bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence Of Progerin Expression On The Nature Of DNA Double‐Strand Break Repair
Authors: Waldman Alan S. , Chowdhary Sona , Patrick Andrew , Hersey Melinda , Waldman Barbara Criscuolo 
Published: June 2021

Hutchinson‐Gilford Progeria Syndrome (HGPS) is a rare, fatal autosomal dominant genetic condition characterized by many features of accelerated aging in children. Children with HGPS die at an average age of fourteen, usually from heart disease. It has been known for some time that the syndrome is most commonly caused by a point mutation in the LMNA gene which normally codes for lamin A and its splice variant lamin C. The LMNA mutation commonly associated with HGPS leads to increased usage of a cryptic splice site which leads to the production of a truncated, farnesylated form of lamin A referred to as “progerin.” Interestingly, and quite significantly, progerin is also expressed at very low levels in healthy individuals and has been implicated in the normal aging process, possibly by increased expression over time. Progerin overexpression in progeria disrupts nuclear architecture and chromatin organization. Previous studies by others have indicated that progerin slows the kinetics of DNA double‐strand break (DSB) repair and leads to the accumulation of spontaneous DSBs. Strikingly, there has been little investigation into how progerin expression may alter the nature of DSB repair. DSB repair may occur through one of two ways: homologous recombination (HR), which is accurate, or non‐homologous end joining (NHEJ), which is intrinsically mutagenic. We aimed to assess whether progerin expression alters the DSB repair pathway of choice or whether it alters the nature of individual repair events. To do so, we stably expressed a GFP‐progerin fusion protein, or GFP alone, in a human cell line containing an integrated DNA substrate that served as a reporter for DSB repair. A DSB was introduced in the integrated substrate by transient expression of endonuclease I‐SceI. Events involving DSB repair via HR or NHEJ were recoverable by selection for G418‐resistant clones, and these events were analyzed at the nucleotide level and by Southern blotting analysis. We present results indicating there was an increased frequency of DSB events occurring via NHEJ in cells expressing GFP‐progerin in comparison to those expressing GFP alone, and the difference in pathway usage was highly significant (p < 0.004 by a two‐sided Fisher exact test). There was no evidence that progerin impacted the accuracy of HR events. In future work, the finding that progerin expression appears to alter the DSB repair pathway of choice within the human genome will be explored further, as will the possibility that progerin alters the homology requirements for HR. Our long‐term goal is to better understand the relationship between aging and the corruption of genome maintenance pathways.Support or Funding InformationThis work was supported by grant MCB‐1157416 from the NSF to ASW and BCW, and from an ASPIRE grant from the University of South Carolina to ASW.
Distal Radius Physeal Bar and Ulnar Overgrowth: Indications for Treatment
Authors: Samora Julie Balch 
Published: June 2021

Background:
Distal radius physeal bar with associated growth arrest can occur because of fractures, ischemia, infection, radiation, tumor, blood dyscrasias, and repetitive stress injuries. The age of the patient as well as the size, shape, and location of the bony bridge determines the deformity and associated pathology that will develop.

Methods:
A search of the English literature was performed using PubMed and multiple search terms to identify manuscripts dealing with the evaluation and treatment of distal radius physeal bars and ulnar overgrowth. Single case reports and level V studies were excluded.

Results:
Manuscripts evaluating distal radial physeal bars and their management were identified. A growth discrepancy between the radius and ulna can lead to distal radioulnar joint instability, ulnar impaction, and degenerative changes in the carpus and triangular fibrocartilage complex. Advanced imaging aids in the evaluation and mapping of a physeal bar. Treatment options for distal radius physeal bars include observation, bar resection±interposition, epiphysiodeses of the ulna±completion epiphysiodesis of the radius, ulnar shortening osteotomy±diagnostic arthroscopy to manage associated triangular fibrocartilage complex pathology, radius osteotomy, and distraction osteogenesis.

