bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 infections and outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers
Authors: Hultcrantz Malin , Richter Joshua , Rosenbaum Cara , Patel Dhwani , Smith Eric , Korde Neha , Lu Sydney , Mailankody Sham , Shah Urvi , Lesokhin Alexander , Hassoun Hani , Tan Carlyn , Maura Francesco , Derkacs Andriy , Diamond Benjamin , Rossi Adriana , Pearse Roger N. , Madduri Deepu , Chari Ajai , Kaminetsky David , Braunstein Marc , Gordillo Christian , Davies Faith , Jagannath Sundar , Niesvizky Ruben , Lentzsch Suzanne , Morgan Gareth , Landgren Ola 
Published: June 2020

AbstractImportanceNew York City is a global epicenter for the SARS-CoV-2 outbreak with a significant number of individuals infected by the virus. Patients with multiple myeloma have a compromised immune system, due to both the disease and anti-myeloma therapies, and may therefore be particularly susceptible to coronavirus disease 2019 (COVID-19); however, there is limited information to guide clinical management.ObjectiveTo assess risk factors and outcomes of COVID-19 in patients with multiple myeloma.DesignCase-series.SettingFive large academic centers in New York City.ParticipantsPatients with multiple myeloma and related plasma cell disorders who were diagnosed with COVID-19 between March 10th, 2020 and April 30th,2020.ExposuresClinical features and risk factors were analyzed in relation to severity of COVID-19.Main Outcomes and MeasuresDescriptive statistics as well as logistic regression were used to estimate disease severity reflected in hospital admissions, intensive care unit (ICU) admission, need for mechanical ventilation, or death.ResultsOf 100 multiple myeloma patients (male 58%; median age 68, range 41-91) diagnosed with COVID-19, 74 (74%) were admitted; of these 13 (18%) patients were placed on mechanical ventilation, and 18 patients (24%) expired. None of the studied risk factors were significantly associated (P>0.05) with adverse outcomes (ICU-admission, mechanical ventilation, or death): hypertension (N=56) odds ratio (OR) 2.3 (95% confidence interval [CI] 0.9-5.9); diabetes (N=18) OR 1.1 (95% CI 0.3-3.2); age >65 years (N=63) OR 2.0 (95% CI 0.8-5.3); high dose melphalan with autologous stem cell transplant <12 months (N=7) OR 1.2 (95% CI 0.2-7.4), IgG<650 mg/dL (N=42) OR=1.2 (95% CI 0.4-3.1). In the entire series of 127 patients with plasma cell disorders, hypertension was significantly associated with the combined end-point (OR 3.4, 95% CI 1.5-8.1).Conclusions and RelevanceAlthough multiple myeloma patients have a compromised immune system due to both the disease and therapy; in this largest disease specific cohort to date of patients with multiple myeloma and COVID-19, compared to the general population, we found risk factors for adverse outcome to be shared and mortality rates to be within the higher range of officially reported mortality rates.
Microsomal reductase activity in patients with thyroid neoplasms
Authors: Proskurnina Elena V. , Fedorova Maria V. , Sozarukova Madina M. , Mitichkin Aleksandr E. , Panteleev Igor V. , Svetlov Evgeny V. 
Published: June 2020

AbstractObjectiveCytochrome b5 reductase (CYB5R) and cytochrome P450 reductase (CYPOR) play an important role in cell metabolism; however, their role in thyroid hormonogenesis and carcinogenesis has not been studied. The activity of CYB5R correlates with metastasizing in breast cancer, but there are no similar studies for CYB5R and CYPOR for thyroid cancer. The aim was to assess the activity of CYB5R and CYPOR in thyroid tissues in benign and malignant thyroid neoplasms.Methods36 patients with thyroid neoplasms participated in the study. The control euthyroid goiter group included 10 patients; the thyrotoxic nodular goiter group included 14 patients; the papillary thyroid cancer T1-2N0-1M0 (PTC) group included 12 patients. The activity of CYB5R and CYPOR was assessed with lucigenin-enhanced chemiluminescence stimulated by NADH and NADPH, respectively.ResultsThe activity of CYB5R and CYPOR increased several times in thyrotoxicosis and approximately by an order of magnitude in some cases of PTC, but the activity change of CYPOR was more pronounced compared to CYB5R. For the PTC group, the subgroups with low and high activity of microsomal reductases were detected. Microsomal reductases in follicular adenoma was 2–4-fold less active compared to nontoxic goiter and the low-activity PTC group.ConclusionsActivity of microsomal reductases varies in thyroid pathology and can serve as a diagnostic and prognostic parameter in papillary thyroid cancer.
A Diffusion tensor imaging study to compare normative fractional anisotropy values with patients suffering from Parkinson’s disease in the brain grey and white matter
Authors: Kotian Rahul P , Prakashini K , Nair N Sreekumaran 
Published: June 2020

