bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing editosome function in high-throughput
Authors: Del Campo Cristian , Leeder Wolf-Matthias , Reißig Paul , Göringer H Ulrich 
Published: July 2020

Abstract
Mitochondrial gene expression in African trypanosomes and other trypanosomatid pathogens requires a U-nucleotide specific insertion/deletion-type RNA-editing reaction. The process is catalyzed by a macromolecular protein complex known as the editosome. Editosomes are restricted to the trypanosomatid clade and since editing is essential for the parasites, the protein complex represents a near perfect target for drug intervention strategies. Here, we report the development of an improved in vitro assay to monitor editosome function. The test system utilizes fluorophore-labeled substrate RNAs to analyze the processing reaction by automated, high-throughput capillary electrophoresis (CE) in combination with a laser-induced fluorescence (LIF) readout. We optimized the assay for high-throughput screening (HTS)-experiments and devised a multiplex fluorophore-labeling regime to scrutinize the U-insertion/U-deletion reaction simultaneously. The assay is robust, it requires only nanogram amounts of materials and it meets all performance criteria for HTS-methods. As such the test system should be helpful in the search for trypanosome-specific pharmaceuticals.
Tumor suppressor p53: from engaging DNA to target gene regulation
Authors: Sammons Morgan A , Nguyen Thuy-Ai T , McDade Simon S , Fischer Martin 
Published: July 2020

Abstract
The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network of target genes. The recent explosion of next generation sequencing protocols has enabled the study of the p53 gene regulatory network (GRN) and underlying mechanisms at an unprecedented depth and scale, helping us to understand precisely how p53 controls gene regulation. Here, we discuss our current understanding of where and how p53 binds to DNA and chromatin, its pioneer-like role, and how this affects gene regulation. We provide an overview of the p53 GRN and the direct and indirect mechanisms through which p53 affects gene regulation. In particular, we focus on delineating the ubiquitous and cell type-specific network of regulatory elements that p53 engages; reviewing our understanding of how, where, and when p53 binds to DNA and the mechanisms through which these events regulate transcription. Finally, we discuss the evolution of the p53 GRN and how recent work has revealed remarkable differences between vertebrates, which are of particular importance to cancer researchers using mouse models.
SPRINT: a Cas13a-based platform for detection of small molecules
Authors: Iwasaki Roman S , Batey Robert T 
Published: July 2020

AbstractRecent efforts in biological engineering have made detection of nucleic acids in samples more rapid, inexpensive and sensitive using CRISPR-based approaches. We expand one of these Cas13a-based methods to detect small molecules in a one-batch assay. Using SHERLOCK-based profiling of in vitrotranscription (SPRINT), in vitro transcribed RNA sequence-specifically triggers the RNase activity of Cas13a. This event activates its non-specific RNase activity, which enables cleavage of an RNA oligonucleotide labeled with a quencher/fluorophore pair and thereby de-quenches the fluorophore. This fluorogenic output can be measured to assess transcriptional output. The use of riboswitches or proteins to regulate transcription via specific effector molecules is leveraged as a coupled assay that transforms effector concentration into fluorescence intensity. In this way, we quantified eight different compounds, including cofactors, nucleotides, metabolites of amino acids, tetracycline and monatomic ions in samples. In this manner, hundreds of reactions can be easily quantified in a few hours. This increased throughput also enables detailed characterization of transcriptional regulators, synthetic compounds that inhibit transcription, or other coupled enzymatic reactions. These SPRINT reactions are easily adaptable to portable formats and could therefore be used for the detection of analytes in the field or at point-of-care situations.
Activation of viral transcription by stepwise largescale folding of an RNA virus genome
Authors: Chkuaseli Tamari , White K Andrew 
Published: July 2020

