bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life history of the Big Sandy crayfish Cambarus callainus Thoma, Loughman & Fetzner, 2014 (Decapoda: Astacoidea: Cambaridae), an imperiled crayfish in the central Appalachian coalfields, USA
Authors: Vopal Christopher G , Loughman Zachary J 
Published: May 2021

AbstractThe Big Sandy crayfish, Cambarus callainusThoma, Loughman & Fetzner, 2014, endemic to the Big Sandy River basin in the central Appalachians, USA, was listed by the United States Fish & Wildlife Service as threatened under the Endangered Species Act in 2016 due to limited and declining range. In March 2018 we began a twelve-month study of the species at the Dry Fork watershed in West Virginia, USA and the Russell Fork watershed in Virginia, USA to document annual life history, reveal if seasonal molting occurs, determine the reproductive season and fecundity, and define its life history strategy. Egg-bearing females were only captured in August; however, a single female was collected with free-living craylings in April, suggesting possible overwintering maternal care or a potential early spring oviposition event. Mating likely occurred between May and June and potentially into the fall and early winter. Five to six size-class cohorts were observed, and we speculate that C. callainus could live up to five years or more. Analysis of morphometric data suggests that females undergo form change, displaying larger chelae and wider abdomens. The smallest Form I male collected had a total carapace length (TCL) of 31.5 mm and the smallest Form I female 32.8 mm. The largest male collected was Form I with a TCL of 55.9 mm. Similar to other species of Cambarus, C. callainus appears to exhibit K-selected life history traits: Fewer and larger eggs, relatively longer maternal care, larger but slow growing, and long lived. The life history information described should prove invaluable to those engaging in conservation efforts for this threatened species.
A Chromosome-Level Assembly of Blunt Snout Bream (Megalobrama amblycephala) Genome Reveals an Expansion of Olfactory Receptor Genes in Freshwater Fish
Authors: Liu Han , Chen Chunhai , Lv Maolin , Liu Ning , Hu Yafei , Zhang Hailin , Enbody Erik D , Gao Zexia , Andersson Leif , Wang Weimin 
Published: May 2021

Abstract
The number of olfactory receptor genes (ORs), which are responsible for detecting diverse odor molecules varies extensively among mammals as a result of frequent gene gains and losses that contribute to olfactory specialization. However, how OR expansions/contractions in fish are influenced by habitat and feeding habit and which OR subfamilies are important in each ecological niche is unknown. Here, we report a major OR expansion in a freshwater herbivorous fish, Megalobrama amblycephala, using a highly contiguous, chromosome-level assembly. We evaluate the possible contribution of OR expansion to habitat and feeding specialization by comparing the OR repertoire in 28 phylogenetically and ecologically diverse teleosts. In total, we analyzed &gt; 4,000 ORs including 3,253 intact, 122 truncated, and 913 pseudogenes. The number of intact ORs is highly variable ranging from 20 to 279. We estimate that the most recent common ancestor of Osteichthyes had 62 intact ORs, which declined in most lineages except the freshwater Otophysa clade that has a substantial expansion in subfamily β and ε ORs. Across teleosts, we found a strong association between duplications of β and ε ORs and freshwater habitat. Nearly, all ORs were expressed in the olfactory epithelium (OE) in three tested fish species. Specifically, all the expanded β and ε ORs were highly expressed in OE of M. amblycephala. Together, we provide molecular and functional evidence for how OR repertoires in fish have undergone gain and loss with respect to ecological factors and highlight the role of β and ε OR in freshwater adaptation.
CRISPRloci: comprehensive and accurate annotation of CRISPR–Cas systems
Authors: Alkhnbashi Omer S , Mitrofanov Alexander , Bonidia Robson , Raden Martin , Tran Van Dinh , Eggenhofer Florian , Shah Shiraz A , Öztürk Ekrem , Padilha Victor A , Sanches Danilo S , de Carvalho André C P L F , Backofen Rolf 
Published: May 2021

