bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide Receptor Radionuclide Therapy Combined With Chemotherapy in Patients With Neuroendocrine Tumors
Authors: Yordanova Anna , Ahrens Harriet , Feldmann Georg , Brossart Peter , Gaertner Florian C. , Fottner Christian , Weber Matthias M. , Ahmadzadehfar Hojjat , Schreckenberger Mathias , Miederer Matthias , Essler Markus 
Published: April 2019

Purpose
Combinations of therapies may enhance therapeutic effects without significantly increasing the incidence of adverse events. However, there are few data regarding survival after concomitant chemotherapy and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-octreotate in patients with neuroendocrine tumors (NETs). Thus, we explored the outcome of this combination of therapies.

Methods
Fifteen patients with somatostatin receptor–positive, rapidly progressive G2/G3 NETs during chemotherapy or PRRT alone from 2 German cancer centers were included in the retrospective analysis. The patients received a combination of PRRT and chemotherapy with temozolomide (n = 3) or temozolomide plus capecitabine (n = 12). To evaluate the effects of the combined treatment, we assessed the responses, survival, and adverse events.

Results
The cumulative administered activity of [177Lu]Lu-octreotate had a median of 21.3 GBq after 3 cycles of combination therapy. The patients exhibited a median progression-free survival of 7.1 months and a median overall survival of 25.3 months. The clinical benefit (objective response and stable disease) rates were as follows: 55% of patients according to CT, 38% in [18F]F-FDG PET/CT, and 44% in [68Ga]Ga-DOTATOC PET/CT. One patient with rapidly progressing liver metastases experienced grade 4 liver failure according to the Common Terminology Criteria for Adverse Events (version 5.0). Four other patients (27%) experienced significantly elevated (grade 3) liver parameters.

Conclusions
According to different imaging modalities, the combination of PRRT and temozolomide +/− capecitabine led to disease control in 38% to 55% of the progressive NETs after PRRT or chemotherapy alone failed. The overall survival in this extensively pretreated group of patients was nearly 25 months. The majority of patients did not experience any serious adverse events.
Reduced Scan Time in 123I-FP-CIT SPECT Imaging Using a Large-Field Cadmium-Zinc-Telluride Camera
Authors: Bani Sadr Alexandre , Testart Nathalie , Tylski Perrine , Scheiber Christian 
Published: April 2019

Abstract
We evaluated the reproducibility of 123I-ioflupane (123I-FP-CIT) SPECT with shorter scan times using a CZT camera. One hundred ninety-nine 123I-FP-CIT SPECT scans obtained with standard scan time (30 minutes) were truncated to provide 24-, 18-, and 15-minute study simulations. Striatal binding ratios were automatically calculated and remained stable for all series. At 15 minutes, only 10 of 398 striata (2.5%) showed statistically significant different striatal binding ratios compared with reference series. These series were reviewed by 2 operators, and a perfect agreement was found for each patient. Therefore, CZT camera allows a 2-fold scan time reduction in 123I-FP-CIT SPECT.
FDG PET in Diffuse Spinal Carcinomatous Meningitis
Authors: Cuvilliers Cécile , Ahrweiller Flora , Vauléon Elodie , Castelli Joël , Palard-Novello Xavier 
Published: April 2019

Abstract
A 65-year-old man, diagnosed with right paranasal sinus neuroendocrine carcinoma with skull base invasion and ipsilateral lymph node involvement underwent chemotherapy. Six months later, the patient underwent radiation therapy for right cervical lymph node recurrence. Two months after the end of the radiation therapy, the patient was referred to our department to perform a whole-body FDG PET for therapeutic assessment. It showed diffuse intense FDG uptake of the whole spinal canal. The physical examination revealed walking disorders. Meningeal contrast enhancement on MRI of the brain and the spinal cord was leading to the diagnosis of carcinomatous meningitis.
X-ray Raman scattering: a building block for nonlinear spectroscopy
Authors: Rohringer Nina 
Published: April 2019

