bluuebunny/crossref_metadata_2025 huggingface dataset:
Citizens’ digital footprints to support health promotion at the local level—PUHTI study, Finland
Authors: Kilpeläinen Katri , Ståhl Timo , Ylöstalo Tiina , Keski-Kuha Teemu , Nyrhinen Riku , Koponen Päivikki , Gissler Mika
Published: April 2024

Background

We aimed to explore to the possibilities of utilizing automatically accumulating data on health—owned for example by local companies and non-governmental organizations—to complement traditional health data sources in health promotion work at the local level.

Methods

Data for the PUHTI study consisted of postal code level information on sport license holders, drug purchase and sales advertisements in a TOR online underground marketplace, and grocery sales in Tampere. Additionally, open population register data were utilized. An interactive reporting tool was prepared to show the well-being profile for each postal code area. Feedback from the tool’s end-users was collected in interviews.

Results

The study showed that buying unhealthy food and alcohol, selling or buying drugs, and participating in organized sport activities differed by postal code areas according to its socioeconomic profile in the city of Tampere. The health and well-being planners and managers of Tampere found that the new type of data brought added value for the health promotion work at the local level. They perceived the interactive reporting tool as a good tool for planning, managing, allocating resources and preparing forecasts.

Conclusions

Traditional health data collection methods—administrative registers and health surveys—are the cornerstone of local health promotion work. Digital footprints, including data accumulated about people’s everyday lives outside the health service system, can provide additional information on health behaviour for various population groups. Combining new sources with traditional health data opens a new perspective for health promotion work at local and regional levels.
On the estimation of genome-average recombination rates
Authors: Dutheil Julien Y
Published: April 2024

The rate at which recombination events occur in a population is an indicator of its effective population size and the organism’s reproduction mode. It determines the extent of linkage disequilibrium along the genome and, thereby, the efficacy of both purifying and positive selection. The population recombination rate can be inferred using models of genome evolution in populations. Classic methods based on the patterns of linkage disequilibrium provide the most accurate estimates, providing large sample sizes are used and the demography of the population is properly accounted for. Here, the capacity of approaches based on the sequentially Markov coalescent (SMC) to infer the genome-average recombination rate from as little as a single diploid genome is examined. SMC approaches provide highly accurate estimates even in the presence of changing population sizes, providing that (1) within genome heterogeneity is accounted for and (2) classic maximum-likelihood optimization algorithms are employed to fit the model. SMC-based estimates proved sensitive to gene conversion, leading to an overestimation of the recombination rate if conversion events are frequent. Conversely, methods based on the correlation of heterozygosity succeed in disentangling the rate of crossing over from that of gene conversion events, but only when the population size is constant and the recombination landscape homogeneous. These results call for a convergence of these two methods to obtain accurate and comparable estimates of recombination rates between populations.
Making Sense of Dementia: Older Adults’ Subjective Representations of Dementia and Alzheimer’s Disease
Authors: Marhánková Jaroslava Hasmanová , Honelová Michaela
Published: April 2024

Objectives

This research explores how the representations and meanings of living with dementia are constructed by older adults.

Methods

Focus groups (N = 19) and in-depth interviews (N = 29) were conducted with older adults aged 65+ living in the Czech Republic, representing different levels of personal familiarity with care for an individual experiencing dementia.

Results

We identified 2 different discourses: (1) Tragedy discourse with two distinctive repertoires “dementia as a thief of personality” and “dementia as a thief of humanity.” Within such discourse, dementia transcends mere medical terminology, serving as a symbolic representation of existential anxieties linked to aging and the perceived loss of control. (2) The discourse of Dementia as a specific way in which people approach the world was articulated mainly by caregivers, providing them with a coping mechanism and a means to reconstruct the agency of the person experiencing dementia. In older adults’ representations, references to suffering among family members emerged as a primary association with dementia. Dementia was portrayed as “contagious” in its effect on the family members who were, in a sense, depicted as the primary sufferers of the disease.

Discussion

Dementia often serves as a symbolic tool for older adults to articulate concerns about advanced old age, extending beyond its clinical definition to convey deep-seated fears associated with aging. The experience of people surrounding those diagnosed with dementia and the permeability of the impacts of this disease between bodies represented crucial frameworks for conceptualizing dementia in the narratives of older adults.
Pangenome databases improve host removal and mycobacteria classification from clinical metagenomic data
Authors: Hall Michael B , Coin Lachlan J M
Published: April 2024

Background

Culture-free real-time sequencing of clinical metagenomic samples promises both rapid pathogen detection and antimicrobial resistance profiling. However, this approach introduces the risk of patient DNA leakage. To mitigate this risk, we need near-comprehensive removal of human DNA sequences at the point of sequencing, typically involving the use of resource-constrained devices. Existing benchmarks have largely focused on the use of standardized databases and largely ignored the computational requirements of depletion pipelines as well as the impact of human genome diversity.

