bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anomaly detection in the Zwicky Transient Facility DR3
Authors: Malanchev K L , Pruzhinskaya M V , Korolev V S , Aleo P D , Kornilov M V , Ishida E E O , Krushinsky V V , Mondon F , Sreejith S , Volnova A A , Belinski A A , Dodin A V , Tatarnikov A M , Zheltoukhov S G ,   (The SNAD Team)
Published: February 2021

ABSTRACT
We present results from applying the SNAD anomaly detection pipeline to the third public data release of the Zwicky Transient Facility (ZTF DR3). The pipeline is composed of three stages: feature extraction, search of outliers with machine learning algorithms, and anomaly identification with followup by human experts. Our analysis concentrates in three ZTF fields, comprising more than 2.25 million objects. A set of four automatic learning algorithms was used to identify 277 outliers, which were subsequently scrutinized by an expert. From these, 188 (68 per cent) were found to be bogus light curves – including effects from the image subtraction pipeline as well as overlapping between a star and a known asteroid, 66 (24 per cent) were previously reported sources whereas 23 (8 per cent) correspond to non-catalogued objects, with the two latter cases of potential scientific interest (e.g. one spectroscopically confirmed RS Canum Venaticorum star, four supernovae candidates, one red dwarf flare). Moreover, using results from the expert analysis, we were able to identify a simple bi-dimensional relation that can be used to aid filtering potentially bogus light curves in future studies. We provide a complete list of objects with potential scientific application so they can be further scrutinised by the community. These results confirm the importance of combining automatic machine learning algorithms with domain knowledge in the construction of recommendation systems for astronomy. Our code is publicly available.1
Recent Evolutionary History of Tigers Highlights Contrasting Roles of Genetic Drift and Selection
Authors: Armstrong Ellie E , Khan Anubhab , Taylor Ryan W , Gouy Alexandre , Greenbaum Gili , Thiéry Alexandre , Kang Jonathan T , Redondo Sergio A , Prost Stefan , Barsh Gregory , Kaelin Christopher , Phalke Sameer , Chugani Anup , Gilbert Martin , Miquelle Dale , Zachariah Arun , Borthakur Udayan , Reddy Anuradha , Louis Edward , Ryder Oliver A , Jhala Yadvendradev V , Petrov Dmitri , Excoffier Laurent , Hadly Elizabeth , Ramakrishnan Uma 
Published: February 2021

Abstract
Species conservation can be improved by knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, their evolutionary history and genomic variation remain poorly known, especially for Indian tigers. With 70% of the world’s wild tigers living in India, such knowledge is critical. We re-sequenced 65 individual tiger genomes representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding or founding events, possibly due to small and fragmented protected areas. We suggest the impacts of ongoing connectivity loss on inbreeding and persistence of Indian tigers be closely monitored. Surprisingly, demographic models suggest recent divergence (within the last 20,000 years) between subspecies and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection related to metabolic adaptation to cold, whereas Sumatran tigers show evidence of weak selection for genes involved in body size regulation. We recommend detailed investigation of local adaptation in Amur and Sumatran tigers prior to initiating genetic rescue.
B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse
Authors: Ichiyanagi Tomoko , Katoh Hirokazu , Mori Yoshinobu , Hirafuku Keigo , Boyboy Beverly Ann , Kawase Masaki , Ichiyanagi Kenji 
Published: February 2021

Abstract
More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of SINE B1 and B2 families within Mus musculus. Using a novel RNA sequencing method designated as melRNA-seq, we detected the expression of SINEs in male germ cells at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs originated from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses in liver revealed that polymorphic B2 insertions served as a boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, genomic B2 copies were enriched at the boundary of various histone modifications, and chromatin insulator protein, CCCTC-binding factor, a well-known chromatin boundary protein, bound to &gt;100 polymorphic and &gt;10,000 non-polymorphic B2 insertions. These results suggest that the currently active B2 copies are mobile boundary elements that can modulate chromatin modifications and gene expression, and are likely involved in epigenomic and phenotypic diversification of the mouse species.
Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding
Authors: Cao Chen , He Jingni , Mak Lauren , Perera Deshan , Kwok Devin , Wang Jia , Li Minghao , Mourier Tobias , Gavriliuc Stefan , Greenberg Matthew , Morrissy A Sorana , Sycuro Laura K , Yang Guang , Jeffares Daniel C , Long Quan 
Published: February 2021

Abstract
DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or “haplotypes.” However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.
Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma
Authors: Otani Yoshihiro , Sur Hannah P , Rachaiah Guruprasad , Namagiri Sriya , Chowdhury Ashis , Lewis Cole T , Shimizu Toshihiko , Gangaplara Arunakumar , Wang Xiang , Vézina Amélie , Maric Dragan , Jackson Sadhana , Yan Yuanqing , Zhengping Zhuang , Ray-Chaudhury Abhik , Kumar Sachin , Ballester Leomar Y , Chittiboina Prashant , Yoo Ji Young , Heiss John , Kaur Balveen , Banasavadi-Siddegowda Yeshavanth Kumar 
Published: February 2021

Abstract

Background
Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, the median survival of glioblastoma (GBM) patients is less than 15 months. Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric dimethylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor cells. LB100, a first-in-class small molecular inhibitor of protein phosphatase 2A (PP2A), can sensitize therapy-resistant tumor cells. Here, we tested the anti-GBM effect of concurrent PRMT5 and PP2A inhibition.

