bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Pathologic Complete Response After Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer
Authors: Bandini Marco , Ross Jeffrey S , Raggi Daniele , Gallina Andrea , Colecchia Maurizio , Lucianò Roberta , Giannatempo Patrizia , Farè Elena , Pederzoli Filippo , Bianchi Marco , Colombo Renzo , Gandaglia Giorgio , Fossati Nicola , Marandino Laura , Capitanio Umberto , Deho’ Federico , Ali Siraj M , Madison Russell , Chung Jon H , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Necchi Andrea 
Published: May 2020

AbstractBackgroundIn the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.MethodsIn an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)–combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided.ResultsFrom February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (&gt;11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the “treat-all” option within the clinically meaningful threshold probabilities of 40%-50%.ConclusionsThe study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage.
Loss of total phenols from leaf litter of two shrub species: dual responses to alpine forest gap disturbance during winter and the growing season
Authors: He Wei , Yang Wanqin 
Published: May 2020

AbstractAimsAlpine forest gaps can control understory ecosystem processes by manipulating hydrothermal dynamics. Here, we aimed to test the role of alpine forest gap disturbance on total phenol loss (TPL) from the decomposing litter of two typical shrub species (willow, Salix paraplesia Schneid., and bamboo, Fargesia nitida (Mitford) Keng f.).MethodsWe conducted a field litterbag experiment within a representative fir (Abies faxoniana Rehd.) forest based on ‘gap openness treatments’ (plot positions in the gap included the gap center south, gap center north, canopy edge, expanded edge and closed canopy). The TPL rate and litter surface microbial abundance (fungi and bacteria) of the two shrub species were measured during the following periods over 2 years: snow formation (SF), snow cover (SC), snow melting (ST), the early growing season (EG) and the late growing season (LG).Important FindingsAt the end of the study, we found that snow cover depth, freeze–thaw cycle frequency and the fungal copies g−1 to bacterial copies g−1 ratio had significant effects on litter TPL. The abundances of fungi and bacteria decreased from the gap center to the closed canopy during the SF, SC, ST and LG periods and showed the opposite trend during the EG periods. The rate of TPL among plot positions closely followed the same trend as microbial abundance during the first year of incubation. In addition, both species had higher rates of TPL in the gap center than at other positions during the first winter, first year and entire 2-year period. These findings suggest that alpine forest gap formation accelerates litter TPL, although litter TPL exhibits dual responses to gap disturbance during specific critical periods. In conclusion, reduced snow cover depth and duration during winter warming under projected climate change scenarios or as gaps vanish may slow litter TPL in alpine biomes.
Malignant triton tumor below the peritoneal reflection: a case report
Authors: Seddighzadeh Rachael Price , Brower Steven , Tzeng Jausheng , Serur Anna 
Published: May 2020

AbstractMalignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumors (MPNSTs) histologically defined by rhabdomyoblastic differentiation. MTTs are primarily found in the head, neck, extremities and trunk, but rare cases of MTT within the buttock, the mediastinum and the retroperitoneum have also been documented. We present the case of a 47-year-old male patient who initially presented with right flank pain and hematuria in July 2019, who was found to have a large pelvic mass below peritoneal reflection. Complete resection of the mass was performed, and pathology identified the mass as a MTT.
Retrograde orbits excess among observable interstellar objects
Authors: Marčeta Dušan , Novaković Bojan 
Published: May 2020