Results

We benchmarked host removal pipelines on simulated and artificial real Illumina and Nanopore metagenomic samples. We found that construction of a custom kraken database containing diverse human genomes results in the best balance of accuracy and computational resource usage. In addition, we benchmarked pipelines using kraken and minimap2 for taxonomic classification of Mycobacterium reads using standard and custom databases. With a database representative of the Mycobacterium genus, both tools obtained improved specificity and sensitivity, compared to the standard databases for classification of Mycobacterium tuberculosis. Computational efficiency of these custom databases was superior to most standard approaches, allowing them to be executed on a laptop device.

Conclusions

Customized pangenome databases provide the best balance of accuracy and computational efficiency when compared to standard databases for the task of human read removal and M. tuberculosis read classification from metagenomic samples. Such databases allow for execution on a laptop, without sacrificing accuracy, an especially important consideration in low-resource settings. We make all customized databases and pipelines freely available.
The current ‘dramatically’ high paternal ages at childbirth are not unprecedented
Authors: Willführ Kai P , Klüsener Sebastian
Published: April 2024

There is strong individual-level evidence that late fatherhood is related to a wide range of health disorders and conditions in offspring. Over the last decades, mean paternal ages at childbirth have risen drastically. This has alarmed researchers from a wide range of fields. However, existing studies have an important shortcoming in that they lack a long-term perspective. This article is a step change in providing such a long-term perspective. We unveil that in many countries the current mean paternal ages at childbirth and proportions of fathers of advanced age at childbirth are not unprecedented. Taking the detected U-shaped trend pattern into account, we discuss individual- and population-level implications of the recent increases in paternal ages at childbirth and highlight important knowledge gaps. At the individual level, some of the biological mechanisms that are responsible for the paternal age-related health risk might, at least to some degree, be counterbalanced by various social factors. Further, how these individual-level effects are linked to population health and human cognitive development might be influenced by various factors, including technical advances and regulations in prenatal diagnostics.
Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study
Authors: Lin Zong-Han , Li Chung-Pin , Sun Cheuk-Kwan , Cho Der-Yang , Tsai Fuu-Jen , Yip Hei-Tung , Chang Renin , Hung Yao-Min
Published: April 2024

Background

Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD.

Methods

Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation.

Results

The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn’s disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19).

Conclusions

Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.
TAK1-binding protein 2 (TAB2) and TAB3 are redundantly required for TLR-induced cytokine production in macrophages
Authors: Ali Tanveer , Nguyen Huong Minh , Abbas Naeem , Takeuchi Osamu , Akira Shizuo , Suzuki Toshihiko , Matsuzaki Goro , Takaesu Giichi
Published: April 2024

Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to the lysine 63-linked polyubiquitin chain through TAK1-binding protein 2 (TAB2) and TAB3. However, the physiological importance of TAB2 and TAB3 in macrophages is still controversial. A previous study has shown that mouse bone marrow-derived macrophages (BMDMs) isolated from mice double deficient for TAB2 and TAB3 produced tumor necrosis factor (TNF)-α and interleukin (IL)-6 to the similar levels as control wild-type BMDMs in response to TLR ligands such as lipopolysaccharide (LPS) or Pam3CSK4, indicating that TAB2 and TAB3 are dispensable for TLR signaling. In this study, we revisited the role of TAB2 and TAB3 using an improved mouse model. We observed a significant impairment in the production of pro-inflammatory cytokines and chemokine in LPS- or Pam3CSK4-treated BMDMs deficient for both TAB2 and TAB3. Double deficiency of TAB2 and TAB3 resulted in the decreased activation of NF-κB and MAPK pathways as well as the slight decrease in TAK1 activation in response to LPS or Pam3CSK4. Notably, the TLR-mediated expression of inhibitor of NF-κB (IκB)ζ was severely compromised at the protein and messenger RNA (mRNA) levels in the TAB2/TAB3 double-deficient BMDMs, thereby impeding IL-6 production. Our results suggest that TAB2 and TAB3 play a redundant and indispensable role in the TLR signaling pathway.
Influence of ultrafiltration conditions on the measurement of unbound drug concentrations: flucloxacillin as an example
Authors: Jager Nynke G L , Van Ewijk-Beneken Kolmer Eleonora , Aarnoutse Rob , Te Brake Lindsey H M
Published: April 2024

Background

When performing therapeutic drug monitoring (TDM) for flucloxacillin, it is advised to measure the unbound, not the total, flucloxacillin concentration. To be able to accurately quantify unbound flucloxacillin concentrations, a reliable analytical method is indispensable.

