bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Autonomic Neuropathy Is Not Reversed by Euglycemia Following Islet Transplantation
Authors: Deshmukh Tejas , Emerson Peter , Anderson Patricia , Kizana Eddy , O’Connell Philip J. , Holmes-Walker D. Jane , Chong James J.H. 
Published: June 2020

Background.
Cardiac autonomic neuropathy (CAN) is a significant cause of morbidity and mortality for people with type 1 (T1D) and type 2 (T2D) diabetes. Heart rate variability (HRV) has been shown to be a marker of CAN with 24-hour Holter monitoring being a robust modality to assess HRV.

Methods.
To investigate the impact of hypoglycemia on CAN and its potential reversibility with islet transplantation, we compared HRV assessment by 24-hour Holter monitor on a total of 109 subjects from 5 cohorts: (1) T1D with recurrent severe hypoglycemia and on waiting list for islet transplant, (2) T1D following islet cell transplantation (ICT), (3) T2D without hypoglycemia, (4) individuals with prediabetes, and (5) controls without diabetes. SD of the normal-normal interval, square root of the mean squared differences of successive normal-normal intervals (rMSSD) and total spectral power were analyzed.

Results.
There was no significant difference in HRV parameters between T1D subjects and T1D post ICT suggesting CAN is not reversible at a median of 4 years postislet transplant. There was a significant difference in controls and T1D in rMSSD and between controls and T2D in total power. The differential effect on rMSSD in T1D and T2D suggests potential greater impact of hypoglycemia on rMSSD.

Conclusions.
Achieving euglycemia after ICT may not reverse CAN once established with no significant difference in HRV parameters at a median of 4 years postislet transplant. Differential effects of T1D as compared with T2D on CAN were identified.
Clinical Impact of Antecedent Bariatric Surgery on Liver Transplant Outcomes: A Retrospective Matched Case-control Study
Authors: Serrano Oscar K. , Peterson Kent J. , Vock David M. , Berglund Danielle , Kandaswamy Raja , Lake John R. , Pruett Timothy L. , Chinnakotla Srinath 
Published: June 2020

Background.
Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies.

Methods.
Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date.

Results.
We analyzed outcomes in 132 LT recipients (33 BS; 99 non-BS). The BS cohort comprised 26 (79%) women with a mean age of 52.4 years. The BS procedures included 20 Roux-en-Y gastric bypass (61%), 6 jejunoileal bypass (18%), 3 gastric band (9%), 2 sleeve gastrectomy (6%), and 1 duodenal switch (3%). The primary indications for LT listing were alcoholic cirrhosis (9; 27%), nonalcoholic steatohepatitis (7; 21%), hepatitis C (8; 24%), and hepatocellular carcinoma (3; 9%). At LT, body mass index for the BS cohort was 29.6, and MELD was 24. Compared with matched controls, BS recipients did not have longer LT length of hospital stay (17.8 versus 15.7 d, P = 0.71), longer intensive care unit length of stay (5.3 versus 4.1 d, P = 0.16), or higher 30-day complication rate (76% versus 85%, P = 0.43). Overall patient survival was similar (1- and 3-y survival was 90.1% and 75.9% for BS; 90.9% and 76.4% for non-BS, P = 0.34).

Conclusions.
A history of BS does not portend a deleterious effect on LT outcomes.
COVID-19 related concerns of people with long-term respiratory conditions: A qualitative study
Authors: Philip Keir EJ , Lonergan Bradley , Cumella Andrew , Farrington-Douglas Joe , Laffan Michael , Hopkinson Nicholas S 
Published: June 2020

