bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abemaciclib as initial therapy for advanced breast cancer: MONARCH 3 updated results in prognostic subgroups
Authors: Johnston Stephen , O’Shaughnessy Joyce , Martin Miguel , Huober Jens , Toi Masakazu , Sohn Joohyuk , André Valérie A. M. , Martin Holly R. , Hardebeck Molly C. , Goetz Matthew P. 
Published: June 2021

AbstractIn MONARCH 3, continuous dosing of abemaciclib with an aromatase inhibitor (AI) conferred significant clinical benefit to postmenopausal women with HR+, HER2− advanced breast cancer. We report data for clinically prognostic subgroups: liver metastases, progesterone receptor status, tumor grade, bone-only disease, ECOG performance status, and treatment-free interval (TFI) from an additional 12-month follow-up (after final progression-free survival [PFS] readout). In the intent-to-treat population, after median follow-up of approximately 39 months, the updated PFS was 28.2 versus 14.8 months (hazard ratio [HR], 0.525; 95% confidence interval, 0.415–0.665) in abemaciclib versus placebo arms, respectively. Time to chemotherapy (HR, 0.513), time to second disease progression (HR, 0.637), and duration of response (HR, 0.466) were also statistically significantly prolonged with the addition of abemaciclib to AI. Treatment benefit was observed across all subgroups, as evidenced by objective response rate change from the addition of abemaciclib to AI, with the largest effects observed in patients with liver metastases, progesterone receptor-negative tumors, high-grade tumors, or TFI < 36 months. Extended follow-up in the MONARCH 3 trial further confirmed that the addition of abemaciclib to AI conferred significant treatment benefit to all subgroups, including those with poorer prognosis.
Optimal two-qubit circuits for universal fault-tolerant quantum computation
Authors: Glaudell Andrew N. , Ross Neil J. , Taylor Jacob M. 
Published: June 2021

AbstractWe study two-qubit circuits over the Clifford+CS gate set, which consists of the Clifford gates together with the controlled-phase gate CS = diag(1, 1, 1, i). The Clifford+CS gate set is universal for quantum computation and its elements can be implemented fault-tolerantly in most error-correcting schemes through magic state distillation. Since non-Clifford gates are typically more expensive to perform in a fault-tolerant manner, it is often desirable to construct circuits that use few CS gates. In the present paper, we introduce an efficient and optimal synthesis algorithm for two-qubit Clifford+CS operators. Our algorithm inputs a Clifford+CS operator U and outputs a Clifford+CS circuit for U, which uses the least possible number of CS gates. Because the algorithm is deterministic, the circuit it associates to a Clifford+CS operator can be viewed as a normal form for that operator. We give an explicit description of these normal forms and use this description to derive a worst-case lower bound of $$5{{\rm{log}}}_{2}(\frac{1}{\epsilon })+O(1)$$

5

log

2

(

1

ϵ

)

+
O

(

1

)

on the number of CS gates required to ϵ-approximate elements of SU(4). Our work leverages a wide variety of mathematical tools that may find further applications in the study of fault-tolerant quantum circuits.
Psoriatic disease is associated with systemic inflammation, endothelial activation, and altered haemostatic function
Authors: Visser Maria J. E. , Venter Chantelle , Roberts Timothy J. , Tarr Gareth , Pretorius Etheresia 
Published: June 2021

AbstractPsoriasis is a chronic, immune-mediated inflammatory skin disease, affecting approximately 2% of the general population, which can be accompanied by psoriatic arthritis (PsA). The condition has been associated with an increased cardiovascular burden. Hypercoagulability is a potential underlying mechanism that may contribute to the increased risk of major cardiovascular events in psoriatic individuals. Whole blood samples were collected from 20 PsA patients and 20 healthy individuals. The concentrations of inflammatory molecules (C-reactive protein, serum amyloid A, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble P-selectin) were determined by enzyme-linked immunosorbent assays. In addition, clotting efficiency was evaluated by thromboelastography. The fibrin network architecture was also assessed by scanning electron microscopy. Elevated levels of circulating inflammatory molecules were significantly associated with the presence of psoriatic disease. Furthermore, an increased tendency towards thrombus formation was significantly predictive of disease presence. Scanning electron microscopy revealed that fibrin clots were denser in psoriatic individuals, compared to healthy controls, with an increased fibrin fibre diameter associated with psoriatic disease. Our results add to the accumulating evidence of the systemic nature of psoriasis and the subsequent risk of cardiovascular comorbidities, potentially due to an acquired hypercoagulability. We suggest that haemostatic function should be monitored carefully in psoriatic patients that present with severe disease, due to the pre-eminent risk of developing thrombotic complications.
DotMotif: an open-source tool for connectome subgraph isomorphism search and graph queries
Authors: Matelsky Jordan K. , Reilly Elizabeth P. , Johnson Erik C. , Stiso Jennifer , Bassett Danielle S. , Wester Brock A. , Gray-Roncal William 
Published: June 2021