Methods
Patient-derived primary GBM neurospheres (GBMNS), transfected with PRMT5 target-specific siRNA, were treated with LB100 and subjected to in vitro assays including PP2A activity and western blot. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment.

Results
We found that PRMT5 depletion increased PP2A activity in GBMNS. LB100 treatment significantly reduced the viability of PRMT5-depleted GBMNS compared to PRMT5-intact GBMNS. LB100 enhanced G1 cell cycle arrest induced by PRMT5 depletion. Combination therapy also increased the expression of phospho-MLKL. Necrostatin-1 rescued PRMT5-depleted cells from the cytotoxic effects of LB100, indicating that necroptosis caused the enhanced cytotoxicity of combination therapy. In the in vivo mouse tumor xenograft model, LB100 treatment combined with transient depletion of PRMT5 significantly decreased tumor size and prolonged survival, while LB100 treatment alone had no survival benefit.

Conclusion
Overall, combined PRMT5 and PP2A inhibition had significantly greater antitumor effects than PRMT5 inhibition alone.
Role of 3D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study
Authors: Graillon Thomas , Ferrer Loic , Siffre Jason , Sanson Marc , Peyre Matthieu , Peyrière Hadrien , Mougel Grégory , Autran Didier , Tabouret Emeline , Figarella-Branger Dominique , Barlier Anne , Kalamarides Michel , Dufour Henry , Colin Thierry , Chinot Olivier 
Published: February 2021

Abstract

Background
We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome.

Methods
We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment.

Results
Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = −18.7%/month within 3 first months and −0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = −0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones.

Conclusions
Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.
Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight
Authors: Zuckerman Scott L , Yengo-Kahn Aaron M , Tang Alan R , Bailes Julian E , Beauchamp Kathryn , Berger Mitchel S , Bonfield Christopher M , Camarata Paul J , Cantu Robert C , Davis Gavin A , Ellenbogen Richard G , Ellis Michael J , Feuer Hank , Guazzo Eric , Harris Odette A , Heppner Peter , Honeybul Stephen , Manley Geoff , Maroon Joseph C , Miele Vincent J , Nahed Brian V , Okonkwo David O , Oppenlander Mark E , Petty Jerry , Sabin H Ian , Samadani Uzma , Sherburn Eric W , Sheridan Mark , Tator Charles H , Theodore Nicholas , Timmons Shelly D , Woodworth Graeme F , Solomon Gary S , Sills Allen K 
Published: February 2021

Abstract

BACKGROUND
Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI.

OBJECTIVE
To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions.

METHODS
A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted.

RESULTS
Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (β = –0.58, 95% CI –0.111, –0.005, P = .033).

CONCLUSION
RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.
Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner
Authors: Li Chunyan , White Timothy G , Shah Kevin A , Chaung Wayne , Powell Keren , Wang Ping , Woo Henry H , Narayan Raj K 
Published: February 2021

Abstract

BACKGROUND
The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm.

OBJECTIVE
To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature.

METHODS
In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats.

RESULTS
The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm.

CONCLUSION
Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.
Soybean Yellow Stripe-like 7 is a symbiosome membrane peptide transporter important for nitrogen fixation
Authors: Gavrin Aleksandr , Loughlin Patrick C , Brear Ella , Griffith Oliver W , Bedon Frank , Suter Grotemeyer Marianne , Escudero Viviana , Reguera Maria , Qu Yihan , Mohd-Noor Siti N , Chen Chi , Osorio Marina Borges , Rentsch Doris , González-Guerrero Manuel , Day David A , Smith Penelope Mary Collina 
Published: February 2021