AbstractBackgroundDiffusion tensor imaging (DTI) appears as a sensitive method to study Parkinson’s disease (PD) pathophysiology and severity. Fractional anisotropy (FA) value is one of the scalar derivatives of DTI used to find out anisotropy within a voxel in a tissue and used for determining white matter integrity in aging and neurodegenerative diseases. We studied DTI derived FA in early PD subjects as their routine MRI scans were normal.Methods40 patients with early PD and 40 healthy controls were employed to evaluate changes in microstructural white and grey matter in the brain’s using DTI derived FA values. Comparison of FA values in the brain’s white and grey matter of patients with PD and age matched controls at the corpus callosum, centrum semiovale, pons, putamen, caudate nucleus, substantia nigra, cerebral peduncles and cerebellar peduncles, was done using a region of interest (ROI) technique, with b-value 1000s/mm2 and TE=100 milliseconds using 1.5T MRI system.ResultsPD patients showed differences in FA values in both the grey and white matter areas of the brain’s compared to healthy controls. Our study revealed the presence of damage in the substantia nigra, corpus callosum, putamen and cerebral peduncles mainly in the PD group.ConclusionOur findings indicate that DTI and region of interest (ROI) methods can be used in patients with early PD to study microstructural alterations mainly in the substantia nigra, putamen and corpus callosum.
Global RNA-seq identified FBXL8 as a novel E3 ligase which modulates tumor suppressors to promote BRCA advancement
Authors: Chang Shu-Chun , Hsu Wayne , Su Emily Chia-Yu , Hung Chin-Sheng , Ding Jeak Ling 
Published: June 2020

AbstractThe initiation and progression of breast cancer (BRCA) is associated with inflammation and immune-overactivation. The E3 ubiquitin ligase is known to subtly balance immune-overactivation and pro-tumorigenesis. Here, by global transcriptional profiling of BRCA patient tissues, we identified a signature expression profile of F-box factors, of which FBXL8 emerged as a novel key component of E3 ligase. Our ex vivo studies (n=1349) indicate that FBXL8 promotes tumorigenesis and its level escalates with BRCA advancement. Knockdown of FBXL8 caused: (i) accumulation of two tumor-suppressors,CCND2 and IRF5, suggesting their collaborative regulation of BRCA status, (ii) intrinsic apoptosis in BRCA, (iii) inhibition of cell migration and invasion and (iv) downregulation of cancer-promoting cytokines/ chemokines; all of these effects curtailed the tumor microenvironment and suppressed cancer progression. Our findings highlight the translational impact of exploiting FBXL8 and its interaction partners (CCND2 and IRF5) for developing anti-cancer strategies and potential therapeutics to limit BRCA progression.
Using machine learning to predict COVID-19 infection and severity risk among 4,510 aged adults: a UK Biobank cohort study
Authors: Willette Auriel A. , Willette Sara A. , Wang Qian , Pappas Colleen , Klinedinst Brandon S. , Le Scott , Larsen Brittany , Pollpeter Amy , Li Tianqi , Brenner Nicole , Waterboer Tim 
Published: June 2020

