bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing quantitative PCR with color cycle multiplex amplification
Authors: Chen Wei , Zhang Kerou , Huang Fei , Zhao Lan , Waldren George C , Jiang Qi , Chen Sherry X , Wang Bonnie , Guo Wei , Zhang David Y , Zhang Jinny X
Published: August 2024

Quantitative PCR (qPCR) is the gold standard for detection and quantitation of known DNA targets, but the scarcity of spectrally distinct fluorophores and filter sets limits the number of detectable targets. Here, we introduce color cycle multiplex amplification (CCMA) to significantly increase the number of detectable DNA targets in a single qPCR reaction using standard instrumentation. In CCMA, presence of one DNA target species results in a pre-programmed pattern of fluorescence increases. This pattern is distinguished by cycle thresholds (Cts) through rationally designed delays in amplification. For example, we design an assay wherein Staphylococcus aureus sequentially induces FAM, then Cy5.5, then ROX fluorescence increases with more than 3 cycles between each signal. CCMA offers notably higher potential for multiplexing because it uses fluorescence permutation rather than combination. With 4 distinct fluorescence colors, CCMA theoretically allows the detection of up to 136 distinct DNA target sequences using fluorescence permutation. Experimentally, we demonstrated a single-tube qPCR assay screening 21 sepsis-related bacterial DNA targets in samples of blood, sputum, pleural effusion and bronchoalveolar lavage fluid, with 89% clinical sensitivity and 100% clinical specificity, showing its potential as a powerful tool for advanced quantitative screening in molecular diagnostics.
junctionCounts: comprehensive alternative splicing analysis and prediction of isoform-level impacts to the coding sequence
Authors: Ritter Alexander J , Wallace Andrew , Ronaghi Neda , Sanford Jeremy R
Published: August 2024

Alternative splicing (AS) is emerging as an important regulatory process for complex biological processes. Transcriptomic studies therefore commonly involve the identification and quantification of alternative processing events, but the need for predicting the functional consequences of changes to the relative inclusion of alternative events remains largely unaddressed. Many tools exist for the former task, albeit each constrained to its own event type definitions. Few tools exist for the latter task; each with significant limitations. To address these issues we developed junctionCounts, which captures both simple and complex pairwise AS events and quantifies them with straightforward exon-exon and exon-intron junction reads in RNA-seq data, performing competitively among similar tools in terms of sensitivity, false discovery rate and quantification accuracy. Its partner utility, cdsInsertion, identifies transcript coding sequence (CDS) information via in silico translation from annotated start codons, including the presence of premature termination codons. Finally, findSwitchEvents connects AS events with CDS information to predict the impact of individual events to the isoform-level CDS. We used junctionCounts to characterize splicing dynamics and NMD regulation during neuronal differentiation across four primates, demonstrating junctionCounts’ capacity to robustly characterize AS in a variety of organisms and to predict its effect on mRNA isoform fate.
The Claim for An Institutional Identity in Healthcare Activities: the Italian Case
Authors: Madera Adelaide
Published: August 2024

The aim of this article is to analyse the status of religiously affiliated health facilities in Italy. Many faith-based healthcare institutions are currently entrapped between the expectation to participate in the healthcare public delivery, and the need for a preservation of their religious identity. Indeed, they are facing an increasing risk of a weakening of their religious identity, due to the evolution of civil law regulating ethically controversial issues, which is increasingly distancing from the religious approach, undermining the traditional religious accommodation granted to faith-based healthcare institutions. However, the preservation of their religious ethos requires dealing with a ‘web of relationships’ which includes the founding religious order, patients, practitioners, the State and a ‘highly competitive market’. This article explores the feasibility of an intermediate path between complete immunity and strict non-tolerance of their religious ethos, in the pursuit of the constitutional principles of pluralism, positive neutrality, and subsidiarity.
Viscoelastic performance of bagasse/glass fiber hybrid epoxy composites: effects of fiber hybridization on storage modulus, loss modulus, and damping behavior
Authors: Sumaila Malachy , Samuel Bassey Okon
Published: August 2024

