julilili42/papers huggingface dataset:
RIBECCA: A phase IIIb, multicenter, open label study for women with estrogen receptor-positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole—Results of the second interim analysis.
2019-05-20

1061 Background: RIBECCA is a national, multi-center, open-label, single-arm phase IIIb trial assessing the efficacy and safety of ribociclib in combination with letrozole in a patient population similar to the populations of MONALEESA-2, -3 and -7. Here we present the results of the second preplanned interim analysis. Methods: Main inclusion criteria allowed enrollment of men or women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, and histological or cytological confirmation of ER+, HER2- breast cancer, irrespective of their menopausal status. The primary objective is to assess the clinical benefit rate (CBR) after 6 months. Secondary objectives include: progression free survival (PFS), overall survival (OS), safety and changes in quality of life. Results: The cut-off date for this second interim analysis was 12 months after the last patient was enrolled in the pretreated and premenopausal cohort. Here we report a preliminary analysis on safety, efficacy and quality of life. We describe the baseline characteristics, safety data and the clinical benefit rate (CBR) at 24 weeks, of patients (pts) with at least 24 weeks follow up (n = 411). The median observation time for all patients in this analysis was 8.1 months. Baseline characteristics: of 411 pts, 409 were female and 2 male. Median age: 64 yrs; 46 pts pre-or perimenopausal, 363 postmenopausal; ECOG 0-1: 97.0%; median time since first recurrence: 1.6 months; 72.5 % pts had bone metastases (40.6% bone only), 30.7% liver, 27.3% lung and 29.2% other metastases. Median relative dose intensity was 0.905 for ribociclib and 1 for letrozole. The most common treatment emergent AEs (all grades) were neutropenia and/or neutrophil count decreased (54.5%), nausea (40.6%), fatigue (36.5%), alopecia (32.6%), leukopenia or WBC decreased (29%), nasopharyngitis (23.1%), diarrhea (21.4%), ALT increased (20.7%), AST increased (19%). The CBR by week 24 was 67.6%. Preliminary information on quality of life will be provided. Conclusions: The results of the second interim analysis in this additional patient population are in line with data published from the pivotal phase III studies MONALEESA-2, MONALEESA-3 and MONALEESA-7. Clinical trial information: NCT03096847.
Clinical Parameters Outperform Molecular Subtypes for Predicting Outcome in Bladder Cancer: Results from Multiple Cohorts, Including TCGA
2019-05-21

Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.
Manipulating patterns of dynamic deformation elicits the impression of cloth with varying stiffness
2019-05-21

Cloth is a common material, and humans can visually estimate its mechanical properties by observing how it deforms under external forces. Here, we ask whether and how dynamic deformation can affect the perception of mechanical properties of cloth. In Experiment 1, we find that both intrinsic mechanical properties and optical properties affect stiffness perception when the stimuli are presented as images. By contrast, in videos, humans can partially discount the effect of optical appearances and exhibit higher sensitivity to stiffness. We further identified an idiosyncratic deformation pattern (i.e., movement uniformity) to differentiate stiffness, which can be reliably measured by six optical flow features. In Experiment 2, we isolate the deformation by creating dynamic dot stimuli from the 3-D mesh of the cloth. We directly alter the movement pattern by manipulating the uniformity of the displacement vectors on the dot stimuli and show that changing the pattern of dynamic deformation alone can alter the perceived stiffness of cloth in a variety of scene setups. Furthermore, by analyzing optical flow fields extracted from the manipulated dynamic dot stimuli, we confirmed the same six optical flow features can be diagnostic of the degree of stiffness of moving cloth across different scenes. Overall, our study demonstrates that manipulating patterns of dynamic deformation alone can elicit the impression of cloth with varying stiffness, suggesting that the human visual system might rely on the idiosyncratic pattern of dynamic deformation for estimating stiffness.
Increased Cognitive Load Reveals Unilateral Neglect and Altitudinal Extinction in Chronic Stroke
2019-05-21

