bluuebunny/crossref_metadata_2025_split huggingface dataset:
R-based method for quantitative analysis of biofilm thickness by using Confocal Laser Scanning Microscopy
Authors: Frühauf Hanna Marianne , Stöckl Markus , Holtmann Dirk 
Published: February 2022

AbstractMicroscopy is mostly the method of choice to analyse biofilms. Due to the high local heterogeneity of biofilms, single and punctual analyses only give an incomplete insight into the local distribution of biofilms. In order to retrieve statistically significant results a quantitative method for biofilm thickness measurements was developed based on confocal laser scanning microscopy and the programming language R. The R-script allows the analysis of large image volumes with little hands-on work and outputs statistical information on homogeneity of surface coverage and overall biofilm thickness. The applicability of the script was shown in microbial fuel cell experiments. It was found that G. sulfurreducens responds differently to poised anodes of different material so that the optimum potential for MFC on poised ITO anodes had to be identified with respect to maximum current density, biofilm thickness and MFC start-up time. Thereby, a positive correlation between current density and biofilm thickness was found, but with no direct link to the applied potential. The optimum potential turned out to be +0.1 V vs SHE. The script proved to be a valuable stand-alone tool to quantify biofilm thickness in a statistically valid manner, which is required in many studies.Practical applicationBiofilm communities are ubiquitous. They can be found in every habitat in which water, nutrients and a colonisable surface are present. Depending on the surface, biofilms can cause economic losses due to bio-corrosion (pipelines and ship walls are prominent examples) or are a severe threat to human health when important medical devices or body tissues are colonised [1]. Desirable biofilms are catalytic biofilms how they are used in bioelectrochemical production processes, for example. In all cases, quantitative and qualitative biofilm analysis is necessary in order to prevent or promote biofilm formation. In bioelectrochemistry quantitative biofilm analysis is essential to link productivity (current or chemicals) with biomass deposited on the electrode. Microscopic analysis (e.g. with CLSM) of stained biofilms allows the recording of high volumes of image data but often image analysis then remains at a qualitative stage. In terms of biofilm thickness determination this limits analysis to an estimated thickness of a small amount of images, mostly. The presented R-script allows the calculation of biofilm thickness based on a larger amount of image sets and allows conclusions on the homogeneity of biofilm coverage on the electrode surface. The script is a stand-alone tool if only biofilm thickness should be determined and does not require any image segmentation or processing.
Clock Work: Deconstructing the Epigenetic Clock Signals in Aging, Disease, and Reprogramming
Authors: Levine Morgan E , Higgins-Chen Albert , Thrush Kyra , Minteer Christopher , Niimi Peter 
Published: February 2022

ABSTRACTEpigenetic clocks have come to be regarded as powerful tools for estimating aging. However, a major drawback in their application is our lack of mechanistic understanding. We hypothesize that uncovering the underlying biology is difficult due to the fact that epigenetic clocks are multifactorial composites: They are comprised of disparate parts, each with their own causal mechanism and functional consequences. Thus, only by deconstructing epigenetic clock signals will it be possible to glean biological insight. Here we clustered 5,717 clock CpGs into twelve distinct modules using multi-tissue and in-vitro datasets. We show that epigenetic clocks are comprised of different proportions of modules, which may explain their discordance when simultaneously applied in a given study. We also observe that epigenetic reprogramming does not ‘reset’ the entire clock and instead the observed rejuvenation is driven by a subset of modules. Overall, two modules stand-out in terms of their unique features. The first is one of the most responsive to epigenetic reprogramming; is the strongest predictor of all-cause mortality; and shows increases with in vitro passaging up until senescence burden begins to emerge. The light-second module is moderately responsive to reprogramming; is very accelerated in tumor vs. normal tissues; and tracks with passaging in vitro even as population doublings decelerate. Overall, we show that clock deconstruction can identify unique DNAm alterations and facilitate our mechanistic understanding of epigenetic clocks.
Glutamate indicators with improved activation kinetics and localization for imaging synaptic transmission
Authors: Aggarwal Abhi , Liu Rui , Chen Yang , Ralowicz Amelia J , Bergerson Samuel J , Tomaska Filip , Hanson Timothy L , Hasseman Jeremy P , Reep Daniel , Tsegaye Getahun , Yao Pantong , Ji Xiang , Kloos Marinus , Walpita Deepika , Patel Ronak , Mohr Manuel A , Tilberg Paul W , Mohar Boaz ,   The GENIE Project Team, Looger Loren L , Marvin Jonathan S , Hoppa Michael B , Konnerth Arthur , Kleinfeld David , Schreiter Eric R , Podgorski Kaspar 
Published: February 2022