AbstractBackgroundMany risk factors have emerged for novel 2019 coronavirus disease (COVID-19). It is relatively unknown how these factors collectively predict COVID-19 infection risk, as well as risk for a severe infection (i.e., hospitalization).MethodsAmong aged adults (69.3 ± 8.6 years) in UK Biobank, COVID-19 data was downloaded for 4,510 participants with 7,539 test cases. We downloaded baseline data from 10-14 years ago, including demographics, biochemistry, body mass, and other factors, as well as antibody titers for 20 common to rare infectious diseases. Permutation-based linear discriminant analysis was used to predict COVID-19 risk and hospitalization risk. Probability and threshold metrics included receiver operating characteristic curves to derive area under the curve (AUC), specificity, sensitivity, and quadratic mean.ResultsThe “best-fit” model for predicting COVID-19 risk achieved excellent discrimination (AUC=0.969, 95% CI=0.934-1.000). Factors included age, immune markers, lipids, and serology titers to common pathogens like human cytomegalovirus. The hospitalization “best-fit” model was more modest (AUC=0.803, 95% CI=0.663-0.943) and included only serology titers.ConclusionsAccurate risk profiles can be created using standard self-report and biomedical data collected in public health and medical settings. It is also worthwhile to further investigate if prior host immunity predicts current host immunity to COVID-19.
Neuroinflammation in the normal appearing white matter of multiple sclerosis brain causes abnormalities at the node of Ranvier
Authors: Delgado Patricia Gallego , James Rachel , Browne Eleanor , Meng Joanna , Umashankar Swetha , Picon Carmen , Mazarakis Nicholas D. , Faisal A. Aldo , Howell Owain W. , Reynolds Richard 
Published: June 2020

AbstractChanges to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of MS brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. These pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the lymphotoxin-α (LTα) and interferon-γ (IFNγ) genes. We show that tumour necrosis factor (TNF), IFNγ and glutamate can provoke paranodal elongation in cerebellar slice cultures, which could be reversed by an NMDA blocker. When these changes were inserted into a computational model to simulate axonal conduction, a rapid decrease in velocity was observed, reaching conduction failure in small diameter axons. We suggest that glial cells activated by proinflammatory cytokines can produce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and conduction deficits.
Genome modularization reveals overlapped gene topology is necessary for efficient viral reproduction
Authors: Wright Bradley W , Ruan Juanfang , Molloy Mark P , Jaschke Paul R 
Published: June 2020

ABSTRACTSequence overlap between two genes is common across all genomes, with viruses having high proportions of these gene overlaps. The biological function and fitness effects of gene overlaps are not fully understood, and their effects on gene cluster and genome-level refactoring are unknown. The bacteriophage ϕX174 genome has ∼26% of nucleotides involved in encoding more than one gene. In this study we use an engineered ϕX174 phage containing a genome with all gene overlaps removed, to show that gene overlap is critical to maintaining optimal viral fecundity. Through detailed phenotypic measurements we reveal that genome modularization in ϕX174 causes virion replication, stability, and attachment deficiencies. Quantitation of the complete phage proteome across an infection cycle reveals almost half the proteins display abnormal expression patterns. Taken together, we have for the first time comprehensively demonstrated that gene modularization severely perturbs the coordinated functioning of a bacteriophage replication cycle. This work highlights the biological importance of gene overlap in natural genomes and that reducing gene overlap disruption should be an integral part of future genome engineering projects.
Anatomical correlates of face patches in macaque inferotemporal cortex
Authors: Arcaro Michael J. , Mautz Theodora , Livingstone Margaret S. 
Published: June 2020

AbstractPrimate brains typically have regions within the ventral visual stream that are selectively responsive to faces. These face patches are located in similar parts of macaque inferotemporal (IT) cortex across individuals though correspondence with particular anatomical features has not been previously reported. Here, using high resolution functional and anatomical imaging, we show that small “bumps” along the lower bank of the superior temporal sulcus are predictive of the location of face-selective regions. Recordings from implanted multi-electrode arrays verified that these bumps contain face-selective neurons. These bumps were present in monkeys raised without seeing faces and that lack face patches, indicating that these anatomical landmarks are predictive, of but not sufficient for, the presence of face selectivity. These bumps are found across primate species, indicating common evolutionary developmental mechanisms.
A cautionary note on the use of haplotype callers in Phylogenomics
Authors: Duchen Pablo , Salamin Nicolas 
Published: June 2020