Objective

To determine the influence of temperature and pH of the sample during ultrafiltration on the measured unbound fraction of flucloxacillin.

Materials and methods

We performed three different experiments. In a single laboratory experiment, we investigated the influence of ultrafiltration temperature (10°C, room temperature and 37°C) on the measured unbound fraction of flucloxacillin for three concentration levels. In a multiple laboratory experiment, the results of eight laboratories participating in an international quality control programme measuring unbound flucloxacillin concentrations were analysed. In the third experiment, patient samples were ultrafiltrated using four different conditions: (i) physiological pH and room temperature; (ii) unadjusted pH (pH 9 after freezing) and room temperature; (iii) physiological pH and 37°C and (iv) unadjusted pH and 37°C.

Results

For all experiments, measurement of samples that were ultrafiltrated at room temperature resulted in a substantially lower unbound fraction compared to samples that were ultrafiltrated at 37°C. Adjusting the pH to physiological pH only had a minimal impact on the measured unbound fraction.

Conclusions

On the basis of these findings and considering the need for fast, simple and reproducible sample pretreatment for TDM purposes, we conclude that ultrafiltration of flucloxacillin should be performed at physiological temperature (37°C), but adjustment of pH does not seem to be necessary.
Creative Incoherence: 303 Creative and First Amendment Exemptions to Antidiscrimination Law
Authors: DeLise James M
Published: April 2024

In 303 Creative, the US Supreme Court examined the conflict between state laws designed to protect gay persons from stigmatic and material harm in the public marketplace and the First Amendment freedoms of business owners who objected to same-sex marriage on religious grounds. Writing for the majority, Justice Gorsuch concluded, “When a state public accommodations law and the Constitution collide, there can be no question which must prevail.” In this essay, I use two elements of late philosopher John Rawls’s Political Liberalism (2005)—the “criterion of reciprocity” and “liberty and integrity of the person”—to better understand the broad implications of the court’s ruling. My analysis reveals that the majority opinion in 303 Creative fails to acknowledge the need for achieving a coherent scheme of liberty within a liberal democracy and, in so doing, it undermines, rather than furthers, pluralism. Additionally, the logic of the court’s ruling produces incoherent and inconsistent results—results that simultaneously expand and contract religious freedom and unjustifiably treat sexual-orientation discrimination differently from other types of odious discrimination. However, supplanting the court’s approach with Rawls’s “criterion of reciprocity” provides a coherent and consistent adjudicatory method for balancing religious freedom and the demands of equal citizenship. Furthermore, the argument I offer comports with legal analyses that focus on religious exemptions and third-party harm and the value of equal citizenship in religious liberty debates. Thus, my work supplements existing arguments against religious exemptions to antidiscrimination law and provides another substantive rejoinder to those seeking to scale back civil rights.
Coccinellid predation efficiency on Aphis gossypii (Hemiptera: Aphididae) under laboratory conditions
Authors: El-Sayad Mahmoud G S , El-Maghraby Mohamed M A , Hammad Kamel A A , Alwutayd Khairiah M , Al-Ghamdi Mariam S , Youssif Mohammed A I
Published: April 2024

In this study, we investigated the biological aspects and predation efficiency of 3 aphidophagous ladybird beetles, Coccinella novemnotata, Hippodamia variegata, and Coccinella septempunctata, on the cotton aphid, Aphis gossypii, reared on cucumber plants (Cucumis sativus L. cultivar barracuda) under laboratory conditions. The developmental periods of C. novemnotata, H. variegata, and C. septempunctata were observed to be 16.00 ± 0.25, 16.00 ± 0.25, and 20.58 ± 0.40 days, respectively. The larvae of these ladybird beetles consumed an average of 218.93 ± 8.86, 254.77 ± 8.86, and 537.36 ± 10.49 aphids, respectively. Fourth-instar larvae were particularly efficient, consuming 53.68%, 52.68%, and 52.64% of total aphids for C. novemnotata, H. variegata, and C. septempunctata, respectively. Adult emergence rates were promising, with 91.67%, 100.00%, and 92.86%, accompanied by sex ratios of 63.64%, 53.84%, and 61.54%, respectively. Notably, a single female of C. novemnotata, H. variegata, and C. septempunctata consumed an average of 2,215.30, 2,232.00, and 3,364.50 aphids, respectively, over its lifespan. Coccinella septempunctata demonstrated the highest predation efficiency among the 3 species, suggesting its potential for biological control of A. gossypii in both open fields and greenhouses, promoting sustainable agricultural practices.
Gian Giacomo Poldi Pezzoli and the decorative arts
Authors: Tasso Francesca
Published: April 2024