AbstractThe fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit saturating activation kinetics and are excluded from post-synaptic densities, limiting their ability to distinguish synaptic from extrasynaptic glutamate. Using a multi-assay screen in bacteria, soluble protein, and cultured neurons, we generated novel variants with improved kinetics and signal-to-noise ratios. We also developed surface display constructs that improve iGluSnFR’s nanoscopic localization to post-synapses. The resulting indicator, iGluSnFR3, exhibits rapid non-saturating activation kinetics and reports synaptic glutamate release with improved linearity and increased specificity versus extrasynaptic signals in cultured neurons. In mouse visual cortex, imaging of iGluSnFR3 at individual boutons reported single electrophysiologically-observed action potentials with high specificity versus non-synaptic transients. In vibrissal sensory cortex Layer 4, we used iGluSnFR3 to characterize distinct patterns of touch-evoked feedforward input from thalamocortical boutons and both feedforward and recurrent input onto L4 cortical neuron dendritic spines.
Heart rate variability as biomarker for bipolar disorder
Authors: Stautland Andrea , Jakobsen Petter , Fasmer Ole Bernt , Osnes Berge , Torresen Jim , Nordgreen Tine , Oedegaard Ketil J 
Published: February 2022

AbstractBipolar disorder (BD) is characterized by alterations in mood, energy levels and the ability to function. Accordingly, it is also associated with dysfunction of the autonomic nervous system (ANS), indexed by heart rate variability (HRV). Literature concerning differences in ANS functioning between mood states is still sparse. The main aim of the study was to investigate within-individual changes in HRV from manic to euthymic states in bipolar disorder (BD). This is the first study to do so using wrist-worn sensors. Seventeen patients with BD were equipped with photoplethysmography (PPG) sensor wristbands and provided 24-hour recordings both during a manic state and a euthymic state. We calculated mean heart rate and the commonly used HRV measures SDNN, RMSSD, HF, LF and Sample Entropy in 5-minute segments during rest at night. We compared HRV by mood state within individuals using paired t-tests and linear regression to control for age and sex. Recordings from 15 BD patients were analyzed. There were statistically significant increases in HRV measures SDNN, RMSSD, LF and Sample Entropy from mania to euthymia. Effect sizes were predominately large. Our findings reveal lower HRV in the manic state compared to the euthymic state. This indicates that HRV collected by wrist-worn PPG sensors is a possible biomarker for bipolar mood states. Movement artifacts were problematic and sampling during rest or in combination with actigraphy is recommended. Our findings can be further implemented to develop a monitoring device for bipolar patients.
Neuroimmune transcriptome changes in brains of psychiatric and neurological disorder patients
Authors: Chen Yu , Dai Jiacheng , Tang Longfei , Mikhailova Tatiana , Liang Qiuman , Li Miao , Zhou Jiaqi , Weickert Cynthia , Chen Chao , Liu Chunyu 
Published: February 2022