This study aimed to investigate the viscoelastic properties of bagasse/glass fiber multilayered hybrid reinforced epoxy composites, focusing on how fiber hybridization affects dynamic mechanical performance. Epoxy composites with various layering sequences, including all-glass (AG), all-bagasse (AB), bagasse-glass-bagasse (BGB), and glass-bagasse-glass (GBG), were fabricated and analyzed using dynamic mechanical analysis (DMA) to measure storage modulus (E′), loss modulus (E″), and damping factor (tan δ). The results showed that hybrid composites (GBG and BGB) experienced a decrease in storage modulus by approximately 25% compared to AG, indicating enhanced polymer molecular chain mobility and improved interfacial adhesion between bagasse fibers and the epoxy matrix. The glass transition temperature (Tg) was slightly lower in hybrid composites, with GBG at 61°C and BGB at 60°C, compared to 62°C for AG. In terms of energy dissipation, AG exhibited the highest loss modulus peak at 62°C, while AB showed the lowest with a Tg at 53°C. The damping factor analysis revealed that AB had the highest damping peak (tan δ = 0.9) at 61°C, although this occurred at a lower temperature than the AG composite (tan δ = 0.7 at 76°C). These findings suggest that bagasse and glass fiber hybrid composites offer tailored viscoelastic properties, making them suitable for applications in automotive components, aerospace structures, and sports equipment.
The British Political Tradition and Constitutional Policy: The Offer of Deliberative Mini Publics
Authors: Coulter Steph , McKee Rebecca , Pannell Jack , Sargeant Jess
Published: August 2024

The Review of the UK Constitution was an eighteen-month project assessing the functioning of the UK constitution resulting in a set of practical, innovative, and robust recommendations. This article draws out one theme from this research, the offer of Deliberative Mini Publics (DMPs) in the process of constitutional change in the UK. Using Marsh, Richards, and Smith’s ‘Asymmetric Power Model’ as a mechanism for understanding the centralised and top–down nature of British democracy, we argue that the integration of DMPs can offer an opportunity to mitigate some of the core problems with the functioning of the UK constitution and produce better constitutional policy.
Natural Variation in Sexual Traits and Gene Expression between Selfing and Outcrossing Arabidopsis lyrata Suggests Sexual Selection at Work
Authors: İltaş Ömer , Čertner Martin , Lafon Placette Clément
Published: August 2024

Flowering plants show significant diversity in sexual strategies, profoundly impacting the evolution of sexual traits and associated genes. Sexual selection is one of the primary evolutionary forces driving sexual trait variation, particularly evident during pollen–pistil interactions, where pollen grains compete for fertilization and females select mating partners. Multiple mating may intensify competition among pollen donors for siring, while in contrast, self-fertilization reduces sire–sire competition, relaxing the sexual selection pressure. Traits involved in male–male competition and female choice are well described, and molecular mechanisms underlying pollen development and pollen–pistil interactions have been extensively studied in the model species Arabidopsis thaliana. However, whether these molecular mechanisms are involved in sexual selection in nature remains unclear. To address this gap, we measured intrinsic pollen performance and its interaction with female choice and investigated the associated gene expression patterns in a selfing and an outcrossing population of Arabidopsis lyrata. We found that pollen germination and pollen tube growth were significantly higher in outcrossers than selfers, and this difference was accompanied by changes in the expression of genes involved in vesicle transport and cytoskeleton. Outcrosser mother plants showed a negative impact on pollen tube growth compared to selfer mother plants, together with a difference of expression for genes involved in auxin and stress response, suggesting a potential mechanism for female choice through molecular cross talk at the post-pollination stage. Our study provides insight into the impact of sexual selection on the evolution of sexual gene expression in plants.
Alternating between even and odd ploidy levels switches on and off the recombination control, even near the centromeres
Authors: Boideau Franz , Huteau Virginie , Maillet Loeiz , Brunet Anael , Coriton Olivier , Deniot Gwenaëlle , Trotoux Gwenn , Taburel-Lodé Maryse , Eber Frédérique , Gilet Marie , Baron Cécile , Boutte Julien , Richard Gautier , Aury Jean-Marc , Belser Caroline , Labadie Karine , Morice Jérôme , Falentin Cyril , Martin Olivier , Falque Matthieu , Chèvre Anne-Marie , Rousseau-Gueutin Mathieu
Published: August 2024

Meiotic recombination is a key biological process in plant evolution and breeding, as it generates genetic diversity in each generation through the formation of crossovers (COs). However, due to their importance in genome stability, COs are highly regulated in frequency and distribution. We previously demonstrated that this strict regulation of COs can be modified, both in terms of CO frequency and distribution, in allotriploid Brassica hybrids (2n = 3x = 29; AAC) resulting from a cross between Brassica napus (2n = 4x = 38; AACC) and Brassica rapa (2n = 2x = 20; AA). Using the recently updated B. napus genome now including pericentromeres, we demonstrated that COs occur in these cold regions in allotriploids, as close as 375 kb from the centromere. Reverse transcription quantitative PCR (RT-qPCR) of various meiotic genes indicated that Class I COs are likely involved in the increased recombination frequency observed in allotriploids. We also demonstrated that this modified recombination landscape can be maintained via successive generations of allotriploidy (odd ploidy level). This deregulated meiotic behavior reverts to strict regulation in allotetraploid (even ploidy level) progeny in the second generation. Overall, we provide an easy way to manipulate tight recombination control in a polyploid crop.
Dosage sensitivity shapes balanced expression and gene longevity of homoeologs after whole-genome duplications in angiosperms
Authors: Shi Tao , Gao Zhiyan , Chen Jinming , Van de Peer Yves
Published: August 2024