Ultraintense X-ray free-electron laser pulses of attosecond duration can enable new nonlinear X-ray spectroscopic techniques to observe coherent electronic motion. The simplest nonlinear X-ray spectroscopic concept is based on stimulated electronic X-ray Raman scattering. We present a snapshot of recent experimental achievements, paving the way towards the goal of realizing nonlinear X-ray spectroscopy. In particular, we review the first proof-of-principle experiments, demonstrating stimulated X-ray emission and scattering in atomic gases in the soft X-ray regime and first results of stimulated hard X-ray emission spectroscopy on transition metal complexes. We critically asses the challenges that have to be overcome for future successful implementation of nonlinear coherent X-ray Raman spectroscopy.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Charge migration in photo-ionized aromatic amino acids
Authors: Trabattoni A. , Galli M. , Lara-Astiaso M. , Palacios A. , Greenwood J. , Tavernelli I. , Decleva P. , Nisoli M. , Martín F. , Calegari F. 
Published: April 2019

Attosecond pump–probe spectroscopy is a unique tool for the direct observation of the light-activated electronic motion in molecules and it offers the possibility to capture the first instants of a chemical reaction. Recently, advances in attosecond technology allowed the charge migration processes to be revealed in biochemically relevant molecules. Although this purely electronic process might be key for a future chemistry at the electron time scale, the influence of this ultrafast charge flow on the reactivity of a molecule is still debated. In this work, we exploit extreme ultraviolet attosecond pulses to activate charge migration in two aromatic amino acids, namely phenylalanine and tryptophan. Advanced numerical calculations are performed to interpret the experimental data and to discuss the effects of the nuclear dynamics on the activated quantum coherences. By comparing the experimental results obtained in the two molecules, we show that the presence of different functional groups strongly affects the fragmentation pathways, as well as the charge rearrangement. The observed charge dynamics indeed present peculiar aspects, including characteristic periodicities and decoherence times. Numerical results indicate that, even for a very large molecule such as tryptophan, the quantum coherences can survive the nuclear dynamics for several femtoseconds. These results open new and important perspectives for a deeper understanding of the photo-induced charge dynamics, as a promising tool to control the reactivity of bio-relevant molecules via photo-excitation.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Accuracy and precision of the RABBIT technique
Authors: Isinger M. , Busto D. , Mikaelsson S. , Zhong S. , Guo C. , Salières P. , Arnold C. L. , L'Huillier A. , Gisselbrecht M. 
Published: April 2019

One of the most ubiquitous techniques within attosecond science is the so-called reconstruction of attosecond beating by interference of two-photon transitions (RABBIT). Originally proposed for the characterization of attosecond pulses, it has been successfully applied to the accurate determination of time delays in photoemission. Here, we examine in detail, using numerical simulations, the effect of the spatial and temporal properties of the light fields and of the experimental procedure on the accuracy of the method. This allows us to identify the necessary conditions to achieve the best temporal precision in RABBIT measurements.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Measuring non-equilibrium dynamics in complex solids with ultrashort X-ray pulses
Authors: Buzzi Michele , Först Michael , Cavalleri Andrea 
Published: April 2019

Strong interactions between electrons give rise to the complexity of quantum materials, which exhibit exotic functional properties and extreme susceptibility to external perturbations. A growing research trend involves the study of these materials away from equilibrium, especially in cases in which the stimulation with optical pulses can coherently enhance cooperative orders. Time-resolved X-ray probes are integral to this type of research, as they can be used to track atomic and electronic structures as they evolve on ultrafast timescales. Here, we review a series of recent experiments where femtosecond X-ray diffraction was used to measure dynamics of complex solids.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Ultrafast dynamics of spin and orbital correlations in quantum materials: an energy- and momentum-resolved perspective
Authors: Cao Y. , Mazzone D. G. , Meyers D. , Hill J. P. , Liu X. , Wall S. , Dean M. P. M. 
Published: April 2019

