bluuebunny/crossref_metadata_2025 huggingface dataset:
MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle‐invasive bladder cancer
Authors: Olkhov‐Mitsel Ekaterina , Oberc Alexander , Craddock Kenneth J , Sherman Christopher , Slodkowska Elzbieta , Downes Michelle R
Published: September 2024

Aims

Loss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of CDKN2A and MTAP genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single‐centrre retrospective study examined the incidence of CDKN2A deletions and MTAP loss in muscle‐invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes.

Methods

Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy‐proven metachronous urothelial metastases to assess CDKN2A deletions and MTAP protein expression.

Results

CDKN2A homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal‐URO subtype, FGFR3 mutations, and normal/wildtype p53 IHC (P < 0.05). Loss of MTAP expression was significantly correlated with CDKN2A HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression‐free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant.

Conclusion

Our findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal‐URO subtype and FGFR3‐mutated, p53‐normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.
The predictive utility of the in utero exposome for childhood adiposity in independent and integrated frameworks
Authors: VanHawkins Jonathan , Peterson Ryan , Harrall Kylie , Moon Brandy , Dabelea Dana , Kechris Katerina , Perng Wei
Published: September 2024

Objectives

To assess the predictive potential of the in utero exposome in relation to childhood adiposity as indicated by body mass index z‐scores (BMIz) and the fourth versus first quartile of % fat mass (FM) at median age of 4.6 years.

Methods

We leveraged data on clinical risk factors for childhood obesity during the perinatal period, along with cord blood per/polyfluoroalkyl substances (PFAS) and cord blood DNA methylation, in 268 mother–offspring pairs. We used the sparsity ranked LASSO penalized regression framework for each outcome and assessed model performance based on % variability explained for BMIz and area under the receiver operating characteristic curve (AUC) for the fourth versus first quartile of %FM. We employed cross‐validation for model tuning and split‐sample validation for model evaluation.

Results

Mean ± SD BMIz was 0.01 ± 1.1, %FM was 19.8 ± 6.34%. The optimal model for predicting BMIz explained 19.1% of the variability in the validation set and included only clinical characteristics: maternal pre‐pregnancy BMI, paternal BMI, gestational weight gain, physical activity during pregnancy and child race/ethnicity. The optimal model for fourth versus first quartiles of %FM achieved an AUC of 0.82 ± 0.01 in the validation set, with the clinical features again emerging as the strongest predictors.

Conclusion

In this study sample, perinatal chemical exposures and the epigenome have low utility in predicting childhood adiposity, beyond known clinical risk factors.
From fat to fire: The lipid–inflammasome connection
Authors: Anand Paras K.
Published: September 2024

Inflammasomes are multiprotein complexes that play a crucial role in regulating immune responses by governing the activation of Caspase‐1, the secretion of pro‐inflammatory cytokines, and the induction of inflammatory cell death, pyroptosis. The inflammasomes are pivotal in effective host defense against a range of pathogens. Yet, overt activation of inflammasome signaling can be detrimental. The most well‐studied NLRP3 inflammasome has the ability to detect a variety of stimuli including pathogen‐associated molecular patterns, environmental irritants, and endogenous stimuli released from dying cells. Additionally, NLRP3 acts as a key sensor of cellular homeostasis and can be activated by disturbances in diverse metabolic pathways. Consequently, NLRP3 is considered a key player linking metabolic dysregulation to numerous inflammatory disorders such as gout, diabetes, and atherosclerosis. Recently, compelling studies have highlighted a connection between lipids and the regulation of NLRP3 inflammasome. Lipids are integral to cellular processes that serve not only in maintaining the structural integrity and subcellular compartmentalization, but also in contributing to physiological equilibrium. Certain lipid species are known to define NLRP3 subcellular localization, therefore directly influencing the site of inflammasome assembly and activation. For instance, phosphatidylinositol 4‐phosphate plays a crucial role in NLRP3 localization to the trans Golgi network. Moreover, new evidence has demonstrated the roles of lipid biosynthesis and trafficking in activation of the NLRP3 inflammasome. This review summarizes and discusses these emerging and varied roles of lipid metabolism in inflammasome activation. A deeper understanding of lipid‐inflammasome interactions may open new avenues for therapeutic interventions to prevent or treat chronic inflammatory and autoimmune conditions.
Low‐dielectric‐loss ZnZrNb2O8 ceramics combined with H3BO3 for low‐temperature co‐fired ceramics applications
Authors: Huang Zipeng , Qiao Jianli , Jia Wenxiao , Li Lingxia
Published: September 2024