This article focuses on the abandoned project for a Museo d'Arte Industriale in Milan, conceived by the Associazione degli Industriali. Although the project was never accomplished, it eventually led to the creation of the Museo Artistico Municipale in 1878. At the time, the Associazione degli Industriali of which Gian Giacomo Poldi Pezzoli was a member, was trying to establish a network of international relationships with museums and cultural institutions such as the South Kensington Museum in London, in order to emulate them in creating a modern museum where their private collections would eventually find a home. This paper sets out the cultural and artistic background in which Poldi Pezzoli and other Milanese noblemen and collectors operated, and in which they tried to transform their private and historical collections into new public museums.
Insight into the adaptive role of arachnid genome-wide duplication through chromosome-level genome assembly of the Western black widow spider
Authors: Miles Lindsay S , Waterman Hannah , Ayoub Nadia A , Garb Jessica E , Haney Robert A , Rosenberg Michael S , Krabbenhoft Trevor J , Verrelli Brian C
Published: April 2024

Although spiders are one of the most diverse groups of arthropods, the genetic architecture of their evolutionary adaptations is largely unknown. Specifically, ancient genome-wide duplication occurring during arachnid evolution ~450 mya resulted in a vast assembly of gene families, yet the extent to which selection has shaped this variation is understudied. To aid in comparative genome sequence analyses, we provide a chromosome-level genome of the Western black widow spider (Latrodectus hesperus)—a focus due to its silk properties, venom applications, and as a model for urban adaptation. We used long-read and Hi-C sequencing data, combined with transcriptomes, to assemble 14 chromosomes in a 1.46 Gb genome, with 38,393 genes annotated, and a BUSCO score of 95.3%. Our analyses identified high repetitive gene content and heterozygosity, consistent with other spider genomes, which has led to challenges in genome characterization. Our comparative evolutionary analyses of eight genomes available for species within the Araneoidea group (orb weavers and their descendants) identified 1,827 single-copy orthologs. Of these, 155 exhibit significant positive selection primarily associated with developmental genes, and with traits linked to sensory perception. These results support the hypothesis that several traits unique to spiders emerged from the adaptive evolution of ohnologs—or retained ancestrally duplicated genes—from ancient genome-wide duplication. These comparative spider genome analyses can serve as a model to understand how positive selection continually shapes ancestral duplications in generating novel traits today within and between diverse taxonomic groups.
Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments
Authors: Schott Ryan K , Fujita Matthew K , Streicher Jeffrey W , Gower David J , Thomas Kate N , Loew Ellis R , Bamba Kaya Abraham G , Bittencourt-Silva Gabriela B , Guillherme Becker C , Cisneros-Heredia Diego , Clulow Simon , Davila Mateo , Firneno Thomas J , Haddad Célio F B , Janssenswillen Sunita , Labisko Jim , Maddock Simon T , Mahony Michael , Martins Renato A , Michaels Christopher J , Mitchell Nicola J , Portik Daniel M , Prates Ivan , Roelants Kim , Roelke Corey , Tobi Elie , Woolfolk Maya , Bell Rayna C
Published: April 2024

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.
Inter-species Transcriptomic Analysis Reveals a Constitutive Adaptation Against Oxidative Stress for the Highly Virulent Leptospira Species
Authors: Giraud-Gatineau Alexandre , Ayachit Garima , Nieves Cecilia , Dagbo Kouessi C , Bourhy Konogan , Pulido Francisco , Huete Samuel G , Benaroudj Nadia , Picardeau Mathieu , Veyrier Frédéric J
Published: April 2024