AbstractNext-generation-sequencing haplotype callers are commonly used in studies to call variants from newly-sequenced species. However, due to the current availability of genomic resources, it is still common practice to use only one reference genome for a given genus, or even one reference for an entire clade of a higher taxon. The problem with traditional haplotype callers such as the one from GATK, is that they are optimized for variant calling at the population level, but not at the phylogenetic level. Thus, the consequences for downstream analyses can be substantial. Here, through simulations, we compare the performance between the haplotype callers of GATK and ATLAS, and present their differences at various phylogenetic scales. We show how the haplotype caller of GATK substantially underestimates the number of variants at the phylogenetic level, but not at the population level. We also quantified the level at which the accuracy of heterozygote calls declines with increasing distance to the reference genome. Such decrease is very sharp in GATK, while ATLAS maintains a high accuracy in variant calling, even at moderately-divergent species from the reference. We further suggest that efforts should be taken towards acquiring more reference genomes per species, before pursuing high-scale phylogenomic studies.
Laboratory based surveillance of SARS-CoV-2 in Pakistan
Authors: Badar Nazish , Ikram Aamer , Mirza Hamza Ahmad , Ahad Abdul , Alam Muhammad Masroor , Arshad Yasir , Umair Massab , Sharif Salmaan , Hassan Afreenish , Salman Muhammad 
Published: June 2020

AbstractCOVID-19 cases are alarmingly increasing in Pakistan since May 2020. Laboratory based surveillance system has been in place since the start of the pandemic. The genomic surveillance of SARS-CoV-2 strains isolated locally has been conducted based on partial ORF1b. The sequences were classified to show the phylogenetic correlation and showed 100% homology with those detected in neighboring countries India and China. The rapid increase in cases has led to development of robust strategies to enhance the laboratory testing capacity. We are currently meeting the country requirement to diagnose the virus in the community. Nonetheless, factors like recent ease in lockdown measures has led to massive rise in number of cases in few weeks time.
Correlation between meteorological factors and COVID-19 infection in the Belém Metropolitan Region
Authors: da Silva Félix Lélis , Gomes Maryjane Diniz A. , da Silva Andréa P. Lélis , de Sousa Samio Costa , de Souza Marcos Francisco Serafim , da Silva Gabriel Lélis P. 
Published: June 2020

AbstractMany factors can influence the spread of viruses and respiratory infections. Studies have suggested that there is a direct relationship between environmental issues and population density with cases of COVID-19. In this sense, this research aims to analyze, through correlational study and Krigagem, the relationship of meteorological and demographic variables with cases of COVID-19 in regions of subtropical climate in Brazil. The results suggest that population and demographic density (hab/km2) are risk factors for the spread of SAR-Cov-2 and an increase in the daily case record of COVID-19. The distribution of cases according to age group did not present a significant disparity between men and women. Relative humidity (RH)%, average temperature °C, minimum temperature °C, maximum temperature °C, wind speed m/s and daily precipitation (rain) mm show negative relationships with cases of COVID-19 in regions of humid equatorial climate. Analysis between associations of environmental factors, wind, temperature and HR in a region is extremely important to understand the dynamics of SARS-Cov-2 in the environment. In the northern region of Brazil, low wind speed, high temperatures and high RH are observed, environmental factors that, when associated, reduce the transmission process because it hinders the movement of the virus in the environment. In this sense, it is suggested that the transmission of SARS-CoV-2 in this region is disseminated through fluids in the air between man/man and by contact between objects/men. Therefore, strategic public policies to combat the pandemic must consider the environmental factors of the regions involved and control and/or blocking the transit of people.
Effect of social distancing on COVID-19 incidence and mortality in the US
Authors: VoPham Trang , Weaver Matthew D. , Hart Jaime E. , Ton Mimi , White Emily , Newcomb Polly A. 
Published: June 2020

AbstractSocial distancing policies were implemented in most US states as a containment strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of these policy interventions on morbidity and mortality remains unknown. Our analysis examined the associations between statewide policies and objective measures of social distancing, and objective social distancing and COVID-19 incidence and mortality. We used nationwide, de-identified smartphone GPS data to estimate county-level social distancing. COVID-19 incidence and mortality data were from the Johns Hopkins Coronavirus Resource Center. Generalized linear mixed models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between objective social distancing and COVID-19 incidence and mortality. Stay-at-home orders were associated with a 35% increase in social distancing. Higher social distancing was associated with a 29% reduction in COVID-19 incidence (adjusted IRR 0.71; 95% CI 0.57-0.87) and a 35% reduction in COVID-19 mortality (adjusted IRR 0.65; 95% CI 0.55-0.76). These findings provide evidence to inform ongoing national discussions on the effectiveness of these public health measures and the potential implications of returning to normal social activity.
Diatom Modulation of Microbial Consortia Through Use of Two Unique Secondary Metabolites
Authors: Shibl Ahmed A. , Isaac Ashley , Ochsenkühn Michael A. , Cárdenas Anny , Fei Cong , Behringer Gregory , Arnoux Marc , Drou Nizar , Santos Miraflor P. , Gunsalus Kristin C. , Voolstra Christian R. , Amin Shady A. 
Published: June 2020

