bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae
Authors: Qiu Chenxi , Jin Huiyan , Vvedenskaya Irina , Llenas Jordi Abante , Zhao Tingting , Malik Indranil , Visbisky Alex M. , Schwartz Scott L. , Cui Ping , Čabart Pavel , Han Kang Hoo , Lai William K. M. , Metz Richard P. , Johnson Charles D. , Sze Sing-Hoi , Pugh B. Franklin , Nickels Bryce E. , Kaplan Craig D. 
Published: June 2020

Abstract
Background
The majority of eukaryotic promoters utilize multiple transcription start sites (TSSs). How multiple TSSs are specified at individual promoters across eukaryotes is not understood for most species. In Saccharomyces cerevisiae, a pre-initiation complex (PIC) comprised of Pol II and conserved general transcription factors (GTFs) assembles and opens DNA upstream of TSSs. Evidence from model promoters indicates that the PIC scans from upstream to downstream to identify TSSs. Prior results suggest that TSS distributions at promoters where scanning occurs shift in a polar fashion upon alteration in Pol II catalytic activity or GTF function.

Results
To determine the extent of promoter scanning across promoter classes in S. cerevisiae, we perturb Pol II catalytic activity and GTF function and analyze their effects on TSS usage genome-wide. We find that alterations to Pol II, TFIIB, or TFIIF function widely alter the initiation landscape consistent with promoter scanning operating at all yeast promoters, regardless of promoter class. Promoter architecture, however, can determine the extent of promoter sensitivity to altered Pol II activity in ways that are predicted by a scanning model.

Conclusions
Our observations coupled with previous data validate key predictions of the scanning model for Pol II initiation in yeast, which we term the shooting gallery. In this model, Pol II catalytic activity and the rate and processivity of Pol II scanning together with promoter sequence determine the distribution of TSSs and their usage.
Assembly and annotation of an Ashkenazi human reference genome
Authors: Shumate Alaina , Zimin Aleksey V. , Sherman Rachel M. , Puiu Daniela , Wagner Justin M. , Olson Nathan D. , Pertea Mihaela , Salit Marc L. , Zook Justin M. , Salzberg Steven L. 
Published: June 2020

AbstractBackgroundThousands of experiments and studies use the human reference genome as a resource each year. This single reference genome, GRCh38, is a mosaic created from a small number of individuals, representing a very small sample of the human population. There is a need for reference genomes from multiple human populations to avoid potential biases.ResultsHere, we describe the assembly and annotation of the genome of an Ashkenazi individual and the creation of a new, population-specific human reference genome. This genome is more contiguous and more complete than GRCh38, the latest version of the human reference genome, and is annotated with highly similar gene content. The Ashkenazi reference genome, Ash1, contains 2,973,118,650 nucleotides as compared to 2,937,639,212 in GRCh38. Annotation identified 20,157 protein-coding genes, of which 19,563 are > 99% identical to their counterparts on GRCh38. Most of the remaining genes have small differences. Forty of the protein-coding genes in GRCh38 are missing from Ash1; however, all of these genes are members of multi-gene families for which Ash1 contains other copies. Eleven genes appear on different chromosomes from their homologs in GRCh38. Alignment of DNA sequences from an unrelated Ashkenazi individual to Ash1 identified ~ 1 million fewer homozygous SNPs than alignment of those same sequences to the more-distant GRCh38 genome, illustrating one of the benefits of population-specific reference genomes.ConclusionsThe Ash1 genome is presented as a reference for any genetic studies involving Ashkenazi Jewish individuals.
Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children
Authors: Grimaud Marion , Starck Julie , Levy Michael , Marais Clémence , Chareyre Judith , Khraiche Diala , Leruez-Ville Marianne , Quartier Pierre , Léger Pierre Louis , Geslain Guillaume , Semaan Nada , Moulin Florence , Bendavid Matthieu , Jean Sandrine , Poncelet Géraldine , Renolleau Sylvain , Oualha Mehdi 
Published: June 2020

Abstract
Background
A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020.

Results
20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25–55); troponin, 269 ng/mL (31–4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1–10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge.