Transcriptomic analyses across large scales of evolutionary distance have great potential to shed light on regulatory evolution but are complicated by difficulties in establishing orthology and limited availability of accessible software. We introduce here a method and a graphical user interface wrapper, called Annotator-RNAtor, for performing interspecies transcriptomic analysis and studying intragenus evolution. The pipeline uses third-party software to infer homologous genes in various species and highlight differences in the expression of the core-genes. To illustrate the methodology and demonstrate its usefulness, we focus on the emergence of the highly virulent Leptospira subclade known as P1+, which includes the causative agents of leptospirosis. Here, we expand on the genomic study through the comparison of transcriptomes between species from P1+ and their related P1- counterparts (low-virulent pathogens). In doing so, we shed light on differentially expressed pathways and focused on describing a specific example of adaptation based on a differential expression of PerRA-controlled genes. We showed that P1+ species exhibit higher expression of the katE gene, a well-known virulence determinant in pathogenic Leptospira species correlated with greater tolerance to peroxide. Switching PerRA alleles between P1+ and P1- species demonstrated that the lower repression of katE and greater tolerance to peroxide in P1+ species was solely controlled by PerRA and partly caused by a PerRA amino-acid permutation. Overall, these results demonstrate the strategic fit of the methodology and its ability to decipher adaptive transcriptomic changes, not observable by comparative genome analysis, that may have been implicated in the emergence of these pathogens.
Developing a National Longitudinal Tobacco Cohort of Youth and Young Adults: The Tobacco Epidemic Evaluation Network (TEEN+) Study
Authors: Seaman Elizabeth L , Kreslake Jennifer M , Cordova Jamie , Schillo Barbara , Barlas Frances , Marynak Kristy
Published: April 2024

Introduction

Timely and relevant data are critical to monitoring the rapidly changing youth vaping epidemic and for understanding the prevalence, patterns of use, knowledge, and perceptions of tobacco products. While e-cigarettes have been the most used tobacco product among youth for nearly a decade, new nicotine delivery products continue to be introduced to the US market. Flavored tobacco products, including flavored e-cigarettes, menthol cigarettes, and flavored cigars, drive disparities in use by young people.

Aims and Methods

To examine tobacco use among youth and young adults, the Monitoring E-Cigarette Use among Youth project established a longitudinal cohort of youth and young adults (13–24)—the Tobacco Epidemic Evaluation Network (TEEN+) study. TEEN+ focuses on e-cigarette and other tobacco products use and also includes questions about other substance use (eg, marijuana, alcohol), physical health, mental health, and social determinants of health (eg, discrimination, poverty, sexual and gender identity). Geocoding of responses allows for the evaluation of local tobacco control policies. The cohort includes an oversample of California residents to generate reliable and representative state-level estimates. This manuscript provides an overview of methods and baseline demographics from Wave 1.

Results

The initial Wave 1 TEEN+ cohort included 10 255 in the national sample and 2761 in the California sample.

Conclusions

TEEN+ study data complement nationally-representative cross-sectional studies and allow for rapid evaluation of local and state policies. This manuscript describes the study’s probability-based sample recruitment. Furthermore, we identify this initiative as a resource for evaluating the impact of flavored tobacco restriction policies and informing policy implementation efforts.

Implications

This manuscript provides an overview of the methodology and baseline characteristics for a new longitudinal cohort of youth and young adults, the Tobacco Epidemic Evaluation Network (TEEN+) study. The TEEN+ study data can be used to evaluate the impact of flavored tobacco product restriction policies and informing policy implementation efforts.
‘Sacred to the Memory’: Thomas Hardy’s Tombstones
Authors: Dema Eva
Published: April 2024

Thomas Hardy often composed with two distinct media in mind: print and inscription. Designing epitaphs for the tombstones of family members before turning to verse to reflect upon this largely frustrating inscriptive work, Hardy expressed a particular interest in the divergent capacities for alteration afforded by paper and stone. Reading Hardy’s monumental inscriptions alongside the poems they inspired, this article assesses the extent to which Hardy’s simultaneous engagement with manuscripts and tombstones—two surfaces that presented drastically different capacities for amendment—shaped his understanding of the function and potential of revision. Turning first to Hardy’s lifelong interest in stonework, this article considers the poet’s personal experience with letter-cutting and epitaphic design, before offering a close textual reading of the poetry this activity inspired. Considering three key verses penned in reflection upon the poet’s lapidary endeavours, I examine the compositional tension between media that emerges through revision, and the problem this poses for Hardy’s curious tendency to conflate the act of writing with the act of carving.
Buying into new ideas: the ECB’s evolving justification of unlimited liquidity
Authors: Hesse Casimir , Steininger Lea
Published: April 2024

