bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional control of the lacZ promoter is under directional and diversifying selection
Authors: Vlková Markéta , Silander Olin K. 
Published: March 2022

AbstractBacterial cells often respond to changes in the environment by modifying protein expression. This can be achieved through changes in transcriptional or translational activity, or both. Recent research has shed some light on how natural selection shapes overall protein expression. Still, little is known about how selection acts on transcription or translation individually. To address part of this question, we implement an experimental system which allows us to measure how genetic changes affect transcription only, excluding the effects on translation. We use this system to quantify changes in three regulatory phenotypes of the lacZ promoter: transcriptional activity, plasticity, and cell-to-cell variability. We compare these phenotypes from segregating variants that have been subject to natural selection, and random variants that have never been subjected to natural selection. We show that natural selection filters out mutations causing large changes in transcriptional levels from the lacZ promoter. Further, we detect directional selection acting on transcriptional plasticity in combinations of glucose, galactose and lactose environments. Focusing on cell-to-cell variability in transcription, we describe both directional and diversifying selection acting on this phenotype depending on the environment used. We also observe a link between the phylogeny of the environmental E. coli strains and high and low transcriptional noise levels in glucose which are mediated by just one or two SNPs. Our results thus provide new insight into how one of the most well-characterized bacterial promoters is shaped in nature by selection.
Effects of different environmental intervention durations on the intestinal mucosal barrier and the brain-gut axis in rats with colorectal cancer
Authors: Dun Liu , Mei-Jing Chen , Si-Ting Huang , Xin-Yuan Yu , Yu-Xuan Wu 
Published: March 2022

ABSTRACTObjectivesEnriched environment (EE) is a promising strategy to protect the intestinal mucosal barrier and regulate brain-gut peptide expression. However, the optimal enriched environment intervention duration is unknown. Here, different EE intervention durations were applied to assess the optimal intervention duration in rats with colorectal cancer.MethodsWe used a rat model of 1,2-dimethylhydrazine-induced colorectal cancer. Rats were housed in an EE for 0, 2, 4 or 8 weeks. The intestinal mucosa and serum TNF-α, IL-6, IL-10, DAO, ATP, CRF, and occludin levels and bacterial translocation (BT) were measured, and the intestinal mucosa morphology was evaluated.ResultsEight-week EE intervention was more beneficial to the intestinal mucosal mechanical barrier than 2-week or 4-week intervention (P<0.05). There was a significant different between the 4-week and 8-week groups on BT (P=0.049). However, which intervention duration had the greatest advantages in intestinal mucosa and serum inflammatory factor regulation was not determined. There were no significant differences in the effects of different EE intervention durations on BT or brain intestinal peptide levels among the other groups (P>0.05).ConclusionsThe effect of an 8-week environmental intervention duration on the intestinal mucosal barrier was better than that of 2-week and 4-week durations overall, but the effect of different environmental intervention durations on brain-gut peptide levels was not obvious. In the future, we can further explore the molecular biological mechanism of the effect of different EE intervention durations on the intestinal mucosal barrier and analyze the effect of an EE on other brain-gut peptides.
Medical Evaluation of Unanticipated Monogenic Disease Risks Identified through Newborn Genomic Screening: Findings from the BabySeq Project
Authors: Green Robert C. , Shah Nidhi , Genetti Casie A. , Yu Timothy , Zettler Bethany , Schwartz Talia S. , Uveges Melissa K. , Ceyhan-Birsoy Ozge , Lebo Matthew S. , Pereira Stacey , Agrawal Pankaj B. , Parad Richard B. , McGuire Amy L. , Christensen Kurt , Rehm Heidi L. , Holm Ingrid A. , Beggs Alan H. ,   the BabySeq Project
Published: March 2022