ABSTRACT
In this work, we investigate the orbital distribution of interstellar objects (ISOs), observable by the future wide-field National Science Foundation Vera C. Rubin Observatory (VRO). We generate synthetic population of ISOs and simulate their ephemerides over a period of 10 yr, in order to select those that may be observed by the VRO, based on the nominal characteristics of this survey. We find that the population of the observable ISOs should be significantly biased in favour of retrograde objects. The intensity of this bias is correlated with the slope of the size-frequency distribution (SFD) of the population, as well as with the perihelion distances. Steeper SFD slopes lead to an increased fraction of the retrograde orbits, and also of the median orbital inclination. On the other hand, larger perihelion distances result in more symmetric distribution of orbital inclinations. We believe that this is a result of Holetschek’s effects, which is already suggested to cause observational bias in orbital distribution of long-period comets. The most important implication of our findings is that an excess of retrograde orbits depends on the sizes and the perihelion distances. Therefore, the prograde/retrograde orbits ratio and the median inclination of the discovered population could, in turn, be used to estimate the SFD of the underlying true population of ISOs.
Probing compact dark matter with gravitational wave fringes detected by the Einstein Telescope
Authors: Liao Kai , Tian Shuxun , Ding Xuheng 
Published: May 2020

ABSTRACT
Unlike the electromagnetic radiation from astrophysical objects, gravitational waves (GWs) from binary star mergers have much longer wavelengths and are coherent. For ground-based GW detectors, when the lens object between the source and the Earth has mass ∼1−105 M⊙, the diffraction effect should be considered since the chirping wavelengths are comparable to the scale of the barrier (its Schwarzschild radius). The waveform will thus be distorted as the fringes. In this work, we show that signals from the third-generation GW detectors like the Einstein Telescope (ET) would be a smoking gun for probing the nature of compact dark matter (CDM) or primordial black holes. Detection of the lensing effects becomes harder when the lens mass is smaller. ET is more sensitive than LIGO, the constraint is available for CDM mass &gt;5 M⊙ while LIGO can only detect the mass &gt;100 M⊙. For a null search of the fringes, one-year observation of ET can constrain the CDM density fraction to ∼10−2 to 10−5 in the mass range MCDM = 10−100 M⊙.
Stellar activity with LAMOST. III. Temporal variability pattern in Pleiades, Praesepe, and Hyades
Authors: Fang Xiang-Song , Bidin Christian Moni , Zhao Gang , Zhang Li-Yun , Bharat Kumar Yerra 
Published: May 2020

ABSTRACT
We present the results from a systematic study of temporal variation of stellar activity in young late-type stars. We used multi-epoch LAMOST (Large sky Area Multi-Object fiber Spectroscopic Telescope) low-resolution spectra of over 300 member candidates in three young open clusters: Pleiades, Praesepe, and Hyades. The spectral measurements of TiO band strength near 7050 Å (TiO2) and equivalent width of H α line (EWH α) are used as the tracers of cool spot coverage and chromospheric emission strength, respectively. The analysis of time-variation patterns of these two tracers suggested that there exist detectable variabilities in TiO2 and EWH α, and their time-scales are in the wide range from days to years. Results showed that more active stars, younger and fast rotators, tend to have larger activity variations. There is a tendency of anticorrelation between temporal variations in TiO2 and EWH α. Also, appreciable anticorrelation in the rotational phase between H α emission and K2 brightness is detected in some M dwarfs, indicating spatial co-location of the plages with cool star-spots; however, cool stars do not always show such co-location features. Furthermore, spot coverage and H α emission were evident at all rotational phases of several M dwarfs, indicating a basal level of activity, perhaps due to many small and randomly located active regions in the atmosphere.
New constraints on the magnetization of the cosmic web using LOFAR Faraday rotation observations
Authors: O’Sullivan S P , Brüggen M , Vazza F , Carretti E , Locatelli N T , Stuardi C , Vacca V , Vernstrom T , Heald G , Horellou C , Shimwell T W , Hardcastle M J , Tasse C , Röttgering H 
Published: May 2020