Many remarkable properties of quantum materials emerge from states with intricate coupling between the charge, spin and orbital degrees of freedom. Ultrafast photo-excitation of these materials holds great promise for understanding and controlling the properties of these states. Here, we introduce time-resolved resonant inelastic X-ray scattering (tr-RIXS) as a means of measuring the charge, spin and orbital excitations out of equilibrium. These excitations encode the correlations and interactions that determine the detailed properties of the states generated. After outlining the basic principles and instrumentations of tr-RIXS, we review our first observations of transient antiferromagnetic correlations in quasi two dimensions in a photo-excited Mott insulator and present possible future routes of this fast-developing technique. The increasing number of X-ray free electron laser facilities not only enables tackling long-standing fundamental scientific problems, but also promises to unleash novel inelastic X-ray scattering spectroscopies.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Recent advances in ultrafast X-ray sources
Authors: Schoenlein Robert , Elsaesser Thomas , Holldack Karsten , Huang Zhirong , Kapteyn Henry , Murnane Margaret , Woerner Michael 
Published: April 2019

Over more than a century, X-rays have transformed our understanding of the fundamental structure of matter and have been an indispensable tool for chemistry, physics, biology, materials science and related fields. Recent advances in ultrafast X-ray sources operating in the femtosecond to attosecond regimes have opened an important new frontier in X-ray science. These advances now enable: (i) sensitive probing of structural dynamics in matter on the fundamental timescales of atomic motion, (ii) element-specific probing of electronic structure and charge dynamics on fundamental timescales of electronic motion, and (iii) powerful new approaches for unravelling the coupling between electronic and atomic structural dynamics that underpin the properties and function of matter. Most notable is the recent realization of X-ray free-electron lasers (XFELs) with numerous new XFEL facilities in operation or under development worldwide. Advances in XFELs are complemented by advances in synchrotron-based and table-top laser-plasma X-ray sources now operating in the femtosecond regime, and laser-based high-order harmonic XUV sources operating in the attosecond regime.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Development of ultrafast capabilities for X-ray free-electron lasers at the linac coherent light source
Authors: Coffee Ryan N. , Cryan James P. , Duris Joseph , Helml Wolfram , Li Siqi , Marinelli Agostino 
Published: April 2019

The ability to produce ultrashort, high-brightness X-ray pulses is revolutionizing the field of ultrafast X-ray spectroscopy. Free-electron laser (FEL) facilities are driving this revolution, but unique aspects of the FEL process make the required characterization and use of the pulses challenging. In this paper, we describe a number of developments in the generation of ultrashort X-ray FEL pulses, and the concomitant progress in the experimental capabilities necessary for their characterization and use at the Linac Coherent Light Source. This includes the development of sub-femtosecond hard and soft X-ray pulses, along with ultrafast characterization techniques for these pulses. We also describe improved techniques for optical cross-correlation as needed to address the persistent challenge of external optical laser synchronization with these ultrashort X-ray pulses.
This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Landscape drivers of genomic diversity and divergence in woodland Eucalyptus
Authors: Murray Kevin , Janes Jasmine , Bothwell Helen , Jones Ashley , Andrew Rose , Borevitz Justin 
Published: April 2019

AbstractSpatial genetic patterns are influenced by numerous factors, and they can vary even among coexisting, closely related species due to differences in dispersal and selection. Eucalyptus (L’Héritier 1789; the “eucalypts”) are foundation tree species that provide essential habitat and modulate ecosystem services throughout Australia. Here we present a study of landscape genomic variation in two woodland eucalypt species, using whole genome sequencing of 388 individuals ofEucalyptus albensandEucalyptus sideroxylon. We found exceptionally high genetic diversity (π≈ 0.05) and low genome-wide, inter-specific differentiation (FST= 0.15). We found no support for strong, discrete population structure, but found substantial support for isolation by geographic distance (IBD) in both species. Using generalised dissimilarity modelling, we identified additional isolation by environment (IBE).Eucalyptus albensshowed moderate IBD, and environmental variables have a small but significant amount of additional predictive power (i.e., IBE).Eucalyptus sideroxylonshowed much stronger IBD, and moderate IBE. These results highlight the vast adaptive potential of these species, and set the stage for testing evolutionary hypotheses of interspecific adaptive differentiation across environments.
A Comparative Assessment of Visceral Leishmaniasis Burden in Two Eco-epidemiologically Different Countries, India and Sudan
Authors: Barley Kamal , Mubayi Anuj , Safan Muntaser , Castillo-Chavez Carlos 
Published: April 2019