Abstract
The genomes of RNA viruses contain regulatory elements of varying complexity. Many plus-strand RNA viruses employ largescale intra-genomic RNA-RNA interactions as a means to control viral processes. Here, we describe an elaborate RNA structure formed by multiple distant regions in a tombusvirus genome that activates transcription of a viral subgenomic mRNA. The initial step in assembly of this intramolecular RNA complex involves the folding of a large viral RNA domain, which generates a discontinuous binding pocket. Next, a distally-located protracted stem-loop RNA structure docks, via base-pairing, into the binding site and acts as a linchpin that stabilizes the RNA complex and activates transcription. A multi-step RNA folding pathway is proposed in which rate-limiting steps contribute to a delay in transcription of the capsid protein-encoding viral subgenomic mRNA. This study provides an exceptional example of the complexity of genome-scale viral regulation and offers new insights into the assembly schemes utilized by large intra-genomic RNA structures.
Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons
Authors: Mohan Radhe , Liu Amy Y , Brown Paul D , Mahajan Anita , Dinh Jeffrey , Chung Caroline , McAvoy Sarah , McAleer Mary Frances , Lin Steven H , Li Jing , Ghia Amol J , Zhu Cong , Sulman Erik P , de Groot John F , Heimberger Amy B , McGovern Susan L , Grassberger Clemens , Shih Helen , Ellsworth Susannah , Grosshans David R 
Published: July 2020

Abstract

Background
We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of &lt;500 cells/µL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM).

Methods
Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis.

Results
Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P &lt; 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5‒40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95‒22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05‒0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03‒1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79–0.94) for the final G3+L prediction model.

Conclusions
Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.
Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache
Authors: Leplus Aurélie , Fontaine Denys , Donnet Anne , Regis Jean , Lucas Christian , Buisset Nadia , Blond Serge , Raoul Sylvie , Guegan-Massardier Evelyne , Derrey Stéphane , Jarraya Bechir , Dang-Vu Bich , Bourdain Frederic , Valade Dominique , Roos Caroline , Creach Christelle , Chabardes Stéphan , Giraud Pierric , Voirin Jimmy , Bloch Jocelyne , Colnat-Coulbois Sophie , Caire François , Rigoard Philippe , Tran Laurie , Cruzel Coralie , Lantéri-Minet Michel ,   French ONS registry group
Published: July 2020

Abstract

BACKGROUND
Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series.

OBJECTIVE
To evaluate ONS long-term efficacy in rCCH.

METHODS
We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption.

RESULTS
At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%).

CONCLUSION
Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.
Do Respondents Get used to Answering Sensitive Questions?
Authors: Müller Bettina , Schmiedeberg Claudia 
Published: July 2020

Abstract
Issues associated with collecting data on sensitive topics are widely studied in survey research. Respondents’ reactions to sensitive questions have rarely been addressed from a longitudinal perspective, however, despite panel surveys representing a fundamental data source for social research. This article evaluates whether respondents’ acceptance of sensitive questions increases with repeated interviewing in a panel survey. Drawing on data from the German Family Panel (pairfam), we apply fixed-effects regression models to assess within-respondent changes in refusal to items on sexuality and fertility. The analysis reveals that refusal attenuates for some, but not all questions under study and increases for other items over time, with patterns varying across age groups. We conclude that a general beneficial effect of panel experience on the refusal to answer questions regarding sexuality and fertility does not exist. Rather, refusal patterns appear to stem from aging processes and specific life situations.
Rituximab in the treatment of systemic sclerosis–related interstitial lung disease: a systematic review and meta-analysis
Authors: Goswami Rudra P , Ray Animesh , Chatterjee Moumita , Mukherjee Arindam , Sircar Geetabali , Ghosh Parasar 
Published: July 2020

Abstract

Objectives
To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients.

Methods
PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up.

Results
A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47).

Conclusions
Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.
Genomic Characterization and Curation of UCEs Improves Species Tree Reconstruction
Authors: Van Dam Matthew H , Henderson James B , Esposito Lauren , Trautwein Michelle 
Published: July 2020