AbstractRecent advances in neuroscience have enabled the exploration of brain structure at the level of individual synaptic connections. These connectomics datasets continue to grow in size and complexity; methods to search for and identify interesting graph patterns offer a promising approach to quickly reduce data dimensionality and enable discovery. These graphs are often too large to be analyzed manually, presenting significant barriers to searching for structure and testing hypotheses. We combine graph database and analysis libraries with an easy-to-use neuroscience grammar suitable for rapidly constructing queries and searching for subgraphs and patterns of interest. Our approach abstracts many of the computer science and graph theory challenges associated with nanoscale brain network analysis and allows scientists to quickly conduct research at scale. We demonstrate the utility of these tools by searching for motifs on simulated data and real public connectomics datasets, and we share simple and complex structures relevant to the neuroscience community. We contextualize our findings and provide case studies and software to motivate future neuroscience exploration.
Impact of antibiotic usage on extended-spectrum β-lactamase producing Escherichia coli prevalence
Authors: Kim Jeong Yeon , Yum Yunjin , Joo Hyung Joon , An Hyonggin , Yoon Young Kyung , Kim Jong Hun , Sohn Jang Wook 
Published: June 2021

AbstractAn increase in antibiotic usage is considered to contribute to the emergence of antimicrobial resistance.
Although experts are counting on the antimicrobial stewardship programs to reduce antibiotic usage, their effect remains uncertain. In this study, we aimed to evaluate the impact of antibiotic usage and forecast the prevalence of hospital-acquired extended spectrum β-lactamase (ESBL)—producing Escherichia coli (E. coli) using time-series analysis. Antimicrobial culture information of E. coli was obtained using a text processing technique that helped extract free-text electronic health records from standardized data. The antimicrobial use density (AUD) of antibiotics of interest was used to estimate the quarterly antibiotic usage. Transfer function model was applied to forecast relationship between antibiotic usage and ESBL-producing E. coli. Of the 1938 hospital-acquired isolates, 831 isolates (42.9%) were ESBL-producing E. coli. Both the proportion of ESBL-producing E. coli and AUD increased over time. The transfer model predicted that ciprofloxacin AUD is related to the proportion of ESBL-producing E. coli two quarters later. In conclusion, excessive use of antibiotics was shown to affect the prevalence of resistant organisms in the future. Therefore, the control of antibiotics with antimicrobial stewardship programs should be considered to restrict antimicrobial resistance.
Hippocampus-retrosplenial cortex interaction is increased during phasic REM and contributes to memory consolidation
Authors: de Almeida-Filho Daniel Gomes , Koike Bruna Del Vechio , Billwiller Francesca , Farias Kelly Soares , de Sales Igor Rafael Praxedes , Luppi Pierre-Hervé , Ribeiro Sidarta , Queiroz Claudio Marcos 
Published: June 2021

AbstractHippocampal (HPC) theta oscillation during post-training rapid eye movement (REM) sleep supports spatial learning. Theta also modulates neuronal and oscillatory activity in the retrosplenial cortex (RSC) during REM sleep. To investigate the relevance of theta-driven interaction between these two regions to memory consolidation, we computed the Granger causality within theta range on electrophysiological data recorded in freely behaving rats during REM sleep, both before and after contextual fear conditioning. We found a training-induced modulation of causality between HPC and RSC that was correlated with memory retrieval 24 h later. Retrieval was proportional to the change in the relative influence RSC exerted upon HPC theta oscillation. Importantly, causality peaked during theta acceleration, in synchrony with phasic REM sleep. Altogether, these results support a role for phasic REM sleep in hippocampo-cortical memory consolidation and suggest that causality modulation between RSC and HPC during REM sleep plays a functional role in that phenomenon.
Autophagy of mucin granules contributes to resolution of airway mucous metaplasia
Authors: Sweeter J. M. , Kudrna K. , Hunt K. , Thomes P. , Dickey B. F. , Brody S. L. , Dickinson J. D. 
Published: June 2021

AbstractExacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations.
Validity and safety of ID-JPL934 in lower gastrointestinal symptom improvement
Authors: Shin Cheol Min , Choi Yoon Jin , Lee Dong Ho , Moon Jin Seok , Kim Tae-Yoon , Kim Yoon-Keun , Lee Won-Hee , Yoon Hyuk , Park Young Soo , Kim Nayoung 
Published: June 2021