AbstractGenomic sequencing of healthy newborns to screen for medically important genetic information has long been anticipated but data around downstream medical consequences are lacking. Among 159 infants randomized to the sequencing arm in the BabySeq Project, an unanticipated monogenic disease risk (uMDR) was discovered in 18 (11.3%). We assessed uMDR actionability by visualizing scores from a modified ClinGen Actionability SemiQuantitative Metric and tracked medical outcomes in these infants for 3-5 years. All uMDRs scored as highly actionable (mean 9, range: 7-11 on a 0-12 scale) and had readily available clinical interventions. In 4 cases, uMDRs revealed unsuspected genetic etiologies for existing phenotypes, and in the remaining 14 cases provided risk stratification for future surveillance. In 8 cases, uMDRs prompted screening for multiple at-risk family members. These results suggest that actionable uMDRs are more common than previously thought and support ongoing efforts to evaluate population-based newborn genomic screening.
SARS-CoV-2 Omicron potently neutralized by a novel antibody with unique Spike binding properties
Authors: Fenwick Craig , Turelli Priscilla , Ni Dongchun , Perez Laurent , Lau Kelvin , Lana Erica , Pellaton Céline , Raclot Charlène , Esteves-Leuenberger Line , Campos Jérémy , Farina Alex , Fiscalini Flurin , Herate Cécile , Marlin Romain , Abdelnabi Rana , Foo Caroline S. , Neyts Johan , Leyssen Pieter , LeGrand Roger , Lévy Yves , Pojer Florence , Stahlberg Henning , Trono Didier , Pantaleo Giuseppe 
Published: March 2022

AbstractThe SARS-CoV-2 Omicron variant exhibits very high levels of transmission, pronounced resistance to authorized therapeutic human monoclonal antibodies and reduced sensitivity to vaccine-induced immunity. Here we describe P2G3, a human monoclonal antibody (mAb) isolated from a previously infected and vaccinated donor, which displays picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other current variants, and is thus markedly more potent than all authorized or clinically advanced anti-SARS-CoV-2 mAbs. Structural characterization of P2G3 Fab in complex with the Omicron Spike demonstrates unique binding properties to both down and up spike trimer conformations at an epitope that partially overlaps with the receptor-binding domain (RBD), yet is distinct from those bound by all other characterized mAbs. This distinct epitope and angle of attack allows P2G3 to overcome all the Omicron mutations abolishing or impairing neutralization by other anti-SARS-COV-2 mAbs, and P2G3 accordingly confers complete prophylactic protection in the SARS-CoV-2 Omicron monkey challenge model. Finally, although we could isolate in vitro SARS-CoV2 mutants escaping neutralization by P2G3 or by P5C3, a previously described broadly active Class 1 mAb, we found these viruses to be lowly infectious and their key mutations extremely rare in the wild, and we could demonstrate that P2G3/P5C3 efficiently cross-neutralized one another’s escapees. We conclude that this combination of mAbs has great prospects in both the prophylactic and therapeutic settings to protect from Omicron and other VOCs.
Alpha-mannosidase-2 modulates arbovirus infection in a pathogen- and Wolbachia-specific manner in Aedes aegypti mosquitoes
Authors: Urakova Nadya , Joseph Renuka E. , Huntsinger Allyn , Macias Vanessa M. , Jones Matthew J. , Sigle Leah T. , Li Ming , Akbari Omar S. , Xi Zhiyong , Lymperopoulos Konstantinos , Sayre Richard T , McGraw Elisabeth A. , Rasgon Jason L. 
Published: March 2022