ABSTRACTBACKGROUNDThe COVID-19 pandemic is having profound psychological impacts on populations globally, with increasing levels of stress, anxiety, and depression being reported, especially in people with pre- existing medical conditions who appear to be particularly vulnerable. There are limited data on the specific concerns people have about COVID-19 and what these are based on.METHODSThe aim of this study was to identify and explore the concerns of people with long-term respiratory conditions in the UK regarding the impact of the COVID-19 pandemic and how these concerns were affecting them. We conducted a thematic analysis of free text responses to the question “What are your main concerns about getting coronavirus?”, which was included in the British Lung Foundation/Asthma UK (BLF-AUK) partnership COVID-19 survey, conducted between the 1st and 8th of April. This was during the 3rd week of the UK’s initial social distancing measures.RESULTS7,039 responses were analysed, with respondents from a wide range of ages, gender, and all UK nations. Respondents reported having asthma (85%), COPD (9%), bronchiectasis (4%), interstitial lung disease (2%), or ‘other’ lung diseases (e.g. lung cancer) (1%). Four main themes were identified: 1) vulnerability to COVID-19; 2) anticipated experience of contracting COVID-19; 3) wide-reaching uncertainty; and 4) inadequate national response.CONCLUSIONSThe COVID-19 pandemic is having profound psychological impacts. The concerns we identified largely reflect objective, as well as subjective, aspects of the current situation. Hence, key approaches to reducing these concerns require changes to the reality of their situation, and are likely to include i) helping people optimise their health, limit risk of infection, and access necessities; ii) minimising the negative experience of disease where possible, iii) providing up-to-date, accurate and consistent information, iv) improving the government and healthcare response.
Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
Authors: Mikulska Malgorzata , Nicolini Laura Ambra , Signori Alessio , Di Biagio Antonio , Sepulcri Chiara , Russo Chiara , Dettori Silvia , Berruti arco , Sormani Maria Pia , Giacobbe Daniele Roberto , Vena Antonio , De Maria Andrea , Dentone Chiara , Taramasso Lucia , Mirabella Michele , Magnasco Laura , Mora Sara , Delfino Emanuele , Toscanini Federica , Balletto Elisa , Alessandrini Anna Ida , Baldi Federico , Briano Federica , Camera Marco , Dodi Ferdinando , Ferrazin Antonio , Labate Laura , Mazzarello Giovanni , Pincino Rachele , Portunato Federica , Tutino Stefania , Barisione Emanuela , Bruzzone Bianca , Orsi Andrea , Schenone Eva , Rosseti Nirmala , Sasso Elisabetta , Rin Giorgio Da , Pelosi Paolo , Beltramini Sabrina , Giacomini Mauro , Icardi Giancarlo , Gratarola Angelo , Bassetti Matteo 
Published: June 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy.The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome.MethodsThis observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW).ResultsOverall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n=29, 22.3%), methylprednisolone (n=45, 34.6%), or both (n=56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW0.48, 95%CI, 0.23-0.99; p=0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW0.41, 95%CI: 0.19-0.89, p=0.025.ConclusionEarly adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.
Ethnic variation in outcome of people hospitalised with Covid-19 in Wales (UK): A rapid analysis of surveillance data using Onomap, a name-based ethnicity classification tool
Authors: Thomas Daniel Rh , Orife Oghogho , Plimmer Amy , Williams Christopher , Karani George , Evans Meirion R , Longley Paul A , Janiec Janusz , Saltus Roiyah , Shankar A Giri 
Published: June 2020

AbstractThere is growing evidence that ethnic minorities in Europe are disproportionately affected by Covid-19. Using a name-based ethnicity classifier, we found that hospitalised Black, Asian and minority ethnic cases were younger and more likely to be admitted to intensive care (ICU). Pakistani, Bangladeshi and White - other than British or Irish, ethnic groups were most at risk. In this study, older age and male gender, but not ethnicity, were associated with death in hospitalised patients.
Diversity of Antimicrobial-Resistant Aeromonas Species Isolated from Aquatic Environments in Brazil
Authors: Conte Danieli , Palmeiro Jussara Kasuko , de Almeida Bavaroski Adriane , Rodrigues Luiza Souza , Cardozo Daiane , Tomaz Ana Paula , Camargo Josué Oliveira , Dalla-Costa Libera Maria 
Published: June 2020

