals: Body/Appearance, Contact, Competition/Performance, Aesthetics, Distraction/Catharsis, Fitness and Health. It is recommended as an economical inventory for the individual diagnosis of important psychological conditions for exercise and sport.
The prediction of cyclic proximal humerus fracture fixation failure by various bone density measures
2018-02-22

ABSTRACT Fixation of osteoporotic proximal humerus fractures has remained challenging, but may be improved by careful pre‐operative planning. The aim of this study was to investigate how well the failure of locking plate fixation of osteoporotic proximal humerus fractures can be predicted by bone density measures assessed with currently available clinical imaging (realistic case) and a higher resolution and quality modality (theoretical best‐case). Various density measures were correlated to experimentally assessed number of cycles to construct failure of plated unstable low‐density proximal humerus fractures ( N = 18). The influence of density evaluation technique was investigated by comparing local (peri‐implant) versus global evaluation regions; HR‐pQCT‐based versus clinical QCT‐based image data; ipsilateral versus contralateral side; and bone mineral content (BMC) versus bone mineral density (BMD). All investigated density measures were significantly correlated with the experimental cycles to failure. The best performing clinically feasible parameter was the QCT‐based BMC of the contralateral articular cap region, providing significantly better correlation ( R 2 = 0.53) compared to a previously proposed clinical density measure ( R 2 = 0.30). BMC had consistently, but not significantly stronger correlations with failure than BMD. The overall best results were obtained with the ipsilateral HR‐pQCT‐based local BMC ( R 2 = 0.74) that may be used for implant optimization. Strong correlations were found between the corresponding density measures of the two CT image sources, as well as between the two sides. Future studies should investigate if BMC of the contralateral articular cap region could provide improved prediction of clinical fixation failure compared to previously proposed measures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2250–2258, 2018.
Cytological evidence for automictic thelytoky in parthenogenetic oribatid mites (Acari, Oribatida): Synaptonemal complexes confirm meiosis in Archegozetes longisetosus
2018-02-22

Diplo-diploid parthenogenesis (thelytoky) is a widespread phenomenon in the mite taxon Sarcoptiformes, and is unusually frequent in the suborder Oribatida, where it characterizes almost 10% of extant species, including whole genera and families. Based on molecular and cytological data, terminal fusion automixis with an inverted meiotic sequence based on holokinetic chromosomes has been suggested as the reproductive mode in these mites. However, unequivocal structural evidence for meiosis is missing. The model organism Archegozetes longisetosus, a thelytokous member of the parthenogenetic family Trhypochthoniidae, was studied to gain ultrastructural insight in oocyte progression and meiotic processes. In this study, ovarian nuclear organization of its tritonymphal instar was examined by transmission electron microscopy (TEM). Numerous synaptonemal complexes were observed in the ovary, unequivocally confirming automixis (meiotic thelytoky) in oribatid mites for the first time. No recombination nodules were found. The nuclei are transcriptionally active in late prophase. Inverted meiosis is discussed as a result of the spatial arrangement of chromatid segregation.
The hemodynamic initial-dip consists of both volumetric and oxymetric changes correlated to localized spiking activity
2018-02-22

Abstract The “initial-dip” is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, and is believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed and its neuronal correlates unknown. Here, we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in HbR, with an early decrease and later rebound. However, HbT decreases were always large enough to counter spiking-induced increases in HbR. Moreover, the HbT-dip and HbR-rebound were strongly coupled to highly localized spiking activity. Our results suggest that the HbT-dip helps prevent accumulation of spiking-induced HbR-concentration in capillaries by flushing out HbT, probably by active venule dilation.
The timing of hemodynamic changes reliably reflects spiking activity
2018-02-22