Following whole-genome duplication (WGD), duplicate gene pairs (homoeologs) can evolve varying degrees of expression divergence. However, the determinants influencing these relative expression level differences (RFPKM) between homoeologs remain elusive. In this study, we analyzed the RFPKM between homoeologs in 3 angiosperms, Nymphaea colorata, Nelumbo nucifera, and Acorus tatarinowii, all having undergone a single WGD since the origin of angiosperms. Our results show significant positive correlations in RFPKM of homoeologs among tissues within the same species, and among orthologs across these 3 species, indicating convergent expression balance/bias between homoeologous gene copies following independent WGDs. We linked RFPKM between homoeologs to gene attributes associated with dosage-balance constraints, such as protein–protein interactions, lethal-phenotype scores in Arabidopsis (Arabidopsis thaliana) orthologs, domain numbers, and expression breadth. Notably, homoeologs with lower RFPKM often had more interactions and higher lethal-phenotype scores, indicating selective pressures favoring balanced expression. Also, homoeologs with lower RFPKM were more likely to be retained after WGDs in angiosperms. Within Nelumbo, greater RFPKM between homoeologs correlated with increased cis- and trans-regulatory differentiation between species, highlighting the ongoing escalation of gene expression divergence. We further found that expression degeneration in 1 copy of homoeologs is inclined toward nonfunctionalization. Our research highlights the importance of balanced expression, shaped by dosage-balance constraints, in the evolutionary retention of homoeologs in plants.
Exogenous application of the apocarotenoid retinaldehyde negatively regulates auxin-mediated root growth
Authors: Xu Kang , Zeng Haoran , Lin Feiyang , Yumoto Emi , Asahina Masashi , Hayashi Ken-ichiro , Fukaki Hidehiro , Ito Hisashi , Watahiki Masaaki K
Published: August 2024

Root development is essential for plant survival. The lack of carotenoid biosynthesis in the phytoene desaturase 3 (pds3) mutant results in short primary roots (PRs) and reduced lateral root formation. In this study, we showed that short-term inhibition of PDS by fluridone suppresses PR growth in wild type, but to a lesser extent in auxin mutants of Arabidopsis (Arabidopsis thaliana). Such an inhibition of PDS activity increased endogenous indole-3-acetic acid levels, promoted auxin signaling, and partially complemented the PR growth of an auxin-deficient mutant, the YUCCA 3 5 7 8 9 quadruple mutant (yucQ). The exogenous application of retinaldehyde (retinal), an apocarotenoid derived from β-carotene, complemented the fluridone-induced suppression of root growth, as well as the short roots of the pds3 mutant. Retinal also partially complemented the auxin-induced suppression of root growth. These results suggest that retinal may play a role in regulating root growth by modulating endogenous auxin levels.
Associations between 1930s HOLC grades and estimated population burden of cardiovascular disease risk factors in 2020
Authors: Wei Hanxue , Spoer Benjamin R , Titus Andrea R , Lampe Taylor M , Gourevitch Marc N , Faber Jacob W , Korzeniewski Steven J , Bauer Samantha J , Thorpe Lorna E
Published: August 2024

Studies have recently begun to explore the potential long-term health impacts of homeownership policies implemented in the New Deal era. We investigated the association between assigned grades of lending risk by the Home Owners’ Load Corporation (HOLC) maps from the 1930s and present-day prevalence of three cardiovascular risk factors (diabetes and obesity in 2020, and hypertension in 2019), estimated at the census tract level in the United States. To minimize potential confounding, we adjusted for sociodemographic data from the time period when HOLC maps were made. We calculated propensity scores (predicted probability of receiving a HOLC grade) and created a pseudo-population using inverse probability weighting. We then employed marginal structural models to estimate prevalence differences comparing A vs. B, B vs. C, and C vs. D HOLC grades. Adjusting only for regions, a less desirable HOLC grade was associated with higher estimated prevalence rates of present-day cardiovascular risk factors; however, most differences were no longer significant after applying propensity score methods. The one exception was that the prevalence of diabetes, hypertension, and obesity were all higher in C vs. B graded census tracts, while no differences were observed for C and D and A and B comparisons. These results contribute to a small body of evidence that suggests historical “yellowlining” (as C grade was in color yellow) may have had persistent impacts on neighborhood-level cardiovascular risk factors 80 years later.
Mantis: High-throughput 4D imaging and analysis of the molecular and physical architecture of cells
Authors: Ivanov Ivan E , Hirata-Miyasaki Eduardo , Chandler Talon , Cheloor-Kovilakam Rasmi , Liu Ziwen , Pradeep Soorya , Liu Chad , Bhave Madhura , Khadka Sudip , Arias Carolina , Leonetti Manuel D , Huang Bo , Mehta Shalin B
Published: August 2024