ABSTRACTIn the present study, we characterized antimicrobial resistance profile and genetic relatedness of Aeromonas spp. isolated from healthcare and urban effluents, wastewater treatment plant (WWTP), and river water. We detected the presence of genes responsible for the resistance to β-lactam, quinolone, and aminoglycoside. Enterobacterial Repetitive Intergenic Consensus PCR and multilocus sequence typing (MLST) were carried out to differentiate the strains and multilocus phylogenetic analysis (MLPA) was used to identify species. A total of 28 Aeromonas spp. cefotaxime-resistant strains were identified that carried a variety of resistance determinants, including uncommon GES-type β-lactamases. Multidrug-resistant Aeromonas spp. were found in hospital wastewater, WWTP, and sanitary effluent. Among these isolates, we detected A. caviae producing GES-1 or GES-5, as well as A. veronii harboring GES-7 or GES-16. We successfully identified Aeromonas spp. by using MLPA and found that A. caviae was the most prevalent species (85.7%). In contrast, it was not possible to determine sequence type of all isolates, suggesting incompleteness of the Aeromonas spp. MLST database. Our findings reinforce the notion about the ability of Aeromonas spp. to acquire determinants of antimicrobial resistance from the environment. Such ability can be enhanced by the release of untreated healthcare effluents, in addition to the presence of antimicrobials, recognized as potential factors for the spread of resistance. Thus, Aeromonas spp. could be included as priority pathogens under the One Health concept.IMPORTANCEAeromonas species are native bacteria in aquatic ecosystems worldwide. However, they have also been isolated from humans and animals. Globally, aquatic environments have been affected by anthropogenic activities. For example, the excessive use of antimicrobials in medical and veterinary practice causes the development of bacterial resistance. In addition, eliminated hospital and sanitary effluents can also serve as potential sources of bacteria carrying antimicrobial resistance genes. Thereby, impacted environments play an important role in the transmission of these pathogens, their evolution, and dissemination of genes conferring resistance to antimicrobials. Aeromonas spp. have been reported as a reservoir of antimicrobial resistance genes in the environment. In this study, we identified a great repertoire of antimicrobial resistance genes in Aeromonas spp. from diverse aquatic ecosystems, including those that encode enzymes degrading broad-spectrum antimicrobials widely used to treat healthcare-associated infections. These are a public health threat as they may spread in the population.
Anti-inflammatory Activity of Lefamulin in a Lipopolysaccharide-Induced Lung Neutrophilia Model
Authors: Hafner Michael , Paukner Susanne , Wicha Wolfgang W. , Hrvačić Boška , Gelone Steven P. 
Published: June 2020

ABSTRACTLefamulin is a novel pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia. This study demonstrated anti-inflammatory activity of lefamulin in a murine lipopolysaccharide-induced lung neutrophilia model. Pretreatment of mice at clinically relevant lefamulin subcutaneous doses (35, 70, 140 mg/kg [free base]) followed by intranasal lipopolysaccharide challenge (5 μg/50 μL/mouse) demonstrated significant, dose-dependent reductions in total and neutrophil cell counts in bronchoalveolar lavage fluid samples, with reductions comparable to oral dexamethasone (0.5 mg/kg) pretreatment.
A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies
Authors: Tiu Gerald C. , Kerr Craig H. , Forester Craig M. , Krishnarao Pallavi S. , Rosenblatt Hannah D. , Raj Nitin , Zhulyn Olena , Bowen Margot E. , Shokat Leila , Attardi Laura D. , Ruggero Davide , Barna Maria 
Published: June 2020

SUMMARYIn ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes, such as limb and craniofacial defects as well as bone marrow failure. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining comprehensive mouse genetics andin vivoribosome profiling, we observe limb patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos and uncover corresponding selective translational changes of transcripts controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are reconciled by the unexpected identification that p53 functions as a master regulator of protein synthesis through transcriptional activation of 4E-BP1. 4E-BP1, a key regulator of translation, in turn, facilitates selective changes in the translatome downstream of p53 and thereby explains, at least in part, how RP haploinsufficiency elicits specificity to gene expression. These results provide an integrative model to explain howin vivotissue-specific phenotypes emerge from a mutation in a ribosome component.
Fungi ligE-typeglutathione S-transferaseshorizontally transferred into plants and a protozoan
Authors: Li Dan , Zhang Meng 
Published: June 2020

AbstractHorizontal gene transfers (HGT) were considered as common evolution approaches for organisms. However, most HGT especially those HGT among distant species, like microbes to plants, were over-estimated because they were just identified based on the criteria of Blast searches and gene tree–species tree reconciliation. Recently, a ligE-type glutathione S-transferase (GST),Fhb7-GSTwas considered as an HGT fromEpichloëtoThinopyrum elongatum. To confirm and clarify the occurring patterns of this HGT, homologue searches were conducted. AlthoughTeFhb7-GSTwas not found in other plants, ligE-GSTs were found in not only plants but also an ameba protozoan. Additionally,ligE-GSTswere likely to horizontally transfer from fungi to other organisms. LigE-GSTs evolve in various fungi, but they only exist in some liverworts and green algae. Interestingly, all theseligE-GSTgenes in these plants share more than 90% similarities with that from fungusConiosporium apollinis. More than that, the protozoan homologue fromAcanthamoeba castellaniihave 94.9% similiarity with that fromC. apollinis. Actually, only a few substitutions were found in two homologues except a 111-bp lost inA. castellanii ligE-GST. All these results suggested HGT is an important evolutionary method for all organisms. Notably, natural HGT remind us to reevaluate the transgenic crops.
Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis
Authors: Mekonnen Gebeyaw G. , Tedla Bemnet A. , Pickering Darren , Becker Luke , Wang Lei , Zhan Bin , Bottazzi Maria Elena , Loukas Alex , Sotillo Javier , Pearson Mark S. 
Published: June 2020

AbstractHelminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) from adultSchistosoma haematobiumworms. A total of 57 and 330 proteins were identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such asSm-TSP2,Sm23, glutathione S-tranferase, saposins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.
Structure-aware Protein Solubility Prediction From Sequence Through Graph Convolutional Network And Predicted Contact Map
Authors: Chen Jianwen , Zheng Shuangjia , Zhao Huiying , Yang Yuedong 
Published: June 2020

AbstractMotivationProtein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information.ResultsIn this study, we have developed a new structure-aware method to predict protein solubility by attentive graph convolutional network (GCN), where the protein topology attribute graph was constructed through predicted contact maps from the sequence. GraphSol was shown to substantially out-perform other sequence-based methods. The model was proven to be stable by consistent R2of 0.48 in both the cross-validation and independent test of theeSOLdataset. To our best knowledge, this is the first study to utilize the GCN for sequence-based predictions. More importantly, this architecture could be extended to other protein prediction tasks.AvailabilityThe package is available athttp://biomed.nscc-gz.cnContactyangyd25@mail.sysu.edu.cnSupplementary informationSupplementary data are available atBioinformaticsonline.
SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes
Authors: Lieu Yen K. , Liu Zhaoqi , Ali Abdullah M. , Wei Xin , Penson Alex , Zhang Jian , An Xiuli , Rabadan Raul , Raza Azra , Manley James L. , Mukherjee Siddhartha 
Published: June 2020

ABSTRACTSF3B1 is the most frequently mutated RNA splicing factor in multiple neoplasms, including ~25% of myelodysplastic syndromes (MDS) patients. Mortality in MDS frequently results from severe anemia, but the underlying mechanism is largely unknown. Here we elucidate the detailed, elusive pathway by whichSF3B1mutations cause anemia. We demonstrate, in CRISPR-edited cell models, normal human primary cells, and MDS patient cells, that mutant SF3B1 induces a splicing error in transcripts encoding the kinase MAP3K7, resulting in reduced MAP3K7 protein levels and deactivation of downstream target p38 MAPK. We show that disruption of this MAP3K7-p38 MAPK pathway leads to premature downregulation of GATA1, a master regulator of erythroid differentiation, and that this is sufficient to trigger accelerated differentiation and apoptosis. As a result, the overproduced, late staged erythroblasts undergo apoptosis and are unable to mature in the bone marrow. Our findings provide a detailed mechanism explaining the origins of anemia in MDS patients harboringSF3B1mutations.
A Total-Group Phylogenetic Metatree for Cetacea and the Importance of Fossil Data in Diversification Analyses
Authors: Lloyd Graeme T. , Slater Graham J. 
Published: June 2020

AbstractPhylogenetic trees provide a powerful framework for testing macroevolutionary hypotheses, but it is becoming increasingly apparent that inferences derived from extant species alone can be highly misleading. Trees incorporating living and extinct taxa are are needed to address fundamental questions about the origins of diversity and disparity but it has proved challenging to generate robust, species–rich phylogenies that include large numbers of fossil taxa. As a result, most studies of diversification dynamics continue to rely on molecular phylogenies. Here, we extend and apply a recently developed meta–analytic approach for synthesizing previously published phylogenetic studies to infer a well–resolved set of species level, time–scaled phylogenetic hypotheses for extinct and extant cetaceans (whales, dolphins and allies). Our trees extend sampling from the ∼ 90 extant species to over 400 living and extinct species, and therefore allow for more robust inference of macroevolutionary dynamics. While the diversification scenarios we recover are broadly concordant with those inferred from molecular phylogenies they differ in critical ways, most notably in the relative contributions of extinction and speciation rate shifts in driving rapid radiations. Supertrees are often viewed as poor substitute for phylogenies inferred directly from character data but the metatree pipeline overcomes many of the past criticisms leveled at these approaches. Meta–analytic phylogenies provide the most immediate route for integrating fossils into macroevolutionary analyses, the results of which range from untrustworthy to nonsensical without them.