Abstract Objective : Neuropsychological studies suggest that the ability to compensate for the presence of spatial neglect highly depends on the attentional resources a patient can rely on. The present research aimed to study neglect in situations where attentional resources are limited due to multitasking. Method : We examined two patients more than 3 years after a right-hemispheric stroke. Both had received neuropsychological rehabilitation for left neglect and did not show any impairment in standard tests. We used a dual-task paradigm combining a peripheral target detection task with a central shape recognition task. Peripheral targets could appear in left/right positions but also in lower/upper positions. Results : In patient #1, dual-task condition exacerbated left neglect and extinction. Patient #2 did not show any sign of neglect along the horizontal axis, but omitted half of the lower targets when they were presented simultaneously with upper targets under dual-task condition. This behavior reflects altitudinal extinction as the detection of single targets appearing either in upper or lower position was preserved. Conclusion : The present findings show that dual-tasking is a sensitive tool for the quantitative and qualitative assessment of spatial attention deficits, which are often overlooked by standard methods, especially in chronic stage. ( JINS , 2019, 25 , 644–653)
The dynamics of the skeletal muscle: A systems biophysics perspective on muscle modeling with the focus on Hill‐type muscle models
2019-05-21

Skeletal muscle is one of the most fascinating and crucial ingredients of motion generation in nature. Since the beginning of science, people dedicate their life as researchers to enhance knowledge about this biological motor. Thus, the scientific knowledge about the skeletal muscle is overwhelmingly broad and detailed. This contribution collects knowledge about the active and passive dynamics of skeletal muscle. Furthermore, it highlights a special perspective in which not only the muscle itself, but also the role muscles play in the interaction with other structures is studied. The first section introduces this systems biophysics perspective, which clusters the investigation of the relations, interactions and dependencies between muscles and the other structures in the movement apparatus. In the second section, the muscles are considered in more detail by describing three approaches to muscle modeling. The third section deals with recent advances based on Hill‐type models, such as, for example, the integration of mass.
Response of a Rheologically Stratified Lithosphere to Subduction of an Indenter‐Shaped Plate: Insights Into Localized Exhumation at Orogen Syntaxes
2019-05-21

Abstract This study investigates the influence of the 3‐D geometry of a down‐going plate, the rheological structure of the upper plate, and the migration of the overriding plate toward the trench in relation to the overall subduction velocity on the exhumation pattern in orogen syntaxes. Using a thermomechanical numerical code (DOUAR), we analyze the strain localization, rock uplift, and exhumation response of a rheologically stratified continental lithosphere to subduction of a convex‐upward‐shaped indenter. The models consider three thermorheological lithospheric profiles that determine the degree of mechanical coupling between the upper crust and lithospheric mantle. These models include a strong, cratonic lithosphere; a weaker, younger (and hotter) continental plate; and an intermediate case. The strongly coupled case predicts a localization of high rock uplift rates along narrow linear bands crossing the entire model domain parallel to the trench. In contrast, in a weakly coupled lithosphere, rock uplift is concentrated within a curved ellipse region of anomalously high exhumation rates located above the indenter apex. The aspect ratio of the localized area of rapid rock uplift is controlled by the initial width of the rigid indenter and the relationship between boundary velocities. In particular, the combination of little or no upper plate migration with a narrow indenter causes a nearly circular region (~100‐km diameter) of rapid exhumation that resembles the pattern of thermochronometer ages observed in orogen syntaxes such as the Southeast Alaska and the Olympic Mountains of the Cascadia subduction zone (western USA).
Facile synthesis of model 2,4-diaryl-1,3,4-thiadiazino[5,6-h]fluoroquinolones
2019-05-21

Abstract A Selected set of 2,4-diaryl-7-oxo-1,2,4-thiadiazino[5,6- h ]quinoline-8-carboxylic acids 6a–e has been prepared via reaction of the parent 7-chloro-8-nitro-10-cyclopropyl-6-fluoroquinolone 4 with the appropriate N ′-(aryl)benzothiohydrazide 5a–e in presence of triethylamine. Structures of the new heterocyclics 6a–e are supported by spectral data and confirmed by single-crystal X-ray crystallography for 6a .
Calcification and distribution of extant coccolithophores across the Drake Passage during late austral summer 2016
2019-05-21