Abstract
CRISPR–Cas systems are adaptive immune systems in prokaryotes, providing resistance against invading viruses and plasmids. The identification of CRISPR loci is currently a non-standardized, ambiguous process, requiring the manual combination of multiple tools, where existing tools detect only parts of the CRISPR-systems, and lack quality control, annotation and assessment capabilities of the detected CRISPR loci. Our CRISPRloci server provides the first resource for the prediction and assessment of all possible CRISPR loci. The server integrates a series of advanced Machine Learning tools within a seamless web interface featuring: (i) prediction of all CRISPR arrays in the correct orientation; (ii) definition of CRISPR leaders for each locus; and (iii) annotation of cas genes and their unambiguous classification. As a result, CRISPRloci is able to accurately determine the CRISPR array and associated information, such as: the Cas subtypes; cassette boundaries; accuracy of the repeat structure, orientation and leader sequence; virus-host interactions; self-targeting; as well as the annotation of cas genes, all of which have been missing from existing tools. This annotation is presented in an interactive interface, making it easy for scientists to gain an overview of the CRISPR system in their organism of interest. Predictions are also rendered in GFF format, enabling in-depth genome browser inspection. In summary, CRISPRloci constitutes a full suite for CRISPR–Cas system characterization that offers annotation quality previously available only after manual inspection.
A cleavage-based surrogate reporter for the evaluation of CRISPR–Cas9 cleavage efficiency
Authors: Jung Soo Bin , Lee Chae young , Lee Kwang-Ho , Heo Kyu , Choi Si Ho 
Published: May 2021

Abstract
CRISPR–Cas9 is a powerful tool for genome engineering, but its efficiency largely depends on guide RNA (gRNA). There are multiple methods available to evaluate the efficiency of gRNAs, including the T7E1 assay, surveyor nuclease assay, deep sequencing, and surrogate reporter systems. In the present study, we developed a cleavage-based surrogate that we have named the LacI-reporter to evaluate gRNA cleavage efficiency. The LacI repressor, under the control of the EF-1α promoter, represses luciferase or EGFP reporter expression by binding to the lac operator. Upon CRISPR–Cas9 cleavage at a target site located between the EF-1α promoter and the lacI gene, repressor expression is disrupted, thereby triggering luciferase or EGFP expression. Using this system, we can quantitate gRNA cleavage efficiency by assessing luciferase activity or EGFP expression. We found a strong positive correlation between the cleavage efficiency of gRNAs measured using this reporter and mutation frequency, measured using surveyor and deep sequencing. The genome-editing efficiency of gRNAs was validated in human liver organoids. Our LacI-reporter system provides a useful tool to select efficient gRNAs for genome editing.
Homologous recombination, cancer and the ‘RAD51 paradox’
Authors: Matos-Rodrigues Gabriel , Guirouilh-Barbat Josée , Martini Emmanuelle , Lopez Bernard S 
Published: May 2021

Abstract
Genetic instability is a hallmark of cancer cells. Homologous recombination (HR) plays key roles in genome stability and variability due to its roles in DNA double-strand break and interstrand crosslink repair, and in the protection and resumption of arrested replication forks. HR deficiency leads to genetic instability, and, as expected, many HR genes are downregulated in cancer cells. The link between HR deficiency and cancer predisposition is exemplified by familial breast and ovarian cancers and by some subgroups of Fanconi anaemia syndromes. Surprisingly, although RAD51 plays a pivotal role in HR, i.e., homology search and in strand exchange with a homologous DNA partner, almost no inactivating mutations of RAD51 have been associated with cancer predisposition; on the contrary, overexpression of RAD51 is associated with a poor prognosis in different types of tumours. Taken together, these data highlight the fact that RAD51 differs from its HR partners with regard to cancer susceptibility and expose what we call the ‘RAD51 paradox’. Here, we catalogue the dysregulations of HR genes in human pathologies, including cancer and Fanconi anaemia or congenital mirror movement syndromes, and we discuss the RAD51 paradox.
Impact of Bamlanivimab Monoclonal Antibody Treatment on Hospitalization and Mortality Among Nonhospitalized Adults With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Bariola J Ryan , McCreary Erin K , Wadas Richard J , Kip Kevin E , Marroquin Oscar C , Minnier Tami , Koscumb Stephen , Collins Kevin , Schmidhofer Mark , Shovel Judith A , Wisniewski Mary Kay , Sullivan Colleen , Yealy Donald M , Nace David A , Huang David T , Haidar Ghady , Khadem Tina , Linstrum Kelsey , Seymour Christopher W , Montgomery Stephanie K , Angus Derek C , Snyder Graham M 
Published: May 2021

