bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnic minority groups in England and Wales - factors affecting the size and timing of elevated COVID-19 mortality: a retrospective cohort study linking Census and death records
Authors: Ayoubkhani Daniel , Nafilyan Vahé , White Chris , Goldblatt Peter , Gaughan Charlotte , Blackwell Louisa , Rogers Nicky , Banerjee Ami , Khunti Kamlesh , Glickman Myer , Humberstone Ben , Diamond Ian 
Published: August 2020

AbstractObjectivesTo estimate population-level associations between ethnicity and coronavirus disease 2019 (COVID-19) mortality, and to investigate how ethnicity-specific mortality risk evolved over the course of the pandemic.DesignRetrospective cohort study using linked administrative data.SettingEngland and Wales, deaths occurring 2 March to 15 May 2020.ParticipantsRespondents to the 2011 Census of England and Wales aged ≤100 years and enumerated in private households, linked to death registrations and adjusted to account for emigration before the outcome period, who were alive on 1 March 2020 (n=47,872,412).Main outcome measureDeath related to COVID-19, registered by 29 May 2020.Statistical methodsWe estimated hazard ratios (HRs) for ethnic minority groups compared with the White population using Cox regression models, controlling for geographical, demographic, socio-economic, occupational, and self-reported health factors. HRs were estimated on the full outcome period and separately for pre- and post-lockdown periods in the UK.ResultsIn the age-adjusted models, people from all ethnic minority groups were at elevated risk of COVID-19 mortality; the HRs for Black males and females were 3.13 [95% confidence interval: 2.93 to 3.34] and 2.40 [2.20 to 2.61] respectively. However, in the fully adjusted model for females, the HRs were close to unity for all ethnic groups except Black (1.29 [1.18 to 1.42]). For males, COVID-19 mortality risk remained elevated for the Black (1.76 [1.63 to 1.90]), Bangladeshi/Pakistani (1.35 [1.21 to 1.49]) and Indian (1.30 [1.19 to 1.43]) groups. The HRs decreased after lockdown for all ethnic groups, particularly Black and Bangladeshi/Pakistani females.ConclusionsDifferences in COVID-19 mortality between ethnic groups were largely attenuated by geographical and socio-economic factors, although some residual differences remained. Lockdown was associated with reductions in excess mortality risk in ethnic minority populations, which has major implications for a second wave of infection or local spikes. Further research is needed to understand the causal mechanisms underpinning observed differences in COVID-19 mortality between ethnic groups.
Development of a Flow Cytometry-Based Whole-Blood Prognostic Immune Signature in Metastatic Cancer Patients treated with immune checkpoint inhibitors
Authors: Zhou Jian-Guo , Donaubauer Anna-Jasmina , Frey Benjamin , Becker Ina , Rutzner Sandra , Eckstein Markus , Sun Roger , Ma Hu , Schubert Philipp , Schweizer Claudia , Fietkau Rainer , Deutsch Eric , Gaipl Udo S. , Hecht Markus 
Published: August 2020

AbstractRecent biomarker research focuses on early immunological changes to predict treatment response to immune checkpoint inhibitors (ICI). Within this prospective ST-ICI trial, pre-planned biomarker analysis was performed and we developed a flow cytometry-based whole-blood prognostic immune signature (FCBPS) to predict overall survival (OS) benefit of cancer patients treated with ICI. For this, fifty-four immune cell subsets were analyzed in the patients’ peripheral blood before the second administration of the ICI. Patients were randomly allocated to a training and validation cohort. Univariate Cox proportional hazards regression analysis and LASSO Cox model were used to develop a predictive and prognostic signature. 104 patients were prospectively enrolled. 89 patients provided blood samples. The identified FCBPS signature bases on five immune cell subtypes: neutrophils, plasmacytoid dendritic cells (pDCs), natural killer (NK)T cells (CD56+/CD16+), monocytes (CD14high) and CD8+ T cells (PD-1+). This signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting OS benefit in the training and validation cohort. Both in the training and validation cohort, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI: 0.12-0.56, p=0.00025; HR 0.30, 95% CI: 0.10 −0.91, p=0.024,respectively). In the whole cohort, FCBPS is a predictor of OS (HROS=0.28, 95% CI: 0.15-0.52) and progression-free survival (HRPFS=0.22, 95% CI: 0.12-0.39) that remained independent in multivariate analyses and subgroup analyses after adjusting for clinical and pathological factors. The identified flow cytometry-based whole-blood prognostic signature (FCBPS) is a powerful predictor for metastatic cancer patients who benefit from ICI treatment.Trial registrationProspectively registered in ClinicalTrials.gov (NCT03453892) on January 24, 2018.
Cost burden of type 2 diabetes mellitus (DM) in an urban area of Bangladesh: A hospital-based mix method study
Authors: Saha Monidipa , Kader Shirmin Bintay , Chowdhury Shafquat Haider , Hasan Md. Khaledul , Ashraf Mir Nabila , Rahman Md. Marufur , Koly Kamrun Nahar 
Published: August 2020

