bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress Lymphoscintigraphy for Early Detection and Management of Secondary Limb Lymphedema
Authors: Tartaglione Girolamo , Visconti Giuseppe , Bartoletti Roberto , Gentileschi Stefano , Salgarello Marzia , Rubello Domenico , Colletti Patrick M. 
Published: December 2017

Purpose
Cancer treatments with axillary or pelvic lymph nodes dissection and radiation place patients at lifelong risk for the development of secondary lymphedema. Our aim was to evaluate the role of stress lymphoscintigraphy for early detection and management of secondary lymphedema.

Methods
Stress lymphoscintigraphy was performed within 1 year after surgery and the completion of chemotherapy and radiation treatments. All patients were classified by the International Society of Lymphology clinical stages from 0 to 3. A dose of 50 MBq of 99mTc-HSA-nanocolloidal in 0.4mL was injected intradermally at the first and fourth intermetacarpal spaces on the hand, for the upper limb with edema, or at the first intermetatarsal space and at the lateral malleolus for lower extremities. Two planar static scans at rest were acquired immediately after tracer injection. Stress scans were acquired after weight lifting for upper extremity or stepping for 2 minutes for lower-extremity edema. After that, the patients underwent prolonged muscular exercise limited by symptoms, and later scans were acquired at 60 minutes to visualize regional lymph nodes and the effects of sustained muscular exercise. Transport Index was evaluated.

Results
Five patterns of lymphoscintigraphy were observed. In our experience, patients with types I to III pattern benefit from an exercise program as a first-line treatment. Patterns IVand V seem to be predictive of lymphedema.

Conclusions
The abnormal patterns found may provide the basis for earlier complex physical therapy or microsurgical treatment of lymphatic disorders in patients resulting in improved outcomes.
Extramedullary Infiltration of Acute Lymphoblastic Leukemia in Multiple Organs on FDG PET/CT
Authors: Zhang Shuxin , Wang Wei , Kan Ying , Liu Jie , Yang Jigang 
Published: December 2017

Abstract
Concurrent extramedullary infiltration in multiple organs is uncommon in adults with acute lymphoblastic leukemia. A 21-year-old woman who presented fatigue had a new diagnosis of acute lymphoblastic leukemia underwent FDG PET/CT. The images demonstrated extramedullary infiltration in multiple organs, including the liver, pancreas, kidney and the bone. However, no clinical signs or laboratory tests were suggestive of the involvement of these organs. After four cycles of chemotherapy, the patient’s symptoms were relieved and all previously visualized abnormal activity disappeared on the follow-up FDG PET/CT.
Relationship Between the Elevated Muscle FDG Uptake in the Distal Upper Extremities on PET/CT Scan and Prescan Utilization of Mobile Devices in Young Patients
Authors: Bai Xia , Wang Xuemei , Zhuang Hongming 
Published: December 2017

Purpose
It is common to notice increased FDG activity in the muscles of the forearms or hands on PET/CT images. The purpose of this study was to determine relationship between the prevalence of increased FDG activity in the forearms or hands and using mobile devices prior to the FDG PET/CT study.

Methods
A total of 443 young patients with ages between 5 and 19 years who underwent FDG PET/CT scan were included in this retrospective analysis. All patients had FDG PET/CT with their arms within the field of views. The images were reviewed for elevated activity in the muscles of the distal upper extremities (DUEs), which include forearms and hands. The preimaging questionnaire/interview records regarding using mobile devices prior to FDG PET/CT were also reviewed and compared with the imaging findings.

Results
Most patients (72.0% [319/443]) used mobile devices more than 60 minutes in the period of 24 hours prior to the FDG PET/CT study. Elevated uptake in the muscles in the DUEs was observed in 38.6% (123/319) of these patients. In contrast, among 124 patients who did not use the mobile devices or used the mobile device minimally prior to the study, only 6.5% (8/124) of them had elevated FDG activity in the DUEs. The difference persisted following stratification analysis for sex, age, and serum glucose level in our patient population.