AbstractUltraconserved genomic elements (UCEs) are generally treated as independent loci in phylogenetic analyses. The identification pipeline for UCE probes does not require prior knowledge of genetic identity, only selecting loci that are highly conserved, single copy, without repeats, and of a particular length. Here, we characterized UCEs from 11 phylogenomic studies across the animal tree of life, from birds to marine invertebrates. We found that within vertebrate lineages, UCEs are mostly intronic and intergenic, while in invertebrates, the majority are in exons. We then curated four different sets of UCE markers by genomic category from five different studies including: birds, mammals, fish, Hymenoptera (ants, wasps, and bees), and Coleoptera (beetles). Of genes captured by UCEs, we find that many are represented by two or more UCEs, corresponding to nonoverlapping segments of a single gene. We considered these UCEs to be nonindependent, merged all UCEs that belonged to a particular gene, constructed gene and species trees, and then evaluated the subsequent effect of merging cogenic UCEs on gene and species tree reconstruction. Average bootstrap support for merged UCE gene trees was significantly improved across all data sets apparently driven by the increase in loci length. Additionally, we conducted simulations and found that gene trees generated from merged UCEs were more accurate than those generated by unmerged UCEs. As loci length improves gene tree accuracy, this modest degree of UCE characterization and curation impacts downstream analyses and demonstrates the advantages of incorporating basic genomic characterizations into phylogenomic analyses. [Anchored hybrid enrichment; ants; ASTRAL; bait capture; carangimorph; Coleoptera; conserved nonexonic elements; exon capture; gene tree; Hymenoptera; mammal; phylogenomic markers; songbird; species tree; ultraconserved elements; weevils.]
Addressing the Linnean shortfall in a cryptic species complex
Authors: Walters Ashley D , Cannizzaro Andrew G , Trujillo Daniel A , Berg David J 
Published: July 2020

AbstractBiodiversity is being lost at an alarming rate, but the rate of this loss is likely to be underestimated as a result of a deficit in taxonomic knowledge (i.e. the Linnean shortfall). This knowledge gap is more extensive for morphologically indistinct taxa. The advancement of molecular techniques and delimitation methods has facilitated the identification of such cryptic species, but a majority of these taxa remain undescribed. To investigate the effects of taxonomic uncertainty on understanding of biodiversity, we applied the general lineage concept of species to an amphipod species complex, the Gammaruslacustris lineage that occupies springs of the northern Chihuahuan Desert, which is emerging in contemporary times. We investigated species boundaries using a validation-based approach and examined genetic structure of the lineage using a suite of microsatellite markers to identify independently evolving metapopulations. Our results show that each spring contains a genetically distinct population that is geographically isolated from other springs, suggesting evolutionary independence and status as separate species. Additionally, we observed subtle interspecific morphological variation among the putative species. We used multiple lines of evidence to formally describe four new species (Gammarus langi sp. nov., G. percalacustris sp. nov., G. colei sp. nov. and G. malpaisensis sp. nov.) endemic to the northern Chihuahuan Desert. Cryptic speciation is likely to be high in other aquatic taxa within these ecosystems, and across arid landscapes throughout North America and elsewhere, suggesting that the magnitude of the Linnean shortfall is currently underestimated in desert springs worldwide.
Loss to Follow-Up After Newborn Hearing Screening: Analysis of Risk Factors at a Massachusetts Urban Safety-Net Hospital
Authors: Razak Alina , Fard Darian , Hubbell Richard , Cohen Michael , Hartman-Joshi Kristin , Levi Jessica R. 
Published: July 2020

Objectives:
This study examines the unique factors that influence loss to follow-up after newborn hearing screening for patients at a Massachusetts urban safety-net hospital. We seek to characterize our patient population, investigate correlations between patient factors and rates of follow-up, and understand gaps in care.

Design:
A retrospective chart review was conducted of patients born at an urban safety-net hospital from January 2015 through May 2018 who did not pass the newborn hearing screening in one or both ears. A total of 197 infants were included in our study. Outcomes of interest included rates and latency of follow-up appointments, infant demographics (sex, race, birth weight, risk factors for hearing loss), and maternal factors (age, marital status, smoking status, number of children).

Results:
From January 2015 through May 2018, 17% (n = 34) of infants were lost to follow-up. Of those who attended an initial audiology evaluation, the median time between screening and appointment was 29 days. Newborns were 3.5 times at risk of being lost to follow-up if their mothers smoked during pregnancy compared to those whose mothers did not smoke. Further, newborns with multiple siblings in the home were less likely to utilize any audiological services. High-risk infants, such as those with an extended stay in the neonatal intensive care unit, were found to have higher rates of loss to follow-up.

