bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of Gausemycin A-resistant Staphylococcus aureus
Authors: Poshvina Darya V. , Dilbaryan Diana S. , Kasyanov Sergey P. , Sadykova Vera S. , Lapchinskaya Olda A. , Rogozhin Eugene A. , Vasilchenko Alexey S. 
Published: May 2022

ABSTRACTGausemycins A and B are the first members of the novel lipoglycopeptides family produced by Streptomyces roseoflavus INA-Ac-5812, which showed the ability to fight clinically important Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. However, new antibiotics need to be studied in depth to determine their full potential. In this study, we concentrated our efforts to investigate resistance emerging within S. aureus upon gausemycin A application.Using serial passaging of S. aureus FDA209P in increasing concentrations of gausemycin A, we obtained the resistant variant S. aureus 5812R which are 80-times more resistant comparing to the origin strain. Moreover, obtained resistance is stable, since 15 passages in a drug-free medium did not restore bacterial susceptibility to gausemycin A.Elucidating of the differences between resistant and parent strains was concerned antibiotic cross-resistance, structure of bacterial membrane, and response at genetic level.Susceptibility testing of S. aureus 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, and tetracycline, while resistance to vancomycin, nisin and ramoplanin absence. The composition of fatty acids constituting the cytoplasmic membrane of S. aureus 5812R, was represented by increased content of anteiso- branched chain fatty acids, while iso-branched chain fatty acids was decreased comparing the origin S. aureus FDA209P strain. The relative expression of the cls gene catalyzing the synthesis of cardiolipin in the resistant cells was higher compared to the S. aureus FDA209P.
Efficacy and Specificity of Melanopsin Reporters for Retinal Ganglion Cells
Authors: Maloney Ryan , Quattrochi Lauren , Yoon James , Souza Rachel , Berson David 
Published: May 2022

AbstractIntrinsically photosensitive retinal ganglion cells (ipRGCs) are specialized retinal output neurons that mediate behavioral, neuroendocrine, and developmental responses to environmental light. There are diverse molecular strategies for marking ipRGCs, especially in mice, making them among the best characterized retinal ganglion cells. With the development of more sensitive reporters, new subtypes of ipRGCs have emerged. We therefore tested high-sensitivity reporter systems to see whether we could reveal yet more. Substantial confusion remains about which of the available methods, if any, label all and only ipRGCs. Here, we compared many different methods for labeling of ipRGCs, including anti-melanopsin immunofluorescence, Opn4-GFP BAC transgenic mice, and Opn4cre mice crossed with three different Cre-specific reporters (Z/EG; Ai9; and Ai14) or injected with Cre-dependent (DIO) AAV2. We show that Opn4cre mice, when crossed with sensitive Cre-reporter mice, label numerous ganglion cell types that lack intrinsic photosensitivity. Though other methods label ipRGCs specifically, they do not label the entire population of ipRGCs. We conclude that no existing method labels all and only ipRGCs. We assess the appropriateness of each reporter for particular applications and integrate findings across reporters to estimate that the overall abundance of ipRGCs among mouse retinal ganglion cells may approach 11%.
Computational analysis of 4-1BB-induced NFκB signaling suggests improvements to CAR cell design
Authors: Tserunyan Vardges , Finley Stacey D. 
Published: May 2022

AbstractBackgroundChimeric antigen receptor (CAR)-expressing cells are a powerful modality of adoptive cell therapy against cancer. The strength and dynamics of signaling events initiated upon antigen binding depend on the costimulatory domain within the structure of the CAR. One such costimulatory domain is 4-1BB, which affects cellular response via the NFκB pathway. However, the quantitative aspects of 4-1BB-induced NFκB signaling are not fully understood.MethodsWe developed an ordinary differential equation-based mathematical model representing canonical NFκB signaling activated by CAR-4-1BB. We first performed a global sensitivity analysis on our model to quantify the impact of kinetic parameters and initial protein concentrations. We ran Monte Carlo simulations of cell population-wide variability in NFκB signaling and used Kraskov’s algorithm to quantify the mutual information between the extracellular signal and different levels of the NFκB signal transduction pathway.ResultsWe determined that in response to a wide range of antigen concentrations, the magnitude of the transient peak in the nuclear concentration of NFκB varies significantly, while the timing of this peak is relatively consistent. Our global sensitivity analysis showed that the model is robust to variations in parameter values, and thus, its quantitative predictions would remain applicable to a broad range of parameter values. Next, we found that overexpressing NEMO and disabling IKKβ deactivation are predicted to increase the mutual information between antigen levels and NFκB activation.ConclusionsOur modeling predictions provide actionable insights to guide CAR development. Particularly, we propose specific manipulations to the NFκB signal transduction pathway that can fine-tune the response of CAR-4-1BB cells to the antigen concentrations they are likely to encounter.
T32 training is associated with increased likelihood of obtaining an academic research faculty position: a cross-sectional study
Authors: Mueller Adrienne L. , Schnirel Addie , Kleppner Sofie , Tsao Philip , Leeper Nicholas J. 
Published: May 2022