In 2012, Draghi put an end to rising euro area sovereign bond yield spreads by resolving to do ‘whatever it takes’. The crisis rhetoric and institutional practices of unlimited liquidity have since become commonplace, as countermeasures to recent market turmoil show. This article sets out to explain how and why ‘unlimited liquidity’ ideas moved to the ECB’s center of economic analysis during the euro crisis. Previous work fails to decipher that the ideational shift was highly anomalous when viewed against German ordoliberalism or scholarly support for ‘expansionary austerity’. Addressing this relative neglect in other accounts, we draw on qualitative text analysis and expert interviews to argue that this shift was due to norm entrepreneurs who capitalized on the uncertainty of the crisis. We employ constructivist arguments to identify four scoping conditions that account for the ascendance of ‘unlimited liquidity’: an indicative reference, credibility, institutional positioning and—as an extension to the literature—intellectual sensitivity. Our analysis suggests that the euro crisis changed economic ideas, and fundamentally remodels the constructivist framework for studying monetary policy in crisis times.
The state and the state-of-the-art: prefiguring private insurance for US flood risk
Authors: Elliott Rebecca
Published: April 2024

States not only govern markets, but they also create them, often with the intention of expanding or improving the delivery of specific policy objectives. This article outlines one way they do this: prefiguration. States prefigure markets, and private market actors, when they imagine and instantiate new market products, logics, and practices. I illustrate prefiguration through an analysis of the history of the National Flood Insurance Program (NFIP), the federal program that underwrites flood insurance in the United States. From the time of the NFIP’s establishment, policymakers and officials have fashioned and continuously reformed a public program, and an insurance product, in ways that emulate an imagined primary private flood insurer. In doing so, though, they have gradually established the conditions under which private flood insurers can do business. This article contributes to scholarship on state ‘marketcraft’. Whereas many scholars have addressed why governments turn to markets in the first place, and the consequences of doing so, this article offers a closer examination of what takes place in between: the specific activities that governments undertake as they pursue market creation.
Perturbation of the insomnia WDR90 genome-wide association studies locus pinpoints rs3752495 as a causal variant influencing distal expression of neighboring gene, PIG-Q
Authors: Sonti Shilpa , Littleton Sheridan H , Pahl Matthew C , Zimmerman Amber J , Chesi Alessandra , Palermo Justin , Lasconi Chiara , Brown Elizabeth B , Pippin James A , Wells Andrew D , Doldur-Balli Fusun , Pack Allan I , Gehrman Phillip R , Keene Alex C , Grant Struan F A
Published: April 2024

Although genome-wide association studies (GWAS) have identified loci for sleep-related traits, they do not directly uncover the underlying causal variants and corresponding effector genes. The majority of such variants reside in non-coding regions and are therefore presumed to impact cis-regulatory elements. Our previously reported ‘variant-to-gene mapping’ effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in both Drosophila and zebrafish, implicated phosphatidyl inositol glycan (PIG)-Q as a functionally relevant gene at the insomnia “WDR90” GWAS locus. However, importantly that effort did not characterize the corresponding underlying causal variant. Specifically, our previous 3D genomic datasets nominated a shortlist of three neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium within an intronic enhancer region of WDR90 that contacted the open PIG-Q promoter. We sought to investigate the influence of these SNPs collectively and then individually on PIG-Q modulation to pinpoint the causal “regulatory” variant. Starting with gross level perturbation, deletion of the entire region in NPCs via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specific PIG-Q transcripts. Results from individual luciferase reporter assays for each SNP in iPSCs revealed that the region with the rs3752495 risk allele (RA) induced a ~2.5-fold increase in luciferase expression. Importantly, rs3752495 also exhibited an allele-specific effect, with the RA increasing the luciferase expression by ~2-fold versus the non-RA. In conclusion, our variant-to-function approach and in vitro validation implicate rs3752495 as a causal insomnia variant embedded within WDR90 while modulating the expression of the distally located PIG-Q.
The Soybean Rpp3 Gene Encodes a TIR-NBS-LRR Protein that Confers Resistance to Phakopsora pachyrhizi
Authors: Bish Mandy D. , Ramachandran Sowmya R. , Wright Amy , Lincoln Lori M. , Whitham Steven A. , Graham Michelle A. , Pedley Kerry F.
Published: April 2024

Soybean rust is an economically significant disease caused by the fungus Phakopsora pachyrhizi that negatively impacts soybean ( Glycine max [L.] Merr.) production throughout the world. Susceptible plants infected by P. pachyrhizi develop tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci ( Rpp1 to Rpp7) that provide race-specific resistance to P. pachyrhizi ( Rpp) have been identified. Rpp3 was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two Rpp genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the Rpp3 locus to a 371-kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify Rpp3, we designed oligonucleotide primers to amplify Rpp3 candidate ( Rpp3C) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five Rpp3C genes were identified in both Rpp3-resistant soybean lines, and co-silencing these genes compromised resistance to P. pachyrhizi. Gene expression analysis and sequence comparisons of the Rpp3C genes in PI 462312 and PI 506764 suggest that a single candidate gene, Rpp3C3, is responsible for Rpp3-mediated resistance.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Grove-Level Analysis of the Titer and Prevalence of ‘Candidatus Liberibacter asiaticus’ and Wolbachia in Diaphorina citri, Vector of Citrus Huanglongbing
Authors: Mann Marina , Thompson Luke , Johnson Lynn , Heck Michelle
Published: April 2024