H3BO3 was used as the sintering additive to enable Zn0.997Cu0.003ZrNb2O8 ceramics to accomplish low‐temperature sintering and outstanding microwave dielectric performances. Composite ceramics were created using typical solid‐state processes. The effects of added H3BO3 on the sintering behavior, microstructural characteristics, vibrational properties, and microwave dielectric performances of Zn0.997Cu0.003ZrNb2O8 + x wt% H3BO3 (2  x  8) ceramics have been systematically investigated by means of X‐ray diffraction, Raman scattering spectroscopy, scanning electron microscopy, and complex chemical bond theory. The results of relative density and microscopic morphology demonstrated that the application of an adequate quantity of H3BO3 additive can significantly enhance sintering properties. The doped H3BO3 alters the inter‐ionic interactions so that the structural features become intrinsic to the microwave dielectric performances. The particularly satisfactory microwave dielectric performances ( = 10.61,  = 33 980 GHz, and  = ‐45.10 ppm/°C) were detected in x = 6 ceramic specimens sintered at 950°C, which would make it promising for use in modern low temperature co‐fired ceramics technology.
Chronic Kidney Disease and Kidney Stone in a Wild Chimpanzee (Pan troglodytes verus) in Côte d'Ivoire
Authors: Jaffe Jenny E. , Mätz‐Rensing Kerstin , Ulrich Markus , Gräßle Tobias , Behringer Verena , Wittig Roman M. , Leendertz Fabian H.
Published: September 2024

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin‐creatinine‐ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed.
Low‐Dose Oral Minoxidil and Associated Adverse Events: Analyses of the FDA Adverse Event Reporting System (FAERS) With a Focus on Pericardial Effusions
Authors: Gupta Aditya K. , Bamimore Mary A. , Abdel‐Qadir Husam , Williams Greg , Tosti Antonella , Piguet Vincent , Talukder Mesbah
Published: September 2024

Background

Low‐dose oral minoxidil (LDOM) is used to treat hair loss, but the literature on its safety profile is relatively sparse.

Aims

Using the FDA Adverse Event Reporting System (FAERS) database, we determined signals for adverse events (AEs) with LDOM use.

Methods

Four sets of case/noncase study disproportionality analyses were conducted to determine reporting odds ratio (ROR) for 10 AEs including pericardial effusion (PE). The oral minoxidil dose ranges were: (i) ≤1.25 mg (i.e., 0–1.25 mg), (ii) ≤2.5 mg (i.e., 0–2.5 mg), (iii) ≤5 mg (i.e., 0–5 mg), and (iv) ≤10 mg (i.e., 0–10 mg).

Results

For ≤1.25 mg, we detected a signal for PE (ROR = 16.41, 95% CI: 2.29, 117.37, p < 0.05). For ≤2.5 mg, the analyses detected a signal for PE (ROR = 13.30, 95% CI: 5.96, 29.68, p < 0.05); the ROR in the absence of cardiac impairment was 5.34 (95% CI: 1.33, 21.37, p < 0.05); in the presence of cardiac impairment, the ROR was 49.42 (95% CI: 18.27, 133.66, p < 0.05). A signal for PE was also detected at ≤5 and ≤10 mg. For PE, there was a significant (p < 0.05) association with a patient outcome of “life threatening” only at the ≤10 mg dose range.

Conclusions

Our study, the first FAERS‐based signal detection study for LDOM, found significant associations between LDOM use and several AEs. In the absence of causal evidence, these correlations warrant more attention regarding safe use of LDOM. Until more safety data are available, we recommend using LDOM at the lowest effective dose (≤5 mg/day).
Radiofrequency Improves Facial Fine Lines by Thermal Effect: Damage or Just Stimulation?
Authors: Bai Yubing , Ni Wei , Zhang Yiqiu , Jiang Zhixuan , Zhou Shengzhe , Yao Min
Published: September 2024

Background

Radiofrequency (RF) has been widely used for rejuvenation treatments, but without knowledge of the effective temperature of the target tissues or guidance on treatment parameters, it often leads to adverse reactions and pain. The aim of this study was to demonstrate that thermal stimulation can produce facial rejuvenation effects and to determine the optimal bipolar RF treatment parameters for treating facial fine lines.