AbstractThe study evaluated the efficacy of ID-JPL934, a probiotic preparation containing Lactobacillus johnsonii IDCC 9203, Lactobacillus plantarum IDCC 3501 and Bifidobacterium lactis IDCC 4301, in relieving lower gastrointestinal symptoms. A total of 112 subjects with lower gastrointestinal symptoms were consecutively enrolled. They were randomized into either ID-JPL934 administration group or placebo group. Bristol stool form, stool frequency, and abnormal bowel movement symptoms were recorded at baseline and week 2, 6, and 8. Primary endpoint was improvement in overall symptoms at week 8. Fecal samples were collected to measure the probiotic levels in feces using quantitative polymerase chain reaction (qPCR), and to perform metagenomic analysis of microbiome originating from bacteria-derived extracellular vesicles and bacterial cells via 16S rDNA sequencing. Of the 112 subjects, 104 (54 in ID-JPL934 group and 50 in placebo group) completed the entire study protocol. A higher relief of overall symptoms was found in ID-JPL934 group than in placebo group (p = 0.016). Among lower gastrointestinal symptoms, abdominal pain and bloating scores were more decreased in ID-JPL934 group than in placebo group (p < 0.05). The fecal microbiome profiles of the two groups did not differ. However, the qPCR analysis showed significant increase in the levels of Lactobacillus johnsonii and Bifidobacterium lactis in feces post-treatment in ID-JPL934 group than in placebo group (p < 0.05 by repeated measure ANOVA). In conclusion, ID-JPL934 is effective in relieving lower gastrointestinal symptoms. Exposure to ID-JPL934 may increase the abundance of Lactobacillus johnsonii and Bifidobacterium lactis in the gut.Trial registration: ClinicalTrials.gov number, NCT03395626.
RNAseq reveals different transcriptomic responses to GA3 in early and midseason varieties before ripening initiation in sweet cherry fruits
Authors: Kuhn Nathalie , Maldonado Jonathan , Ponce Claudio , Arellano Macarena , Time Alson , Multari Salvatore , Martens Stefan , Carrera Esther , Donoso José Manuel , Sagredo Boris , Meisel Lee A. 
Published: June 2021

AbstractGibberellin (GA) negatively affects color evolution and other ripening-related processes in non-climacteric fruits. The bioactive GA, gibberellic acid (GA3), is commonly applied at the light green-to-straw yellow transition to increase firmness and delay ripening in sweet cherry (Prunus avium L.), though causing different effects depending on the variety. Recently, we reported that GA3 delayed the IAD parameter (a ripening index) in a mid-season variety, whereas GA3 did not delay IAD but reduced it at ripeness in an early-season variety. To further explore this contrasting behavior between varieties, we analyzed the transcriptomic responses to GA3 applied on two sweet cherry varieties with different maturity time phenotypes. At harvest, GA3 produced fruits with less color in both varieties. Similar to our previous report, GA3 delayed fruit color initiation and IAD only in the mid-season variety and reduced IAD at harvest only in the early-season variety. RNA-seq analysis of control- and GA3-treated fruits revealed that ripening-related categories were overrepresented in the early-season variety, including ‘photosynthesis’ and ‘auxin response’. GA3 also changed the expression of carotenoid and abscisic acid (ABA) biosynthetic genes in this variety. In contrast, overrepresented categories in the mid-season variety were mainly related to metabolic processes. In this variety, some PP2Cs putative genes were positively regulated by GA3, which are negative regulators of ABA responses, and MYB44-like genes (putative repressors of PP2Cs expression) were downregulated. These results show that GA3 differentially modulates the transcriptome at the onset of ripening in a variety-dependent manner and suggest that GA3 impairs ripening through the modification of ripening associated gene expression only in the early-season variety; whereas in the mid-season variety, control of the ripening timing may occur through the PP2C gene expression regulation. This work contributes to the understanding of the role of GA in non-climacteric fruit ripening.
Mobility-based real-time economic monitoring amid the COVID-19 pandemic
Authors: Spelta Alessandro , Pagnottoni Paolo 
Published: June 2021