AbstractMultiple Wolbachia strains can block pathogen infection, replication, and/or transmission in Aedes aegypti mosquitoes under both laboratory and field conditions. However, Wolbachia effects on pathogens can be highly variable across systems and the factors governing this variability are not well understood. It is increasingly clear that the mosquito host is not a passive player in which Wolbachia governs pathogen transmission phenotypes; rather, the genetics of the host can significantly modulate Wolbachia-mediated pathogen blocking. Specifically, previous work linked variation in Wolbachia pathogen blocking to polymorphisms in the mosquito alpha-mannosidase 2 (αMan2) gene. Here we use CRISPR-Cas9 mutagenesis to functionally test this association. We developed αMan2 knockouts and examined effects on both Wolbachia and virus levels, using both dengue virus (DENV; Flaviviridae) and Mayaro virus (MAYV; Togaviridae). Wolbachia titers were significantly elevated in αMan2 knockout (KO) mosquitoes, but there were complex interactions with virus infection and replication. In Wolbachia-uninfected mosquitoes, the αMan2 KO mutation was associated with decreased DENV titers, but in a Wolbachia-infected background, the αMan2 KO mutation significantly modulated virus blocking. In contrast, the αMan2 KO mutation significantly increased MAYV replication in Wolbachia-uninfected mosquitoes and did not affect Wolbachia-mediated virus blocking. These results demonstrate that αMan2 modulates arbovirus infection in Ae. aegypti mosquitoes in a pathogen- and Wolbachia-specific manner, and that Wolbachia-mediated pathogen blocking is a complex phenotype dependent on the mosquito host genotype and the pathogen. These results have significant impact for the design and use of Wolbachia-based strategies to control vector-borne pathogens.
Impact of Maternal Protein Restriction on Hypoxia-Inducible Factor (HIF) Expression in Male Fetal Kidney Development
Authors: Gomes Júlia Sevá , de Barros Sene Letícia , Lamana Gabriela Leme , Boer Patricia Aline , Gontijo José Antônio Rocha 
Published: March 2022

ABSTRACTBackgroundThe kidney ontogenesis is the most structurally affected by gestational protein restriction, reducing close to 30% of their functional units. The reduced nephron number is predictive of hypertension and cardiovascular dysfunctions generally observed in the adult age of most fetal programming models. We demonstrate HIF-1 predicts molecular pathway changes may be associated with the decreased nephron numbers in the 17 gestational days (17GD) low protein (LP) intake male fetal kidney compared to regular protein (NP) progeny intake. Here, we evaluated the predicted targets and related pathways in the fetal kidneys of 17-GD LP offspring to elucidate the molecular modulations during nephrogenesis.MethodsPregnant Wistar rats were allocated into two groups: NP (regular protein diet −17%) or LP (diet-6%). Taking into account miRNA transcriptome sequencing previous study (miRNA-Seq) in 17-GD male offspring kidneys using previously described methods, was investigated predicted target genes and proteins, in particular, related to HIF-1 pathway by RT-qPCR and immunohistochemistry.Results and conclusionsThe current study data supported that nephron onset impairment in the 17-DG fetus’s kidney, programmed by gestational low-protein intake, is, at least in part, related to alterations in the HIF-1α signaling pathway. Factors that facilitate the transposition of HIF-1α to the mesenchymal cell’s nucleus, such as NOS, Ep300, and HSP90, may have an essential role in this regulatory process. This alteration leads to the inhibition of adaptive responses to the adverse environment, secondary to an increase in ungraded HIF-1α, possibly associated with a reduction in the transcription factor elF-4 and proteins of their respective signaling pathways. Consequently, we may suggest an early maturation process of renal cells, inhibition of nephron progenitor cell division, and reduction of renal functional units in the offspring of rats submitted to severe gestational protein restriction.
Perceptions of users and non-users of an early contact tracing mobile application to fight COVID-19 spread: a value-based empirical investigation
Authors: Cocosila Mihail , Farrelly Glen , Trabelsi Houda 
Published: March 2022