Methods

A bipolar RF device combined with CORE Technology was used in this study. Ex vivo studies were conducted on both miniature swine and human skin, utilizing thermographic thermometry and histological analysis. In vivo swine studies were conducted using histological analysis and electron microscopy. A clinical trial was conducted, and the results were evaluated using the Alexiades Comprehensive Grading Scale (ACGS) and Global Aesthetic Improvement Scale (GAIS) scales.

Results

The bipolar RF technology can produce a significant effect by thermally stimulating collagen within just 2 weeks without causing thermal damage. A clinical trial involving 46 patients showed a noticeable rejuvenating effect of the bipolar RF device, especially on fine wrinkles.

Conclusion

This study confirmed that thermal stimulation, rather than thermal damage, is sufficient to achieve rejuvenation effects. The study also found a range of bipolar RF treatment parameters that are both safe and effective for facial fine lines.
The Clinical Efficacy of Lapachol in Facial Redness Reduction
Authors: Draelos Zoe Diana
Published: September 2024

Background

Facial erythema from acne, vascular rosacea, or photoaging is a common difficult–to‐treat dermatologic challenge.

Objective

The objective of this study was to examine the role of lapachol in alleviating facial erythema associated with a variety of common dermatologic conditions.

Methods

Twenty‐five healthy female and male subjects 35–65 years of age of Fitzpatrick skin types I–II with mild‐to‐moderate stable facial erythema from acne, rosacea or photoaging were enrolled in a single‐site monadic study. Subjects received the study cream for twice daily application and were assessed at baseline, Week 4, and Week 8. The dermatologist investigator and subjects assessed efficacy and tolerability and facial photographic images were taken of all subjects at each visit. Noninvasive erythema assessments of the face were conducted using a colorimeter at baseline, Week 4, and Week 8 to document improvement in facial erythema.

Results

Twenty‐five out of 25 subjects successfully completed the study without tolerability issues including 12 subjects with rosacea, 6 subjects with photoaging and 7 subjects with acne. After 8 weeks of use, the investigator rated a 44% decrease in facial erythema while the subjects rated a 40% decrease. Facial erythema was also noninvasively assessed with a colorimeter and dermaspectrophotometer (DSP). There was a 26% decrease in skin redness at Week 4 and a 31% decrease in skin redness at Week 8 on the colorimeter L*a*b* scale. This finding was collaborated by the DSP which registered a 29% decrease on the erythema scale at Week 8.

Conclusion

Lapachol in a moisturizer formulation was found to be effective in reducing facial erythema from acne, rosacea, and photoaging.
Effect of different preparation designs and material types on fracture resistance of minimally invasive posterior indirect adhesive restorations
Authors: Sheir Ahmed Issam , Al‐Zordk Walid , Sakrana Amal Abdelsamad
Published: September 2024

Purpose

To evaluate the impact of various preparation designs and the material type on fracture resistance of minimally invasive posterior indirect adhesive restorations after aging using a digital standardization method.

Materials and Methods

One‐hundred sixty human maxillary premolars free from caries were assigned into 16 groups (n = 10): bevel design on enamel substrate with mesial box only (VEM), butt joint design on enamel substrate with mesial box only (BEM), bevel design on enamel substrate with mesial and distal box (VED), butt joint design on enamel substrate with mesial and distal box (BED), bevel design on dentin substrate with mesial box only (VDM), butt joint design on dentin substrate with mesial box only (BDM), bevel design on dentin substrate with mesial and distal box (VDD), and butt joint design on dentin substrate with mesial and distal box (BDD). Each group was restored with pressable lithium disilicate (LS2) or disperse‐filled polymer composite (DPC) materials. Adhesive resin cement was used to bond the restorations. The specimens were aged for 10,000 thermal cycles (5°C and 55°C), then 240,000 chewing cycles. Each specimen was subjected to compressive axial load until failure. A two‐way analysis of variance (ANOVA) test followed by a post hoc Tukey test was used to analyze the data (α = 0.05).

Results

The two‐way ANOVA test revealed a significant difference among designs (p < 0.001) and materials (p < 0.001) with no interaction effect (p = 0.07) between the variables. The Post hoc Tukey test revealed that the VEM group exhibited the highest mean fracture resistance value, while the BDM group had the lowest. The LS2 groups showed the highest mean fracture resistance values. The DPC groups showed a restorable fracture pattern compared to the LS2 groups.

