bluuebunny/crossref_metadata_2025_split huggingface dataset:
A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch
Authors: Sánchez-Busó Leonor , Yeats Corin A. , Taylor Benjamin , Goater Richard J. , Underwood Anthony , Abudahab Khalil , Argimón Silvia , Ma Kevin C. , Mortimer Tatum D. , Golparian Daniel , Cole Michelle J. , Grad Yonatan H. , Martin Irene , Raphael Brian H. , Shafer William M. , Town Katy , Wi Teodora , Harris Simon R. , Unemo Magnus , Aanensen David M. 
Published: April 2021

Abstract
Background
Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance.

Methods
Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization.

Results
AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern.

Conclusions
The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
Authors: Lau Billy T. , Pavlichin Dmitri , Hooker Anna C. , Almeda Alison , Shin Giwon , Chen Jiamin , Sahoo Malaya K. , Huang Chun Hong , Pinsky Benjamin A. , Lee Ho Joon , Ji Hanlee P. 
Published: April 2021

Abstract
Background
The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contact tracing.

Methods
Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies variants, and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints.

Results
We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and a combination of mutations that appear in only a small number of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of 100 SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome.

Conclusions
We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients and determined their general prevalence when compared to over 70,000 other strains. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.
Understanding patient needs and gaps in radiology reports through online discussion forum analysis
Authors: Alarifi Mohammad , Patrick Timothy , Jabour Abdulrahman , Wu Min , Luo Jake 
Published: April 2021

AbstractOur objective is to investigate patient needs and understand information gaps in radiology reports using patient questions that were posted on online discussion forums. We leveraged online question and answer platforms to collect questions posted by patients to understand current gaps and patient needs. We retrieved six hundred fifty-nine (659) questions using the following sites: Yahoo Answers, Reddit.com, Quora, and Wiki Answers. The questions retrieved were analyzed and the major themes and topics were identified. The questions retrieved were classified into eight major themes. The themes were related to the following topics: radiology report, safety, price, preparation, procedure, meaning, medical staff, and patient portal. Among the 659 questions, 35.50% were concerned with the radiology report. The most common question topics in the radiology report focused on patient understanding of the radiology report (62 of 234 [26.49%]), image visualization (53 of 234 [22.64%]), and report representation (46 of 234 [19.65%]). We also found that most patients were concerned about understanding the MRI report (32%; n = 143) compared with the other imaging modalities (n = 434). Using online discussion forums, we discussed major unmet patient needs and information gaps in radiology reports. These issues could be improved to enhance radiology design in the future.
Multiple Orbitoides d’Orbigny lineages in the Maastrichtian? Data from the Central Sakarya Basin (Turkey) and Arabian Platform successions (Southeastern Turkey and Oman)
Authors: Özcan Ercan , Yücel Ali Osman , Catanzariti Rita , Kayğılı Sibel , Okay Aral I. , Simmons Michael D. , Pignatti Johannes , Abbasi İftikhar Ahmed , Erbil Ümitcan 
Published: April 2021