Huanglongbing (HLB, or citrus greening disease) affects all citrus varieties worldwide. In the United States, Asia, and South America, the causal agent is ‘ Candidatus Liberibacter asiaticus’ ( CLas), a phloem-limited, uncultured alphaproteobacterium. The hemipteran insect vector Diaphorina citri (Asian citrus psyllid) acquires and transmits CLas in a circulative, propagative manner. In addition to CLas, D. citri hosts multiple symbiotic bacterial species including Wolbachia (wDi). In D. citri, wDi has been sequenced and studied, but specific roles in D. citri biology are unknown. Using well-established quantitative PCR methods, we measured CLas titer in D. citri collected from four groves in central Florida with distinct HLB management strategies and tested whether CLas and wDi titer were correlated in a subset of these insects. Grove site had the largest effect on CLas titer. Sex had no effect on CLas titer, whereas a higher wDi titer was correlated with noninfected insects. Our results suggest that more directed follow-up research is necessary and important to clarify whether field management tactics influence CLas titer in D. citri and to better understand gene-by-environment interactions among D. citri, wDi, and CLas. Now that millions of trees in Florida have been treated with injectable formulations of oxytetracycline, which is likely to decrease bacterial populations in D. citri, this study may represent the last biologically meaningful snapshot of grove-level vector-pathogen ecology in the state during the HLB epidemic.
Human umbilical cord mesenchymal stem cell‐derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling
Authors: Zhang Ke , Zheng Shuo , Wu Jiasheng , He Jing , Ouyang Yu , Ao Chunchun , Lang Ruibo , Jiang Yijia , Yang Yifan , Xiao Huan , Li Yu , Li Mao , Wang Huiming , Li Changyong , Wu Dongcheng
Published: April 2024

Diabetic nephropathy (DN) is the leading cause of end‐stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC‐MSCs) and UC‐MSC‐derived exosomes (UC‐MSC‐exo) attenuate kidney damage, and inhibit epithelial‐mesenchymal transition (EMT) and renal fibrosis in streptozotocin‐induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC‐MSC and UC‐MSC‐exo treatment resulted in decrease of SMO expression. In vitro co‐culture experiments revealed that UC‐MSC‐exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC‐MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC‐MSCs and their exosomes are novel anti‐fibrotic therapeutics for treating DN.
Xbp1 promotes odontoblastic differentiation through modulating mitochondrial homeostasis
Authors: Huang Delan , Li Yuanyuan , Han Jiahao , Zuo Huanyan , Liu Huan , Chen Zhi
Published: April 2024

Odontoblast differentiation depends on the orderly recruitment of transcriptional factors (TFs) in the transcriptional regulatory network. The depletion of crucial TFs disturbs dynamic alteration of the chromatin landscape and gene expression profile, leading to developmental defects. Our previous studies have revealed that the basic leucine zipper (bZIP) TF family is crucial in odontoblastic differentiation, but the function of bZIP TF family member XBP1 is still unknown. Here, we showed the stage‐specific expression patterns of the spliced form Xbp1s during tooth development. Elevated Xbp1 expression and nuclear translocation of XBP1S in mesenchymal stem cells (MSCs) were induced by differentiation medium in vitro. Diminution of Xbp1 expression impaired the odontogenic differentiation potential of MSCs. The further integration of ATAC‐seq and RNA‐seq identified Hspa9 as a direct downstream target, an essential mitochondrial chaperonin gene that modulated mitochondrial homeostasis. The amelioration of mitochondrial dysfunction rescued the impaired odontogenic differentiation potential of MSCs caused by the diminution of Xbp1. Furthermore, the overexpression of Hspa9 rescued Xbp1‐deficient defects in odontoblastic differentiation. Our study illustrates the crucial role of Xbp1 in odontoblastic differentiation via modulating mitochondrial homeostasis and brings evidence to the therapy of mitochondrial diseases caused by genetic defects.
Organ preservation in muscle-invasive urothelial bladder cancer
Authors: Niglio Scot A. , Purswani Juhi M. , Schiff Peter B. , Lischalk Jonathan W. , Huang William C. , Murray Katie S. , Apolo Andrea B.
Published: April 2024

Purpose of review

The most common definitive treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. However, removing the bladder and surrounding organs poses risks of morbidity that can reduce quality of life, and raises the risk of death. Treatment strategies that preserve the organs can manage the local tumor and mitigate the risk of distant metastasis. Recent data have demonstrated promising outcomes in several bladder-preservation strategies.