Conclusions

Bevel and butt joint designs with mesial or distal boxes are recommended for conservative posterior indirect adhesive restorations in premolar areas. Enamel substrate improved load distribution and fracture resistance. DPCs have restorable failure patterns, while pressed LS2 may harm underlying structures.
A fungal effector suppresses plant immunity by manipulating DAHPS‐mediated metabolic flux in chloroplasts
Authors: Shang Shengping , Liang Xiaofei , Liu Guangli , Du Youwei , Zhang Song , Meng Yanan , Zhu Junming , Rollins Jeffrey A. , Zhang Rong , Sun Guangyu
Published: September 2024

Plant secondary metabolism represents an important and ancient form of defense against pathogens. Phytopathogens secrete effectors to suppress plant defenses and promote infection. However, it is largely unknown, how fungal effectors directly manipulate plant secondary metabolism.

Here, we characterized a fungal defense‐suppressing effector CfEC28 from Colletotrichum fructicola. Gene deletion assays showed that ∆CfEC28‐mutants differentiated appressoria normally on plant surface but were almost nonpathogenic due to increased number of plant papilla accumulation at attempted penetration sites. CfEC28 interacted with a family of chloroplast‐localized 3‐deoxy‐d‐arabinose‐heptulonic acid‐7‐phosphate synthases (DAHPSs) in apple. CfEC28 inhibited the enzymatic activity of an apple DAHPS (MdDAHPS1) and suppressed DAHPS‐mediated secondary metabolite accumulation through blocking the manganese ion binding region of DAHPS. Dramatically, transgene analysis revealed that overexpression of MdDAHPS1 provided apple with a complete resistance to C. fructicola.

We showed that a novel effector CfEC28 can be delivered into plant chloroplasts and contributes to the full virulence of C. fructicola by targeting the DAHPS to disrupt the pathway linking the metabolism of primary carbohydrates with the biosynthesis of aromatic defense compounds.

Our study provides important insights for understanding plant–microbe interactions and a valuable gene for improving plant disease resistance.
Africa's Christian Zionist Frontiers
Authors: Gidron Yotam
Published: September 2024

Although not a new phenomenon, over the past decade, Christian Zionist theologies that emphasise the central role of the Jewish people in divine history and call on believers to support them and the modern state of Israel have increasingly come to impact religious life and political discourse in many parts of Africa. This paper reviews this development and the limited research on it. It assesses the uptake of Christian Zionist theologies by African Pentecostals and Messianic Jews and sketches out the impact of Christian Zionism on Africa's political landscape. The paper offers some directions for future scholarship on the subject, which may contribute not only to the fields of World Christianity and the anthropology of Christianity, but also to the historical, sociological, and anthropological study of African popular cultures, and to the study of African politics.
The Jesuit and the ‘false princess of China’: a contested exile narrative in 1690s Paris☆
Authors: Heath Sean
Published: September 2024

This article examines the fabrication and contestation of a false exile narrative in early modern France. At its centre was Ina, a young woman found on the streets of Paris in the winter of 1692. Claiming to be a Chinese princess who had ended up penniless in France after a long sequence of misfortunes, she gained the attention of members of the Parisian elite but was subsequently shown to be a fraud by Louis Le Comte, a Jesuit and former missionary in China. Ina had refashioned herself as an exile, pretending to be abandoned in a foreign land, far from her home, family and culture. This was not normally a desirable situation, but in her case, ‘faking’ the status of a lonely royal exile was an innovative strategy through which certain tendencies of the late seventeenth‐century French elites – including religious impulses to charity and fascination with China – were leveraged to improve (temporarily) her standing in French society. However, the concurrence of her imposture with the intensification of the Chinese Rites controversy turned the debate over her authenticity into a proxy for a broader struggle over Jesuit expertise.
Disintegration highway: Towards a psychogeography of planetary urban breakdown
Authors: Wilson Japhy
Published: September 2024

This paper develops a psychogeographical approach to our apocalyptic urban present, based on a journey down a highway on the outskirts of the city of Iquitos in the Peruvian Amazon. The intensity of psychogeographical method brings out elements of the senselessness and violence of planetary urbanization imperceptible at more abstract levels of analysis, while the subjective impact of this spatial unravelling demands a surrealist psychogeography less attuned to the oneiric and marvellous than the chaotic and absurd. These conceptual reflections are interspersed with depictions of my walk along the highway, as fragments of a psychogeography of planetary urban breakdown. Instead of seeking to explain the political ecology of the road, I aim to contribute to an aesthetic of accelerating collapse that can undermine the normalizing ideological function of our sense‐making mechanisms.
The diffusion of American fair housing law and policy
Authors: Bullock Charles S. , Lamb Charles M.
Published: September 2024

Objective

We investigate the contributions of state and local governments to the diffusion of American fair housing law and policy, focusing on the period from 1919 to 1968, prior to similar legal requirements and policies being approved at the federal level.