AbstractThe standard reconstruction of species of Orbitoides d’Orbigny into a single lineage during the late Santonian to the end of the Maastrichtian is based upon morphometric data from Western Europe. An irreversible increase in the size of the embryonic apparatus, and the formation of a greater number of epi-embryonic chamberlets (EPC) with time, is regarded as the main evolutionary trends used in species discrimination. However, data from Maastrichtian Orbitoides assemblages from Central Turkey and the Arabian Platform margin (Southeastern Turkey and Oman) are not consistent with this record. The Maastrichtian Besni Formation of the Arabian Platform margin in Southeastern Turkey yields invariably biconvex specimens, with small, tri- to quadrilocular embryons and a small number of EPC, comparable to late Campanian Orbitoides medius (d’Archiac). The upper Maastrichtian Taraklı Formation from the Sakarya Basin of Central Turkey contains two distinct, yet closely associated forms of Orbitoides, easily differentiated by both external and internal features. Flat to biconcave specimens possess a small, tri- to quadrilocular embryonic apparatus of Orbitoides medius-type and a small number of EPC, whereas biconvex specimens possess a large, predominantly bilocular embryonic apparatus, and were assigned to Orbitoides ex. interc. gruenbachensis Papp–apiculatus Schlumberger based on morphometry. The flat to biconcave specimens belong to a long overlooked species Orbitoides pamiri Meriç, originally described from the late Maastrichtian of the Tauride Mountains in SW Turkey. This species is herein interpreted to be an offshoot from the main Orbitoides lineage during the Maastrichtian, as are forms that we term Orbitoides ‘medius’, since they recall this species, yet are younger than normal occurrence with the accepted morphometrically defined lineage. The consistent correlation between the external and internal test features in O. pamiri implies that the shape of the test is not an ecophenotypic variation, but appears to be biologically controlled. We, therefore, postulate that more than one lineage of Orbitoides exists during the Maastrichtian, with a lineage that includes O. ‘medius’ and O. pamiri displaying retrograde evolutionary features.
Carbon footprint reduction associated with a surgical outreach clinic
Authors: Forner David , Purcell Chad , Taylor Victoria , Noel Christopher W. , Pan Larry , Rigby Matthew H. , Corsten Martin , Trites Jonathan R. , Eskander Antoine , McDonald Ted , Taylor S. Mark 
Published: April 2021

Background Healthcare systems generate substantial carbon footprints that may be targeted to decrease greenhouse gas emissions. Outreach clinics may represent tools to assist in this reduction by optimizing patient related travel. Therefore, we sought to estimate the carbon footprint savings associated with a head and neck surgery outreach clinic. Methods This study was a cross-sectional survey of patient travel patterns to a surgical outreach clinic compared to a regional cancer treatment centre from December 2019 to February 2020. Participants completed a self-administered survey of 12 items eliciting travel distance, vehicle details, and ability to combine medical appointments. Canadian datasets of manufacturer provided vehicular efficiency were used to estimate carbon emissions for each participant. Geographic information systems were used for analyses. Results One hundred thirteen patients were included for analysis. The majority of patients (85.8%) used their own personal vehicle to travel to the outreach clinic. The median distance to the clinic and regional centre were 29.0 km (IQR 6.0–51.9) and 327.0 km (IQR 309.0–337.0) respectively. The mean carbon emission reduction per person was therefore 117,495.4 g (SD: 29,040.0) to 143,570.9 g (SD: 40,236.0). This represents up to 2.5% of an average individual's yearly carbon footprint. Fewer than 10% of patients indicated they were able to carpool or group their appointments. Conclusion Surgical outreach clinics decrease carbon footprints associated with patient travel compared to continued care at a regional centre. Further research is needed to determine possible interventions to further reduce carbon emissions associated with the surgical care of patients. Graphical Abstract
Underestimated responses of Walker circulation to ENSO-related SST anomaly in atmospheric and coupled models
Authors: Wang Xin-Yue , Zhu Jiang , Chang Chueh-Hsin , Johnson Nathaniel C. , Liu Hailong , Li Yadi , Song Chentao , Xin Meijiao , Zhou Yi , Li Xichen 
Published: April 2021

AbstractThe Pacific Walker circulation (WC) is a major component of the global climate system. It connects the Pacific sea surface temperature (SST) variability to the climate variabilities from the other ocean basins to the mid- and high latitudes. Previous studies indicated that the ENSO-related atmospheric feedback, in particular, the surface wind response is largely underestimated in AMIP and CMIP models. In this study, we further investigate the responses in the WC stream function and the sea level pressure (SLP) to the ENSO-related SST variability by comparing the responses in 45 AMIP and 63 CMIP models and six reanalysis datasets. We reveal a diversity in the performances of simulated SLP and WC between different models. While the SLP responses to the El Niño-related SST variability are well simulated in most of the atmospheric and coupled models, the WC stream function responses are largely underestimated in most of these models. The WC responses in the AMIP5/6 models capture ~ 75% of those in the reanalysis, whereas the CMIP5/6 models capture ~ 58% of the responses. Further analysis indicates that these underestimated circulation responses could be partially attributed to the biases in the precipitation scheme in both the atmospheric and coupled models, as well as the biases in the simulated ENSO-related SST patterns in the coupled models. One should pay special attention to these biases when studying the WC or the tropical atmosphere–ocean interactions using numerical models.
Damage to cardiac vasculature may be associated with breast cancer treatment-induced cardiotoxicity
Authors: Hoffman Rebecca K. , Kim Bang-Jin , Shah Payal D. , Carver Joseph , Ky Bonnie , Ryeom Sandra 
Published: April 2021