Abstract

Background
Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications.

Methods
In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression.

Results
Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24–0.69; P &lt; .001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35–0.82; P = .004). The results were most strongly associated with patients age 65 years and older.

Conclusions
Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19.
Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older
From Rab to Raab: The Construction of the Office of First Secretary of State
Authors: Thornton Stephen , Kirkup Jonathan 
Published: May 2021

Abstract
Through information gained from interviews with key political actors, archival research and close examination of biographical material, this article aims to provide the first detailed account of what it means to be the British First Secretary of State. Sometimes regarded simply as a synonym for Deputy Prime Minister, it will be demonstrated that the reality is far more complicated. Not all First Secretaries have been regarded as the Prime Minister’s second-in-command, indeed there have been many years where the post has ceased to exist. Yet, at other times, First Secretaries have led the country, albeit briefly. The main argument to be made is that the office of First Secretary of State is only as important as the person holding that office is perceived to be important, but there is potential for that to change.
Spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina
Authors: Chen Zhong , Stanbouly Seta , Nishiyama Nina C , Chen Xin , Delp Michael D , Qiu Hongyu , Mao Xiao W , Wang Charles 
Published: May 2021

Abstract
Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight. The purpose of this study was to determine whether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock. The mice were flown for 37 days in animal enclosure modules on the International Space Station; ground-based control animals were maintained under similar housing conditions. Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. We found that a large number of genes were differentially methylated with spaceflight, whereas there were fewer differentially expressed genes at the transcriptome level. Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered. Our results indicated that spaceflight decelerated the retinal epigenetic clock. This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels, and such changes could be involved in the etiology of eye-related disorders among astronauts.
Nitric oxide coordinates growth, development, and stress response via histone modification and gene expression
Authors: Ageeva-Kieferle Alexandra , Georgii Elisabeth , Winkler Barbro , Ghirardo Andrea , Albert Andreas , Hüther Patrick , Mengel Alexander , Becker Claude , Schnitzler Jörg-Peter , Durner Jörg , Lindermayr Christian 
Published: May 2021

Abstract
Nitric oxide (NO) is a signaling molecule with multiple regulatory functions in plant physiology and stress response. In addition to direct effects on transcriptional machinery, NO executes its signaling function via epigenetic mechanisms. We report that light intensity-dependent changes in NO correspond to changes in global histone acetylation (H3, H3K9, and H3K9/K14) in Arabidopsis (Arabidopsis thaliana) wild-type leaves, and that this relationship depends on S-nitrosoglutathione reductase and histone deacetylase 6 (HDA6). The activity of HDA6 was sensitive to NO, demonstrating that NO participates in regulation of histone acetylation. Chromatin immunoprecipitation sequencing and RNA-seq analyses revealed that NO participates in the metabolic switch from growth and development to stress response. This coordinating function of NO might be particularly important in plant ability to adapt to a changing environment, and is therefore a promising foundation for mitigating the negative effects of climate change on plant productivity.
Researcher experiences in practice-based interdisciplinary research
Authors: Leigh Jennifer , Brown Nicole 
Published: May 2021