Abstract. Coccolithophores are globally distributed microscopic marine algae that exert a major influence on the global carbon cycle through calcification and primary productivity. There is recent interest in coccolithophore polar communities, however field observations regarding their biogeographic distribution are scarce for the Southern Ocean. This study documents the latitudinal variability in the coccolithophore assemblage composition and the coccolith mass variation of the ecologically dominant Emiliania huxleyi across the Drake Passage. Ninety-six water samples were taken between 10 and 150 m water depth from 18 stations during POLARSTERN Expedition PS97 (February–April, 2016). A minimum of 200 coccospheres per sample were classified in scanning electron microscope and coccolith mass was estimated with light microscopy, using the C-Calcita software. We find that coccolithophore abundance and diversity decrease southwards marking different oceanographic fronts as ecological boundaries. We characterize three zones: (1) the Chilean margin, where E. huxleyi type A (normal and overcalcified) and type R are present; (2) the Subantarctic Zone (SAZ), where E. huxleyi reaches maximum values of 212.5×103cells/L and types B/C, C, O are dominant. (3) The Polar Front Zone (PFZ), where E. huxleyi types B/C and C dominate. We link the decreasing trend in E. huxleyi coccolith mass to the poleward latitudinal succesion from type A to type B group. Remarkably, we find that coccolith mass is strongly anticorrelated to total alkalinity, total CO2, bicarbonate ion and pH. We speculate that low temperatures are a greater limiting factor than carbonate chemistry in the Southern Ocean. However, further in situ oceanographical data is needed to verify the proposed relationships. We hypothesize that assemblage composition and calcification modes of E. huxleyi in the Drake Passage will be strongly influenced by the ongoing climate change.
Implantability of endaurally insertable active vibratory middle-ear implants – an anatomical study
2019-05-21

<b>Background:</b> Hearing loss is often treated with an acoustic hearing aid. However, distortion and insufficient gain may cause problems. Active non-acoustic vibratory middle-ear implants (AMEI) may contribute to solve this problem. We recently developed an AMEI which is to be implanted completely through the patient's external auditory canal. The device uses a light-emitting diode (LED) in the external auditory canal that stimulates a photovoltaic sensor, placed in the middle ear, through the intact tympanic membrane. This results in activation of a vibratory miniaturized piezoelectric displacement transducer (MDT) (actuator) coupled to the auditory organ. <b>Aims/objectives:</b> The aim of this study was to evaluate the anatomical implantability of the novel AMEI using an exclusively endaural approach. <b>Materials and methods:</b> The internal components of our AMEI were implanted into 39 human temporal bones. The surgical procedure and the optimal size and anatomical fitting were systematically evaluated. <b>Results:</b> We can show here that implantation of all components of this novel AMEI into anatomical specimens proves to be a quick and easy procedure, performed using an endaural approach. <b>Conclusions and significance:</b> The anatomical data of this study establish the basis for further technical development of our AMEI and other future implantable hearing systems.
Hadroproduction of open heavy flavour for PDF analyses
2019-05-21

Due to the large masses of the charm and bottom quarks, their production cross sections are calculable within the perturbative QCD. This makes the heavy-quark mesons important observables in high-energy collisions of protons and nuclei. However, the available calculations for heavy-flavored-meson hadroproduction have been somewhat problematic in reliably describing the cross sections across the full kinematic range from zero to very high pT. This has put some question marks on the robustness of LHC heavy-flavored-meson measurements in studying the partonic structure of the colliding hadrons and nuclei. Here, we introduce SACOT-mT - a novel scheme for open heavy-flavour hadroproduction within the general-mass variable-flavour-number formalism that solves this problem. The introduced scheme is an analogue of the SACOT-χ scheme often used for deeply-inelastic scattering in global analyses of PDFs.
Reliability of Magnetoencephalography and High-Density Electroencephalography Resting-State Functional Connectivity Metrics
2019-05-22