AbstractMobility restrictions have been identified as key non-pharmaceutical interventions to limit the spread of the SARS-COV-2 epidemics. However, these interventions present significant drawbacks to the social fabric and negative outcomes for the real economy. In this paper we propose a real-time monitoring framework for tracking the economic consequences of various forms of mobility reductions involving European countries. We adopt a granular representation of mobility patterns during both the first and second waves of SARS-COV-2 in Italy, Germany, France and Spain to provide an analytical characterization of the rate of losses of industrial production by means of a nowcasting methodology. Our approach exploits the information encoded in massive datasets of human mobility provided by Facebook and Google, which are published at higher frequencies than the target economic variables, in order to obtain an early estimate before the official data becomes available. Our results show, in first place, the ability of mobility-related policies to induce a contraction of mobility patterns across jurisdictions. Besides this contraction, we observe a substitution effect which increases mobility within jurisdictions. Secondly, we show how industrial production strictly follows the dynamics of population commuting patterns and of human mobility trends, which thus provide information on the day-by-day variations in countries’ economic activities. Our work, besides shedding light on how policy interventions targeted to induce a mobility contraction impact the real economy, constitutes a practical toolbox for helping governments to design appropriate and balanced policy actions aimed at containing the SARS-COV-2 spread, while mitigating the detrimental effect on the economy. Our study reveals how complex mobility patterns can have unequal consequences to economic losses across countries and call for a more tailored implementation of restrictions to balance the containment of contagion with the need to sustain economic activities.
Heterotrophic euglenid Rhabdomonas costata resembles its phototrophic relatives in many aspects of molecular and cell biology
Authors: Soukal Petr , Hrdá Štěpánka , Karnkowska Anna , Milanowski Rafał , Szabová Jana , Hradilová Miluše , Strnad Hynek , Vlček Čestmír , Čepička Ivan , Hampl Vladimír 
Published: June 2021

AbstractEuglenids represent a group of protists with diverse modes of feeding. To date, only a partial genomic sequence of Euglena gracilis and transcriptomes of several phototrophic and secondarily osmotrophic species are available, while primarily heterotrophic euglenids are seriously undersampled. In this work, we begin to fill this gap by presenting genomic and transcriptomic drafts of a primary osmotroph, Rhabdomonas costata. The current genomic assembly length of 100 Mbp is 14× smaller than that of E. gracilis. Despite being too fragmented for comprehensive gene prediction it provided fragments of the mitochondrial genome and comparison of the transcriptomic and genomic data revealed features of its introns, including several candidates for nonconventional types. A set of 39,456 putative R. costata proteins was predicted from the transcriptome. Annotation of the mitochondrial core metabolism provides the first data on the facultatively anaerobic mitochondrion of R. costata, which in most respects resembles the mitochondrion of E. gracilis with a certain level of streamlining. R. costata can synthetise thiamine by enzymes of heterogenous provenances and haem by a mitochondrial-cytoplasmic C4 pathway with enzymes orthologous to those found in E. gracilis. The low percentage of green algae-affiliated genes supports the ancestrally osmotrophic status of this species.
Directivity enhancement of a cylindrical wire antenna by a graded index dielectric shell designed using strictly conformal transformation optics
Authors: Eskandari Hossein , Saviz Soorena , Tyc Tomáš 
Published: June 2021

AbstractA transformation-optical method is presented to enhance the directivity of a cylindrical wire antenna by using an all-dielectric graded index medium. The strictly conformal mapping between two doubly connected virtual and physical domains is established numerically. Multiple directive beams are produced, providing directive emission. The state-of-the-art optical path rescaling method is employed to mitigate the superluminal regions. The resulting transformation medium is all-dielectric and nondispersive, which can provide broadband functionality and facilitate the realization of the device using available fabrication technologies. The realization of the device is demonstrated by dielectric perforation based on the effective medium theory. The device’s functionality is verified by carrying out both ray-tracing and full-wave simulations using finite-element-based software COMSOL Multiphysics.
Life cycle assessment and energy comparison of aseptic ohmic heating and appertization of chopped tomatoes with juice
Authors: Ghnimi Sami , Nikkhah Amin , Dewulf Jo , Van Haute Sam 
Published: June 2021

AbstractThe energy balance and life cycle assessment (LCA) of ohmic heating and appertization systems for processing of chopped tomatoes with juice (CTwJ) were evaluated. The data included in the study, such as processing conditions, energy consumption, and water use, were experimentally collected. The functional unit was considered to be 1 kg of packaged CTwJ. Six LCA impact assessment methodologies were evaluated for uncertainty analysis of selection of the impact assessment methodology. The energy requirement evaluation showed the highest energy consumption for appertization (156 kWh/t of product). The energy saving of the ohmic heating line compared to the appertization line is 102 kWh/t of the product (or 65% energy saving). The energy efficiencies of the appertization and ohmic heating lines are 25% and 77%, respectively. Regarding the environmental impact, CTwJ processing and packaging by appertization were higher than those of ohmic heating systems. In other words, CTwJ production by the ohmic heating system was more environmentally efficient. The tin production phase was the environmental hotspot in packaged CTwJ production by the appertization system; however, the agricultural phase of production was the hotspot in ohmic heating processing. The uncertainty analysis results indicated that the global warming potential for appertization of 1 kg of packaged CTwJ ranges from 4.13 to 4.44 kg CO2eq. In addition, the global warming potential of the ohmic heating system ranges from 2.50 to 2.54 kg CO2eq. This study highlights that ohmic heating presents a great alternative to conventional sterilization methods due to its low environmental impact and high energy efficiency.