AbstractLegumes form a symbiosis with rhizobia that convert atmospheric nitrogen (N2) to ammonia and provide it to the plant in return for a carbon and nutrient supply. Nodules, developed as part of the symbiosis, harbor rhizobia that are enclosed in a plant-derived symbiosome membrane (SM) to form an organelle-like structure called the symbiosome. In mature nodules exchanges between the symbionts occur across the SM. Here we characterize Yellow Stripe-like 7 (GmYSL7), a Yellow stripe-like family member localized on the SM in soybean (Glycine max) nodules. It is expressed specifically in infected cells with expression peaking soon after nitrogenase becomes active. Unlike most YSL family members, GmYSL7 does not transport metals complexed with phytosiderophores. Rather, it transports oligopeptides of between four and 12 amino acids. Silencing GmYSL7 reduces nitrogenase activity and blocks infected cell development so that symbiosomes contain only a single bacteroid. This indicates the substrate of YSL7 is required for proper nodule development, either by promoting symbiosome development directly or by preventing inhibition of development by the plant. RNAseq of nodules where GmYSL7 was silenced suggests that the plant initiates a defense response against rhizobia with genes encoding proteins involved in amino acid export downregulated and some transcripts associated with metal homeostasis altered. These changes may result from the decrease in nitrogen fixation upon GmYSL7 silencing and suggest that the peptide(s) transported by GmYSL7 monitor the functional state of the bacteroids and regulate nodule metabolism and transport processes accordingly. Further work to identify the physiological substrate for GmYSL7 will allow clarification of this role.
Genome-wide analysis in response to nitrogen and carbon identifies regulators for root AtNRT2 transporters
Authors: Ruffel Sandrine , Chaput Valentin , Przybyla-Toscano Jonathan , Fayos Ian , Ibarra Catalina , Moyano Tomas , Fizames Cécile , Tillard Pascal , O’Brien Jose Antonio , Gutiérrez Rodrigo A , Gojon Alain , Lejay Laurence 
Published: February 2021

Abstract
In Arabidopsis (Arabidopsis thaliana), the High-Affinity Transport System (HATS) for root nitrate (NO3−) uptake depends mainly on four NRT2 NO3− transporters, namely NRT2.1, NRT2.2, NRT2.4, and NRT2.5. The HATS is the target of many regulations to coordinate nitrogen (N) acquisition with the N status of the plant and with carbon (C) assimilation through photosynthesis. At the molecular level, C and N signaling pathways control gene expression of the NRT2 transporters. Although several regulators of these transporters have been identified in response to either N or C signals, the response of NRT2 gene expression to the interaction of these signals has never been specifically investigated, and the underlying molecular mechanisms remain largely unknown. To address this question we used an original systems biology approach to model a regulatory gene network targeting NRT2.1, NRT2.2, NRT2.4, and NRT2.5 in response to N/C signals. Our systems analysis of the data identified three transcription factors, TGA3, MYC1, and bHLH093. Functional analysis of mutants combined with yeast one-hybrid experiments confirmed that all three transcription factors are regulators of NRT2.4 or NRT2.5 in response to N or C signals. These results reveal a role for TGA3, MYC1, and bHLH093 in controlling the expression of root NRT2 transporter genes.
Transcription-associated metabolomic adjustments in maize occur during combined drought and cold stress
Authors: Guo Qianqian , Li Xia , Niu Li , Jameson Paula E , Zhou Wenbin 
Published: February 2021

Abstract
Although simultaneous drought and cold stress occurs, especially in northwestern and eastern regions of China, and is an important factor limiting agricultural productivity, there are few studies focusing on plant responses to a combination of drought and cold stress. Here, by partially overlapping drought and cold stresses, we characterized the acclimation of maize (Zea mays B73) to these two stresses using physiological measurements, as well as comparative transcriptomics combined with metabolomics and hormonal analyses during the stress treatments and recovery stages. The combined drought and cold stress and drought stress alone were accompanied by a decline in photosynthetic capacity and enhanced transcriptional response, and subsequent recovery of these following removal from stress, whereas cold stress alone was accompanied by irreversible damage to photosynthetic capacity and chloroplast structure. The stress combination induced transcription-associated metabolomic alterations, in which raffinose, trehalose-6-phosphate, and proline accumulated, and monosaccharide abundance increased. Concomitantly, the increased abscisic acid (ABA) content and upregulated ABA signaling pathway may have provided the transcriptional regulation for the metabolic changes. In a parallel experiment, ABA treatments prior to exposure of the plants to cold stress primed the plants to survive the cold stress, thus confirming a key role for the endogenous ABA activated by the drought pretreatment in acclimation of the plants to cold. We present a model showing that the plant response to the combined stress is multi-faceted and reveal an ABA-dependent maize acclimation mechanism to the stress combination.
Non-SUSY heterotic string vacua of Gepner models with vanishing cosmological constant
Authors: Aoyama Koji , Sugawara Yuji 
Published: February 2021

Abstract
We study a natural generalization of the results given in K. Aoyama and Y. Sugawara, Prog. Theor. Exp. Phys. 2020, 103B01 (2020) to heterotic strings. Namely, starting from the generic Gepner models for Calabi –Yau three-folds, we construct non-SUSY heterotic string vacua with vanishing cosmological constant at the one-loop level. We especially focus on asymmetric orbifolding based on some discrete subgroup of the chiral $U(1)$ action which acts on both the Gepner model and the $SO(32)$ or $E_8\times E_8$ sector. We present a classification of the relevant orbifold models leading to the string vacua with the properties mentioned above. In some cases, the desired vacua can be constructed in a manner quite similar to those given in the previous paper for the type II string, in which the orbifold groups contain two generators with discrete torsions. On the other hand, we also have simpler models that are just realized as asymmetric orbifolds of cyclic groups with only one generator.