ABSTRACTBackgroundLongtime treatment of diabetic patients is an added burden for countries that had low GDP and no health insurance facilities like Bangladesh. Urgent cost assessment and proper strategy needs to be developed to overcome the economic burden of a diabetic patient.MethodologyWe have conducted a mixed-methods study in a Bangladesh Institute of Health Sciences (BIHS), a sister concern of BIRDEM hospital between August 2019 to January 2020. Quantitative data was collected by a survey questionnaire from the patients and qualitative data was collected by interviewing five key informants of the facility center.Results329 known diabetic patients were enrolled, out of the 70.48% were female and the rest of them were male. The mean age of the respondents was 53.73 years. Nearly 35% of them had a positive family history, and more than 30% of them had both hypertension and dyslipidemia along with DM. The total average cost per year was ∼600USD, which includes drug, investigation, consultancy & transportation costs. Among which drug costs were the most (∼350 USD).We had found that drug cost & investigation cost had a significant associated with increased age, level of education, and the duration of DM. Investigation cost was also associated with positive family history.ConclusionsAs there is no insurance coverage in Bangladesh and subsidy are not available, many of the patients from the lower socio-economic group might discontinue the treatment. Further prospective research is needed to develop a proper guideline for policymakers.Strength & LimitationIt’s the first mixed method study which discuss about the cost burden of type 2 DMKII was performed and perspective about the cost burden of type 2 DM from doctors view was reported.Described that treatment of DM is often hampered due to lack of family & workplace support.Our only methodological limitation is our sample size, which was smaller than other quantitave studies.
Effect of Aerobic Exercise on Amyloid Accumulation in Preclinical Alzheimer’s: A 1-Year Randomized Controlled Trial
Authors: Vidoni Eric D. , Morris Jill K. , Watts Amber , Perry Mark , Clutton Jon , Van Sciver Angela , Kamat Ashwini S , Mahnken Jonathan , Hunt Suzanne L. , Townley Ryan , Honea Robyn , Shaw Ashley R. , Johnson David K. , Vacek James , Burns Jeffrey M. 
Published: August 2020

ABSTRACTBackgroundOur goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer’s-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging.Methods and FindingsThis 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 older adults (mean age 72.9 [7.7]) without evidence of cognitive impairment, with elevated (n=79) or subthreshold (n=38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control.ConclusionsAerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects.Trial RegistrationClinicalTrials.govNCT02000583.
Antibiofilm activity of Fmoc-phenylalanine against Gram-positive and Gram-negative bacterial biofilms
Authors: Singh Himanshi , Gahane Avinash Y. , Singh Virender , Ghosh Shreya , Thakur Ashwani Kumar 
Published: August 2020

AbstractBackgroundBiofilm associated infections are the major contributor of mortality, morbidity and financial burden in patients with bacterial infection. Molecules with surfactant behaviour are known to show significant antibiofilm effect against these infections. Thus, newly discovered antibacterial Fmoc-phenylalanine (Fmoc-F) and other Fmoc-amino acids (Fmoc-AA) with surfactant properties, could have potential antibiofilm properties.ObjectivesTo evaluate and characterise the antibiofilm activity of Fmoc-F and some Fmoc-AA against various clinically relevant bacteria.MethodsBiofilm inhibition and eradication was evaluated by crystal violet staining procedure along with scanning electron microscopy (SEM). Attenuated Total Reflection - Fourier Transform Infrared Spectroscopy (ATR-FTIR), Biochemical assays and Congo red staining were employed to investigate mechanism of antibiofilm action.ResultsWe showed that Fmoc-F not only inhibits the biofilm formation inS. aureusandP. aeruginosa, but also eradicates the already formed biofilms over the surface. Further, Fmoc-F coated glass surface resistsS. aureusandP. aeruginosabiofilm formation and attachment, when biofilm is grown over the surface. The mechanistic investigation suggests that Fmoc-F reduces the ECM components such as proteins carbohydrates and eDNA in the biofilm and affect its stabilityviadirect interactions with ECM components and/ or indirectly through reducing bacterial cell population. Finally, we showed that Fmoc-F treatment in combination with other antibiotics such as vancomycin and ampicillin synergistically inhibit biofilm formation.ConclusionsOverall, the study demonstrates the potential application of Fmoc-F and other Fmoc-AA molecules individually as well as in combination as antibiofilm agents and antibiofilm coating material for treating biofilm associated infections.
Brain network mechanisms of visual shape completion
Authors: Keane Brian P. , Barch Deanna M. , Mill Ravi D. , Silverstein Steven M. , Krekelberg Bart , Cole Michael W. 
Published: August 2020