Methods

Relying on archival data obtained at two presidential libraries, our findings provide insights into diffusion's political effects.

Results

Myriad state and local laws, constituting breakthroughs that spread horizontally and/or bottom‐up, preceded similar requirements in the national Fair Housing Act of 1968 and implementation policies subsequently adopted by the federal bureaucracy.

Conclusions

Progressive subnational governments can promote the rights of politically marginalized individuals and groups when the national government and other subnational jurisdictions do not. States and localities can use desegregation approaches not available at the federal level.
Does the top two primary system moderate the voting behavior of elected officials?
Authors: Henrickson Kevin E. , Johnson Erica H.
Published: September 2024

Objective

Top two primary systems have been touted to increase moderation in politics. In a top two primary, the two candidates with the most votes continue on to the general election even if they are from the same political party. Candidates no longer have to cater to the extremes of their party in order to make it through the primary, so the thought is that candidates would be encouraged to be moderate throughout the election cycle to attract the median voter.

Methods

Washington State adopted a top two primary system in 2008, which allows us to look at empirical evidence about whether the top two primary actually encourages moderation in politics. We analyze voting records of elected officials before and after the adoption of the top two primary.

Results

We find evidence that the top two primary correlates with moderation in the voting behavior of elected officials, ceteris paribus.

Conclusion

Policymakers may want to consider the structure of primaries and how they could be changed to help encourage moderation in the voting of elected officials.
Detection of the novel HLA‐DQA1*05:73 allele with an amino acid substitution in the α2 extracellular domain
Authors: Gil‐Etayo Francisco Javier , Arroyo‐Sánchez Daniel , Niño Ramírez Jairo Eduardo , Terradillos‐Sánchez Pilar , Tejeda Velarde Amalia
Published: September 2024

A single nucleotide substitution in the exon 3 gives rise to the novel HLA‐DQA1*05:73 allele.
Inland water greenhouse gas emissions offset the terrestrial carbon sink in the northern cryosphere
Authors: Song Chunlin , Liu Shaoda , Wang Genxu , Zhang Liwei , Rosentreter Judith A. , Zhao Gang , Sun Xiangyang , Yao Yuanzhi , Mu Cuicui , Sun Shouqin , Hu Zhaoyong , Lin Shan , Sun Juying , Li Yang , Wang Ying , Li Yuhao , Raymond Peter A. , Karlsson Jan
Published: September 2024

Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide (

1149.2
1004.8
1307.5

teragrams of CO
2
;

median

Q
1

Q
3

) and methane (

14.2
10.1
18.5

teragrams of CH
4
), while the nitrous oxide emission (

5.4

−
1.4

12.2

gigagrams of N
2
O) is minor. The annual CO
2
–equivalent (CO
2
e) GHG emissions from northern cryosphere inland waters total

1.5
1.3
1.8

or

2.3
1.8
2.8

petagrams of CO
2
e using the 100- or 20-year global warming potentials, respectively. Rivers emit 64% more CO
2
e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO
2
e emissions from northern cryosphere inland waters exceed the region’s terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate.
Enormous diversity of RNA viruses in economic crustaceans
Authors: Dong Xuan , Meng Fanzeng , Zhou Chengyan , Li Juan , Hu Tao , Wang Yiting , Wang Guohao , Luo Jingfei , Li Xuan , Liu Shufang , Huang Jie , Shi Weifeng
Published: September 2024

Crustaceans are important food sources worldwide and possess significant ecological status in the marine ecosystem. However, our understanding of the diversity and evolution of RNA viruses in crustaceans, especially in economic crustaceans, is still limited. Here, 106 batches of economic crustaceans including 13 species were collected from 24 locations in China during 2016–2021. We identified 90 RNA viruses, 69 of which were divergent from the known viruses. Viral transcripts were assigned to 18 different viral families/clades and three unclassified groups. Among the identified viruses, five were double-stranded RNA viruses, 74 were positive-sense single-stranded RNA (+ssRNA) viruses, nine were negative-sense single-stranded RNA (−ssRNA) viruses, and two belonged to an unclassified RNA virus group. Phylogenetic analyses showed that crustacean viruses were often clustered with viruses identified from invertebrates. Remarkably, most crustacean viruses were closely related to those from different host species along the same food chain or ecological aquatic niche. In addition, the genome structures of the newly discovered picornaviruses exhibited remarkable diversity. Our study significantly expands the diversity of viruses in important economic crustaceans and provides essential data for the risk assessment of the pathogens spreading in the global aquaculture industry.