AbstractBackgroundThe main mission of NIH-sponsored institutional training programs such as the T32 is to provide strong research and career training for early career scientists, while preparing those individuals to become leaders working to meet the health-related research needs of the nation. One of the main avenues to pursue health-related research is becoming research faculty at an academic institution. It is therefore important to know whether these programs are succeeding in this mission, or, if barriers exist that prevent trainees from pursuing these careers.MethodsOur institution currently trains ~ 2400 post-doctoral scholars per year, approximately 5% of whom are enrolled in one of our 33 T32 programs. In this study, we 1) compare the professional outcomes of T32 trainees with non-T32 trainees at our institution, and 2) survey past and current T32 trainees in a subset of high-performing cardiovascular programs about the barriers and enablers they experienced to pursuing research-oriented careers.ResultsFormer T32 trainees are significantly more likely to attain appointments as primarily research faculty members, compared to other trainees. Trainees report a perceived lack of stability, the paucity of open positions, and the ‘publish or perish’ competitive mentality of academia as their top reasons for abandoning careers in academia. However, they were still more likely to choose research over clinical careers after participating in a dedicated T32 program.ConclusionsOur results support the conclusion that structured training programs strengthen the pipeline of young scientists pursuing careers in academic research, including those from underrepresented backgrounds. However, T32 postdoctoral researchers are held back from pursuing academic careers by a perceived lack of stability and high competition for faculty positions.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Cocoa extract exerts sex-specific anti-diabetic effects in an aggressive type-2 diabetes model: a pilot study
Authors: Racine Kathryn C. , Iglesias-Carres Lisard , Herring Jacob A. , Ferruzzi Mario G. , Kay Colin D. , Tessem Jeffery S. , Neilson Andrew P. 
Published: May 2022

AbstractType 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ (ob/ob) and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT,ob/ob) or with cocoa extract (ob/ob+ c) for 10 weeks. Acute cocoa reduced fasting hyperglycemia in females, but not males, after 2 weeks. Chronic cocoa supplementation (6-10 weeks) ameliorated hyperinsulinemia in males and worsened hyperlipidemia and hyperinsulinemia in females, yet also preserved and enhanced beta cell survival in females. The underlying mechanisms of these differences warrant further study. If sex differences are apparent in subsequent preclinical studies, clinical studies will be warranted to establish whether these differences are relevant in humans. Sex differences may need to be considered when designing human dietary interventions for T2D.
Estimates of excess mortality for the five Nordic countries during the Covid-19 pandemic 2020-2021
Authors: Kepp Kasper P. , Björk Jonas , Bæk Kristoffer T. , Lallukka Tea 
Published: May 2022

AbstractExcess deaths during the covid-19 pandemic are of major scientific and political interest. Here we review excess all-cause death estimates from different methods for the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden), which have been much studied during the covid-19 pandemic. In the comparison of the methods, we use simple sensitivity estimates and linear interpolations of the death data to discuss uncertainties and implications for reporting ratios and infection fatality rates. We show using back-calculation of expected deaths from Nordic all-cause deaths that a recent study in Lancet, which is a clear outlier in the overviewed estimates, most likely substantially overestimates excess deaths of Finland and Denmark, and probably Sweden. The other estimates are more consistent and suggest a range of total Nordic excess deaths of approximately half of that in the Lancet study, a more uniform ability to identify covid-19-related deaths, and more similar infection fatality rates for the Nordic countries.
Reaching the Remote: Dried blood spot analysis for disease diagnosis on a protein microarray platform
Authors: Mowoe Metoboroghene O. , Rensburg Tristan , Ali Hisham , Gqada Joshua , Kotze Urda , Bernon Marc , Africa Bradley , Jonas Eduard , Blackburn Jonathan M. 
Published: May 2022