ABSTRACT
Measuring the properties of extragalactic magnetic fields through the effect of Faraday rotation provides a means to understand the origin and evolution of cosmic magnetism. Here, we use data from the LOFAR Two-Metre Sky Survey (LoTSS) to calculate the Faraday rotation measure (RM) of close pairs of extragalactic radio sources. By considering the RM difference (ΔRM) between physical pairs (e.g. double-lobed radio galaxies) and non-physical pairs (i.e. close projected sources on the sky), we statistically isolate the contribution of extragalactic magnetic fields to ΔRM along the line of sight between non-physical pairs. From our analysis, we find no significant difference between the ΔRM distributions of the physical and non-physical pairs, limiting the excess Faraday rotation contribution to &lt;1.9 rad m−2 (${\sim}95{{\ \rm per\ cent}}$ confidence). We use this limit with a simple model of an inhomogeneous universe to place an upper limit of 4 nG on the cosmological co-moving magnetic field strength on Mpc scales. We also compare the RM data with a more realistic suite of cosmological magnetohydrodynamical simulations that explore different magnetogenesis scenarios. Both magnetization of the large-scale structure by astrophysical processes such as galactic and AGN outflows, and simple primordial scenarios with seed magnetic field strengths &lt;0.5 nG cannot be rejected by the current data; while stronger primordial fields or models with dynamo amplification in filaments are disfavoured.
Modelling fibroid pathology: development and manipulation of a myometrial smooth muscle cell macromolecular crowding model to alter extracellular matrix deposition
Authors: Winter Ann , Salamonsen Lois A , Evans Jemma 
Published: May 2020

ABSTRACTCurrent treatment options for uterine fibroids are limited to hormonal manipulation or surgical intervention. We aimed to develop an in vitro model to mirror collagen deposition and extracellular matrix (ECM) formation, the principal features of uterine fibroids, to enable testing of novel therapeutics. Macromolecular crowding with Ficoll 400 and Ficoll 70 in cultures of human uterine myometrial smooth muscle cells containing ascorbic acid, provided the basis for this model. These culture conditions mimic the ‘crowded’ nature of the in vivo extracellular environment by incorporating neutral, space-filling macromolecules into conventional cell cultures. This method of culture facilitates appropriate ECM deposition, thus closely representing the in vivo fibrotic phenotype of uterine fibroids. Macromolecular crowding in Ficoll cultures containing ascorbic acid reduced myometrial smooth muscle cell proliferation and promoted collagen production. Under these conditions, collagen was processed for extracellular deposition as demonstrated by C-propeptide cleavage from secreted procollagen. The fibrosis marker activin was increased relative to its natural inhibitor, follistatin, in crowded culture conditions while addition of exogenous follistatin reduced collagen (Col1A1) gene expression. This in vitro model represents a promising development for the testing of therapeutic interventions for uterine fibroids. However, it does not recapitulate the full in vivo pathology which can include specific genetic and epigenetic alterations that have not been identified in the myometrial smooth muscle (hTERT-HM) cell line. Following screening of potential therapeutics using the model, the most promising compounds will require further assessment in the context of individual subjects including those with genetic changes implicated in fibroid pathogenesis.
Restriction endonucleases that cleave RNA/DNA heteroduplexes bind dsDNA in A-like conformation
Authors: Kisiala Marlena , Kowalska Monika , Pastor Michal , Korza Henryk J , Czapinska Honorata , Bochtler Matthias 
Published: May 2020

Abstract
Restriction endonucleases naturally target DNA duplexes. Systematic screening has identified a small minority of these enzymes that can also cleave RNA/DNA heteroduplexes and that may therefore be useful as tools for RNA biochemistry. We have chosen AvaII (G↓GWCC, where W stands for A or T) as a representative of this group of restriction endonucleases for detailed characterization. Here, we report crystal structures of AvaII alone, in specific complex with partially cleaved dsDNA, and in scanning complex with an RNA/DNA hybrid. The specific complex reveals a novel form of semi-specific dsDNA readout by a hexa-coordinated metal cation, most likely Ca2+ or Mg2+. Substitutions of residues anchoring this non-catalytic metal ion severely impair DNA binding and cleavage. The dsDNA in the AvaII complex is in the A-like form. This creates space for 2′-OH groups to be accommodated without intra-nucleic acid steric conflicts. PD-(D/E)XK restriction endonucleases of known structure that bind their dsDNA targets in the A-like form cluster into structurally similar groups. Most such enzymes, including some not previously studied in this respect, cleave RNA/DNA heteroduplexes. We conclude that A-form dsDNA binding is a good predictor for RNA/DNA cleavage activity.
FATCAT 2.0: towards a better understanding of the structural diversity of proteins
Authors: Li Zhanwen , Jaroszewski Lukasz , Iyer Mallika , Sedova Mayya , Godzik Adam 
Published: May 2020