Conclusions
Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.
An efficient task offloading scheme in vehicular edge computing
Authors: Raza Salman , Liu Wei , Ahmed Manzoor , Anwar Muhammad Rizwan , Mirza Muhammad Ayzed , Sun Qibo , Wang Shangguang 
Published: June 2020

AbstractVehicular edge computing (VEC) is a promising paradigm to offload resource-intensive tasks at the network edge. Owing to time-sensitive and computation-intensive vehicular applications and high mobility scenarios, cost-efficient task offloading in the vehicular environment is still a challenging problem. In this paper, we study the partial task offloading problem in vehicular edge computing in an urban scenario. Where the vehicle computes some part of a task locally, and offload the remaining task to a nearby vehicle and to VEC server subject to the maximum tolerable delay and vehicle’s stay time. To make it cost-efficient, including the cost of the required communication and computing resources, we consider to fully exploit the vehicular available resources. We estimate the transmission rates for the vehicle to vehicle and vehicle to infrastructure communication based on practical assumptions. Moreover, we present a mobility-aware partial task offloading algorithm, taking into account the task allocation ratio among the three parts given by the communication environment conditions. Simulation results validate the efficient performance of the proposed scheme that not only enhances the exploitation of vehicular computation resources but also minimizes the overall system cost in comparison to baseline schemes.
Gaussian beam imaging of fractures near the wellbore using sonic logging tools after removing dispersive borehole waves
Authors: Li David , Tian Xiao , Hu Hao , Tang Xiao-Ming , Fang Xinding , Zheng Yingcai 
Published: June 2020

The ability to image near-wellbore fractures is critical for wellbore integrity monitoring as well as for energy production and waste disposal. Single-well imaging uses a sonic logging instrument consisting of a source and a receiver array to image geologic structures around a wellbore. We use cross-dipole sources because they can excite waves that can be used to image structures farther away from the wellbore than traditional monopole sources. However, the cross-dipole source also will excite large-amplitude, slowly propagating dispersive waves along the surface of the borehole. These waves will interfere with the formation reflection events. We have adopted a new fracture imaging procedure using sonic data. We first remove the strong amplitude borehole waves using a new nonlinear signal comparison method. We then apply Gaussian beam migration to obtain high-resolution images of the fractures. To verify our method, we first test our method on synthetic data sets modeled using a finite-difference approach. We then validate our method on a field data set collected from a fractured natural gas production well. We are able to obtain high-quality images of the fractures using Gaussian beam migration compared with Kirchhoff migration for the synthetic and field data sets. We also found that a low-frequency source (around 1 kHz) is needed to obtain a sharp image of the fracture because high-frequency wavefields can interact strongly with the fluid-filled borehole.
The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups.
Authors: van Tilburg Cornelis Martinus , Pfaff Elke , Pajtler Kristian W. , Langenberg Karin P.S. , Fiesel Petra , Jones Barbara C. , Balasubramanian Gnana Prakash , Stark Sebastian , Johann Pascal D. , Blattner-Johnson Mirjam , Schramm Kathrin , Jäger Natalie , von Deimling Andreas , Dirksen Uta , Freitag Angelika , Witt Ruth , Lichter Peter , Jones David T.W. , Pfister Stefan M. , Witt Olaf 
Published: June 2020

LBA10503 Background: Several pediatric precision oncology programs have identified molecular actionable variants. However, the clinical benefit is largely unknown. We here report a target prioritization algorithm and associated clinical outcome. Methods: INFORM is a prospective, non-interventional, multi-center, multi-national, and feasibility registry collecting clinical and molecular data. Patients with refractory/relapsed/progressive malignant disease, including primary diagnosis high-risk entities, can be enrolled. Fresh frozen tumor material (incl. germline DNA) was subjected to WES, lcWGS, RNA-Seq, RNA expression array and DNA-methylation. A weekly interdisciplinary molecular board reviewed and prioritized alterations based on a 7- step scale from ‘very high’ to ‘very low’, depending on the type of alteration and its entity specific relevance (described by Worst et al. Eur J Cancer 2016). Results: To date, more than 1300 patients were enrolled. 525 patients finished follow-up and were included in this analysis. They were enrolled in 72 centers in 8 countries. The median age was 12.0 (range 0 - 40) years. Average turnaround time from submission to report was 25.4 days. Median PFS and OS were 116 (95% CI 105 – 135) and 289 (95% CI 250 – 335) days. The distribution of the highest priority target per patient was: very high 8.0%, high 14.8%, moderate 20.3%, intermediate 23.6%, borderline 14.4%, low 2.5%, very low 1.0% and no actionable target 15.4%. 149 patients received targeted treatment on the basis of identified targets, of which 20 had a very high priority target (mostly ALK, BRAF and NRAS mutations and MET and NTRK-fusions) with a median PFS of 204.5 (95% CI 91.0 – 628.0) compared to 114 (95% CI 103 – 133) days in all other 505 patients (p = 0.0095). OS did not show clinically relevant differences. Explorative analysis of the time to progression (TTP) ratio (before compared to after enrollment) showed that patients treated according to a very high priority target had a higher TTP ratio (1.0) compared to all other patients (0.7). Possible predisposition syndromes were identified in 7.8% of patients, half of which were newly diagnosed. Methylation analysis provided a diagnosis refinement in 8% of CNS tumors. Conclusions: Pediatric precision oncology in a real world, multi-national setting is feasible. The prioritization algorithm identifies subgroups benefitting from molecularly matched targeted treatment. Still, for the patients without a very high priority target further layers of molecular and functional data should be incorporated in future programs.
Intrahepatic Cholangiocarcinoma: Genomic Heterogeneity Between Eastern and Western Patients
Authors: Cao Jingyu , Hu Jing , Liu Siqin , Meric-Bernstam Funda , Abdel-Wahab Reham , Xu Junjie , Li Qiang , Yan Maolin , Feng Yujie , Lin Jianzhen , Zhao Songhui , Wang Jian , Kwong Lawrence N. , Hu Jinwei , Carapeto Fernando , Borad Mitesh J. , Wang Kai , Javle Milind , Zhao Haitao 
Published: June 2020