Recent findings

Bladder preservation with trimodality therapy (TMT), combining maximal transurethral resection of the bladder tumor, chemotherapy, and radiotherapy (RT), was often reserved for nonsurgical candidates for radical cystectomy. Recent meta-analyses show that outcomes of TMT and radical cystectomy are similar. More recent bladder-preservation approaches include combining targeted RT (MRI) and immune checkpoint inhibitors (ICIs), ICIs and chemotherapy, and selecting patients based on genomic biomarkers and clinical response to systemic therapies. These are all promising strategies that may circumvent the need for radical cystectomy.

MIBC is an aggressive disease with a high rate of systemic progression. Current management includes neoadjuvant cisplatin-based chemotherapy and radical cystectomy with lymph node dissection. Novel alternative strategies, including TMT approaches, combinations with RT, chemotherapy, and/or ICIs, and genomic biomarkers, are in development to further advance bladder-preservation options for patients with MIBC.
Validation of Long-term Recall of Pregnancy-related Weight in the Life-course Experiences And Pregnancy Study
Authors: Farkas Kriszta , Bodnar Lisa M. , Emery Tavernier Rebecca L. , Friedman Jessica K. , Johnson Sydney T. , MacLehose Richard F. , Mason Susan M.
Published: April 2024

Background:

Prepregnancy body mass index (BMI) and gestational weight gain (GWG) are determinants of maternal and child health. However, many studies of these factors rely on error-prone self-reported measures.

Methods:

Using data from Life-course Experiences And Pregnancy (LEAP), a US-based cohort, we assessed the validity of prepregnancy BMI and GWG recalled on average 8 years postpartum against medical record data treated as alloyed gold standard (“true”) values. We calculated probabilities of being classified into a self-reported prepregnancy BMI or GWG category conditional on one’s true category (analogous to sensitivities and specificities) and probabilities of truly being in each prepregnancy BMI or GWG category conditional on one’s self-reported category (analogous to positive and negative predictive values).

Results:

There was a tendency toward under-reporting prepregnancy BMI. Self-report misclassified 32% (95% confidence interval [CI] = 19%, 48%) of those in LEAP with truly overweight and 13% (5%, 27%) with obesity into a lower BMI category. Self-report correctly predicted the truth for 72% (55%, 84%) with self-reported overweight to 100% (90%, 100%) with self-reported obesity. For GWG, both under- and over-reporting were common; self-report misclassified 32% (15%, 55%) with truly low GWG as having moderate GWG and 50% (28%, 72%) with truly high GWG as moderate or low GWG. Self-report correctly predicted the truth for 45% (25%, 67%) with self-reported high GWG to 85% (76%, 91%) with self-reported moderate GWG. Misclassification of BMI and GWG varied across maternal characteristics.

Conclusion:

Findings can be used in quantitative bias analyses to estimate bias-adjusted associations with prepregnancy BMI and GWG.
A Revised System of Radiological Protection Is Needed
Authors: Scott Bobby R.
Published: April 2024

The system of radiological protection has been based on linear no-threshold theory and related dose-response models for health detriment (in part related to cancer induction) by ionizing radiation exposure for almost 70 y. The indicated system unintentionally promotes radiation phobia, which has harmed many in relationship to the Fukushima nuclear accident evacuations and led to some abortions following the Chernobyl nuclear accident. Linear no-threshold model users (mainly epidemiologists) imply that they can reliably assess the cancer excess relative risk (likely none) associated with tens or hundreds of nanogray (nGy) radiation doses to an organ (e.g., bone marrow); for 1,000 nGy, the excess relative risk is 1,000 times larger than that for 1 nGy. They are currently permitted this unscientific view (ignoring evolution-related natural defenses) because of the misinforming procedures used in data analyses of which many radiation experts are not aware. One such procedure is the intentional and unscientific vanishing of the excess relative risk uncertainty as radiation dose decreases toward assigned dose zero (for natural background radiation exposure). The main focus of this forum article is on correcting the serious error of discarding risk uncertainty and the impact of the correction. The result is that the last defense of the current system of radiological protection relying on linear no-threshold theory (i.e., epidemiologic studies implied findings of harm from very low doses) goes away. A revised system is therefore needed.