AbstractFATCAT 2.0 server (http://fatcat.godziklab.org/), provides access to a flexible protein structure alignment algorithm developed in our group. In such an alignment, rotations and translations between elements in the structure are allowed to minimize the overall root mean square deviation (RMSD) between the compared structures. This allows to effectively compare protein structures even if they underwent structural rearrangements in different functional forms, different crystallization conditions or as a result of mutations. The major update for the server introduces a new graphical interface, much faster database searches and several new options for visualization of the structural differences between proteins
One fly–one genome: chromosome-scale genome assembly of a single outbred Drosophila melanogaster
Authors: Adams Matthew , McBroome Jakob , Maurer Nicholas , Pepper-Tunick Evan , Saremi Nedda F , Green Richard E , Vollmers Christopher , Corbett-Detig Russell B 
Published: May 2020

Abstract
A high quality genome assembly is a vital first step for the study of an organism. Recent advances in technology have made the creation of high quality chromosome scale assemblies feasible and low cost. However, the amount of input DNA needed for an assembly project can be a limiting factor for small organisms or precious samples. Here we demonstrate the feasibility of creating a chromosome scale assembly using a hybrid method for a low input sample, a single outbred Drosophila melanogaster. Our approach combines an Illumina shotgun library, Oxford nanopore long reads, and chromosome conformation capture for long range scaffolding. This single fly genome assembly has a N50 of 26 Mb, a length that encompasses entire chromosome arms, contains 95% of expected single copy orthologs, and a nearly complete assembly of this individual's Wolbachia endosymbiont. The methods described here enable the accurate and complete assembly of genomes from small, field collected organisms as well as precious clinical samples.
Misactivation of multiple starvation responses in yeast by loss of tRNA modifications
Authors: Bruch Alexander , Laguna Teresa , Butter Falk , Schaffrath Raffael , Klassen Roland 
Published: May 2020

AbstractPreviously, combined loss of different anticodon loop modifications was shown to impair the function of distinct tRNAs in Saccharomyces cerevisiae. Surprisingly, each scenario resulted in shared cellular phenotypes, the basis of which is unclear. Since loss of tRNA modification may evoke transcriptional responses, we characterized global transcription patterns of modification mutants with defects in either tRNAGlnUUG or tRNALysUUU function. We observe that the mutants share inappropriate induction of multiple starvation responses in exponential growth phase, including derepression of glucose and nitrogen catabolite-repressed genes. In addition, autophagy is prematurely and inadequately activated in the mutants. We further demonstrate that improper induction of individual starvation genes as well as the propensity of the tRNA modification mutants to form protein aggregates are diminished upon overexpression of tRNAGlnUUG or tRNALysUUU, the tRNA species that lack the modifications of interest. Hence, our data suggest that global alterations in mRNA translation and proteostasis account for the transcriptional stress signatures that are commonly triggered by loss of anticodon modifications in different tRNAs.
Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with various chromatin types and reveals transcription dynamics
Authors: Gavrilov Alexey A , Zharikova Anastasiya A , Galitsyna Aleksandra A , Luzhin Artem V , Rubanova Natalia M , Golov Arkadiy K , Petrova Nadezhda V , Logacheva Maria D , Kantidze Omar L , Ulianov Sergey V , Magnitov Mikhail D , Mironov Andrey A , Razin Sergey V 
Published: May 2020