PURPOSE Intrahepatic cholangiocarcinoma (IHCCA), a global health problem, is increasing in incidence and has differing etiologies worldwide. Next-generation sequencing (NGS) is rapidly being incorporated into the clinical management of biliary cancers. IHCCA is enriched with actionable mutations, and there are several promising targeted therapies under development. NGS data from Asia, where IHCCA is most prevalent, are limited. METHODS Comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 164 Asian and 283 Western patients with IHCCA was performed using NGS. We measured the distribution of DNA repair genetic aberrations (GAs) in IHCCA, along with actionable mutations. Also, we evaluated the association between DNA repair GAs and tumor mutation burden (TMB). Based on the TMB status, patients were distinguished into 3 levels: low (< 6 mut/Mb), intermediate (6-10 mut/Mb), and high (TMB-H; ≥ 10 mut/Mb). RESULTS Seventy-two percent of Asian patients had ≥ 1 actionable GA, with a significantly higher frequency in KMT2C , BRCA1/2, and DDR2 compared with Western patients ( P = .02, .003, and .003, respectively); 60.9% of Western patients had ≥ 1 actionable GA and higher frequency of CDKN2A/B and IDH1/2 GAs ( P = .0004 and < .001, respectively). GAs in nuclear factor kappa B pathway regulators and DNA repair genes occurred more frequently in Asian patients ( P = .006 and .001, respectively). There was a higher frequency of TMB-H in Asian compared with the Western cohort (12.2% v 5.9%; P = .07). CONCLUSION A higher burden of DNA repair mutations and frequency of patients with TMB-H in the Asian IHCCA cohort compared with the Western patients suggests a potential role for DNA repair and immune checkpoint inhibitors in the Asian population. Future clinical trials should account for this genetic heterogeneity.
Blood Cell Disorders and the Nervous System
Authors: Merkler Alexander E. 
Published: June 2020

ABSTRACT

purpose of review
This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of common and rare blood cell disorders.

recent findings
A growing number of preventive treatment options are available for stroke in sickle cell disease. Paroxysmal nocturnal hemoglobinuria and immune thrombocytopenia can lead to stroke. Thrombotic thrombocytopenic purpura frequently causes neurologic symptoms and should be considered in the differential diagnosis of a patient with neurologic symptoms, thrombocytopenia, and hemolytic anemia. Polycythemia vera and essential thrombocythemia are rare causes of stroke.

summary
This article discusses sickle cell disease and the most recent advances in stroke preventive therapy as well as neurologic complications of paroxysmal nocturnal hemoglobinuria, immune thrombocytopenia, thrombotic thrombocytopenic purpura, polycythemia vera, and essential thrombocythemia.
The Mre11-Rad50-Nbs1 complex mediates the robust recruitment of Polo to DNA lesions during mitosis in Drosophila
Authors: Landmann Cedric , Pierre-Elies Priscillia , Goutte-Gattat Damien , Montembault Emilie , Claverie Marie-Charlotte , Royou Anne 
Published: June 2020

ABSTRACT
The DNA damage sensor Mre11-Rad50-Nbs1 complex and Polo kinase are recruited to DNA lesions during mitosis. However, their mechanism of recruitment is elusive. Here, using live-cell imaging combined with micro-irradiation of single chromosomes, we analyze the dynamics of Polo and Mre11 at DNA lesions during mitosis in Drosophila. These two proteins display distinct kinetics. Whereas Polo kinetics at double-strand breaks (DSBs) are Cdk1-driven, Mre11 promptly but briefly associates with DSBs regardless of the phase of mitosis and re-associates with DSBs in the proceeding interphase. Mechanistically, Polo kinase activity is required for its own recruitment and that of the mitotic proteins BubR1 and Bub3 to DSBs. Moreover, depletion of Rad50 severely impaired Polo kinetics at mitotic DSBs. Conversely, ectopic tethering of Mre11 to chromatin was sufficient to recruit Polo. Our study highlights a novel pathway that links the DSB sensor Mre11-Rad50-Nbs1 complex and Polo kinase to initiate a prompt, decisive response to the presence of DNA damage during mitosis.
Pt-Pd Nanoalloy for the Unprecedented Activation of Carbon-Fluorine Bond at Low Temperature
Authors: Dhital Raghu Nath , Nomura Keigo , Sato Yoshinori , Haesuwannakij Setsiri , Ehara Masahiro , Sakurai Hidehiro 
Published: June 2020