Conclusions
Increased FDG uptake in the muscles of the DUEs in young patients is commonly seen in those who used mobile devices prior to PET/CT study. Recommendation should be considered to reduce using mobile devices prior to FDG PET/CT study in young patient population.
From number sense to number symbols. An archaeological perspective
Authors: d'Errico Francesco , Doyon Luc , Colagé Ivan , Queffelec Alain , Le Vraux Emma , Giacobini Giacomo , Vandermeersch Bernard , Maureille Bruno 
Published: January 2018

How and when did hominins move from the numerical cognition that we share with the rest of the animal world to number symbols? Objects with sequential markings have been used to store and retrieve numerical information since the beginning of the European Upper Palaeolithic (42 ka). An increase in the number of markings and complexity of coding is observed towards the end of this period. The application of new analytical techniques to a 44–42 ka old notched baboon fibula from Border Cave, South Africa, shows that notches were added to this bone at different times, suggesting that devices to store numerical information were in use before the Upper Palaeolithic. Analysis of a set of incisions on a 72–60 ka old hyena femur from the Les Pradelles Mousterian site, France, indicates, by comparison with markings produced by modern subjects under similar constraints, that the incisions on the Les Pradelles bone may have been produced to record, in a single session, homologous units of numerical information. This finding supports the view that numerical notations were in use among archaic hominins. Based on these findings, a testable five-stage scenario is proposed to establish how prehistoric cultures have moved from number sense to the use of number symbols.
This article is part of a discussion meeting issue ‘The origins of numerical abilities’.
Circuit and cellular mechanisms facilitate the transformation from dense to sparse coding in the insect olfactory system
Authors: Betkiewicz Rinaldo , Lindner Benjamin , Nawrot Martin P. 
Published: December 2017

AbstractTransformations between sensory representations are shaped by neural mechanisms at the cellular and the circuit level. In the insect olfactory system encoding of odor information undergoes a transition from a dense spatio-temporal population code in the antennal lobe to a sparse code in the mushroom body. However, the exact mechanisms shaping odor representations and their role in sensory processing are incompletely identified. Here, we investigate the transformation from dense to sparse odor representations in a spiking model of the insect olfactory system, focusing on two ubiquitous neural mechanisms: spike-frequency adaptation at the cellular level and lateral inhibition at the circuit level. We find that cellular adaptation is essential for sparse representations in time (temporal sparseness), while lateral inhibition regulates sparseness in the neuronal space (population sparseness). The interplay of both mechanisms shapes dynamical odor representations, which are optimized for discrimination of odors during stimulus onset and offset. In addition, we find that odor identity is stored on a prolonged time scale in the adaptation levels but not in the spiking activity of the principal cells of the mushroom body, providing a testable hypothesis for the location of the so-called odor trace.
Deep learning reveals many more inter-protein residue-residue contacts than direct coupling analysis
Authors: Zhou Tian-ming , Wang Sheng , Xu Jinbo 
Published: December 2017

AbstractIntra-protein residue-level contact prediction has drawn a lot of attentions in recent years and made very good progress, but much fewer methods are dedicated to inter-protein contact prediction, which are important for understanding how proteins interact at structure and residue level. Direct coupling analysis (DCA) is popular for intra-protein contact prediction, but extending it to inter-protein contact prediction is challenging since it requires too many interlogs (i.e., interacting homologs) to be effective, which cannot be easily fulfilled especially for a putative interacting protein pair in eukaryotes. We show that deep learning, even trained by only intra-protein contact maps, works much better than DCA for inter-protein contact prediction. We also show that a phylogeny-based method can generate a better multiple sequence alignment for eukaryotes than existing genome-based methods and thus, lead to better inter-protein contact prediction. Our method shall be useful for protein docking, protein interaction prediction and protein interaction network construction.
Localized Recombination Drives Diversification of Killing Spectra for Phage Derived Syringacins
Authors: Baltrus David A. , Clark Meara , Smith Caitlin , Hockett Kevin L. 
Published: December 2017