High-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell imaging technologies: remote-refocus label-free microscopy and oblique light-sheet fluorescence microscopy. Additionally, we report shrimPy (Smart High-throughput Robust Imaging and Measurement in Python), an open-source software for high-throughput imaging, deconvolution, and single-cell phenotyping of 4D data. Using Mantis and shrimPy, we achieved high-content correlative imaging of molecular dynamics and the physical architecture of 20 cell lines every 15 min over 7.5 h. This platform also facilitated detailed measurements of the impacts of viral infection on the architecture of host cells and host proteins. The Mantis platform can enable high-throughput profiling of intracellular dynamics, long-term imaging and analysis of cellular responses to perturbations, and live-cell optical screens to dissect gene regulatory networks.
An exploration of interview breaks in child forensic interviews
Authors: Danby Meaghan C , Sharman Stefanie J
Published: August 2024

Child forensic interview guidelines commonly recommend that interviewers take breaks during interviews to improve children’s comfort and to review the evidence obtained. However, instructions vary on how, when, and why to take breaks. Recent studies have also raised concerns about whether the feedback that interviewers receive during breaks reduces the quality of their post-break questioning. To establish interviewers’ use of breaks and compare their pre- versus post-break questioning, we recruited 54 police child interviewers. Participants provided a recent child interview and completed a questionnaire about their use of breaks in that interview. Breaks were rarely used for children’s comfort but were commonly used to review the evidence obtained. While interviewers’ questioning was proportionally more specific and less open-ended post-break (compared to pre-break), post-break open-ended questioning was positively associated with receiving advice from a colleague monitoring the interview about best practice techniques. Therefore, it is important that interview monitors have child interviewing knowledge.
The exosphere of Mars can be tracked by a high-spectral resolution telescope, such as the Line Emission Mapper
Authors: Carter Jennifer A , Dennerl K , Kuntz K D , Dunn W , Bodewits D , Jackman C M , Sembay S F , Branduardi-Raymont G , Deskins T , Koutroumpa D , Kraft R , Lisse C , McEntee S , Wolk S , Porter F S
Published: August 2024

Mars provides our local analogue for unmagnetized terrestrial planets and is thus key to understanding the habitability of exoplanets. The lack of a global magnetic field means that the atmosphere interacts directly with the solar wind, causing significant loss of the atmosphere. While in situ measurements provide a wealth of detailed local information, they are limited in deriving the global picture. In contrast, remote X-ray observations can provide important global instantaneous coverage over multiple seasons and sampling different solar wind. Previous XMM–Newton observations have detected significant flux via the solar wind charge exchange emission (SWCX) mechanism from an extended planetary halo, and from atmospheric fluorescence. In contrast, Chandra observations only detected a low-luminosity disc and a faint halo. It is postulated that these observational differences are due to transient solar wind with increased heavy ion fractions. Here, we present simulated spectra for the proposed NASA mission Line Emission Mapper, of both halo and disc regions, under quiet and transient solar wind. We show that even under moderate solar wind conditions, both SWCX and fluorescence emission lines are readily detected above the background, providing new insights into the loss of planetary atmospheres and the molecular composition of less well-characterized atmospheric abundances.
Empirical Investigation of a Sufficient Statistic for Monetary Shocks
Authors: Alvarez Fernando , Ferrara Andrea , Gautier Erwan , Le Bihan Hervé , Lippi Francesco
Published: August 2024

In a broad class of sticky-price models, the non-neutrality of nominal shocks is captured by a simple sufficient statistic: the ratio of the kurtosis of the price change distribution over the frequency of price changes. We test the sufficient statistic proposition using data for a large sample of products representative of the French economy. We first extend the theory to allow for empirically relevant monetary shocks with a transitory predictable component. We then use the microdata to measure kurtosis and frequency for about 120 producer price indices industries and 220 consumer price indices categories. We use a Factor-Augmented Vector Autoregressive (FAVAR) model to measure the industries’ response to monetary shocks, under alternative identification schemes. The estimated degree of non-neutrality correlates with the kurtosis and the frequency consistently with the predictions of the theory. Several robustness checks are discussed.
A predictive model for progression to clinical arthritis in at-risk individuals with arthralgia based on lymphocyte subsets and ACPA
Authors: Prajzlerová Klára , Kryštůfková Olga , Kaspříková Nikola , Růžičková Nora , Hulejová Hana , Hánová Petra , Vencovský Jiří , Šenolt Ladislav , Filková Mária
Published: August 2024

Background

The presence of ACPA significantly increases the risk of developing RA. Dysregulation of lymphocyte subpopulations was previously described in RA. Our objective was to propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA.