Abstract
This article reports on a study that followed up on an initial interdisciplinary project and focused specifically on the experiences of researchers involved in practice-based interdisciplinary research. We share an approach to research evaluation that focuses on the experiences of those conducting the research rather than the outputs. The study allowed those involved in the initial successful project to reflect post hoc on their experiences. We show that neglecting fundamental conceptions about how the research is conceptualized can lead to challenges with the research itself. In addition to alternative understandings of research and concepts, practical and logistical issues, whilst seeming trivial, feed into communication issues such as misunderstanding of terms and language. We argue that tensions and confusions around the very nature of the research—what was being researched, and what was valued as research, epistemological differences between the disciplinary perspectives—need to be explored and interrogated in order to maximize the benefits of interdisciplinary research. We conclude with considerations of the relationship between interdisciplinary research in a team and identity work of team members, and the implications this may have for research design, an area of research evaluation that certainly needs further exploration.
A systematic review and network meta-analysis of the safety of early interventional treatments in rheumatoid arthritis
Authors: Adas Maryam A , Allen Victoria B , Yates Mark , Bechman Katie , Clarke Benjamin D , Russell Mark D , Rutherford Andrew I , Cope Andrew P , Norton Sam , Galloway James B 
Published: May 2021

Abstract

Objectives
To evaluate the safety of treatment strategies in patients with early RA.

Methods
Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA).

Results
From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates.

Conclusion
The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful.
A Diagnosis and Biotype Comparison Across the Psychosis Spectrum: Investigating Volume and Shape Amygdala-Hippocampal Differences from the B-SNIP Study
Authors: Guimond Synthia , Gu Feng , Shannon Holly , Kelly Sinead , Mike Luke , Devenyi Gabriel A , Chakravarty M Mallar , Sweeney John A , Pearlson Godfrey , Clementz Brett A , Tamminga Carol , Keshavan Matcheri 
Published: May 2021

Abstract

Objective
Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification.

Methods
A total of 811 participants from 6 sites were included: probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations.

Results
When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1.

Conclusion
These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.
A Machine Learning Classifier Improves Mortality Prediction Compared With Pediatric Logistic Organ Dysfunction-2 Score: Model Development and Validation
Authors: Prince Remi D. , Akhondi-Asl Alireza , Mehta Nilesh M. , Geva Alon 
Published: May 2021

Objectives:
To determine whether machine learning algorithms can better predict PICU mortality than the Pediatric Logistic Organ Dysfunction-2 score.

Design:
Retrospective study.

Setting:
Quaternary care medical-surgical PICU.

Patients:
All patients admitted to the PICU from 2013 to 2019.

Interventions:
None.

Measurements and Main Results:
We investigated the performance of various machine learning algorithms using the same variables used to calculate the Pediatric Logistic Organ Dysfunction-2 score to predict PICU mortality. We used 10,194 patient records from 2013 to 2017 for training and 4,043 patient records from 2018 to 2019 as a holdout validation cohort. Mortality rate was 3.0% in the training cohort and 3.4% in the validation cohort. The best performing algorithm was a random forest model (area under the receiver operating characteristic curve, 0.867 [95% CI, 0.863–0.895]; area under the precision-recall curve, 0.327 [95% CI, 0.246–0.414]; F1, 0.396 [95% CI, 0.321–0.468]) and significantly outperformed the Pediatric Logistic Organ Dysfunction-2 score (area under the receiver operating characteristic curve, 0.761 [95% CI, 0.713–0.810]; area under the precision-recall curve (0.239 [95% CI, 0.165–0.316]; F1, 0.284 [95% CI, 0.209–0.360]), although this difference was reduced after retraining the Pediatric Logistic Organ Dysfunction-2 logistic regression model at the study institution. The random forest model also showed better calibration than the Pediatric Logistic Organ Dysfunction-2 score, and calibration of the random forest model remained superior to the retrained Pediatric Logistic Organ Dysfunction-2 model.

Conclusions:
A machine learning model achieved better performance than a logistic regression-based score for predicting ICU mortality. Better estimation of mortality risk can improve our ability to adjust for severity of illness in future studies, although external validation is required before this method can be widely deployed.