AbstractBackgroundBreast cancer is the most common female cancer worldwide. Effective therapies including doxorubicin and trastuzumab have improved survival, but are associated with a substantial risk of cardiovascular disease. Mechanisms underlying cancer treatment-induced cardiotoxicity (CTC) are poorly understood and have largely focused on cardiomyocyte damage, although other cellular populations in the heart such as the cardiac endothelium, may play an important role in cardiac damage. We treated a breast tumor-bearing mouse model with doxorubicin and trastuzumab to investigate the role of the cardiac endothelium in the development of CTC.MethodsImmune compromised mice were inoculated in the 4th mammary fat pad with human breast cancer cells overexpressing HER2 (BT474). When tumors were palpable, mice were treated weekly with doxorubicin (5 mg/kg) and trastuzumab (4 mg/kg). The cardiac phenotype of mice was assessed by echocardiography and histological evaluation of the heart. Cardiac vascular damage was assayed by in vivo permeability assays and primary cultures of murine cardiac endothelial cells were used to assay doxorubicin toxicity in vitro.ResultsThe growth of BT474 breast tumors in Balb/c Nude mice was suppressed upon treatment with doxorubicin and trastuzumab. Mice treated for 4 months with doxorubicin and trastuzumab maintained body weights, but demonstrated an echocardiographic phenotype consistent with preserved left ventricular (LV) ejection fraction, decreased LV mass and increased filling pressures (E/e’). Histological staining with Masson’s trichrome and Picrosirius red showed extensive fibrosis and increased collagen deposition in the ventricular myocardium surrounding blood vessels of treated mice compared to untreated mice. Evans blue permeability assays demonstrated increased cardiac vasculature permeability while primary cardiac endothelial cells exposed to doxorubicin in vitro showed increased cell death as compared to lung or liver endothelial cells.ConclusionsAn orthotopic mouse model of human breast cancer in Nude mice treated with doxorubicin and trastuzumab resulted in a cardiac vascular defect accompanied by preserved LV ejection fraction, decreased LV mass, suggesting mild diastolic dysfunction and cardiac remodeling consistent with subclinical cardiotoxicity. Our data suggest that cardiac endothelium is more sensitive to doxorubicin therapy as compared to other organ endothelium and cardiac endothelial damage may correlate with breast cancer treatment-induced cardiotoxicity.
Psychotropic medication prescribing in people with autism spectrum disorders with and without psychiatric comorbidity
Authors: Carthy Elliott , Ross Callum , Murphy David 
Published: April 2021

SUMMARYAutism spectrum disorders (ASDs) are a group of lifelong neurodevelopmental disorders characterised by difficulties in social interactions and social communication, and restricted and repetitive behaviours. Relative to the general population, individuals with ASDs are likely to be overrepresented in secure psychiatric care and custodial settings. Outcomes vary and can be problematic in the context of co-occurring intellectual disability, psychiatric disorder and challenging behaviours. To date, there is little in the way of specialised clinical guidance on the prescription of psychotropic medicines for individuals with ASDs, particularly information on any differences in efficacy and/or tolerability of specific medications. This review summarises the key research to date on the prescription of psychotropic medication in ASD with and without comorbid psychiatric or neurodevelopmental disorders, within the context of the existing clinical guidance. Some critical analysis is provided to aid clinicians in following a safe, effective and individualised approach to prescribing for people with ASDs.
Evidence of an interaction between FXR1 and GSK3β polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics
Authors: Rampino Antonio , Torretta Silvia , Gelao Barbara , Veneziani Federica , Iacoviello Matteo , Marakhovskaya Aleksandra , Masellis Rita , Andriola Ileana , Sportelli Leonardo , Pergola Giulio , Minelli Alessandra , Magri Chiara , Gennarelli Massimo , Vita Antonio , Beaulieu Jean Martin , Bertolino Alessandro , Blasi Giuseppe 
Published: April 2021