AbstractThe two hyper–endemic regions for Visceral Leishmaniasis (VL) in the world are located in India and Sudan. These two countries account for more than half of the world’s VL burden. The regional risk factors associated with VL vary drastically per region. A mathematical model of VL transmission dynamics is introduced and parametrized to quantify risk of VL infection in India and Sudan via a careful analysis of VL prevalence level and the control reproductive number,, a metric often used to characterize the degree of endemicity. Parameters, associated with VL-epidemiology for India and Sudan, are estimated using data from health departmental reports, clinical trials, field studies, and surveys in order to assess potential differences between the hyper–endemic regions of India and Sudan. The estimated value of reproduction number for India is found to be 60% higher than that of Sudan (and). It is observed that theis most sensitive to the average biting rate and vector-human transmission rates irrespective of regional differences. The treatment rate is found to be the most sensitive parameter to VL prevalence in humans for both India and Sudan. Although the unexplained higher incidence of VL in India needs to be carefully monitored during long-term empirical follow-up, the risk factors associated with vectors are identified as more critical to dynamics of VL than factors related to humans through this modeling study.Author SummaryThe Visceral Leishmaniasis (VL) is a neglected tropical disease, primarily endemic in five countries, with India and Sudan having the highest burden. The risk factors associated with VL are either unknown in some regions or vary drastically among empirical studies. In this study, we collect VL-related data from multiple sources for the two different countries, India and Sudan, and use techniques from mathematical modeling to understand factors that may be critical in the spread and control of VL. The results suggest that the risk factors associated with disease progression are important in explaining high VL prevalence in both the countries. However, the likelihood of disease outbreak in India is much higher than that in Sudan and the probability of transmission between human and sandfly populations vary significantly between the two. The results have implications towards VL elimination and may require a review of current control priorities.
Relative performance of Oxford Nanopore MinION vs. Pacific Biosciences Sequel third-generation sequencing platforms in identification of agricultural and forest pathogens
Authors: Loit Kaire , Adamson Kalev , Bahram Mohammad , Puusepp Rasmus , Anslan Sten , Kiiker Riinu , Drenkhan Rein , Tedersoo Leho 
Published: April 2019

ABSTRACTCulture-based molecular characterization methods have revolutionized detection of pathogens, yet these methods are either slow or imprecise. The second-generation sequencing tools have much improved precision and sensitivity of detection, but the analysis processes are costly and take several days. Of third-generation techniques, the portable Oxford Nanopore MinION device has received much attention because of its small size and possibility of rapid analysis at reasonable cost. Here, we compare the relative performance of two third-generation sequencing instruments, MinION and Pacific Biosciences Sequel in identification and diagnostics of pathogens from conifer needles and potato leaves and tubers. We demonstrate that Sequel is efficient in metabarcoding of complex samples, whereas MinION is not suited for this purpose due to the high error rate and multiple biases. However, we find that MinION can be utilized for rapid and accurate identification of dominant pathogenic organisms from plant tissues following both amplicon-based and metagenomics-based approaches. Using the PCR-free approach with shortened extraction and incubation times, we performed the entire MinION workflow from sample preparation through DNA extraction, sequencing, bioinformatics and interpretation in two and half hours. We advocate the use of MinION for rapid diagnostics of pathogens, but care needs to be taken to control or account for all potential technical biases.IMPORTANCEWe develop new and rapid protocols for MinION-based third-generation diagnostics of plant pathogens that greatly improves the speed and precision of diagnostics. Due to high error rate and technical biases in MinION, PacBio Sequel platform is more useful for amplicon-based metabarcoding from complex biological samples.
Unusual metabolism and hypervariation in the genome of a Gracilibacteria (BD1-5) from an oil degrading community
Authors: Sieber Christian M.K. , Paul Blair G. , Castelle Cindy J. , Hu Ping , Tringe Susannah G. , Valentine David L. , Andersen Gary L. , Banfield Jillian F. 
Published: April 2019