PurposeThe purpose of this study is to describe a comparative study of the perceptions of users and non-users of an early contact tracing application helping to prevent the spread of the COVID-19 pandemic. The unprecedented incidence of this disease warrants investigating theoretically the use of mobile contact tracing applications as a promising approach to curtail its transmission.Design/methodology/approachA consumption value-based model of the adoption and use of a contact tracing mobile application was built and tested through a cross-sectional survey conducted with 2 samples (of 309 already users and 306 non-users) in the Province of Alberta, Canada.FindingsUtilitarian and social values together with health information seeking and perceived critical mass drive the use of the application while perceived privacy risk is an obstacle to usage for both users and non-users.Research limitations/implicationsStudy participants self-assessed their risk category of potential exposure to the COVID-19 virus, and this was a subjective measure including an emotional component.Practical implicationsNo major differences in the approaches targeting users and non-users of a mobile contact tracing application to encourage its adoption and use are necessary.Social implicationsAdditional efforts are required to convey to people information on the benefits and current rate of use of such an application and to mitigate privacy risk concerns.Originality/valueOverall, the study offers theoretical and practical contributions that may help improve the adoption and usage of contact tracing applications addressing the COVID-19 pandemic or other possible public health crises.
Family caring for the elderly during the pandemic in Hong Kong: perspective from Confucian familism
Authors: Hung Andrew T.W. 
Published: March 2022

PurposeThe aim of this paper is to argue for the values of familial caring and relationships in addition to the provision of social media technology during the COVID-19 pandemic in Hong Kong.Design/methodology/approachThe discussion of this paper has adopted an inter-disciplinary approach by integrating health care system and psychological analysis, based on cultural philosophical argument through the hermeneutic approach of classical texts and critical analysis.FindingsThe COVID-19 pandemic has exposed the dilemma between the public health measures for COVID-19 and sustaining elderly social psychological health through familial connection. From a Confucian perspective, the practice of filial piety (xiao, 孝), which demands taking care of parents, is essential for one’s moral formation, and for one’s becoming a virtuous (ren, 仁) person. The necessity of taking care of elderly parents by adult children is not something that can be explained in terms of consequentialism. Indeed, the rising trend of instrumental rationality seems to weaken rather than strengthen the sense of filial obligation. In the face of the COVID-19 pandemic which tends to separate connections between family members, the author argues that we should emphasize the values of familial caring and relationship because it enhances the elderly’s characteristic of resilience.Originality/valueThis paper shows that while social media technology has mitigated the negative effect of social distancing, such online relationships should never replace the bodily connections between the elderly and their family members from a Confucian perspective.
In search of the vibroseis first arrival
Authors: Trickett Stewart 
Published: March 2022

ABSTRACTThe first step in correcting for time delays of land seismic data due to low‐velocity weathered layers is to pick the first‐arrival times of the refracting energy. But doing so for vibroseis data can be difficult, as the seismic wavelet is often ringy and uncompact, resulting in cycle‐skipped picks. Even when we manage to pick a waveform feature consistently, it is not clear where the first‐arrival time is in relation to it. I present a novel method that shapes the seismic wavelet to a Ricker wavelet whose peak is located at the true arrival time, so the time of the first arrival is unambiguous. Further, the arrivals are less ringy and their energy more focused, so that they are less likely to cycle skip or be overwhelmed by random noise. The result is more accurate and consistent first‐arrival picks.
Whose Streets? Roadway Protests and Weaponised Automobility
Authors: Savitzky Satya , Cidell Julie 
Published: March 2022

AbstractThe article examines the role of automobility in US‐based anti‐racism demonstrations and counter‐demonstrations. We contrast the spatial strategies of highway occupations by racial justice activists, with so‐called “weaponised car” attacks by the American far right. Analysing online memes and anti‐protest legislation, the article explores under‐acknowledged links between “automobile supremacy”—the structure of motorists' privilege as embedded in law, the built environment and the popular imaginary—and the patterns of racial stratification often termed “white supremacy”. We document three ways in which automobility has been enlisted as means of violence against protestors and against wider Black communities in the US: through the use of vehicles, right‐of‐way conventions, and roadways as weapons. The article demonstrates how the imperative to make way for the motorist has long provided cover for racial injustice.
Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)
Authors: Brandman Danielle , Boyle Marie , McPherson Stuart , Van Natta Mark L. , Sanyal Arun J. , Kowdley Kris , Neuschwander‐Tetri Brent , Chalasani Naga , Abdelmalek Manal F. , Terrault Norah A. , McCullough Art , Bettencourt Ricki , Caussy Cyrielle , Kleiner David E. , Behling Cynthia , Tonascia James , Anstee Quentin M. , Loomba Rohit ,   Members of the Nonalcoholic Steatohepatitis Clinical Research Network
Published: March 2022