Abstract

Background
Genome-Wide Association Studies (GWASs) have identified several genes associated with Schizophrenia (SCZ) and exponentially increased knowledge on the genetic basis of the disease. In addition, products of GWAS genes interact with neuronal factors coded by genes lacking association, such that this interaction may confer risk for specific phenotypes of this brain disorder. In this regard, fragile X mental retardation syndrome-related 1 (FXR1) gene has been GWAS associated with SCZ. FXR1 protein is regulated by glycogen synthase kinase-3β (GSK3β), which has been implicated in pathophysiology of SCZ and response to antipsychotics (APs). rs496250 and rs12630592, two eQTLs (Expression Quantitative Trait Loci) of FXR1 and GSK3β, respectively, interact on emotion stability and amygdala/prefrontal cortex activity during emotion processing. These two phenotypes are associated with Negative Symptoms (NSs) of SCZ suggesting that the interaction between these SNPs may also affect NS severity and responsiveness to medication.

Methods
To test this hypothesis, in two independent samples of patients with SCZ, we investigated rs496250 by rs12630592 interaction on NS severity and response to APs. We also tested a putative link between APs administration and FXR1 expression, as already reported for GSK3β expression.

Results
We found that rs496250 and rs12630592 interact on NS severity. We also found evidence suggesting interaction of these polymorphisms also on response to APs. This interaction was not present when looking at positive and general psychopathology scores. Furthermore, chronic olanzapine administration led to a reduction of FXR1 expression in mouse frontal cortex.

Discussion
Our findings suggest that, like GSK3β, FXR1 is affected by APs while shedding new light on the role of the FXR1/GSK3β pathway for NSs of SCZ.
Higher Dispositional Optimism Predicts Better Health-Related Quality of Life After Esophageal Cancer Surgery: A Nationwide Population-Based Longitudinal Study
Authors: Liu Yangjun , Pettersson Erik , Schandl Anna , Markar Sheraz , Johar Asif , Lagergren Pernilla 
Published: April 2021

Abstract
Purpose
To assess whether higher dispositional optimism could predict better health-related quality of life (HRQL) after esophageal cancer surgery.

Methods
This Swedish nationwide longitudinal study included 192 patients who underwent esophagectomy for cancer. The exposure was dispositional optimism measured by the Life Orientation Test-Revised (LOT-R) at 1 year post-surgery. Patients were categorized into four subgroups (very low, moderately low, moderately high, and very high dispositional optimism) based on the quartile of the LOT-R sum score. The outcome was HRQL assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Esophago-Gastric module 25 (QLQ-OG25) at 1, 1.5, and 2 years post-surgery. Linear mixed-effects models, adjusted for potential confounders, were used to examine the mean score difference (MSD) with 95% confidence interval of HRQL among the four patient subgroups.

Results
Patients with very high dispositional optimism reported clinically relevantly better global quality of life, emotional function, and social function (MSD range 10–16) and less severe symptoms in pain, dyspnea, diarrhea, eating difficulty, anxiety, dry mouth, trouble with taste, worry about weight loss, and self-doubt about body image (MSD range − 9 to − 22) than patients with lower dispositional optimism. Patients with moderately high dispositional optimism reported clinically and statistically significantly better global quality of life (MSD 10) and less severe diarrhea (MSD − 9) than patients with lower dispositional optimism. Adjusted MSDs were constant over the three time points in all aspects except for eating difficulty.

Conclusions
Measuring dispositional optimism could help identify patients at higher risk of poor HRQL recovery after esophageal cancer surgery.