bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant nivolumab in resectable non-small cell lung cancer: Extended follow-up and molecular markers of response.
Authors: Reuss Joshua E. , Smith Kellie Nicole , Anagnostou Valsamo , Zhang Jiajia , Zahurak Marianna , Caushi Justina , Chan Hok Yee , Guo Haidan , Hellmann Matthew David , Pardoll Drew M. , Brahmer Julie R. , Chaft Jamie E. , Forde Patrick M. 
Published: February 2020

8524 Background: Improved therapy is needed for patients (pts) with early-stage non-small cell lung cancer (NSCLC), as the majority relapse after curative resection. Our group reported the first trial of neoadjuvant PD-1 blockade in resectable NSCLC, finding therapy to be safe and feasible. Here we report extended clinical follow-up and long-term molecular response data from this trial. Methods: IV nivolumab 3 mg/kg was given every 2 weeks for 2 doses prior to surgery in 20 pts with resectable NSCLC at Johns Hopkins and MSKCC. Blood for correlative studies was taken prior to each dose of nivolumab, prior to surgery, 2-4 weeks post-surgery, and during long-term follow up. In a subgroup of pts, longitudinal molecular data was assessed in peripheral blood for circulating tumor DNA (ctDNA) and dynamics of tumor-infiltrating T-cell clonotypes. Results: At median follow up of 30 months (m), 15 of 20 pts are disease-free and alive. Two pts have died (one from relapsed disease). Median recurrence free survival (RFS) has not been reached. The 24m RFS rate is 69% (95% CI: 51-93). Thus far, presence of ctDNA at diagnosis and major pathologic response (MPR - ≤10% viable tumor in resected specimen) do not associate with RFS. One long-term immune-related adverse event has occurred (skin, G3). All pts who on pathologic review had ≥30% reduction in viable tumor in response to nivolumab demonstrated clearance of detectable ctDNA from blood prior to surgery. Pts with MPR experienced expansion of neoantigen-specific T-cells in peripheral blood. In one patient with ongoing disease free status, expansion of tumor-associated T-cells has persisted in peripheral blood beyond 15m from surgery. By contrast, in a patient who had detectable peri-operative ctDNA and 75% residual disease at surgery, minimal T-cell expansion was observed in peripheral blood, with a decreasing frequency of expanded T-cell clones over time that correlated with eventual cancer relapse. Conclusions: Long-term follow up reinforces the safety of neoadjuvant nivolumab in resectable NSCLC. Analysis of ctDNA and peripheral T-cell expansion in responders compared with non-responders suggests potential biomarkers for response and surveillance. While RFS data is encouraging, phase 3 trials are ongoing to evaluate efficacy of PD-(L)1 blockade in early-stage NSCLC. Clinical trial information: NCT02259621.
Spatiotemporal control of cell growth by CUC3 shapes leaf margins
Authors: Serra Léo , Perrot-Rechenmann Catherine 
Published: February 2020

ABSTRACT
How a shape arises from the coordinated behavior of cells is one of the most fascinating questions in developmental biology. In plants, fine spatial and temporal controls of cell proliferation and cell expansion sustain differential growth that defines organ shape and size. At the leaf margin of Arabidopsis thaliana, interplay between auxin transport and transcription factors named CUP SHAPED COTYLEDON (CUCs), which are involved in the establishment of boundary domain identity, were reported to trigger differential growth, leading to serration. Cellular behaviors behind these differential growths remain scarcely described. Here, we used 3D and time lapse imaging on young leaves at different stages of development to determine the sequence of cellular events resulting in leaf serrations. In addition, we showed that the transcription factor CUC3 is a negative regulator of cell growth and that its expression dynamics in a small number of cells at the leaf margin is tightly associated with the control of differential growth.
CXXC finger protein 1-mediated histone H3 lysine-4 trimethylation is essential for proper meiotic crossover formation in mice
Authors: Jiang Yu , Zhang Hui-Ying , Lin Zhen , Zhu Ye-Zhang , Yu Chao , Sha Qian-Qian , Tong Ming-Han , Shen Li , Fan Heng-Yu 
Published: February 2020