SummaryBackground and AimsPatients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy‐proven cirrhosis in NAFLD.MethodsAdult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB‐4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort.Results147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95–0.97). FIB‐4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84–0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92–0.96), and FIB‐4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87–0.89).ConclusionsThis cross‐sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher‐risk patients maintain access to specialty care.
Psychometric validation of a patient‐reported experience measure of obstetric racism© (The PREM‐OB Scale™ suite)
Authors: White VanGompel Emily , Lai Jin‐Shei , Davis Dána‐Ain , Carlock Francesca , Camara Tamentanefer L. , Taylor Brianne , Clary Chakiya , McCorkle‐Jamieson Ashlee M. , McKenzie‐Sampson Safyer , Gay Caryl , Armijo Amanda , Lapeyrolerie Lillie , Singh Lavisha , Scott Karen A. 
Published: March 2022

AbstractBackgroundPerinatal quality improvement lacks valid tools to measure adverse hospital experiences disproportionately impacting Black mothers and birthing people. Measuring and mitigating harm requires using a framework that centers the lived experiences of Black birthing people in evaluating inequitable care, namely, obstetric racism. We sought to develop a valid patient‐reported experience measure (PREM) of Obstetric Racism© in hospital‐based intrapartum care designed for, by, and with Black women as patient, community, and content experts.MethodsPROMIS© instrument development standards adapted with cultural rigor methodology. Phase 1 included item pool generation, modified Delphi method, and cognitive interviews. Phase 2 evaluated the item pool using factor analysis and item response theory.ResultsItems were identified or written to cover 7 previously identified theoretical domains. 806 Black mothers and birthing people completed the pilot test. Factor analysis concluded a 3 factor structure with good fit indices (CFI = 0.931‐0.977, RMSEA = 0.087‐0.10, R2 > .3, residual correlation < 0.15). All items in each factor fit the IRT model and were able to be calibrated. Factor 1, “Humanity,” had 31 items measuring experiences of safety and accountability, autonomy, communication, and empathy. A 12‐item short form was created to ease respondent burden. Factor 2, “Racism,” had 12 items measuring experiences of neglect and mistreatment. Factor 3, “Kinship,” had 7 items measuring hospital denial and disruption of relationships between Black mothers and their child or support system.ConclusionsThe PREM‐OB Scale™ suite is a valid tool to characterize and quantify obstetric racism for use in perinatal improvement initiatives.
Computing Schematic Layouts for Spatial Hypergraphs on Concentric Circles and Grids
Authors: Bekos M.A. , Dekker D.J.C. , Frank F. , Meulemans W. , Rodgers P. , Schulz A. , Wessel S. 
Published: March 2022

AbstractSet systems can be visualized in various ways. An important distinction between techniques is whether the elements have a spatial location that is to be used for the visualization; for example, the elements are cities on a map. Strictly adhering to such location may severely limit the visualization and force overlay, intersections and other forms of clutter. On the other hand, completely ignoring the spatial dimension omits information and may hide spatial patterns in the data. We study layouts for set systems (or hypergraphs) in which spatial locations are displaced onto concentric circles or a grid, to obtain schematic set visualizations. We investigate the tractability of the underlying algorithmic problems adopting different optimization criteria (e.g. crossings or bends) for the layout structure, also known as the support of the hypergraph. Furthermore, we describe a simulated‐annealing approach to heuristically optimize a combination of such criteria. Using this method in computational experiments, we explore the trade‐offs and dependencies between criteria for computing high‐quality schematic set visualizations.