AbstractNeuroinflammation has been implicated in multiple brain disorders but the extent and the magnitude of change in immune-related genes (IRGs) across distinct brain disorders has not been directly compared. We curated 1,275 IRGs and investigated their expression changes in 2,467 postmortem brains of controls and patients with six major brain disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). More than 60% of the IRGs had significantly altered expression in at least one of the six disorders. The differentially expressed immune-related genes (dIRGs) shared across disorders were mainly related to innate immunity. Moreover, we systematically evaluated sex, tissue, and cell type for immune alterations in different neuropsychiatric disorders. Co-expression networks revealed that neuroimmune systems interacted with neuronal-systems, both of which contribute to the risk of disorders. However, only a few genes with expression changes have also been identified as containing risk variants of genome-wide association studies. The transcriptome alterations at gene and network levels may clarify the immune-related pathophysiology and redefine neuropsychiatric and neurological disorders.One-Sentence SummaryThe brain transcriptome of six neurological and psychiatric disorders showed signature changes in genes related to immunity.
Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome
Authors: Fathi Anahita , Dahlke Christine , Krähling Verena , Kupke Alexandra , Okba Nisreen M. A. , Raadsen Matthijs P. , Heidepriem Jasmin , Müller Marcel A. , Paris Grigori , Lassen Susan , Klüver Michael , Volz Asisa , Koch Till , Ly My L. , Friedrich Monika , Fux Robert , Tscherne Alina , Kalodimou Georgia , Schmiedel Stefan , Corman Victor M. , Hesterkamp Thomas , Drosten Christian , Loeffler Felix F. , Haagmans Bart L. , Sutter Gerd , Becker Stephan , Addo Marylyn M. 
Published: February 2022

AbstractVaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials.One Sentence SummaryA late booster vaccination with the vector vaccine MVA-MERS-S against MERS-CoV is safe and significantly increases humoral immunogenicity including responses to four IgG epitopes.
Class 1 integrons in clinical and swine industry isolates of Salmonella Typhimurium from Colombia, dating 1997 to 2017
Authors: Flórez-Delgado Nancy Yaneth , Ubillus Elizabeth Noelia , Perez-Sepulveda Blanca , Ospina-Ríos Eyda Lizeth , Carrascal-Camacho Ana Karina , Chamorro-Tobar Iliana C , Montaño Lucy Angeline , Li Yan , Zapata-Bedoya Silvana , Hinton Jay C.D. , Villarreal José Miguel , Wiesner Magdalena 
Published: February 2022

AbstractBackgroundSalmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) has been linked to outbreaks of foodborne gastroenteritis disease, and the emergence of antimicrobial-resistant clones. In Colombia, laboratory surveillance of Salmonella spp. between 1997-2018 revealed that S. Typhimurium was the most ubiquitous serovar (27.57% of all Salmonella isolates), with increasing levels of antimicrobial resistance to several families of antibiotics. Hypothesis. Resistant isolates of S. Typhimurium recovered from clinical and swine samples carry class 1 integrons that are linked to antimicrobial resistance genes. Aim. Identify class 1 integrons, and investigate their association with other mobile genetic elements, and their relationship to the antimicrobial resistance of Colombian S. Typhimurium isolates. Methods. In this study, 392 clinical isolates of S. Typhimurium were analyzed, of which 237 were obtained from blood culture, 155 from non-invasive sources and 50 isolates from swine of which 32 were obtained from a slaughterhouse, 10 from a point of sale and 8 from cutting plant. Class 1 integrons and plasmid incompatibility groups were analyzed by PCR and Whole Genome Sequencing (WGS), and the region surrounding of the integrons identified by WGS. The phylogenetic relationship was established by MLST and SNP analysis. Results. Overall, 39.03% (153/392) of the clinical isolates and 22% (11/50) of the swine S. Typhimurium isolates carried complete class 1 integrons. Twelve types of gene cassette arrays were identified, including dfr7-aac-blaOXA-2 (Int1-Col1) as the most frequent in clinical isolates (75.2% = 115/153). Clinical and swine isolates that carried class 1 integrons were resistant to up to 5 and up to 3 antimicrobial families, respectively. The Int1-Col1 integron was most prevalent in stool isolates and was associated with Tn21. The most common plasmid incompatibility group was IncA/C. Conclusions. The widespread presence of the integron (IntI1-Col1) in Colombia since 1997 was striking. We speculate that the relationship between integrons, source and mobile elements favors the dispersion of antibiotic resistance determinants in Colombian S. Typhimurium isolates.
RESIDENTS’ PERCEPTION ON CENTRAL STORAGE OF SOLID WASTES IN ILORIN METROPOLIS, KWARA STATE. NIGERIA
Authors: Raufu Yusuf Olanrewaju , Olayinka Adewoye Solomon , Olawale Sawyerr Henry 
Published: February 2022