ABSTRACT
The most significant feature of meiosis is the recombination process during prophase I. CXXC finger protein 1 (CXXC1) binds to CpG islands and mediates the deposition of H3K4me3 by the SETD1 complex. CXXC1 is also predicted to recruit H3K4me3-marked regions to the chromosome axis for the generation of double-strand breaks (DSBs) in the prophase of meiosis. Therefore, we deleted Cxxc1 before the onset of meiosis with Stra8-Cre. The conditional knockout mice were completely sterile with spermatogenesis arrested at MII. Knockout of Cxxc1 led to a decrease in the H3K4me3 level from the pachytene to the MII stage and caused transcriptional disorder. Many spermatogenesis pathway genes were expressed early leading to abnormal acrosome formation in arrested MII cells. In meiotic prophase, deletion of Cxxc1 caused delayed DSB repair and improper crossover formation in cells at the pachytene stage, and more than half of the diplotene cells exhibited precocious homologous chromosome segregation in both male and female meiosis. Cxxc1 deletion also led to a significant decrease of H3K4me3 enrichment at DMC1-binding sites, which might compromise DSB generation. Taken together, our results show that CXXC1 is essential for proper meiotic crossover formation in mice and suggest that CXXC1-mediated H3K4me3 plays an essential role in meiotic prophase of spermatogenesis and oogenesis.
A single cell transcriptome atlas of the developing zebrafish hindbrain
Authors: Tambalo Monica , Mitter Richard , Wilkinson David G. 
Published: February 2020

ABSTRACT
Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.
Myosin heavy chain-embryonic regulates skeletal muscle differentiation during mammalian development
Authors: Agarwal Megha , Sharma Akashi , Kumar Pankaj , Kumar Amit , Bharadwaj Anushree , Saini Masum , Kardon Gabrielle , Mathew Sam J. 
Published: February 2020

ABSTRACT
Myosin heavy chain-embryonic (MyHC-emb) is a skeletal muscle-specific contractile protein expressed during muscle development. Mutations in MYH3, the gene encoding MyHC-emb, lead to Freeman–Sheldon and Sheldon–Hall congenital contracture syndromes. Here, we characterize the role of MyHC-emb during mammalian development using targeted mouse alleles. Germline loss of MyHC-emb leads to neonatal and postnatal alterations in muscle fiber size, fiber number, fiber type and misregulation of genes involved in muscle differentiation. Deletion of Myh3 during embryonic myogenesis leads to the depletion of the myogenic progenitor cell pool and an increase in the myoblast pool, whereas fetal myogenesis-specific deletion of Myh3 causes the depletion of both myogenic progenitor and myoblast pools. We reveal that the non-cell-autonomous effect of MyHC-emb on myogenic progenitors and myoblasts is mediated by the fibroblast growth factor (FGF) signaling pathway, and exogenous FGF rescues the myogenic differentiation defects upon loss of MyHC-emb function in vitro. Adult Myh3 null mice exhibit scoliosis, a characteristic phenotype exhibited by individuals with Freeman–Sheldon and Sheldon–Hall congenital contracture syndrome. Thus, we have identified MyHC-emb as a crucial myogenic regulator during development, performing dual cell-autonomous and non-cell-autonomous functions.
This article has an associated ‘The people behind the papers’ interview.
W poszukiwaniu rusińskiego separatyzmu
Authors: Michna Ewa 
Published: February 2020

In Search of Rusyn Separatism
Separatism is both a social phenomenon and a political category employed in analysis of diverse types of phenomena by social sciences. Colloquially it is often used to label and deprecate emancipating aspirations of groups that strive for recognition. Whether such aspirations of a given ethnic/national group are, or are not, considered separatism depends on the accepted definition of the term as well as the vantage point assumed in description. This paper attempts to view the process of emancipation of Trans-Carpathian Rusyns from two perspectives: various ways in which this complex phenomenon is approached throughout social sciences as well as an intragroup perspective of the actual participants of the process: Rusyn activists in Trans-Carpathian Ruthenia.
Полицентричне стандардизованє русинского язика
Authors: Фейса Михайло П. 
Published: February 2020