AbstractTo better understand the potential for detrimental interactions between strains of the same bacterial species, we have surveyed bacteriocin killing activity across a diverse suite of strains of the phytopathogenPseudomonas syringae.Our data demonstrate that killing activity from phage derived bacteriocins ofP. syringae(R-type syringacins) is widespread. Despite a high overall diversity of bacteriocin activity, strains can broadly be classified into five main killing types and two main sensitivity types. Furthermore, we show that killing activity switches frequently between strains, and that switches correlate with localized recombination of two genes that together encode the proteins that specify bacteriocin targeting. Lastly, we demonstrate that phage derived bacteriocin killing activity can be swapped between strains simply through expression of these two genesin trans.Overall, our study characterizes extensive diversity of killing activity for phage derived bacteriocins ofP. syringaeacross strains and highlights the power of localized recombination to alter phenotypes that mediate strain interactions during evolution of natural populations and communities.
The Transcriptional Program of Regeneration in the Giant Single Cell,Stentor coeruleus
Authors: Sood Pranidhi , McGillivary Rebecca , Marshall Wallace F. 
Published: December 2017

AbstractThe giant ciliateStentor coeruleusis a classical model system for studying regeneration and morphogenesis at the level of a single cell.Stentorare polarized cells with a complex subcellular architecture. The anterior of the cell is marked by an array of cilia, known as the oral apparatus. This feeding organelle can be induced to shed and regenerate in a series of reproducible morphological steps, previously shown to require transcription. We used RNAseq to assay the dynamic changes inStento’s transcriptome during regeneration with high temporal resolution, allowing us to identify five distinct waves of gene expression. We show that the oral apparatus is a model for organelle regeneration, as well as for centriole assembly and ciliogenesis as many conserved genes involved in those processes are induced. Additionally, we find genes involved in signaling, cell cycle regulation, transcription, and RNA binding to be expressed at distinct stages of organelle regeneration, suggesting that the morphological steps of regeneration are driven by a complex regulatory system.
A Simulation Analysis and Screening of Deleterious Non-Synonymous Single Nucleotide Polymorphisms (SNPs) in Human CDKN1A Gene
Authors: Prince G. M. Shazzad Hossain , Dhar Trayee 
Published: December 2017

AbstractCDKN1A also known as p21CIP1 /p21WAF1, a cyclin dependent kinase 1, interacts with proliferating cell nuclear antigen (PCNA) resulting in cell cycle inhibition in human. Non-synonymous single nucleotide polymorphisms (nsSNPs), which reside in the coding region of a gene, might distort the normal function of the corresponding protein. In silico analysis in this study followed many different algorithms. Following the final screening of 118 nsSNPs from dbSNP (NCBI), 12 missense SNPs (R19C (C→T), G23D (A→G), V25G (G→T), V25L (C→G), Q29P (A→C→G), F51L (C→T), E56K (A→G), T57I (C→T), G61R (C→G), G61D (A→G), Y151C (A→G) and R156W (C→G→T) were predicted to have deleterious effect by all the algorithms. Of them, R19C, G23D, F51L, Y151C and R156W occurred at the highly conserved site. G23D, F51L variants also occurred at the CDI domain. Homology structures of the protein predicted decrease of energy in mutant models. GV-GD scores predicted only two variants as neutral (V25L, F51L).
Cell cycle repression and DNA repair defects follow constricted migration
Authors: Pfeifer Charlotte R. , Xia Yuntao , Zhu Kuangzheng , Liu Dazhen , Irianto Jerome , Harding Shane , Greenberg Roger A. , Discher Dennis E. 
Published: December 2017

AbstractCancer cell invasion into tissue or narrow capillaries often elongates the nucleus and sometimes damages it, but cell cycle effects are unknown and highly relevant to tumorigenesis. Here, nuclear rupture and DNA breaks caused by constricted migration are quantified in different phases of cell cycle - which is effectively repressed. Cancer lines with varying levels of contact inhibition and lamina proteins exhibit diverse frequencies of nuclear lamina rupture after migration, with prerupture dilation of gene-edited RFP-Lamin-B1 preceding DNA repair factor leakage in pressure-controlled distension. Post-migration rupture indeed associates with mis-localized DNA repair factors and increased DNA breaks as quantified by pan-nucleoplasmic foci of γH2AX, with foci counts always suppressed in late cell cycle. When contact-inhibited cells migrate through large pores into sparse microenvironments, cells re-enter cell cycle consistent with release from contact inhibition. In contrast, constricting pores effectively delay re-entry, but the excess DNA damage nonetheless exceeds any cell cycle dependence. Partial depletion of topoisomerase does not strongly affect cell cycle or the excess DNA damage, consistent with weak dependencies on replication stress. Constricted migration thus impacts cell cycle as well as DNA damage.
Precautionary Coherence Unravels Dose Escalation Designs
Authors: Norris David C. 
Published: December 2017