AbstractBackgroundSolid waste management in Nigeria has been a major concern to stakeholders due to inefficient collection and unsafe disposal. In Ilorin, the capital of Kwara state, the problem of wastes is becoming alarming because the more these wastes are evacuated the more they are generated on a daily basis. Thus, the issue of central storage of solid waste situation in Ilorin to say the least, is becoming quite distressing.ObjectivesThis study addressed issues relating to waste management and perception of residence to central waste storage in Ilorin metropolis.MethodsA cross-sectional study was conducted among the residents in the three local government that constitute Ilorin metropolis, residents living close to central wastes storages in Ilorin metropolis are purposively chosen and the registered wastes contractors with the Kwara State Environmental Protection Agency (KWASEPA). In accomplishing these objectives, both primary and secondary data sources were used. The primary data were collected via questionnaires and field observations. Secondary data were extracted from different published and unpublished materials. 120 households located on the main road and close to central wastes storage bins and 30 wastes contractors are administered with questionnaires. The data were analyzed using statistical package for social science (SPSS version 23) for descriptive and inferential at 5% level of significance.ResultsThe operational capacities of wastes contractors showed a low capacity as 66.7% (20) operate with single rickety truck. Dumpsites accessibility and insufficiency is an impediment as the dumpsite was found to be too far and largely inaccessible. Condition of wastes spillage from the central storage and storage on the road meridians are draw backs to effective wastes management and majority of respondents 66.7% are unhappy.ConclusionsIt was discovered that central wastes storage system in Ilorin metropolis was not effective with constant incidence of wastes spillages and storage on road meridians. Therefore, capacity and competence should be considered in wastes management contract award, provision of more central wastes storage, establishing wastes transfer station, provision of adequate dumpsites at different local government, public enlightenment, regular trainings for wastes consultant, provision of loans for wastes consultants for acquisition of trucks and proper monitoring by regulatory agency will ensure a clean and sanitary environment in the metropolis.
Bayesian Space-time SIR modeling of Covid-19 in two US states during the 2020-2021 pandemic
Authors: Lawson Andrew B , Kim Joanne 
Published: February 2022

AbstractThis paper describes the Bayesian SIR modeling of the 3 waves of Covid-19 in two contrasting US states during 2020-2021. A variety of models are evaluated at the county level for goodness-of-fit and an assessment of confounding predictors is also made. It is found that models with three deprivation predictors and neighborhood effects are important. In addition, the work index from Google mobility was also found to provide an increased explanation of the transmission dynamics.
Prediction Model for Detection of Sporadic Pancreatic Cancer (PRO-TECT) in a Population-Based Cohort Using Machine Learning and Further Validation in a Prospective Study
Authors: Chen Wansu , Zhou Yichen , Xie Fagen , Butler Rebecca K. , Jeon Christie Y. , Luong Tiffany Q. , Lin Yu-Chen , Lustigova Eva , Pisegna Joseph R. , Kim Sungjin , Wu Bechien U. 
Published: February 2022