The Polycentric Standardization of the Rusyn Language
Pursuant to the conclusions of the First Rusyn Language Congress held in Bardejovske Kupele (Slovakia) in 1992 Rusyn language planners are advised to follow the so-called Romansh model of the construction of a literary language (the Romansh language is spoken in five standardized idioms in South-Eastern Switzerland). This implies that each country inhabited by Rusyns should codify its own variant of the literary language based on the live local Rusyn language. Thus there emerge four variants of the Rusyn language: the Bačka-Srem variant (in Serbia and Croatia), the Prešov variant (in Slovakia), the Lemko variant (in Poland), and the Trans-Carpathian variant (in Ukraine; used in Romania and Hungary as well). The paper brings attention to the status and perspectives of the four variants of the Rusyn language. The Rusyn language codification process may be viewed as polycentric standardization.
Near-UV luminescence tomography with an aperture-free meta super oscillatory lens for single molecule detection
Authors: Ali Hassan , Ni Haibin , Xu Xin 
Published: February 2020

Medical physics offers super oscillatory lenses (SOL) to attain subwavelength focusing for efficient image resolution in the detection of a single molecule. In this paper, we propose a negative-indexed permeability-controlled meta SOL, which restores the light concentration via exciting surface plasmon resonance and enhances luminescence at our region of interest, i.e., fluid sample (

S
L

). The meta SOL is aperture-free in comparison with other techniques (zero-mode waveguides and nano antennas) and hence avoids the constraints, which are posed by nano apertures, to insert a small volume of

S
L

into these nano apertures for detection purposes. The meta SOL is a unique combination of gold split rings mounted on silicon dioxide (

S
i
O

2

) substrate and operational in the near-ultraviolet (UV) region. We utilized the phenomena of negative index of refraction, and our simulated trails exploit the magnetic (

μ
r

) response of the meta SOL by analyzing its transmission spectra in the frequency range from 3.53 to 3.57 Peta Hz. We observe the methodical response of the meta SOL with its ample potential to surpass the resolution at a working wavelength of

λ
=

84.173

n
m

, which enhances luminescence by restoring the evanescent UV magnetic field (

B

U
V

) at

S
L

. This technique will offer a new and easy approach to uplift the efficiency of super oscillatory lenses in the near-UV regime to benefit single molecule detection techniques and thus the novelty.
Dynamic strain measurement by a single-slope-assisted chaotic Brillouin optical correlation-domain analysis
Authors: Wang Yahui , Zhao Le , Zhang Mingjiang , Zhang Jianzhong , Qiao Lijun , Wang Tao , Gao Shaohua , Zhang Qian , Wang Yuncai 
Published: February 2020

We propose a novel, to the best of our knowledge, method to enhance the measurement range of dynamic strain using a single-slope-assisted chaotic Brillouin optical correlation-domain analysis. The broadband chaos provides a Gaussian-shape pump-probe beat spectrum so that not only the centimeter-level spatial resolution is achieved but also the linewidth of the chaotic Brillouin gain spectrum is naturally broadened. Thus, the enlarged linear region could be employed to dynamically measure a large-range stretched strain. This experiment is the first to accurately identify the maximal strain of 1200

µ
ε

with a high spatial resolution of 3.45 cm using the single-slope-assisted technology. The dynamic frequency is 4.67 Hz in the highest but limited by the practical devices.
Physicians' Perceptions of Proton Pump Inhibitor Risks and Recommendations to Discontinue: A National Survey
Authors: Kurlander Jacob E. , Rubenstein Joel H. , Richardson Caroline R. , Krein Sarah L. , De Vries Raymond , Zikmund-Fisher Brian J. , Yang Yu-Xiao , Laine Loren , Weissman Arlene , Saini Sameer D. 
Published: February 2020

OBJECTIVE:
To provide contemporary estimates of internists' perceptions of adverse effects associated with proton pump inhibitors (PPIs) and self-reported clinical use.