ABSTRACTCancer remains one of the leading causes of death globally with an estimated 19.3 million cases and 10 million mortalities in 2020. In Africa and Asia, where remoteness is prevalent, access to healthcare facilities is limited, providing a significant barrier to effective screening and early detection of cancers in at-risk groups and thus, incomplete registries. Here, we utilised low resource, low-cost dried blood spots (DBS)-based sample collection coupled with robust, protein microarray technology to enable quantitative, multiplexed measurements of diagnostic autoantibody biomarkers of disease, in minimal sample volumes. Specifically, we describe the development of a DBS extraction and elution method from low cost, home-made blood cards. We then show that DBS stored at room temperature (25 □, RT) for up to 15 d yield comparable autoantibody signatures to autologous serum samples stored at -80 □ and those from samples prepared on a commercially available blood card. We further conducted a pilot study, comparing total IgG and three previously identified autoantibodies upregulated in pancreatic cancer (PC), in DBS from 11 PC patients stored at RT for up to 15 d. We found comparable protein profiles across commercially developed blood cards and our low cost, in-house kit with no significant difference in autoantibody profiles over 15 d (p > 0.05). Such low cost, DBSbased sample collection methods, combined with regular, RT courier shipments and ultrasensitive protein microarraybased detection in a remote laboratory, thus have the potential to facilitate future, unbiased, large scale serosurveys and serological diagnostic testing within remote, rural communities.
Exposure to Prenatal Social Disadvantage and Maternal Psychosocial Stress: Relationships to Neonatal White Matter Connectivity
Authors: Lean Rachel E. , Smyser Christopher D. , Brady Rebecca G. , Triplett Regina L. , Kaplan Sydney , Kenley Jeanette K. , Shimony Joshua S. , Smyser Tara A. , Miller J. Phillip , Barch Deanna M. , Luby Joan L. , Warner Barbara B. , Rogers Cynthia E. 
Published: May 2022

ABSTRACTChildhood exposure to poverty and related psychosocial stressors are associated with altered microstructure in fronto-limbic pathways evident at age 8-10 years. How early in neurodevelopment these associations can be detected remains unclear. In this longitudinal study, 399 mothers were oversampled for low income and completed social experience and background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent constructs: Social Disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, nutrition) and Psychosocial Stress (depression, stress, life events, racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social Disadvantage and Psychosocial Stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social Disadvantage, but not Psychosocial Stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical risk in pregnancy and prenatal drug exposure. In moderation analysis, Psychosocial Stress was associated with lower MD in the left inferior CB among the lower-to-higher SES (INR ≥200%) group, but not the extremely low SES (INR <200%) group. Increasing access to social welfare programs that reduce the burden of poverty and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways.
Accurate Prostate Cancer Detection based on Circulating Tumor Cell Profiling
Authors: Limaye Sewanti , Chowdhury Simon , Rohatgi Nitesh , Ranade Anantbhushan , Syed Nelofer , Riedemann Johann , Page Raymond , Patil Darshana , Akolkar Dadasaheb , Datta Vineet , Patil Revati , Bendale Kiran , Fulmali Pooja , Fulmali Pradeep , Apurwa Sachin , Schuster Stefan , Murthy Sudha S , Bose Chirantan , John Jinumary , Srinivasan Ajay , Datar Rajan 
Published: May 2022

ABSTRACTBackgroundEvaluation of serum prostate specific antigen (PSA) is a part of standard prostate cancer diagnostic work-up in symptomatic males as well as for elective prostate cancer screening in asymptomatic males. The low specificity of serum PSA leading to an inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. Further, the low sensitivity of serum PSA leading to false negatives can miss high-grade / aggressive prostate cancers.ObjectiveWe describe a non-invasive prostate cancer detection test based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD-CTCs) from blood samples and their identification via immunostaining for pan-cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl-acyl coenzyme-A racemase (AMACR), epithelial cell adhesion molecule (EpCAM) and common leucocyte antigen (CD45).Design, Setting, and ParticipantsThe analytical validation studies used VCaP reference prostate cancer cell line to evaluate the performance characteristics of the test. The clinical performance characteristics of the test were first evaluated in a case-control study with 160 known prostate cancer cases and 800 healthy males. A prospective clinical study was performed with samples from 210 suspected cases of prostate cancer.Outcome Measurements and Statistical AnalysisAnalytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study.Results and LimitationsThe test accurately detects PrAD-CTCs with high sensitivity and specificity irrespective of stage or grade (Gleason score), which translates into low risks of false negatives or overdiagnosis. The test does not detect minor non-adenocarcinoma subtypes of prostate cancer.ConclusionsThe high accuracy of the test offers advantages over PSA based prostate cancer detection.
The maternal anthropometry and hemoglobin status in relations to newborn birth weight among primiparous mothers at Adama Hospital Medical College, Eastern Ethiopia: a cross-sectional study
Authors: Sento Midekso , Negera Atoma 
Published: May 2022