Abstract Functional neuroimaging is a powerful non-invasive tool for studying brain function, using changes in blood-oxygenation as a proxy for underlying neuronal activity. The neuroimaging signal correlates with both spiking, and various bands of the local field potential (LFP), making the inability to discriminate between them a serious limitation for interpreting hemodynamic changes. Here, we record activity from the striate cortex in two anesthetized monkeys ( Macaca mulatta ), using simultaneous functional near-infrared spectroscopy (fNIRS) and intra-cortical electrophysiology. We find that low-frequency LFPs correlate with hemodynamic signal’s peak amplitude, whereas spiking correlates with its peak-time and initial-dip. We also find spiking to be more spatially localized than low-frequency LFPs. Our results suggest that differences in spread of spiking and low-frequency LFPs across cortical surface influence different parameters of the hemodynamic response. Together, these results demonstrate that the hemodynamic response-amplitude is a poor correlate of spiking activity. Instead, we demonstrate that the timing of the initial-dip and the hemodynamic response are much more reliable correlates of spiking, reflecting bursts in spike-rate and total spike-counts respectively.
Probing Planckian Corrections at the Horizon Scale with LISA Binaries
2018-02-23

Several quantum-gravity models of compact objects predict microscopic or even Planckian corrections at the horizon scale. We explore the possibility of measuring two model-independent, smoking-gun effects of these corrections in the gravitational waveform of a compact binary, namely, the absence of tidal heating and the presence of tidal deformability. For events detectable by the future space-based interferometer LISA, we show that the effect of tidal heating dominates and allows one to constrain putative corrections down to the Planck scale. The measurement of the tidal Love numbers with LISA is more challenging but, in optimistic scenarios, it allows us to constrain the compactness of a supermassive exotic compact object down to the Planck scale. Our analysis suggests that highly spinning, supermassive binaries at 1-20 Gpc provide unparalleled tests of quantum-gravity effects at the horizon scale.
A Primer for Model Selection: The Decisive Role of Model Complexity
2018-02-23

Abstract Selecting a “best” model among several competing candidate models poses an often encountered problem in water resources modeling (and other disciplines which employ models). For a modeler, the best model fulfills a certain purpose best (e.g., flood prediction), which is typically assessed by comparing model simulations to data (e.g., stream flow). Model selection methods find the “best” trade‐off between good fit with data and model complexity. In this context, the interpretations of model complexity implied by different model selection methods are crucial, because they represent different underlying goals of modeling. Over the last decades, numerous model selection criteria have been proposed, but modelers who primarily want to apply a model selection criterion often face a lack of guidance for choosing the right criterion that matches their goal. We propose a classification scheme for model selection criteria that helps to find the right criterion for a specific goal, i.e., which employs the correct complexity interpretation. We identify four model selection classes which seek to achieve high predictive density, low predictive error, high model probability, or shortest compression of data. These goals can be achieved by following either nonconsistent or consistent model selection and by either incorporating a Bayesian parameter prior or not. We allocate commonly used criteria to these four classes, analyze how they represent model complexity and what this means for the model selection task. Finally, we provide guidance on choosing the right type of criteria for specific model selection tasks. (A quick guide through all key points is given at the end of the introduction.)
Karyopherin α-3 is a key protein in the pathogenesis of spinocerebellar ataxia type 3 controlling the nuclear localization of ataxin-3
2018-02-23

Significance Ataxin-3 is the affected protein in the neurodegenerative disorder spinocerebellar ataxia type 3 (SCA3). Nuclear ataxin-3 has been linked to disease progression and formation of aggregates. Our present findings implicate karyopherin alpha 3 (KPNA3) in the in vitro transport of ataxin-3 and in the SCA3-related phenotypes in Drosophila and mouse models. We have demonstrated that altering transport proteins has an effect on both pathogenic mechanisms (e.g., the intracellular localization and the formation of aggregates) and key features of ataxin-3 toxicity such as anxiety, total activity, and gait abnormalities. A better appreciation of this cellular mechanism can enhance our understanding of polyglutamine diseases and the role of nuclear/cytoplasmic compartments in toxicity and clearance of ataxin-3.
Ultraviolet photoelectron spectroscopy reveals energy-band dispersion forπ-stacked 7,8,15,16-tetraazaterrylene thin films in a donor–acceptor bulk heterojunction
2018-02-23