Conclusions:
Decision-making when presented with a distal radius physeal bar is multifactorial and should incorporate the age and remaining growth potential of the patient, the size and location of the bar, and patient and family expectations.
Operative Fixation Versus Cast Immobilization: Tibial Shaft Fractures in Adolescents
Authors: Martus Jeffrey E. 
Published: June 2021

Introduction:
Tibial shaft fractures are common injuries in the adolescent age group. Potential complications from the injury or treatment include infection, implant migration, neurovascular injury, compartment syndrome, malunion, or nonunion.

Methods:
Published literature was reviewed to identify studies which describe the management options, complications, and outcome of tibial shaft fractures in adolescents.

Results:
Acceptable alignment parameters for tibial shaft fractures have been defined. Operative indications include open fractures and other severe soft tissue injuries, vascular injury, compartment syndrome, ipsilateral femoral fractures, and polytrauma. Relative indications for operative treatment are patient/family preference or morbid obesity. Closed reduction and cast immobilization necessitates radiographic observation for loss of reduction over the first 3 weeks. Cast change/wedging or conversion to operative management may be required in 25% to 40%. Flexible nailing provides relative fracture stability while avoiding the proximal tibial physis, but the fracture will still benefit from postoperative immobilization. Rigid nailing provides greater fracture stability and allows early weight bearing but violates the proximal tibial physis. Plate and screw osteosynthesis provide stable anatomic reduction, but there are concerns with delayed union and wound complications related to the dissection. External fixation is an excellent strategy for tibia fractures associated with complex wounds but also requires observation for loss of reduction.

Discussion and Conclusions:
The majority of adolescent tibia shaft fractures can be successfully managed with closed reduction and cast immobilization. Unstable fractures that have failed cast treatment should be treated operatively. Flexible intramedullary nailing, rigid intramedullary nailing, plate and screw osteosynthesis, and external fixation are acceptable treatment options that may be considered for an individual patient depending upon the clinical scenario.
Hematopoietic Stem Cell Transplantation Cures Therapy-refractory Aspergillosis in Chronic Granulomatous Disease
Authors: Dedieu Cinzia , Landwehr-Kenzel Sybille , Thee Stephanie , Oevermann Lena , Voigt Sebastian , Marggraf Katharina , Schulte Johannes , Lau Susanne , Roesler Joachim , Kuehl Jörn-Sven , von Bernuth Horst 
Published: June 2021

Background:
Pulmonary invasive aspergillosis is a frequent and life-threatening complication for patients with chronic granulomatous disease (CGD). Despite combined treatment with several groups of antifungal agents, conservative treatment of invasive aspergillosis often remains refractory. Pulmonary invasive aspergillosis is often treated by surgical resection of consolidated lobes or segments, donor granulocyte transfusions and allogeneic hematopoietic stem cell transplantation (HSCT). These options are not mutually exclusive and often combined.

Methods and Results:
We here describe the treatment of 3 patients with CGD who received HSCT upon active pulmonary invasive aspergillosis: Two of them received HSCT as salvage therapy for refractory aspergillosis, and 1 patient received elective HSCT in infancy but developed pulmonary aspergillosis during secondary graft failure. Based on our experience and available literature, we discuss indication as well as timing of HSCT, granulocyte transfusions and surgery in patients with CGD and pulmonary invasive aspergillosis.

Conclusions:
Upon diagnosis with invasive aspergillosis in CGD, we propose to start antifungal treatment and preparation for HSCT at the same time. Remission of pulmonary invasive aspergillosis before HSCT remains preferable but is not mandatory. When pulmonary aspergillosis in patients with CGD remains refractory for longer than 3 months on conservative treatment, HSCT without prior surgery or accompanying granulocyte transfusions is a feasible option.
Unique Imaging Findings of Neurologic Phantosmia Following Pfizer-BioNtech COVID-19 Vaccination: A Case Report
Authors: Keir Graham , Maria Naomi I. , Kirsch Claudia F.E. 
Published: June 2021