IMPORTANCE

The study delves into the largely uncharted territory of RNA viruses in crustaceans, which are not only vital for global food supply but also play a pivotal role in marine ecosystems. Focusing on economic crustaceans, the research uncovers 90 RNA viruses, with 69 being potentially new to science, highlighting the vast unknown viral diversity within these marine organisms. The findings reveal that these viruses are often related to those found in other invertebrates and tend to share close relationships with viruses from species within the same food web or habitat. This suggests that viruses may move between different marine species more frequently than previously thought. The discovery of such a wide variety of viruses, particularly the diverse genome structures of newly identified picornaviruses, is a significant leap forward in understanding the crustacean virology. This knowledge is crucial for managing disease risks in aquaculture and maintaining the balance of marine ecosystems.
Investigating the adherence factors of
Escherichia coli
at the bovine recto-anal junction
Authors: Nawrocki Erin M. , Kudva Indira T. , Dudley Edward G.
Published: September 2024

Shiga toxin
–
producing
Escherichia coli
(STEC) are major foodborne pathogens that result in thousands of hospitalizations each year in the United States. Cattle, the natural reservoir, harbor STEC asymptomatically at the recto-anal junction (RAJ). The molecular mechanisms that allow STEC and non-STEC
E. coli
to adhere to the RAJ are not fully understood, in part because most adherence studies utilize human cell culture models. To identify a set of bovine-specific
E. coli
adherence factors, we used the primary RAJ squamous epithelial (RSE) cell-adherence assay to coculture RSE cells from healthy Holstein cattle with diverse
E. coli
strains from bovine and nonbovine sources. We hypothesized that a comparative genomic analysis of the strains would reveal factors associated with RSE adherence. After performing adherence assays with historical strains from the
E. coli
Reference Center (
n
= 62) and strains newly isolated from the RAJ (
n
= 15), we used the bioinformatic tool Roary to create a pangenome of this collection. We classified strains as either low or high adherence and using the Scoary program compiled a list of accessory genes correlated with the “high adherence” strains. While none of the correlations were statistically significant, several gene clusters were associated with the high-adherence phenotype, including two that encode uncharacterized proteins. We also demonstrated that non-STEC
E. coli
strains from the RAJ are more adherent than other isolates and can outcompete STEC in coculture with RSEs. Further analysis of adherence-associated gene clusters may lead to an improved understanding of the molecular mechanisms of RSE adherence and may help develop probiotics targeting STEC in cattle.

IMPORTANCE

E. coli
strains that produce Shiga toxin cause foodborne illness in humans but colonize cattle asymptomatically. The molecular mechanisms that
E. coli
uses to adhere to cattle cells are largely unknown. Various strategies are used to control
E. coli
in livestock and limit the risk of outbreaks. These include vaccinating animals against common
E. coli
strains and supplementing their feed with probiotics to reduce the carriage of pathogens. No strategy is completely effective, and probiotics often fail to colonize the animals. We sought to clarify the genes required for
E. coli
adherence in cattle by quantifying the attachment to bovine cells in a diverse set of bacteria. We also isolated nonpathogenic
E. coli
from healthy cows and showed that a representative isolate could outcompete pathogenic strains in cocultures. We propose that the focused study of these strains and their adherence factors will better inform the design of probiotics and vaccines for livestock.
Prolonged reducing and ferruginous oceanic conditions and abrupt global seawater oxidation after oceanic anoxic event 1a
Authors: Matsumoto Hironao , Shibuya Takazo , Shirai Kotaro , Kuroda Junichiro , Suzuki Katsuhiko
Published: September 2024