Resting-state connectivity, for example, based on magnetoencephalography (MEG) or electroencephalography (EEG), is a widely used method for characterizing brain networks and a promising imaging biomarker. However, there is no established standard as to which method, modality, and analysis variant is preferable and there is only limited knowledge on the reproducibility, an important prerequisite for clinical application. We conducted an MEG-/high-density (hd)-EEG-study on 22 young healthy adults, who were measured twice in a scan/rescan design after 7 ± 2 days. Reliability of resting-state (15 min, eyes-closed) connectivity in source space was calculated via intraclass correlation coefficient (ICC) in classical frequency bands (delta-gamma). We investigated the reliability of two commonly used connectivity metrics, namely the imaginary part of coherency and the weighted phase-lag index and the influence of frequency band, vigilance, and the number of trials. We found a strong increase of reliability with more trials and relatively mild effects of vigilance. Reliability was excellent in the alpha band for MEG, as well as hd-EEG (ICC >0.85); in the theta band, reliability was good for MEG and poor for EEG. Other frequency bands showed lower reliability, with delta band being the worst. Furthermore, we investigated the spatial reliability of resting-state connectivity in a vertex-based approach, which reached fair to good reliability (ICC up to 0.67) with 5 min of data. Our results indicate that excellent reliability of global connectivity is achievable in alpha band, and vertex-based connectivity was still fair to good. Moreover, electrophysiological resting-state studies could benefit from more data than used previously. MEG and hd-EEG were similar in their overall performance but showed frequency band-specific differences.
S1 guidelines for dermatofibrosarcoma protuberans (DFSP) – update 2018
2019-05-22

Summary While dermatofibrosarcoma protuberans (DFSP) is a rare cancer entity overall, it is nevertheless the most common type of cutaneous sarcoma. The tumor is of fibroblastic origin and characterized by slow, undermining and locally destructive growth. Metastatic spread is very rare. Given its nonspecific clinical appearance, diagnosis is frequently delayed. Biopsy and subsequent histopathology are key diagnostic tools. Standard treatment for primary tumors consists of complete excision with surgical margins of 1 to 2 cm. Smaller margins are associated with high local recurrence rates. Inoperable and metastatic DFSP may be treated with radiation therapy. Approximately 80–90 % of DFSP lesions harbor a fusion gene that results in continuous activation of the PDGF‐β signaling pathway. Consequently, molecular targeted therapy inhibiting PDGF‐β is an effective option for advanced (inoperable) and metastatic DFSP. The first agent to be approved for systemic treatment of DFSP is the multikinase inhibitor imatinib, showing objective response rates of about 50 % in clinical trials.
Staphylococcus aureus induces DNA damage in host cell
2019-05-22

Abstract Staphylococcus aureus causes serious medical problems in human and animals. Here we show that S. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AX phosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa and osteoblast-like MG-63 cells. This DNA damage is mediated by alpha phenol-soluble modulins (PSMα 1–4 ), while a specific class of lipoproteins (Lpls), encoded on a pathogenicity island in S. aureus , dampens the H2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactive oxygen species (ROS), which promotes oxidation of guanine forming 7,8-dihydro-8-oxoguanine (8-oxoG). DNA damage is followed by the induction of DNA repair that involves the ATM kinase-signaling pathway. An examination of S. aureus strains, isolated from the same patient during acute initial and recurrent bone and joint infections (BJI), showed that recurrent strains produce lower amounts of Lpls, induce stronger DNA-damage and prompt the G2/M transition delay to a greater extent that suggest an involvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findings redefine our understanding of mechanisms of S. aureus -host interaction and suggest that the balance between the levels of PSMα and Lpls expression impacts the persistence of the infection.
Assessment of fetal modified myocardial performance index in early‐onset and late‐onset fetal growth restriction
2019-05-22