Methods

Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA.

Results

Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis.

Conclusions

We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.
Public opinion and expert critique: reconsidering the role of constitutional scholars in Japan’s security policy
Authors: Iseki Tatsuya , Shinomoto Sou
Published: August 2024

Do experts’ opinions influence public opinion? Although experts with academic backgrounds are gaining a presence in policy debates, empirical studies deliver inconclusive results on whether experts have a cueing effect. Moreover, while most studies focus on cases where experts propose or recommend policies, the influence of their criticism on government policy has not received much research attention. To fill this gap, through an online survey in Japan, we test the effect of constitutional scholars’ criticism on people’s support for a dispatch of the Japan Self-Defense Forces (JSDF). Since constitutional academics, regarded as influential experts, have historically criticized the constitutional legitimacy of Japan’s security policy, they provide a suitable case to examine. The results show that such criticism has no causal effect on public attitudes even among the most liberal respondents or those with high confidence in constitutional scholars. Contrary opinions from retired general officers decreased support for the dispatch among individuals who were conservative or had high confidence in the JSDF. These findings imply that though people consciously sift through information from different sources, they mostly reject the opinions of academic experts.
Testicular prostheses: a historical and current review of the literature
Authors: Matthew-Onabanjo Asia N , Honig Stanton
Published: August 2024

Introduction

Testicular prosthesis can be placed at the time of orchiectomy for many benign and malignant testicular conditions. The American Urological Association guidelines recommend discussing the implant prior to the procedure.

Objectives

We review the literature on testicular prosthesis placement with respect to the history, psychological impact, surgical technique, complications, satisfaction, and novel emerging medical implications.

Methods

A Medline search was conducted with several terms related to and including “testicular implant,” “testicular prosthesis,” “testicular implant satisfaction,” and “testicular implant history.” Twenty articles were identified with patient satisfaction data. Satisfaction with the comfort, shape, size, and weight was reported in addition to satisfaction with the device from 13 studies.

Results

Overall satisfaction of testicular prosthesis is reported as high. Patients should be offered an implant at the time of orchiectomy or at any subsequent time based on their preference.

Conclusion

This article presents a contemporary and comprehensive review of the literature on testicular prostheses. Satisfaction rates following implantation remain consistently high. Additionally, innovative approaches are being investigated, including the exploration of novel implants for treating hypogonadism. Moreover, the utilization of 3-dimensional printing technology is revolutionizing the creation of testicular implants, aiming to achieve a texture and density closely resembling human testicles.
“The Explosive Ingredients Are Here” Mexican American Municipal Electoral Challenges in South Texas, 1963–1965
Authors: Campney Brent M S
Published: August 2024

This article examines the unsettled landscape of racial and political relations between and among Mexican Americans and Anglos in South Texas from 1963 to 1965, as liberal Mexican American civil rights activists organized to challenge longstanding Anglo power, driving fear, anger, and backlash among Anglos and exacerbating divisions among Mexican Americans across lines of class and ideology. In three sections, the work investigates a series of threatened, attempted, and successful municipal electoral challenges by Mexican American voters beyond the well-known and widely publicized such event in Crystal City in 1963. In the first section, the study details the embryonic municipal electoral challenges that erupted before and after Crystal City between 1963 and 1965, showing that Mexican American South Texans supported the overthrow of Anglo political domination. In the second, it sketches the responses of Anglos to what they termed “Latin take-overs,” reflecting the erosion of Anglo dominance. In the third, it examines how the electoral challenges mounted by Mexican Americans revealed internecine ideological and class divisions amongst themselves over the most effective ways to challenge racism, demonstrating the conflicts that undermined their efforts and strengthened those of the Anglos. In so doing, the study challenges and revises the historiography of the Crystal City ‘revolt’ and its legacies.
6Economic Criticism
Authors: Stallings Camille L
Published: August 2024

This year’s review of work in economic criticism focuses on three points of interest that reflect the year’s work in economic theory, providing an overview of some of the broader critical enquiries preoccupying the field of economic writing in 2023 and early 2024. The first is the intersection of animal studies and Marxism, exemplified by Leigh Claire La Berge’s Marx for Cats: A Radical Bestiary. The second key aspect of economic writing this year is the overlapping concerns of women, money, and property, represented here in Lana L. Dalley’s edited collection, Women’s Economic Writing in the Nineteenth Century and Jill Rappoport’s Imagining Women’s Property in Victorian Fiction. The third focus lands on speculative time and futurity within the domain of American literature, capitalism, and finance, as Paul Crosthwaite’s Speculative Time: American Literature in an Age of Crisis astutely captures.
Timing of intercontinental faunal migrations: Anguimorph lizards from the earliest Eocene (MP 7) of Dormaal, Belgium
Authors: Čerňanský Andrej , Smith Richard , Smith Thierry , Folie Annelise
Published: August 2024