Abstract
Carbon-fluorine bonds are considered the most inert organic functionality and their selective transformation under mild conditions remains challenging. Herein, we report a highly active Pt-Pd nanoalloy as a robust catalyst for the transformation of C-F bonds into C-H bonds at low temperature, a reaction that has hitherto often required harsh conditions. The alloying of Pt with Pd is crucial to promote the overall C-F bond. DFT calculations elucidated that the key step is the selective oxidative addition of the O-H bond of 2-propanol to a Pd center prior to C-F bond activation at a Pt site, which crucially reduces the activation energy of the C-F bond cleavage. Therefore, both Pt and Pd work independently but synergistically to promote the overall reaction.
COPO: a metadata platform for brokering FAIR data in the life sciences
Authors: Shaw Felix , Etuk Anthony , Minotto Alice , Gonzalez-Beltran Alejandra , Johnson David , Rocca-Serra Phillipe , Laporte Marie-Angélique , Arnaud Elizabeth , Devare Medha , Kersey Paul , Sansone Susanna-Assunta , Davey Robert P. 
Published: June 2020

Scientific innovation is increasingly reliant on data and computational resources. Much of today’s life science research involves generating, processing, and reusing heterogeneous datasets that are growing exponentially in size. Demand for technical experts (data scientists and bioinformaticians) to process these data is at an all-time high, but these are not typically trained in good data management practices. That said, we have come a long way in the last decade, with funders, publishers, and researchers themselves making the case for open, interoperable data as a key component of an open science philosophy. In response, recognition of the FAIR Principles (that data should be Findable, Accessible, Interoperable and Reusable) has become commonplace. However, both technical and cultural challenges for the implementation of these principles still exist when storing, managing, analysing and disseminating both legacy and new data. COPO is a computational system that attempts to address some of these challenges by enabling scientists to describe their research objects (raw or processed data, publications, samples, images, etc.) using community-sanctioned metadata sets and vocabularies, and then use public or institutional repositories to share them with the wider scientific community. COPO encourages data generators to adhere to appropriate metadata standards when publishing research objects, using semantic terms to add meaning to them and specify relationships between them. This allows data consumers, be they people or machines, to find, aggregate, and analyse data which would otherwise be private or invisible, building upon existing standards to push the state of the art in scientific data dissemination whilst minimising the burden of data publication and sharing.
Asymmetric Attention and Stock Returns
Authors: Cziraki Peter , Mondria Jordi , Wu Thomas 
Published: June 2020

This paper constructs a new measure of attention allocation by local investors relative to nonlocals using aggregate search volume from Google. We first present a conceptual framework in which local investors optimally choose to focus their attention on local stocks when they receive private news, leading to an asymmetric allocation of attention between local and nonlocal investors. Consistent with the main prediction of this framework, we find that firms attracting abnormally high asymmetric attention from local relative to nonlocal investors earn higher returns. A portfolio that goes long in stocks with high asymmetric attention and short in stocks with low asymmetric attention has an alpha of 32 basis points per month. The results are stronger for stocks with a greater degree of information friction. The new measure of asymmetric attention allows one to infer the arrival of unobservable private information by observing investors’ attention allocation behavior. This paper was accepted by Karl Diether, finance.
Improvement in Mental Health Outcomes and Caregiver Service Experiences Associated With the START Program
Authors: Kalb Luther G. , Beasley Joan , Caoili Andrea , Klein Ann 
Published: June 2020

Abstract
This study examined outcomes from the Systemic, Therapeutic, Assessment, Resources, and Treatment (START) program, a community-based tertiary care model for individuals with intellectual and developmental disabilities and mental health needs. The sample included 111 START service users and their family caregivers, who were receiving START Clinical Team services, located in the Northeast and Southwest regions of the United States. Results from the analyses found a significant 1-year pre-post improvement in caregiver service experiences and mental health symptoms of the service user. A significant decrease in psychiatric hospitalizations and emergency department visits was also found (all p &lt; .01). These data suggest that START holds promise in improving outcomes, for both the caregiver and service user, while reducing dependence on costly and restrictive hospital-based services.
Backward terahertz difference frequency generation via modal phase-matching in a planar LiNbO3 waveguide
Authors: Carnio B. N. , Elezzabi A. Y. 
Published: June 2020

The backward difference frequency generation process is used to produce narrowband terahertz radiation via modal phase-matching in a

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