AbstractVisual shape completion represents object shape, size, and number from spatially segregated edges. Despite being extensively investigated, the process’s underlying brain regions, networks, and functional connections are still not well understood. To shed light on the topic, we scanned (fMRI) healthy adults during rest and during a task in which they discriminated pac-man configurations that formed or failed to form visually completed shapes (illusory and fragmented condition, respectively). Task activation differences (illusory-fragmented), resting-state functional connectivity, and multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping (ActFlow) was used to evaluate the likely involvement of resting-state connections for shape completion. We identified 34 differentially-active parcels including a posterior temporal region, PH, whose activity was consistent across all 20 observers. Significant task regions primarily occupied the secondary visual network but also incorporated the frontoparietal, dorsal attention, default mode, and cingulo-opercular networks. Each parcel’s task activation difference could be modeled via its resting-state connections with the remaining parcels (r=.62,p<10-9), suggesting that such connections undergird shape completion. Functional connections from the dorsal attention network were key in modeling activation differences in the secondary visual network and across all remaining networks. Taken together, these results suggest that shape completion relies upon a distributed but densely interconnected network coalition that is centered in the secondary visual network, coordinated by the dorsal attention network, and inclusive of at least three other networks.HighlightsShape completion differentially activates regions distributed across five networksThe secondary visual network plays the clearest role in shape completionDorsal attention functional connections likely coordinate activity across networksPosterior temporal region, PH, played a highly consistent role in completion
RNAlign2D – a rapid method for combined RNA structure and sequence-based alignment using a pseudo-amino acid substitution matrix
Authors: Woźniak Tomasz , Sajek Małgorzata , Jaruzelska Jadwiga , Sajek Marcin Piotr 
Published: August 2020

AbstractBackgroundThe functions of RNA molecules are mainly determined by their secondary structures. These functions can also be predicted using bioinformatic tools that enable the alignment of multiple RNAs to determine functional domains and/or classify RNA molecules into RNA families. However, the existing multiple RNA alignment tools, which use structural information, are slow in aligning long molecules and/or a large number of molecules. Therefore, a more rapid tool for multiple RNA alignment may improve the classification of known RNAs and help to reveal the functions of newly discovered RNAs.ResultsHere, we introduce an extremely fast Python-based tool called RNAlign2D. It converts RNA sequences to pseudo-amino acid sequences, which incorporate structural information, and uses a customizable scoring matrix to align these RNA molecules via the multiple protein sequence alignment tool MUSCLE.ConclusionsRNAlign2D produces accurate RNA alignments in a very short time. The pseudo-amino acid substitution matrix approach utilized in RNAlign2D is applicable for virtually all protein aligners.
Homeostatic cerebellar compensation of age-related changes of vestibulo-ocular reflex adaptation: a computational epidemiology study
Authors: Luque Niceto R. , Naveros Francisco , Ros Eduardo , Arleo Angelo 
Published: August 2020

AbstractThe vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the intrinsic plasticity of Purkinje cell (PC) synapses, and long-term spike timing-dependent plasticity at parallel fiber - PC synapses and mossy fiber - medial vestibular nuclei synapses. Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of PC synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime.
SARS-CoV-2 genome sequences from late April in Stockholm, Sweden reveal a novel mutation in the spike protein
Authors: Soratto Tatiany Aparecida Teixeira , Darban Hamid , Bjerkner Annelie , Coorens Maarten , Albert Jan , Allander Tobias , Andersson Björn 
Published: August 2020

AbstractLarge research efforts are going into characterizing, mapping the spread, and studying the biology and clinical features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report four complete SARS-CoV-2 genome sequences obtained from patients confirmed to have the disease in Stockholm, Sweden, in late April. A variant at position 23463 was found for the first time in one genome. It changes an arginine (R) residue to histidine (H) at position 364 in the S1 subunit of the spike protein. The genomes belonged to two different genetic groups, previously reported as two of the three main genetic groups found in Sweden. Three of them are from group B.1/G, corresponding to the Italian outbreak, reported by the Public Health Agency of Sweden to have declined in prevalence by late April, and more investigation is needed in order to ensure that the spread of different types of SARS-CoV-2 is fully characterized.HighlightsFour near-complete genomes of SARS-CoV-2 were assembled from late April in Stockholm.A novel mutation in the spike protein were found.The phylogeny of the strains were discussed.
Temporal experience modifies future thoughts: Manipulation of Libet’s W influences difficulty assessment during a decision-making task
Authors: Isham Eve A. 
Published: August 2020