Here we report on anguimorph lizards from the earliest Eocene (MP 7) of the Dormaal locality in Belgium, from the time of the warmest global climate of the past 66 million years. Several clades can be identified in this site: Glyptosauridae, Varanidae, and Palaeovaranidae. Our study focuses on glyptosaurid specimens previously reported from the site, some of which had been provisionally described as a new species,?Placosaurus ragei, and some assigned to an unnamed Placosauriops-like ‘melanosaurine’. Our study presents data on new material, including an almost complete glyptosaurine frontal that has enabled us to assign much of the previously described material to a single genus and species. The specimens that had been assigned to both ?P ragei and the ‘melanosaurine’ share apomorphies (flat osteoderms and chevron-shaped osteoderms) with Gaultia, a glyptosaurid previously known from the earliest Eocene of Wyoming, USA. The Dormaal material represents the first record of this genus outside North America. In fact, the only potential evidence of the occurrence of ‘Melanosaurinae’ in Dormaal might be a single isolated vertebra described here. Here we also describe previously unfigured material of Saniwa and palaeovaranids from Dormaal. The presence of previously reported helodermatids cannot be supported in this Belgian site.
What Explains Hop Growers’ Fungicide Use Intensity and Management Costs in Response to Powdery Mildew?
Authors: Hwang Jae Young , Bhattacharyya Sharmodeep , Chatterjee Shirshendu , Marsh Thomas L. , Pedro Joshua F. , Gent David H.
Published: August 2024

Methods for causal inference from observational data are common in human disease epidemiology and social sciences but are used relatively little in plant pathology. We draw upon an extensive data set of the incidence of hop plants with powdery mildew (caused by Podosphaera macularis) collected from yards in Oregon from 2014 to 2017 and associated metadata on grower cultural practices, cultivar susceptibility to powdery mildew, and pesticide application records to understand variation in and causes of growers’ fungicide use and associated costs. An instrumental causal forest model identified growers’ spring pruning thoroughness, cultivar susceptibility to two of the dominant pathogenic races of P. macularis, network centrality of yards during May–June and June–July time transitions, and the initial strain of the fungus detected as important variables determining the number of pesticide active constituents applied by growers and the associated costs they incurred in response to powdery mildew. Exposure-response function models fit after covariate weighting indicated that both the number of pesticide active constituents applied and their associated costs scaled linearly with the seasonal mean incidence of plants with powdery mildew. Although the causes of pesticide use intensity are multifaceted, biological and production factors collectively influence the incidence of powdery mildew, which has a direct exposure-response relationship with the number of pesticide active constituents that growers apply and their costs. Our analyses point to several potential strategies for reducing pesticide use and costs for management of powdery mildew on hop. We also highlight the utility of these methods for causal inference in observational studies.
Hypoxia‐inducible factor‐1α can reverse the Adriamycin resistance of breast cancer adjuvant chemotherapy by upregulating transferrin receptor and activating ferroptosis
Authors: Yu Xiaojie , Guo Qingqun , Zhang Haojie , Wang Xiaohong , Han Yong , Yang Zhenlin
Published: August 2024