ABSTRACTBackgroundAnthropometric measurements are quantitative measurements of the human body size, shape, and nutritional status. It is a simple, inexpensive, and non-invasive approach used to identify mothers at risk of labor outcomes. On the other hand, hematological disorders are common during pregnancy with deleterious health effects on the mother and the fetus, which consequently cause fetal growth retardation and low weight.ObjectivesTo assess the relationship between maternal anthropometry and hemoglobin status with the newborn birth weight among primiparous mothers at Adama Hospital Medical College, Eastern Ethiopia 2021.MethodsAn institutional-based cross-sectional study design involving 269 primiparous pregnant mothers was conducted at Adama Hospital Medical College from September 15 to October 30, 2021. The consecutive sampling technique was used till the required sample size was attained. Interviewer-administered questionnaires, instruments for anthropometric measurement, hemoglobinometer, and electronic weighing scales were used to collect the data. The data was entered into EpiData version 3.1 and exported to SPSS software version 21 for analysis. Multivariate logistic regression was used to analyze the relationship between the independent variables and the outcome variables.ResultsAbout 269 mothers and their neonates participated in this study. Multivariate logistic regression shows that maternal ANC visit less than two [AOR=4.149, 95% CI: (1.27, 13.52)], maternal height [AOR= 0.878, 95% CI: (0.806, 0.95)], and maternal Hgb <11g/dl [AOR=4.127, 95% CI: (1.63, 10.43)] were significantly associated with the occurrences of low birth weight (p<0.05).ConclusionThis study has shown that maternal anthropometric characteristics and hemoglobin status were important factors associated birth weight. Health facilities should emphasize routine measurements of maternal anthropometry and hemoglobin during ANC visits in order to reduce complications related to labor outcomes.
Comparison of mechanical homogenization versus enzymatic digestion sample preparation methodologies for SARS-CoV-2 detection in saliva for surveillance of variants of concern on the University of Tennessee campus in early 2021
Authors: Poindexter Magen R. , Xu Tingting , Swift Cynthia M. , Proctor Caleb M , Kara-Murdoch Fadime , Morehouse Zachary P , Ryan Gabriella L , Löffler Frank E. , Nash Rodney J 
Published: May 2022

AbstractThe SARS-CoV-2 pandemic has profoundly impacted communities across the globe, requiring accurate and accessible diagnostic technologies in support of public health mitigation efforts. As testing has evolved throughout the course of the pandemic, varying sample preparation methodologies have been employed. Herein we perform a comparison of three commercial sample preparation methods: two mechanical homogenization workflows and one enzymatic digestion approach for the detection of SARS-CoV-2 from biomarker genes in 20 human saliva pools. SARS-CoV-2 variants of concern were also identified on the University of Tennessee, Knoxville campus during the spring semester of 2021 utilizing the commercial PerkinElmer PKamp VariantDetect SARS-CoV-2 RT-PCR Assay kit. Two hundred and ten (210) human saliva pools were selected and analyzed for the presence of SARS-CoV-2 variants of concern providing insight into the utility of these various commercial workflows for integration into current public health SARS-CoV-2 surveillance measures.
Sleep Duration and the Prevalence of Metabolic Syndrome in adolescents and children: a Systematic Review and Meta-analysis
Authors: Xu Yiyang , Hua Jianian , Shen Yueping 
Published: May 2022

AbstractObjectivePrevious studies discussing the association between sleep duration and the prevalence of metabolic syndrome have reported different results, most of which targeted at adults. We are devoted to investigating the effects of sleep time for metabolic syndrome in children conducting a meta-analysis.MethodsSeveral cross-sectional studies were retrieved from Pubmed, Ovid, Cochrane, and Embase from inception to October 2021. Fixed-effect models and random-effect models were used to analyze the effects of sleep time on metabolic syndrome in adolescents based on the research above.ResultsWe collected data from 10 cross-sectional studies including 15877 children. Using random-effect models, compared with normal sleep time, we found out that both relatively short (OR = 0.81, 95%CI = 0.55-1.07, I-squared = 45.6%, p = 0.075) and long (OR = 0.86, 95%CI = 0.54-1.19, I-squared = 67.8%, p = 0.003) sleep durations were not associated with high prevalence of metabolic syndrome in adolescents and children. Using fixed-effect model on short sleep duration and it turned out to be statistically significant (OR = 0.76, 95%CI = 0.59-0.93).ConclusionsLong sleep duration made no significant difference in the risk of metabolic syndrome in adolescents and children, while short sleep duration seems to be a protective factor. Further studies are required to establish whether the association is causal and modifiable.