Past studies have employed the subjective experience of decision time (Libet’s W) as an index of consciousness, marking the moment at which the agent first becomes aware of a decision. In the current study, we examined whether the temporal experience of W affects subsequent experience related to the action. Specifically, we tested whether W influenced the perception of difficulty in a decision-making task, hypothesizing that temporal awareness of W might influence the sense of difficulty. Consistent with our predictions, when W was perceived as early or late, participants subsequently rated the decision difficulty to be easy or difficult, respectively (Exp.1). Further investigation showed that perceived difficulty, however, did not influence W (Exp.2). Together, our findings suggest a unidirectional relationship such that W plays a role in the metacognition of difficulty evaluation. The results imply that subjective temporal experience of decision time modifies the consequential sense of difficulty.HighlightsPerceived timing of decision (W) can bias the metacognition of difficulty evaluation in a decision-making task.Defined as a temporal index of consciousness, time W’s influence on difficulty evaluation reflects the possibility that the role of consciousness is to modify subsequent thoughts and behaviors.Explicit attention is necessary for the timing of decision (W) to be consciously experienced and effectively influential on subsequent thoughts.
MiRNA expression profiling and zeatin dynamic changes in a new model system ofin vivoindirect regeneration of tomato
Authors: Cao Huiying , Zhang Xinyue , Ruan Yanye , Zhang Lijun , Cui Zhenhai , Li Xuxiao , Jia Bing 
Published: August 2020

AbstractCallus formation and adventitious shoot differentiation could be observed on the cut surface of completely decapitated tomato plants. We propose that this process can be used as a model system to investigate the mechanisms that regulate indirect regeneration of higher plants without the addition of exogenous hormones. This study analyzed the patterns of trans-zeatin and miRNA expression duringin vivoregeneration of tomato. Analysis of trans-zeatin revealed that the hormone cytokinin played an important role inin vivoregeneration of tomato. Among 183 miRNAs and 1168 predicted target genes sequences identified, 93 miRNAs and 505 potential targets were selected based on differential expression levels for further characterization. Expression patterns of six miRNAs, including sly-miR166, sly-miR167, sly-miR396, sly-miR397, novel 156, and novel 128, were further validated by qRT-PCR. We speculate that sly-miR156, sly-miR160, sly-miR166, and sly-miR397 play major roles in callus formation of tomato duringin vivoregeneration by regulating cytokinin, IAA, and laccase levels. Overall, our microRNA sequence and target analyses of callus formation duringin vivoregeneration of tomato provide novel insights into the regulation of regeneration in higher plants.
Combinatorial mathematical modelling approaches to interrogate rear retraction dynamics in 3D cell migration
Authors: Hetmanski Joseph H.R. , Jones Matt , Chunara Fatima , Schwartz Jean-Marc , Caswell Patrick T. 
Published: August 2020

AbstractCell migration in 3D micro-environments is a complex process which depends on the coordinated activity of leading edge protrusive force and rear retraction in a push-pull mechanism. While the potentiation of protrusions has been widely studied, the precise signalling and mechanical events that lead to forward movement of the cell rear are much less well understood, particularly in physiological 3D extra-cellular matrix (ECM). We previously discovered that rear retraction in fast moving cells is a highly dynamic process involving the precise spatiotemporal interplay of mechanosensing by caveolae and signalling through RhoA. To further interrogate the dynamics of rear retraction, we have adopted three distinct mathematical modelling approaches here based on (i) Boolean logic, (ii) deterministic kinetic ordinary differential equations (ODEs) and (iii) stochastic simulations. The aims of this multi-faceted approach are twofold: firstly to derive new biological insight into cell rear dynamics via generation of testable hypotheses and predictions; and secondly to compare and contrast the distinct modelling approaches when used to describe the same, relatively under-studied system. Whilst Boolean logic was not able to fully recapitulate the complexity of rear retraction signalling completely, our ODE model could make plausible population level predictions. Stochastic simulations added a further level of complexity by accurately mimicking previous experimental findings and acting as a single cell simulator. Our approach has also highlighted the unanticipated potential of targeting CDK1 to abrogate cell movement, a prediction we confirmed experimentally. Moreover, we have made a novel prediction regarding the potential existence of a ‘set point’ in local stiffness gradients that promotes polarisation and rapid rear retraction. Overall, our modelling approaches complement each other, suggesting that such a multi-faceted approach is more informative than methods based on a single modelling technique to interrogate biological systems.