Breast cancer is a common malignant tumor in women. Ferroptosis, a programmed cell death pathway, is closely associated with breast cancer and its resistance. The transferrin receptor (TFRC) is a key factor in ferroptosis, playing a crucial role in intracellular iron accumulation and the occurrence of ferroptosis. This study investigates the influence and significance of TFRC and its upstream transcription factor hypoxia‐inducible factor‐1α (HIF1α) on the efficacy of neoadjuvant therapy in breast cancer. The differential gene obtained from clinical samples through genetic sequencing is TFRC. Bioinformatics analysis revealed that TFRC expression in breast cancer was significantly greater in breast cancer tissues than in normal tissues, but significantly downregulated in Adriamycin (ADR)‐resistant tissues. Iron‐responsive element‐binding protein 2 (IREB2) interacts with TFRC and participates in ferroptosis. HIF1α, an upstream transcription factor, positively regulates TFRC. Experimental results indicated higher levels of ferroptosis markers in breast cancer tissue than in normal tissue. In the TAC neoadjuvant regimen‐sensitive group, iron ion (Fe2+) and malondialdehyde (MDA) levels were greater than those in the resistant group (all p < .05). Expression levels of TFRC, IREB2, FTH1, and HIF1α were higher in breast cancer tissue compared to normal tissue. Additionally, the expression of the TFRC protein in the TAC neoadjuvant regimen‐sensitive group was significantly higher than that in the resistant group (all p < .05), while the difference in the level of expression of IREB2 and FTH1 between the sensitive and resistant groups was not significant (p > .05). The dual‐luciferase assay revealed that HIF1α acts as an upstream transcription factor of TFRC (p < .05). Overexpression of HIF1α in ADR‐resistant breast cancer cells increased TFRC, Fe2+, and MDA content. After ADR treatment, the cell survival rate decreased significantly, and ferroptosis could be reversed by the combined application of Fer‐1 (all p < .05). In conclusion, ferroptosis and chemotherapy resistance are correlated in breast cancer. TFRC is a key regulatory factor influenced by HIF1α and is associated with chemotherapy resistance. Upregulating HIF1α in resistant cells may reverse resistance by activating ferroptosis through TFRC overexpression.
Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis
Authors: Gao Xiang , Gao Ning , Du Miaomiao , Xiang Yongguo , Zuo Hangjia , Cao Huijie , Zheng Shijie , Huang Rongxi , Wan Wenjuan , Hu Ke
Published: August 2024

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF‐1α), ATP2A2, P53, α‐SMA, Caspase‐3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF‐1α, ATP2A2, P53, α‐SMA, Caspase‐3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.
Neuropeptide Y Y2 Receptors in Sensory Neurons Tonically Suppress Nociception and Itch but Facilitate Postsurgical and Neuropathic Pain Hypersensitivity
Authors: Basu Paramita , Maddula Akshitha , Nelson Tyler S. , Prasoon Pranav , Winter Michelle K. , Herzog Herbert , McCarson Kenneth E. , Taylor Bradley K.
Published: August 2024

Background:

Neuropeptide Y (NPY) Y2 receptor (Y2) antagonist BIIE0246 can both inhibit and facilitate nociception. We hypothesized that Y2 function depends on inflammation or nerve injury status.

Methods:

We implemented a battery of behavioral tests in mice of both sexes that received: 1) no injury; 2) an incision model of postoperative pain; 3) a spared nerve injury (SNI) model of neuropathic pain; and 4) a latent sensitization model of chronic postsurgical pain. In addition to Y2 gene expression assays, spinal Y2 G-protein coupling was studied with [ 35S]GTPγS binding assays.

Results:

We report that intrathecal BIIE0246 increased mechanical and cold hypersensitivity, produced behavioral signs of spontaneous nociception and itch, and produced conditioned place aversion and preference in normal, uninjured mice. BIIE0246 did not change heat hypersensitivity or motor coordination. Conditional (sensory neuron-specific) Y2 deletion prevented BIIE0246-induced mechanical and cold hypersensitivity, nocifensive behaviors and aversion. Both conditional deletion and pharmacological blockade of Y2 reduced mechanical and thermal hypersensitivity after incision or nerve injury. SNI did not change the sensitivity of Y2 G-protein coupling with the Y2 agonist PYY3-36, but increased the population of Y2 that effectively coupled G-proteins. Intrathecal PYY3-36 failed to reduce SNI- or incision-induced hypersensitivity in C57BL/6N mice. Incision did not change Npy2r gene expression in dorsal root ganglion.

Conclusions:

We conclude that Y2 at central terminals of primary afferent neurons provide tonic inhibition of mechanical and cold nociception and itch. This switches to the promotion of mechanical and thermal hyperalgesia in models of acute and chronic postsurgical and neuropathic pain, perhaps due to an increase in the population of Y2 that effectively couple to G-proteins. These results support the development of Y2 antagonists for the treatment of chronic postsurgical and neuropathic pain.
Within-hospital Temporal Clustering of Postoperative Complications and Implications for Safety Monitoring and Benchmarking Using ACS-NSQIP Data
Authors: Cohen Mark E. , Liu Yaoming , Ko Clifford Y. , Hall Bruce L.
Published: August 2024

Objective:

To determine the extent to which within-hospital temporal clustering of postoperative complications is observed in the American College of Surgeons, National Surgical Quality Improvement Program (ACS-NSQIP).

Background:

ACS-NSQIP relies on periodic and on-demand reports for quality benchmarking. However, if rapid increases in postoperative complication rates (clusters) are common, other reporting methods might be valuable additions to the program. This article focuses on estimating the incidence of within-hospital temporal clusters.