Abstract
Olfactory dysfunction related to SARS-CoV-2 infection and COVID-19 disease is now well established in the literature. In December 2020, the FDA approved the Pfizer-BioNTech and Moderna vaccines for use in preventing COVID-19 in the United States. To the best of our knowledge, this is the first report of a phantosmia post-Pfizer COVID-19 vaccination, with positive magnetic resonance imaging radiographic findings in a patient with documented absence of infection by SARS-CoV-2 virus or concomitant sinonasal disease.
A discussion on electricity prices, or the two sides of the coin
Authors: Pablo Luna Juan , Sagastizábal Claudia , Silva Paulo J. S. 
Published: June 2021

We examine how different pricing frameworks deal with non-convex features typical of day-ahead energy prices when the power system is hydro-dominated, like in Brazil. For the system operator, requirements of minimum generation translate into feasibility issues that are fundamental to carry the generated power through the network. When utilities are remunerated at a price depending on Lagrange multipliers computed for a system with fixed commitment, the corresponding values sometimes fail to capture a signal that recovers costs. Keeping in mind recent discussions for the Brazilian power system, we analyse mechanisms that provide a compromise between the needs of the generators and those of the system operator. After characterizing when a price supports a generation plan, we explain in simple terms dual prices and related concepts, such as minimal uplifts and bi-dual problems. We present a new pricing mechanism that guarantees cost recovery to all agents, without over-compensations. Instead of using Lagrange multipliers, the price is defined as the solution to an optimization problem. The behaviour of the new rule is compared to two other proposals in the literature on illustrative examples, including a small, yet representative, hydro-thermal system.
This article is part of the theme issue ‘The mathematics of energy systems’.
The energy distance for ensemble and scenario reduction
Authors: Ziel Florian 
Published: June 2021

Scenario reduction techniques are widely applied for solving sophisticated dynamic and stochastic programs, especially in energy and power systems, but are also used in probabilistic forecasting, clustering and estimating generative adversarial networks. We propose a new method for ensemble and scenario reduction based on the energy distance which is a special case of the maximum mean discrepancy. We discuss the choice of energy distance in detail, especially in comparison to the popular Wasserstein distance which is dominating the scenario reduction literature. The energy distance is a metric between probability measures that allows for powerful tests for equality of arbitrary multivariate distributions or independence. Thanks to the latter, it is a suitable candidate for ensemble and scenario reduction problems. The theoretical properties and considered examples indicate clearly that the reduced scenario sets tend to exhibit better statistical properties for the energy distance than a corresponding reduction with respect to the Wasserstein distance. We show applications to a Bernoulli random walk and two real data-based examples for electricity demand profiles and day-ahead electricity prices.This article is part of the theme issue ‘The mathematics of energy systems’.
LPMX: A pure rootless composable container system
Authors: Yang Xu , Kasahara Masahiro 
Published: June 2021

AbstractSummaryDelivering tools for genome analysis to users is often difficult given their complex dependencies and conflicts. Container virtualization systems such as Singularity isolate environments, helping developers avoid conflicts between tools. However, they lack composability, an easy way to integrate multiple tools in different containers or multiple tools both in a container and a host, which compromises the use of container systems in genome research. Another issue is that one may not be able to use a single container system of the same version at all sites they use, which discourages the use of container systems. To this end, we present a pure rootless composable container system, LPMX, that provides composability for letting developers easily integrate tools in different existing containers or on host, allowing researchers to compose existing containers. LPMX is pure rootless, so it does not require root privilege neither during installation nor at runtime, allowing researchers to use LPMX across sites without asking permissions from administrators. LPMX provides a pure userspace layered filesystem with at least an order of magnitude lower overhead for launching a new process than existing container systems. LPMX can import Docker and Singularity images.Availability and ImplementationThe source code of LPMX is available at https://github.com/jasonyangshadow/lpmx under Apache 2.0 License.Contactmkasa@k.u-tokyo.ac.jpSupplementary informationSupplementary data are available at Bioinformaticsonline.
Accurate Virus Identification with Interpretable Raman Signatures by Machine Learning
Authors: Ye Jiarong , Yeh Yin-Ting , Xue Yuan , Wang Ziyang , Zhang Na , Liu He , Zhang Kunyan , Yu Zhuohang , Roder Allison , Lopez Nestor Perea , Organtini Lindsey , Greene Wallace , Hafenstein Susan , Lu Huaguang , Ghedin Elodie , Terrones Mauricio , Huang Shengxi , Huang Sharon Xiaolei 
Published: June 2021