METHODS:
We invited 799 internists, including specialists and postgraduate trainees, to complete an online survey. Topics included perceptions of PPI adverse effects (AEs) and effectiveness for upper gastrointestinal bleeding (UGIB) prevention, changes in prescribing, and management recommendations for patients using PPIs for gastroesophageal reflux disease or UGIB prevention. We used logistic regression to identify factors associated with appropriate PPI continuation in the scenario of a patient at high risk for UGIB.

RESULTS:
Among 437 respondents (55% response rate), 10% were trainees and 72% specialized in general medicine, 70% were somewhat/very concerned about PPI AEs, and 76% had somewhat/very much changed their prescribing. A majority believed PPIs increase the risk for 6 of 12 AEs queried. Fifty-two percent perceived PPIs to be somewhat/very effective for UGIB prevention. In a gastroesophageal reflux disease scenario in which PPI can be safely discontinued, 86% appropriately recommended PPI discontinuation. However, in a high-risk UGIB prevention scenario in which long-term PPI use is recommended, 79% inappropriately recommended discontinuation. In this latter scenario, perceived effectiveness for bleeding prevention was strongly associated with continuing PPI (odds ratio 7.68, P < 0.001 for moderately; odds ratio 17.3, P < 0.001 for very effective). Other covariates, including concern about PPI AEs, had no significant association.

DISCUSSION:
Most internists believe PPIs cause multiple AEs and recommend discontinuation even in patients at high risk for UGIB. Future interventions should focus on ensuring that PPIs are prescribed appropriately according to individual risks and benefits.
Entrepreneurial Traits, Entrepreneurial Environment Perception, and New Venture Performance: Empirical Evidence from Chinese Firms
Authors: Cheng Cong , Zhang Wei , Zhang Wenyao , Jiang Yuan 
Published: February 2020

Abstract
Entrepreneurs, as initiators of entrepreneurial activities, have long been one of important research objects in the field of entrepreneurship research and, however, there has been no study reported on how entrepreneurial traits influence venture performance from a perspective of entrepreneurial orientation. This study explored the relationship between entrepreneurial traits and venture performance by focusing on the mediating role of entrepreneurial orientation and the moderating role of entrepreneurial environment perception. Using time-lagged data from 321 private enterprises in China, the results reveal that entrepreneurial traits are positively related to venture performance, and this link is mediated by entrepreneurial orientation. Additionally, moderated path analysis indicates that entrepreneurial environment perception strengthens the direct effect of the entrepreneurial traits on entrepreneurial orientation and its indirect effect on venture performance. This study extends the scope of entrepreneurial traits research, and provides evidence for arguments that entrepreneurship in the context of China.
Improvement of interfacial interaction in impregnated wood via grafting methyl methacrylate onto wood cell walls
Authors: Dong Youming , Altgen Michael , Mäkelä Mikko , Rautkari Lauri , Hughes Mark , Li Jianzhang , Zhang Shifeng 
Published: February 2020