ABSTRACTOBJECTIVESThere is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for PC across two health systems using electronic health records (EHR).METHODSThis retrospective cohort study consisted of patients 50-84 years of age meeting utilization criteria in 2008-2017 at Kaiser Permanente Southern California (KPSC, model training, internal validation) and the Veterans Affairs (VA, external validation). ‘Random survival forests’ models were built to identify the most relevant predictors from >500 variables and to predict PC within 18 months of cohort entry. A prospective study was then conducted in KPSC to assess feasibility of the model for real-time implementation.RESULTSThe KPSC cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PC cases. The estimated 18-month incidence rate of PC was 0.77 (95% CI 0.73-0.80)/1,000 person-years. The three models containing age, abdominal pain, weight change and two laboratory biomarkers (ALT change/HgA1c, rate of ALT change/HgA1c, or rate of ALT change/rate of HgA1c change) had comparable discrimination and calibration measures (c-index: mean=0.77, SD=0.01-0.02; calibration test: p-value 0.2-0.4, SD 0.2-0.3). The VA validation cohort consisted of 2.6 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30). A total of 606 patients were screened in the prospective pilot study at KPSC with 9 patients (1.5%) diagnosed with a pancreatic or biliary cancer.CONCLUSIONSUsing widely available parameters in EHR, we developed a population-based parsimonious model for early detection of sporadic PC suitable for real-time application.Study HighlightsWhat Is KnownPatients with pancreatic cancer are often diagnosed at late stages.Early detection is needed to impact the natural history of disease progression and improve patient survival.What Is New HereMachine-learning was used to develop a population-based model for early detection of pancreatic cancer. The model was internally and externally validated in cohorts of 1.8 million and 2.6 million individuals, respectively.Calibration was excellent in prospective pilot testing for detection of pancreatic malignancy.
Cost-effectiveness of Ezetimibe plus statin lipid-lowering therapy: A systematic review and meta-analysis of cost-utility studies
Authors: Sasidharan Akhil , Kumar S Sajith , Jagadeesh Kayala Venkata , Natarajan Meenakumari , Bagepally Bhavani Shankara 
Published: February 2022

AbstractIntroductionIn addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy.MethodsWe identified economic evaluation studies reporting outcomes of EPS therapy compared with other lipid-lowering therapeutic agents or placebo by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled Incremental Net Benefit (INB) in the US $ with a 95% confidence interval (CI). We used the modified economic evaluations bias checklist and GRADE quality assessment for quality appraisal. The review was apriori registered with PROSPERO, CRD42021248531.ResultsThe pooled INB from twenty-one eligible studies showed that EPS therapy was significantly cost-effective compared to other lipid-lowering therapeutic agents or placebo. The pooled INB (95% CI) was $4,274 (621 to 7,927), but there was considerable heterogeneity (I2=84.21). On subgroup analysis EPS therapy is significantly cost-effective in high-income countries [$4,356 (621 to 8,092)], for primary prevention [$4,814 (2,523 to 7,106)], and for payers’ perspective [$3,255 (571 to 5,939)], and from lifetime horizon [$4,571 (746 to 8,395)].ConclusionEPS therapy is cost-effective compared to other lipid-lowering therapeutic agents or placebo in high-income countries and for primary prevention. However, there is a dearth of evidence from lower-middle-income countries and the societal perspective.
Heterogeneity impacts biomarker discovery for precision medicine
Authors: Smith Kenneth , Climer Sharlee 
Published: February 2022

AbstractPrecision medicine is advancing patient care for complex human diseases. Discovery of biomarkers to diagnose specific subtypes within a heterogeneous diseased population is a key step towards realizing the benefits of precision medicine. However, popular statistical methods for evaluating candidate biomarkers – fold change (FC) and area under the receiver operating characteristic curve (AUC) – were designed for homogeneous data. Herein, we evaluate the performance of these metrics in heterogeneous populations. Using simulated biomarkers that are nearly ‘ideal’ for distinguishing subgroups of various proportions of the diseased population, we observe that AUC misses all up to subset size of 50% and FC misses all biomarkers entirely. We introduce a simple new measure to address this shortfall and run a series of trials comprised of simulated and biological data to demonstrate its utility for evaluating biomarkers associated with disease subtypes.