AbstractRapid identification of newly emerging or circulating viruses is an important first step toward managing the public health response to potential outbreaks. A portable virus capture device coupled with label-free Raman Spectroscopy holds the promise of fast detection by rapidly obtaining the Raman signature of a virus followed by a machine learning approach applied to recognize the virus based on its Raman spectrum. In this paper, we present a machine learning analysis on Raman spectra of human and avian viruses. A Convolutional Neural Network (CNN) classifier specifically designed for spectral data achieves very high accuracy for a variety of virus type or subtype identification tasks. In particular, it achieves 99% accuracy for classifying influenza virus type A vs. type B, 96% accuracy for classifying four subtypes of influenza A, 95% accuracy for differentiating enveloped and non-enveloped viruses, and 99% for differentiating avian coronavirus (infectious bronchitis virus, IBV) from other avian viruses. Furthermore, interpretation of neural net responses in the trained CNN model using a full-gradient algorithm highlights Raman spectral ranges that are most important to virus identification. By correlating ML-selected salient Raman ranges with the signature ranges of known biomolecules and chemical functional groups (e.g. amide, amino acid, carboxylic acid) we verify that our ML model effectively recognizes the Raman signatures of proteins, lipids and other vital functional groups present in different viruses and uses a weighted combination of these signatures to identify viruses. The accurate and interpretable machine learning model developed for Raman virus identification presents promising potential in a real-time virus detection system.Significance StatementA portable micro-fluidic platform for virus capture promises rapid enrichment and label-free optical identification of viruses by Raman spectroscopy. A large Raman dataset collected on a variety of viruses enables the training of machine learning (ML) models capable of highly accurate and sensitive virus identification. The trained ML models can then be integrated with the portable device to provide real-time virus detection and identification capability. We validate this conceptual framework by presenting highly accurate virus type and subtype identification results using a convolutional neural network to classify Raman spectra of viruses.
Deep vascular imaging in the eye with flow-enhanced ultrasound
Authors: Damsgaard Christian , Lauridsen Henrik 
Published: June 2021

ABSTRACTThe eye’s retina is one of the most energy-demanding tissues in the body and thus requires high rates of oxygen delivery from a rich blood supply. The capillary lamina of the choroid lines the outer surface of the retina and is the dominating source of oxygen in most vertebrates, but this vascular bed is challenging to image with traditional optical techniques due to its position behind the highly light-absorbing retina. Here we describe a high-frequency ultrasound technique with flow-enhancement to image deep vascular beds (0.5 – 3 cm) of the eye with a high spatiotemporal resolution. This non-invasive method works well in species with nucleated red blood cells (non-mammalian and fetal animal models), and it generates non-invasive three-dimensional angiographies without the use of contrast agents that is independent of blood flow angles and with a higher sensitivity than Doppler based ultrasound imaging techniques.
Selective pharmaceutical inhibition of PARP14 mitigates allergen-induced IgE and mucus overproduction in a mouse model of pulmonary allergic response
Authors: Eddie Alex M. , Chen Kevin , Schenkel Laurie B. , Swinger Kerren K. , Molina Jennifer R. , Kunii Kaiko , Raybuck Ariel L. , Keilhack Heike , Niepel Mario , Peebles R. Stokes , Boothby Mark R. , Cho Sung Hoon 
Published: June 2021