AbstractUnicellular eukaryotic phytoplankton, such as diatoms, rely on microbial communities for survival despite lacking specialized compartments to house microbiomes (e.g., animal gut). Microbial communities have been widely shown to benefit from diatom excretions that accumulate within the microenvironment surrounding phytoplankton cells, known as the phycosphere. However, mechanisms that enable diatoms and other unicellular eukaryotes to nurture specific microbiomes by fostering beneficial bacteria and repelling harmful ones are mostly unknown. We hypothesized that diatom exudates may attune microbial communities and employed an integrated multi-omics approach using the ubiquitous diatom Asterionellopsis glacialis to reveal how it modulates its naturally associated bacteria. We show that A. glacialis reprograms its transcriptional and metabolic profiles in response to bacteria to secrete a suite of central metabolites and two unusual secondary metabolites, rosmarinic acid and azelaic acid. While central metabolites are utilized by potential bacterial symbionts and opportunists alike, rosmarinic acid promotes attachment of beneficial bacteria to the diatom and simultaneously suppresses the attachment of opportunists. Similarly, azelaic acid enhances growth of beneficial bacteria, while simultaneously inhibiting growth of opportunistic ones. We further show that the bacterial response to azelaic acid is widespread in the world’s oceans and taxonomically restricted to a handful of bacterial genera. Our results demonstrate the innate ability of an important unicellular eukaryotic group to modulate their microbial consortia, similar to higher eukaryotes, using unique secondary metabolites that regulate bacterial growth and behavior inversely in different bacterial populations.
Biosynthesis and chemical characterization of an intracellular red pigment ofTalaromyces islandicusT101
Authors: Pimentel Rodrigues Igor Vinícius , Assunção Borges Katia Regina , da Cruz Neurene , Teles Amanda Mara , Neto da Silva Marcos Antonio Custódio , de Nazaré Silva Alves Rita , de Andrade Marcelo Souza , Khayat André Salim , Pinho Jaqueline Diniz , Marques Vale André Alvares , Araújo Guimarães Sulayne Janayna , Ruiz Jerônimo Conceição , Soares Brandão Nascimento Maria do Desterro , de Barros Bezerra Geusa Felipa 
Published: June 2020

ABSTRACTThe interest in red colorants by the food industry has been increasing recently due to its wide application in many foods and beverages, and also to the carcinogenic and teratogenic effects of some synthetic dyes. Many ascomycetous fungi are able to synthesize and produce pigments, rendering them as alternative sources of natural dyes that are independent of environmental conditions.Talaromyces islandicusTI01 was isolated from a marine-influenced environment that has been suffering for decades from anthropogenic actions in its body of water. Broth microdilution technique was performed to analyze the antimicrobial activity. For analysis of the cytotoxic activity, the MTT [3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide] assay was conducted. The chemical analysis of the extract was performed by LC/MS (liquid chromatography coupled to mass spectrometry). The minimum bactericidal concentration (MBC) ofT. islandicus’intracellular red pigmented extract (IRPE) forE. coliATCC 25922 andS. aureusATCC 25923 was 1000 μg/ml. The minimum inhibitory concentration (MIC) forE. coliwas 250 μg/mL and forS. aureus500 μg/mL, respectively, whereas forC. tropicalisATCC 1369 was 62.5 μg/mL. IC50 for breast cancer cell line (MCF-7) was 45.43 ± 1.657 μg / mL. The major compounds present in the extract were: Luteoskyrin(1)and N-GABA-PP-V (6-[(Z)-2-Carboxyvinyl]-N-GABA-PP-V)(2). The results show that IRPE fromT. islandicusTI01 has a prominent antibacterial activity againstE. coliandS. aureus, making this pigment interesting for development of new food colorants and/or conservative agents, since these bacteria are food-borne pathogens.