During the Cretaceous, several massive volcanic episodes led to significant environmental perturbations, including oceanic anoxic events (OAEs). The volcanic eruption forming Ontong Java Nui (ca. 120 Ma) in the western Pacific Ocean is recognized as the largest volcanic event on Earth and is thought to have caused oceanic anoxic event 1a (OAE1a). Although metal emissions from this volcanism are believed to have played a crucial role in triggering the Aptian oceanic anoxia, no direct evidence has been reported so far. Here, we showed that the iron-bearing minerals in the sedimentary sequence of the Mid-Pacific Mountains, deposited near Ontong Java Nui, gradually changed from pyrite and siderite to hematite after OAE1a. Notably, the presence of enigmatic large siderite (FeCO3) grains during the early to mid-Aptian suggests that strongly ferruginous condition prevailed in the Mid-Pacific region, potentially reflecting the substantial iron input from Ontong Java Nui volcanism through hydrothermal activity and volcanic ash emissions. This iron influx likely stimulated ocean primary production by cyanobacteria and potentially contributed to the oceanic anoxia and associated biotic crises of marine plankton. The stratigraphic distribution of siderite indicates that oxygen-depleted and strongly ferruginous conditions triggered by this volcanic event persisted for ~3 m.y. in the Pacific region, even after OAE1a. The disappearance of siderite grains during the mid-Aptian corresponds to the worldwide appearance of hematite-bearing brownish layers, suggesting that global oceanic conditions abruptly became fully oxic due to the weakening of Ontong Java Nui volcanism.
Associations between maternal body mass index and childhood infections in UK primary care: findings from the Born in Bradford birth cohort study
Authors: Coathup Victoria , Ashdown Helen Frances , Carson Claire , Santorelli Gillian , Quigley Maria A
Published: September 2024

Objective

To explore associations between maternal body mass index (BMI) in early pregnancy and childhood infections.

Design

Birth cohort study linked to primary care records.

Setting

Bradford, UK.

Participants

Live singleton births within the Born in Bradford cohort study between 2007 and 2011.

Exposures

Maternal BMI in early pregnancy.

Main outcome measures

The total number of infections between birth and ~14 years of age with subgroup analysis by infection type and age.

Results

A total of 9037 mothers and 9540 children were included in the main analysis. 45% of women were of Pakistani ethnicity and 6417 women (56%) were overweight or obese. There was an overall trend for an increasing infection rate with increasing maternal BMI. In adjusted models, only those with obesity grade 2–3 had offspring with significantly higher rates of infection during the first year of life (RR 1.12 (95% CI 1.05 to 1.20)) compared with women of healthy weight. However, by age 5 to <15 years, children born to overweight women (RR 1.09 (95% CI 1.02 to 1.16)), obese grade 1 women (RR 1.18 (95% CI 1.09 to 1.28)) or obese grade 2 women (RR 1.31 (95% CI 1.16 to 1.48)) all had significantly higher rates of infection compared with those born to healthy weight mothers. Respiratory tract and skin/soft tissue infections made up the majority of excess infections.

Conclusions

Maternal BMI was positively associated with rates of offspring infection in this study cohort, and suggests that we should be supporting women to achieve a healthy weight for pregnancy. Future research should investigate whether this is replicated in other populations, whether there is a causal association and the potential mechanisms and areas for intervention.
The value of white blood cell count in predicting serious bacterial infections in children presenting to the emergency department: a multicentre observational study
Authors: Kemps Naomi , Vermont Clementien , Tan Chantal D , von Both Ulrich , Carrol Enitan , Emonts Marieke , van der Flier Michiel , Herberg Jethro Adam , Kohlmaier Benno , Levin Michael , Lim Emma , Maconochie Ian , Martinón-Torres Federico , Nijman Ruud Gerard , Pokorn Marko , Rivero-Calle Irene , Rudzāte Aleksandra , Tsolia Maria , Zavadska Dace , Zenz Werner , Moll Henriette A , Zachariasse Joany M
Published: September 2024

Background

White blood cell count (WBC) is a widely used marker for the prediction of serious bacterial infection (SBI); however, previous research has shown poor performance. This study aims to assess the value of WBC in the prediction of SBI in children at the emergency department (ED) and compare its value with C reactive protein (CRP) and absolute neutrophil count (ANC).

Methods

This study is an observational multicentre study including febrile children aged 0–18 years attending 1 of 12 EDs in 8 European countries. The association between WBC and SBI was assessed by multivariable logistic regression, adjusting for age, CRP and duration of fever. Additionally, diagnostic performance was assessed by sensitivity and specificity. Results were compared with CRP and ANC.