ABSTRACTThe type 2 cytokines IL-4 and IL-13, which share use of an IL-4 receptor alpha chain and its nuclear induction of the transcription factor STAT6, are crucial in elicitation and maintenance of allergic conditions that include asthma. Prior work has shown a physical and functional association of STAT6 with PARP14, an ADP-ribosyl monotransferase. Moreover, elimination of all PARP14 expression by gene targeting led to altered recall antibody responses and attenuation of ovalbumin-specific allergic lung inflammation with no apparent health issues for mice lacking this protein. However, an unanswered question is whether or not inhibition of the catalytic function has any biological consequence since PARP14 has multiple functional domains apart from the portion that catalyzes ADP-ribosylation. As reported separately, iterative structural analyses and medicinal chemistry fostered the generation of a compound, RBN2759, that is highly selective in its inhibition of PARP14 with negligible impact on other members of the PARP gene family. We show here that administration of this compound to mice previously sensitized to the allergenAlternaria alternataachieved biochemically active levels and altered physiological responses to the antigen. These results show for the first time that in vivo administration of a specific inhibitor of the ADP-ribosyltransferase activity encoded by PARP14 is sufficient to alter biological responses. Specifically, the orally absorbable pharmaceutical compound decreased allergen-induced mucus, blunted the induced increases in circulating IgE, and prevented suppression of IgG2a. We conclude that the catalytic activity can contribute to pathogenesis in allergic processes and propose that other biological endpoints that depend on ADP-ribosylation by PARP14 can be targeted using selective inhibition.
Modeling DNA opening in the eukaryotic transcription initiation complexes
Authors: Shino Genki , Takada Shoji 
Published: June 2021

AbstractRecently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiation complex remain obscured. In this study, based on the three cryo-electron microscopic yeast structures for the closed, open, and initially transcribing complexes, we performed multiscale molecular dynamics (MD) simulations to model structures and dynamic processes of DNA opening. Combining coarse-grained and all-atom MD simulations, we first obtained the atomic model for the DNA bubble in the open complexes. Then, in the MD simulation from the open to the initially transcribing complexes, we found a previously unidentified intermediate state which is formed by the bottleneck in the fork loop 1 of Pol II: The loop opening triggered the escape from the intermediate, serving as a gatekeeper of the promoter DNA opening. In the initially transcribing complex, the non-template DNA strand passes a groove made of the protrusion, the lobe, and the fork of Rpb2 subunit of Pol II, in which several positively charged and highly conserved residues exhibit key interactions to the non-template DNA strand.Author SummaryTranscription is fundamental phenomenon in all species, and its regulation of the initiation process is important. In eukaryotes, multiple proteins, which is not only RNA polymerase but also transcription factors, assemble on the promotor to form the complex. After that, this complex open the part of DNA duplex, leading to forming single-stranded region for transcription. Previous study, including structural analysis and biochemical experiments, obtained the information about single-stranded region, but the structure is incomplete, so the details of the mechanism remains unclear. In this study, by the calculation using structural information about the protein-DNA complex, we obtained the structure of the complex with complete single-stranded region. As the result of the calculation, it found that the size of single-stranded region was fluctuated, which is related the sequence of the region. Furthermore, we found the intermediate state during the extended process of single-stranded region, which has not been reported in previous study. In this state, we found that the particular region of RNA polymerase is relevant to the extension of single-stranded region. These founding may contribute the understanding about the regulation of transcription initiation.
Siderophores drive invasion dynamics in bacterial communities through their dual role as public good versus public bad
Authors: Figueiredo Alexandre R. T. , Özkaya Özhan , Kümmerli Rolf , Kramer Jos 
Published: June 2021

AbstractMicrobial invasions can compromise ecosystem services and spur dysbiosis and disease in hosts. Nevertheless, the mechanisms determining invasion outcomes often remain unclear. Here, we examine the role of iron-scavenging siderophores in driving invasions of Pseudomonas aeruginosa into resident communities of environmental pseudomonads. Siderophores can be “public goods” by delivering iron to individuals possessing matching receptors; but they can also be “public bads” by withholding iron from competitors lacking these receptors. Accordingly, siderophores should either promote or impede invasion, depending on their dual effects on invader and resident growth. Using supernatant feeding and invasion assays, we show that invasion success indeed decreased when the invader was inhibited (public bad) rather than stimulated (public good) by the residents’ siderophores. Conversely, invasion success often increased when the invader could use its siderophore to inhibit the residents. Our findings identify siderophores as a major driver of invasion dynamics in bacterial communities.