ABSTRACTBackgroundCoherence notions have a long history in statistics, as rhetorical devices that support the critical examination of statistical doctrines and practices. Within the special domain of dose-finding methodology, a widely-discussed coherence criterion has been advanced as a means to guard the conceptual integrity of formal dose-finding designs from ad hoc tinkering. This is not, however, the only possible coherence criterion relevant to dose finding. Indeed, a new coherence criterion emerges naturally when the near-universal practice of cohort-wise dose escalation is examined from a clinical perspective.MethodsThe practice of enrolling drug-naive patients into an escalation cohort is considered from a realistic perspective that acknowledges patients’ heterogeneity with respect to pharmacokinetics and pharmacodynamics. A new coherence criterion thereby emerges, requiring that an escalation dose be tried preferentially in participants who have already tolerated a lower dose, rather than in new enrollees who are drug-naive. The logical implications of this ‘precautionary coherence’ (PC) criterion are worked out in the setting of a 3+3 design. A ‘3+3/PC’ design that satisfies this criterion is described and visualized. A simulation study is performed, evaluating the long-run performance of this new design, relative to optimal 1-size-fits-all dosing.ResultsUnder the PC criterion, the 3+3 dose-escalation design necessarily transmutes into a dose titration design. Two simple rules suffice to enable abandonment of low starting doses, and termination of escalation. The process of conducting the 3+3/PC trial itself models the application of a dose titration algorithm (DTA) that carries over readily into clinical care. The 3+3/PC trial also yields an interval-censored ‘dose-survival curve’ having a semantics that should prove familiar to oncology trialists. Simulated 3+3/PC trials yield DTAs over a median of 6 dose levels, achieving 50% improved population-level efficacy compared to optimal 1-size-fits-all dosing.ConclusionsDose individualization can be accomplished within a trial conducted along ‘algorithmic’ lines resembling those of the inveterate 3+3 design. The dose-survival curve arising from this ‘3+3/PC’ design has semantics that should prove familiar and conceptually accessible to oncology trialists, and also seems capable of supporting more formal statistical treatments of the design. In the presence of sufficient heterogeneity in individualized optimal dosing, a 3+3/PC trial outperforms any conceivable 1-size-fits-all dose-finding design. This fact eliminates the rationale for the latter designs, and should put an end to the further development and promulgation of 1-size-fits-all dose finding.
Membrane potential correlates of network decorrelation and improved SNR by cholinergic activation in the somatosensory cortex
Authors: Meir Inbal , Katz Yonatan , Lampl Ilan 
Published: December 2017

AbstractThe nucleus basalis (NB) projects cholinergic axons to the cortex where they play a major role in arousal, attention and learning. Cholinergic inputs shift cortical dynamics from synchronous to asynchronous and improves the signal to noise ratio (SNR) of sensory response. Yet, the underlying mechanisms of these changes remain unclear. Using simultaneous extracellular and whole cell patch recordings in layer 4 barrel cortex we show that activation of the cholinergic system has a differential effect on ongoing and sensory evoked activities. Cholinergic activation eliminated the large and correlated spontaneous synaptic fluctuations in membrane potential while sparing the synaptic response to whisker stimulation. This differential effect of cholinergic activation provides a unified explanation for the increased SNR of sensory response and for the reduction in both trial to trial variability and noise correlations as well as explaining the shift into desynchronized cortical state which are the hallmarks of arousal and attention.
CandidatusNitrosocaldus cavascurensis, an ammonia oxidizing, extremely thermophilic archaeon with a highly mobile genome
Authors: Abby Sophie S. , Melcher Michael , Kerou Melina , Krupovic Mart , Stieglmeier Michaela , Rossel Claudia , Pfeifer Kevin , Schleper Christa 
Published: December 2017