Methods:

ACS-NSQIP data from 1,547,440 patients, in 425 hospitals, over a 2-year period was examined. Hospital-specific Cox proportional hazards regression was used to estimate the incidence of mortality, morbidity, and surgical site infection (SSI) over a 30-day postoperative period, with risk adjustment for patient and procedure and with additional adjustments for linear trend, day-of-week, and season. Clusters were identified using scan statistics, and cluster counts were compared, using unpaired and paired t tests, for different levels of adjustment and when randomization of cases across time eliminated all temporal influences.

Results:

Temporal clusters were rarely observed. When clustering was adjusted only for patient and procedure risk, an annual average of 0.31, 0.85, and 0.51 clusters were observed per hospital for mortality, morbidity, and SSI, respectively. The number of clusters dropped after adjustment for linear trend, day-of-week, and season (0.31–0.24; P = 0.012; 0.85–0.80; P = 0.034; and 0.51–0.36; P < 0.001; using paired t tests) for mortality, morbidity, and SSI, respectively. There was 1 significant difference in the number of clusters when comparing data with all adjustments and after data were randomized (0.24 and 0.25 for mortality; P = 0.853; 0.80 and 0.82 for morbidity; P = 0.529; and 0.36 and 0.46 [randomized data had more clusters] for SSI; P = 0.001; using paired t tests) for mortality, morbidity, and SSI, respectively.

Conclusions:

Temporal clusters of postoperative complications were rarely observed in ACS-NSQIP data. The described methodology may be useful in assessing clustering in other surgical arenas.
Heart involvement in systemic sclerosis: emerging concepts
Authors: Fairley Jessica L. , Ross Laura , Nikpour Mandana
Published: August 2024

Purpose of review

Systemic sclerosis (SSc)-associated heart involvement (SHI) is a significant cause of both morbidity and mortality in individuals with SSc. SHI can take many different forms, and likely is a spectrum of fibroinflammatory cardiac disease. Presenting features include arrhythmia, ventricular systolic or diastolic dysfunction, pericardial disease, and exercise intolerance. Risk of sudden cardiac death in SSc is likely 10–30-fold greater than general population estimates. In this review, we explore what is known about the pathogenesis of SHI, its prevention and management, and discuss available strategies for screening for SHI in light of new recommendations for the routine screening of SHI in all SSc patients.

Recent findings

We describe the spectrum, clinical features, and pathogenesis of SHI. Furthermore, we review the new recommendations for screening for SHI in individuals with SSc.

There is a large, under-recognized burden of SHI in people living with SSc, which likely contributes to the significant increase in sudden cardiac death observed in SSc. However, a broad-based screening approach, including asymptomatic, low-risk patients should be viewed with caution given the lack of evidence-based treatments and interventions for SHI particularly in this group.
Bacterial outer membrane vesicles in the fight against cancer
Authors: Meng Yiming , Kong Cuicui , Ma Yushu , Sun Jing , Zhang Guirong
Published: August 2024

Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.
Generalizability of Heat-related Health Risk Associations Observed in a Large Healthcare Claims Database of Patients with Commercial Health Insurance
Authors: Milando Chad W. , Sun Yuantong , Romitti Yasmin , Nori-Sarma Amruta , Gause Emma L. , Spangler Keith R. , Sue Wing Ian , Wellenius Gregory A.
Published: August 2024

Background:

Extreme ambient heat is unambiguously associated with a higher risk of illness and death. The Optum Labs Data Warehouse (OLDW), a database of medical claims from US-based patients with commercial or Medicare Advantage health insurance, has been used to quantify heat-related health impacts. Whether results for the insured subpopulation are generalizable to the broader population has, to our knowledge, not been documented. We sought to address this question, for the US population in California from 2012 to 2019.

Methods:

We examined changes in daily rates of emergency department encounters and in-patient hospitalization encounters for all-causes, heat-related outcomes, renal disease, mental/behavioral disorders, cardiovascular disease, and respiratory disease. OLDW was the source of health data for insured individuals in California, and health data for the broader population were gathered from the California Department of Health Care Access and Information. We defined extreme heat exposure as any day in a group of 2 or more days with maximum temperatures exceeding the county-specific 97.5th percentile and used a space-time-stratified case-crossover design to assess and compare the impacts of heat on health.

Results:

Average incidence rates of medical encounters differed by dataset. However, rate ratios for emergency department encounters were similar across datasets for all causes [ratio of incidence rate ratios (rIRR) = 0.989; 95% confidence interval (CI) = 0.969, 1.009], heat-related causes (rIRR = 1.080; 95% CI = 0.999, 1.168), renal disease (rIRR = 0.963; 95% CI = 0.718, 1.292), and mental health disorders (rIRR = 1.098; 95% CI = 1.004, 1.201). Rate ratios for inpatient encounters were also similar.

Conclusions:

This work presents evidence that OLDW can continue to be a resource for estimating the health impacts of extreme heat.