Abstract Aim To investigate the changes of modified myocardial performance index (Mod‐MPI) in early‐onset and late‐onset fetal growth restriction (FGR) cases, and its association with adverse perinatal outcome. Methods This was a prospective study on 77 early‐onset and 100 late‐onset FGR cases. Hundred normal fetuses were matched as control groups for early‐onset and late‐onset FGR groups, respectively. Mod‐MPI and vessel Doppler parameters including umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) were measured. Perinatal outcomes were followed up. Mod‐MPI of FGR cases were compared in normal Doppler, abnormal Doppler, and control groups. The association of Mod‐MPI and perinatal outcome was investigated, and further efficacy of Mod‐MPI predicting adverse outcome was studied. Results Compared with control groups, both abnormal and normal Doppler groups showed increased Mod‐MPI in early‐onset and late‐onset FGR, respectively. Mod‐MPI had no significant difference between abnormal and normal Doppler groups. Mod‐MPI was associated with adverse outcome in early‐onset FGR (OR = 3.307) and late‐onset FGR (OR = 3.412). The sensitivity and specificity of Mod‐MPI predicting adverse outcome were 60% and 80% when cutoff value was 0.47 in early‐onset FGR. And they were 65% and 70% when cutoff value was 0.50 in late‐onset FGR. Conclusion Fetal growth restriction fetuses had increased Mod‐MPI. Mod‐MPI could be used to predict adverse perinatal outcome of FGR fetuses. Mod‐MPI was an effective parameter to supplement vessels’ Doppler parameters in monitoring FGR.
Are there two independent evaluative conditioning effects in relational paradigms? Dissociating the effects of CS-US pairings and their meaning
2019-05-22

Recent research into evaluative conditioning (EC) shows that information about the relationship between the conditioned and unconditioned stimuli can exert strong effects on the size and direction of the EC effect. Additionally, the co-occurrence of these stimuli seems to exert an orthogonal effect on evaluations. This finding has been interpreted as support for two independent types of EC effects. However, previous research devoted to this question relied on aggregated evaluative measures, allowing for alternative interpretations. In four experiments, we developed and validated a multinomial processing tree model that distinguishes effects of the pairings from effects of the meaning of the pairings. Our findings suggest that two independent EC effects contribute to overall evaluative change in a relational EC paradigm. The model that we developed offers a helpful method for future research in that it allows for an assessment of the effects of manipulations on processes rather than overall performance on an evaluative measure.
Two DevBCA‐like ABC transporters are involved in the multidrug resistance of the cyanobacterium Anabaena sp. PCC 7120
2019-05-22

The filamentous heterocyst‐forming cyanobacterium Anabaena sp. PCC 7120 is an important model organism for studying cell differentiation, nitrogen fixation, and photosynthesis. This cyanobacterium possesses a high number of membrane transporters. Not much is known about the roles of the membrane transporters, especially the ATP‐binding cassette (ABC) transporters, in the multidrug resistance of this cyanobacterium. In the present work, we performed a mutational analysis of the genes alr4280/alr4281/alr4282 and alr3647/alr3648/alr3649 that code for the components of putative ABC exporters and are homologous to the DevBCA heterocyst‐specific glycolipid exporter. We show that these genes are essential for resistance to different drugs and are not essential for heterocyst development.
Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3β inhibitors
2019-05-22

The dataset related to the publication: Andreev et al. Design, Synthesis and Biological Evaluation of 7 Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3β inhibitors.<br> <br> The files include: 1) Movies of the MD simulations of compounds 14b (<strong>Cmpd14b.mpg</strong>) and 24 (<strong>Cmpd24.mpg</strong>). 2) Raw trajectory files of the Desmond MD simulations of the compounds 14b (<strong>14b.zip</strong>), 24 (<strong>24.zip</strong>) and 24 (3a<em>R</em>, 7a<em>S</em>) (<strong>24_3aR_7aS.zip</strong>) (contains out.cms and the full trj files). 3) Output conformations of the QM Tautomer &amp; Conformation Predictor of Maestro (Schrödinger, LLC, New York, NY, 2019) of the compounds<br> 14b (<strong>Cmpd14b_QMconftauto_output.mae</strong>; <strong>Cmpd14b_QMconftauto_output.sdf</strong>), <br> 24 (<strong>Cmpd24_QMconftauto_output.mae</strong>; <strong>Cmpd24_QMconftauto_output.sdf</strong>) and <br> 24 (3a<em>R</em>, 7a<em>S</em>) (<strong>Cmpd24_3aR_7aS_QMconftauto_output.mae</strong>; <strong>Cmpd24_3aR_7aS_QMconftauto_output.sdf</strong>) 4) Jaguar pKa calculation (conformations) output-files for compounds 14b, 14c, 14d, 14e, 14f, 14g, 14h, 14i, 14j, 14k, 14l, 14m, 14n <strong>pKa.zip</strong> (contains conformation in .mae file and Final weighted pKa value in .out file).