Conclusions:
Our results indicate that patients at urban safety-net hospitals require increased support to decrease rates of loss to follow-up. In particular, strategies to aid mothers who smoke, have multiple children, or have high-risk infants can address gaps in care for newborns after hearing screening.
Treatment for Severe Coronavirus Disease 2019 With the Seraph-100 Microbind Affinity Blood Filter
Authors: Olson Stephen W. , Oliver James D. , Collen Jacob , Bunin Jessica , Gleeson Todd D. , Foster Brian E. , Simmons Mark P. , Chen Hua W. , Ficke Jennifer B. , Brown Tara E. , Nau Mark T. , Cebula Brennan R. , Kielstein Jan , Chung Kevin K. 
Published: July 2020

Objectives:
To determine whether Seraph-100 (Exthera Medical Corporation, Martinez, CA) treatment provides clinical benefit for severe coronavirus disease 2019 cases that require mechanical ventilation and vasopressor support.

Data Sources:
The first two patients in the United States treated with the novel Seraph-100 device. These cases were reviewed by the Food and Drug Administration prior to granting an emergency use authorization for treatment of coronavirus disease 2019.

Study Selection:
Case series.

Data Extraction:
Vasopressor dose, mean arterial pressure, temperature, interleukin-6, C-reactive protein, and other biomarker levels were documented both before and after Seraph-100 treatments.

Data Synthesis:
Vasopressor dose, temperature, interleukin-6, and C-reactive protein levels declined after Seraph-100 treatments. Severe acute respiratory syndrome coronavirus 2 viremia was confirmed in the one patient tested and cleared by the completion of treatments.

Conclusions:
Seraph-100 use may improve hemodynamic stability in coronavirus disease 2019 cases requiring mechanical ventilation and vasopressor support. These findings warrant future study of a larger cohort with the addition of mortality and total hospital day outcomes.
Dressings and Securement Devices of Peripheral Arterial Catheters in Intensive Care Units and Operating Theaters
Authors: Gravante Francesco , Lombardi Andrea , Gagliardi Anna Maria , Pucci Antonello , Latina Roberto 
Published: July 2020

Background
Hemodynamic monitoring, implemented by the placement of peripheral arterial catheters (PACs), is a characterizing aspect of the intensive care units. Peripheral arterial catheters can continually detect blood pressure and quickly conduct blood sampling. The use of PACs is generally considered safe, without serious complications. Currently, only 25% of the implanted catheters are actually subject to complications, including accidental removal, dislocation, occlusion, and infection. All of these complications arise from inadequate catheter stabilization at the level of the skin. This study aimed to summarize and describe the effectiveness and characteristics of dressings and securement devices for catheter stabilization.

Methods
A systematic review of literature from the following databases was conducted: MEDLINE, CINAHL, Cochrane, EMBASE, and OvidSP. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to guide article selection and reporting.

Results
Herein 626 articles were referred, with 5 directly related to the topic under discussion. We found 3 studies that describe PAC failure and 4 about dislodgement. We described 6 types of dressings or securement devices and classified them into 3 categories for classifying PAC dressings or securement devices. These were detected and grouped as adhesive tissues, sutureless devices, and transparent polyurethane dressings.

Conclusions
Current research indicates that transparent polyurethane dressings offer the most effective catheter stabilization, but adhesive tissues may constitute a valid alternative. However, there are limited high-quality studies about effective dressings and securement devices for PACs.
Consensus Statement on the Management of Waldenström Macroglobulinemia Patients During the COVID‐19 Pandemic
Authors: Talaulikar Dipti , Advani Ranjana H. , Branagan Andrew R. , Buske Christian , Dimopoulos Meletios A. , D'Sa Shirley , Kersten Maria J. , Leblond Veronique , Minnema Monique C. , Owen Roger G. , Palomba Maria Lia , Tedeschi Alessandra , Trotman Judith , Varettoni Marzia , Vos Josephine M. , Treon Steven P. , Kastritis Efstathios , Castillo Jorge J. 
Published: July 2020

AbstractIn the light of the COVID‐19 pandemic, the International Workshop on Waldenström Macroglobulinemia (IWWM) Treatment Recommendations Panel felt the need to provide a consensus statement for the management of Waldenström Macroglobulinemia (WM) patients during this challenging time. We followed the current recommendations by the American Society of Hematology, which have been modified accordingly to fit the specific realities associated with the management of WM. In this Consensus Statement, the Panel addresses questions related to treatment initiation, preferred therapies, minimizing visit to clinics and infusions centers, supportive care and guidance for WM patients in clinical trials. Finally, we also provide information on timing and appropriateness of testing and management of COVID‐19 infected patients, as well as ways to get physicians and patients involved in registry studies that could help others.