AbstractAmmonia oxidizing archaea (AOA) of the phylum Thaumarchaeota are widespread in moderate environments but their occurrence and activity has also been demonstrated in hot springs. Here we present the first cultivated thermophilic representative with a sequenced genome, which allows to search for adaptive strategies and for traits that shape the evolution of Thaumarchaeota.CandidatusNitrosocaldus cavascurensis has been cultivated from a hot spring in Ischia, Italy. It grows optimally at 68°C under chemolithoautotrophic conditions on ammonia or urea converting ammonia stoichiometrically into nitrite with a generation time of approximately 25h. Phylogenetic analyses based on ribosomal proteins place the organism as a sister group to all known mesophilic AOA. The 1.58 Mb genome ofCa.N. cavascurensis harbors an amoAXCB gene cluster encoding ammonia monooxygenase, genes for a 3-hydroxypropionate/4-hydroxybutyrate pathway for autotrophic carbon fixation, but also genes that indicate potential alternative energy metabolisms. Although a bona fide gene for nitrite reductase is missing, the organism is sensitive to NO-scavenging, underlining the importance of this compound for AOA metabolism.Ca.N. cavascurensis is distinct from all other AOA in its gene repertoire for replication, cell division and repair. Its genome has an impressive array of mobile genetic elements and other recently acquired gene sets, including conjugative systems, a provirus, transposons and cell appendages. Some of these elements indicate recent exchange with the environment, whereas others seem to have been domesticated and might convey crucial metabolic traits.
Crosstalk Between One Carbon Metabolism and Eph Signaling Promotes Neural Stem Cells Differentiation Through Epigenetic Remodeling
Authors: Fawal Mohamad-Ali , Jungas Thomas , Kischel Anthony , Audouard Christophe , Iacovoni Jason S. , Davy Alice 
Published: December 2017

SUMMARYMetabolic pathways, once seen as a mere consequence of cell states, have emerged as active players in dictating different cellular events such as proliferation, self-renewal and differentiation. Several studies have reported a role for folate-dependent 1-carbon (1C) metabolism in stem cells, however, its exact mode of action and how it interacts with other cues is largely unknown. Here, we report a link between the Eph:ephrin cell-cell communication pathway and 1C metabolism in controlling differentiation of neural stem cells. Transcriptional and functional analyses following ephrin stimulation revealed alterations in folate metabolism-related genes and enzymatic activity. In vitro and in vivo data indicate that Eph-B forward signaling alters the methylation state of H3K4 by regulating 1C metabolism, and locks neural stem cells in a differentiation-ready state. The functional link between cell-cell communication, metabolism and epigenetic remodeling identifies a novel triad in the control of stem cell self-renewal vs. differentiation.HIGHLIGHTS1C folate metabolism is regulated by local cell-to-cell communicationDescription of Eph-B transcriptional response in NSCEph activation decreases the expression and activity of DHFRInhibition of DHFR modifies epigenetic marks and impairs self-renewal of neural stem cellsDecreased H3K4 methylation locks neural stem cells in a pro-differentiation stateeTOC BLURBFawal et al. present evidence that Eph-B forward signaling inhibits 1C folate metabolism in neural stem cells leading to alteration of H3K4 methylation on key progenitor genes. In addition, they show that these epigenetic changes are inherited and maintained in the long term, thus locking NSC into a differentiation ready state.
A genome-wide association study for shared risk across major psychiatric disorders in a nation-wide birth cohort implicates fetal neurodevelopment as a key mediator
Authors: Schork Andrew J. , Won Hyejung , Appadurai Vivek , Nudel Ron , Gandal Mike , Delaneau Olivier , Hougaard David M. , Bækved-Hansen Marie , Bybjerg-Grauholm Jonas , Giørtz Pedersen Marianne , Agerbo Esben , Bøcker Pedersen Carsten , Neale Benjamin M. , Daly Mark J. , Nordentoft Merete , Mors Ole , Børglum Anders D. , Mortensen Preben Bo , Buil Alfonso , Thompson Wesley K. , Geschwind Daniel , Werge Thomas 
Published: December 2017

AbstractThere is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here, we leverage the unique iPSYCH study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder SNP-heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during midgestation. This epoch is supported by partitioning cross-disorder SNP-heritability which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings indicate that dysregulation of genes that direct neurodevelopment by common genetic variants results in general liability for many later psychiatric outcomes.