7,8,15,16-tetraazaterrylene (TAT) thin films grown on highly oriented pyrolytic graphite (HOPG) substrates were studied extensively with regard to their intrinsic and interfacial electronic properties by means of ultraviolet photoelectron spectroscopy (UPS). Merely weak substrate-adsorbate interaction occurs at the TAT/HOPG interface, with interface energetics being only little affected by the nominal film thickness. Photon energy-dependent UPS performed perpendicular to the molecular planes of TAT multilayer films at room temperature clearly reveals band-like intermolecular dispersion of the TAT highest occupied molecular orbital (HOMO) energy. Based on a comparison with a tight-binding model, a relatively narrow bandwidth of 54 meV is derived, which points to the presence of an intermediate regime between hopping and band-like hole transport. Upon additional deposition of 2,2':5',2′′:5′′,2′′'-quaterthiophene (4T), a 4T:TAT donor-acceptor bulk heterojunction with a considerable HOMO-level offset at the donor-acceptor interface is formed. The 4T:TAT bulk heterojunction likewise exhibits intermolecular dispersion of the TAT HOMO energy, yet with a significant decreased bandwidth.
Dynamic speech adaptation to unreliable cues during intonational processing
2018-02-23

Human behavior is often remarkably flexible, showing the ability to quickly adapt to the statistical peculiarities of a particular local context. When it comes to language, previous work has shown that listeners' anticipatory interpretations of intonational cues are adapted dynamically when cues are observed to be stochastically unreliable. This paper reports novel empirical data from manual response dynamics (mouse-tracking) on how listeners adapt their predictive interpretation when some intonational cues are occasionally unreliable while others are consistently reliable. A model of rational belief dynamics predicts that listeners adapt differently to different unreliable intonational cues, as a function of their initial evidential strength. These predictions are borne out by our data.
The fungal ligand chitin directly binds and signals inflammation dependent on oligomer size and TLR2
2018-02-23

Abstract Chitin is a highly abundant polysaccharide and linked to fungal infection and asthma. Unfortunately, its polymeric structure has hampered the identification of immune receptors directly binding chitin and signaling immune activation and inflammation, because purity, molecular structure and molarity are not well definable for a polymer typically extracted from biomass. Therefore, by using defined chitin (N-acetyl-glucosamine) oligomers, we identified six subunit long chitin chains as the smallest immunologically active motif and the innate immune receptor Toll-like receptor (TLR) 2 as the primary fungal chitin receptor on human and murine immune cells. Chitin oligomers directly bound TLR2 with nanomolar affinity and showed both overlapping and distinct signaling outcomes compared to known mycobacterial TLR2 ligands. Conversely, chitin oligomers shorter than 6 subunits were inactive or showed antagonistic effects on chitin/TLR2-mediated signaling, hinting to a size-dependent sensing/activation system unexpectedly conserved in plants and humans. Since blocking the chitin-TLR2 interaction effectively prevented chitin-mediated inflammation in vitro and in vivo , our study highlights the chitin TLR2 interaction as a potential target for developing novel therapies in chitin-related pathologies and fungal disease.
Narrating narratives of international investment law: History and epistemic forces
2018-02-23

Telling the history of something requires choosing a perspective. This perspective is the lens through which we look at a specific topic or field. Thus, one cannot but present such history from certain perspectives. Once accounts of events, facts or material are being presented from a certain perspective, they turn into narratives. This chapter seeks to illustrate how certain stakeholders in the investment community present certain narratives of the history of international investment law, asserting – sometimes deliberately, sometimes inadvertently – the narratives' objectivity and thereby shaping certain perceptions of the history according to their view on the present and future of the field. Insights from historiography, the philosophy of language and modern linguistics inform such inquiry. It is the chapter's aim to demonstrate how certain epistemic communities employ such narratives and thereby to enhance investment law scholars' and practitioners' awareness vis-à-vis the constructive character of these narratives.
Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G
2018-02-24

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.