Abstract
Non-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the genome for all RNA molecules present in the nucleus. Using Red-C, we uncovered the RNA–DNA interactome of human K562 cells and identified hundreds of ncRNAs enriched in active or repressed chromatin, including previously undescribed RNAs. Analysis of the RNA–DNA interactome also allowed us to trace the kinetics of messenger RNA production. Our data support the model of co-transcriptional intron splicing, but not the hypothesis of the circularization of actively transcribed genes.
Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2
Authors: Wu Jun , Xue Yuhua , Gao Xiang , Zhou Qiang 
Published: May 2020

Abstract
The Siah1 and Siah2 ubiquitin ligases are implicated in diverse biological processes ranging from cellular stress responses, signaling to transcriptional regulation. A key substrate of Siah1 is ELL2, which undergoes proteolysis upon polyubiquitination. ELL2 stimulates transcriptional elongation and is a subunit of the Super Elongation Complex (SEC) essential for HIV-1 transactivation. Previously, multiple transcriptional and post-translational mechanisms are reported to control Siah's expression and activity. Here we show that the activity of Siah1/2 can also be suppressed by host cell factor 1 (HCF1), and the hitherto poorly characterized HCF2, which themselves are not degraded but can bind and block the substrate-binding domain (SBD) of Siah1/2 to prevent their autoubiquitination and trans-ubiquitination of downstream targets including ELL2. This effect stabilizes ELL2 and enhances the ELL2-SEC formation for robust HIV-1 transactivation. Thus, our study not only identifies HCF1/2 as novel activators of HIV-1 transcription through inhibiting Siah1 to stabilize ELL2, but also reveals the SBD of Siah1/2 as a previously unrecognized new target for HCF1/2 to exert this inhibition.
Topological constraints of RNA pseudoknotted and loop-kissing motifs: applications to three-dimensional structure prediction
Authors: Xu Xiaojun , Chen Shi-Jie 
Published: May 2020

AbstractAn RNA global fold can be described at the level of helix orientations and relatively flexible loop conformations that connect the helices. The linkage between the helices plays an essential role in determining the structural topology, which restricts RNA local and global folds, especially for RNA tertiary structures involving cross-linked base pairs. We quantitatively analyze the topological constraints on RNA 3D conformational space, in particular, on the distribution of helix orientations, for pseudoknots and loop-loop kissing structures. The result shows that a viable conformational space is predominantly determined by the motif type, helix size, and loop size, indicating a strong topological coupling between helices and loops in RNA tertiary motifs. Moreover, the analysis indicates that (cross-linked) tertiary contacts can cause much stronger topological constraints on RNA global fold than non-cross-linked base pairs. Furthermore, based on the topological constraints encoded in the 2D structure and the 3D templates, we develop a 3D structure prediction approach. This approach can be further combined with structure probing methods to expand the capability of computational prediction for large RNA folds.
Importance of the lactation period in developmental programming in rodents
Authors: Rodríguez-González Guadalupe L , Bautista Claudia J , Rojas-Torres Karen I , Nathanielsz Peter W , Zambrano Elena 
Published: May 2020

AbstractLactation is a critical period during which maternal nutritional and environmental challenges affect milk composition and, therefore, organ differentiation, structure, and function in offspring during the early postnatal period. Evidence to date shows that lactation is a vulnerable time during which transient insults can have lasting effects, resulting in altered health outcomes in offspring in adult life. Despite the importance of the developmental programming that occurs during this plastic period of neonatal life, there are few comprehensive reviews of the multiple challenges—especially to the dam—during lactation. This review presents milk data from rodent studies involving maternal nutritional challenges and offspring outcome data from studies involving maternal manipulations during lactation. Among the topics addressed are maternal nutritional challenges and the effects of litter size and artificial rearing on offspring metabolism and neural and endocrine outcomes. The lactation period is an opportunity to correct certain functional deficits resulting from prenatal challenges to the fetus, but, if not personalized, can also lead to undesirable outcomes related to catch up-growth and overnutrition.