Abstract
Improving the interaction between the wood cell wall and a modifying agent is fundamental to enhancing the efficacy of wood modification. The extent of interaction is, nevertheless, difficult to evaluate due to the highly heterogeneous nature of the modified wood. In this study, methacryl groups were grafted onto the wood cell wall polymers, via the reaction between 2-isocyanatoethyl methacrylate (IEMA) and hydroxyl groups, to improve their compatibility and reactivity. Subsequently, methyl methacrylate (MMA) was introduced into methacrylated wood and copolymerized with the bonded methacryl groups. The distribution of IEMA and poly MMA (PMMA) in the wood cell walls was investigated by scanning electron microscopy (SEM) and confocal Raman microscopy. The results showed that MMA penetrated the wood cell walls and formed strong interfacial interaction, which was confirmed by confocal Raman microscopy combined with principal component analysis (PCA). With copolymerization, the highest anti-swelling efficiency (ASE) (57%) was achieved, because of the effect of methacrylation. Compared to the reference, the water resistance and hardness were significantly improved. In addition, the dynamic wettability was also altered largely due to copolymerization.
Stochastic model specification in Markov switching vector error correction models
Authors: Hauzenberger Niko , Huber Florian , Pfarrhofer Michael , Zörner Thomas O. 
Published: February 2020

AbstractThis paper proposes a hierarchical modeling approach to perform stochastic model specification in Markov switching vector error correction models. We assume that a common distribution gives rise to the regime-specific regression coefficients. The mean as well as the variances of this distribution are treated as fully stochastic and suitable shrinkage priors are used. These shrinkage priors enable to assess which coefficients differ across regimes in a flexible manner. In the case of similar coefficients, our model pushes the respective regions of the parameter space towards the common distribution. This allows for selecting a parsimonious model while still maintaining sufficient flexibility to control for sudden shifts in the parameters, if necessary. We apply our modeling approach to real-time Euro area data and assume transition probabilities between expansionary and recessionary regimes to be driven by the cointegration errors. The results suggest that the regime allocation is governed by a subset of short-run adjustment coefficients and regime-specific variance-covariance matrices. These findings are complemented by an out-of-sample forecast exercise, illustrating the advantages of the model for predicting Euro area inflation in real time.
Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells
Authors: Chow Louis W.C. , Wong Kar-Lok , Shiao Lian-Ru , Wu King-Chuen , Leung Yuk-Man 
Published: February 2020

Abstract
Intracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca2+ signals, but the latter were unlikely triggered via Ca2+-sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca2+ response composed of both Ca2+ release and Ca2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca2+ influx pore opened by spermine was Mn2+-impermeable, distinct from the CPA-triggered store-operated Ca2+ channel, which was Mn2+-permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca2+ overload, Ca2+ store depletion, and ER stress.
Highly Dispersed CuNi Nanoparticles Supported on Reduced Graphene Oxide as Efficient Catalysts for Hydrogen Generation from NH3BH3
Authors: Du Xigang , Tai Yuping , Liu Hongyu , Zhang Jun , Su Mengfan , Li Fengyu , Wang Shumeng 
Published: February 2020

Abstract
Highly dispersed CuNi nanoparticles (NPs) immobilized on reduced graphene oxide (RGO) were synthesized via the simple in situ co-reduction of an aqueous solution of Copper(II) sulfate pentahydrate, nickel chloride hexahydrate, and graphene oxide (GO) by the reduction of ammonia borane (AB) at room temperature. The powder XRD, FTIR, EDS, and TEM techniques were used to charaterize the structure, size, and composition of the CuNi/RGO catalysts. The as-prepared CuNi/RGO catalysts showed excellent catalytic performance toward the hydrolysis of AB at room temperature. Compared to Cu/RGO, Ni/RGO, and the RGO-free Cu0.6Ni0.4 counterpart, the as-prepared Cu0.6Ni0.4/RGO catalysts showed much better catalytic activity. Furthermore, kinetic studies showed that the catalytic hydrolysis of AB by Cu0.6Ni0.4/RGO has zero order dependence on the AB concentration, but first order dependence on the catalyst concentration. The turnover frequency (TOF) of Cu0.6Ni0.4/RGO catalyst for the hydrolytic dehydrogenation of AB was determined to be about 20.2 mol H2 (mol Cu0.6Ni0.4/RGO)−1 min−1 at 25 °C. In addition, the activation energy (Ea
) of Cu0.6Ni0.4/RGO was determined to be around 17.7 kJ mol−1, which is one of the lowest activation energy’s of the reported metal-based catalysts.