AbstractThe Candidate Phyla Radiation (CPR) comprises a large monophyletic group of bacterial lineages known almost exclusively based on genomes obtained using cultivation-independent methods. Within the CPR, Gracilibacteria (BD1-5) are particularly poorly understood due to undersampling and the inherent fragmented nature of available genomes. Here, we report the first closed, curated genome of a Gracilibacteria from an enrichment experiment inoculated from the Gulf of Mexico and designed to investigate hydrocarbon degradation. The gracilibacterium rose in abundance after the community switched to dominance byColwellia. Notably, we predict that this gracilibacterium completely lacks glycolysis, the pentose phosphate and Entner-Doudoroff pathways. It appears to acquire pyruvate, acetyl-CoA and oxaloacetate via degradation of externally derived citrate, malate and amino acids and may use compound interconversion and oxidoreductases to generate and recycle reductive power. The initial genome assembly was fragmented in an unusual gene that is hypervariable within a repeat region. Such extreme local variation is rare, but characteristic of genes that confer traits under pressure to diversify within a population. Notably, the four major repeated 9-mer nucleotide sequences all generate a proline-threonine-aspartic acid (PTD) repeat. The genome of an abundantColwellia psychrerythraeapopulation has a large extracellular protein that also contains the repeated PTD motif. Although we do not know the host for the BD1-5 cell, the high relative abundance of theC. psychrerythraeapopulation and the shared surface protein repeat may indicate an association between these bacteria.ImportanceCPR bacteria are generally predicted to be symbionts due to their extensive biosynthetic deficits. Although monophyletic, they are not monolithic in terms of their lifestyles. The organism described here appears to have evolved an unusual metabolic platform not reliant on glucose or pentose sugars. Its biology appears to be centered around bacterial host-derived compounds and/or cell detritus. Amino acids likely provide building blocks for nucleic acids, peptidoglycan and protein synthesis. We resolved an unusual repeat region that would be invisible without genome curation. The nucleotide sequence is apparently under strong diversifying selection but the amino acid sequence is under stabilizing selection. The amino acid repeat also occurs in a surface protein of a coexisting bacterium, suggesting co-location and possibly interdependence.
Three-phase transitions to reproductive isolation: The roles of utilization mismatch and residual selection
Authors: Meszéna Géza , Dieckmann Ulf 
Published: April 2019

AbstractThe adaptive emergence of reproductive isolation is increasingly recognized as a key mechanism of sympatric speciation. Here we aim at establishing a deeper understanding of the complex multilocus dynamics underlying such speciation transitions under resource competition. In reality, a single population’s resource utilization can never exactly match a resource distribution, making residual selection pressures inevitable. We find that this commonly leads to three-phase transitions to reproductive isolation. First, partial assortativity emerges, quickly adjusting a population’s variance to the resource distribution’s variance. Second, allelic variance slowly erodes across loci, allowing an increasingly bimodal phenotype distribution to emerge. Third, a fast transition occurs toward full bimodality in conjunction with practically complete reproductive isolation of the emerging two species. The first phase is driven by frequency-dependent divergent ecological selection. The second phase is driven by self-accelerating residual ecological selection: the more loci code for the selected phenotype, the slower is this intermediate phase. The third phase is driven by self-accelerating sexual selection. We study three types of mismatch-driven speciation, resulting from (i) incongruences between the shapes of resource distributions and competition kernels, (ii) low numbers of loci, and (iii) premature cessations of the first phase’s variance expansion. Our results suggest that the incomplete separation of incipient species, a characteristic of the second phase, is common in nature, which is likely resulting in detectable genetic footprints of three-phase transitions to reproductive isolation occurring in nature.