Results

We included 17 082 children with WBC measurements, of which 1854 (10.9%) had an SBI. WBC >15 had an adjusted OR of 1.9 (95% CI 1.7 to 2.1) for prediction of SBI, after adjusting for confounders. Sensitivity and specificity were 0.56 (95% CI 0.54 to 0.58) and 0.74 (0.73 to 0.75) for WBC >15, and 0.32 (0.30 to 0.34) and 0.91 (0.91 to 0.91) for WBC >20, respectively. In comparison, CRP >20 mg/L had a sensitivity of 0.87 (95% CI 0.85 to 0.88) and a specificity of 0.59 (0.58 to 059). For CRP >80 mg/L, the sensitivity was 0.55 (95% CI 0.52 to 057) and the specificity was 0.91 (0.90 to 0.91). Additionally, for ANC >10, the sensitivity was 0.55 (95% CI 0.53 to 0.58) and the specificity was 0.75 (0.75 to 0.76). The combination of WBC and CRP did not improve performance compared with CRP alone.

Conclusion

WBC does not have diagnostic benefit in identifying children with an SBI compared with CRP and should only be measured for specific indications.
Cerebral injury and retinopathy as risk factors for blindness in extremely preterm infants
Authors: Honan Benjamin M , McDonald Scott A , Travers Colm P , Shukla Vivek V , Ambalavanan Namasivayam , Cotten C Michael , Jain Viral G , Arnold Hope E , Parikh Nehal A , Tyson Jon E , Hintz Susan R , Walker Stephen A , Gantz Marie G , Das Abhik , Carlo Waldemar A
Published: September 2024

Objective

This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP).

Design

Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18–26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants.

Exposures

Severe ROP and cerebral injury, the latter defined as any of the following on cranial imaging: ventriculomegaly; blood/increased echogenicity in the parenchyma; cystic periventricular leukomalacia.

Main outcome measures

Bilateral blindness, defined as a follow-up examination meeting criteria of ‘blind—some functional vision’ or ‘blind—no useful vision’ in both eyes.

Results

The 19 863 children included had a mean gestational age of 25.6±1.7 weeks, mean birth weight of 782±158 g and 213 (1%) had bilateral blindness. Multiplicative interaction between ROP and cerebral injury was statistically significant. For infants with only severe ROP (n=3130), odds of blindness were 8.14 times higher (95% CI 4.52 to 14.65), and for those with only cerebral injury (n=2836), odds were 8.38 times higher (95% CI 5.28 to 13.28), compared with the reference group without either condition. Risks were not synergistic for infants with both severe ROP and cerebral injury (n=1438, adjusted OR=28.7, 95% CI 16.0 to 51.7, p<0.0001).

Conclusions

In a group of extremely preterm infants, severe ROP and cerebral injury were equally important risk factors for blindness. Besides ROP, clinicians should consider cerebral injury as a cause of blindness in children born extremely preterm.

Trial registration number

NCT00063063.
Modelling pile foundations under biaxial loading with a plasticity-based p–y methodology
Authors: McCarron W.O.
Published: September 2024

Comparison of three-dimensional continuum finite element and p–y analyses illustrate the accuracy and efficiency of biaxial laterally loaded pile solutions obtained with a plasticity-based p–y methodology. The analyzed pile conditions correspond to a test pile founded in a stiff over-consolidated glacial till. The numerical analyses are first benchmarked against observed test responses for planar loading. Hypothetical cyclic pile responses are then investigated for two conditions with biaxial loading that produce anisotropic displacement responses due to the developing plastic foundation responses. The p–y model is based on a bounding surface plasticity theory facilitating analysis of loading in arbitrary directions relative to the pile axis. The three-dimensional continuum finite element model allows for the formation of a soil–pile gap in conjunction with an elastic perfectly-plastic Tresca soil model. The numerical analyses show that the p–y methodology captures the characteristic displacement and energy responses observed in the continuum analyses under biaxial loading with far less computational effort. Analyses demonstrate that significant anisotropic plastic responses may develop in simple cyclic biaxial loading conditions, perhaps rendering planar p–y model formulations inadequate with respect to a need to accurately predict responses and ensure they satisfy design performance criteria.
A surrogate safety assessment of scrambled phase intersections
Authors: Ghaneei Zakiye , Momeni Rad Faeze , El-Basyouny Karim
Published: September 2024

Traffic safety remains a top priority for policymakers and researchers, prompting numerous investigations to enhance safety for all road users, particularly pedestrians. This paper evaluates the safety impact of implementing scramble phases at intersections with a high concentration of vulnerable road users in Edmonton, Canada. The study spans three periods: prior to the scramble phase installation, immediately post-installation, and 6 months post-installation. The evaluation employs two key methodologies. Firstly, it observes the frequency of right-turn-on-red violations to assess driver behaviour. Secondly, the study investigates the frequency of serious conflicts, utilizing safety indicators such as time to collision, time difference to point of intersection, and distance between stop position and pedestrian. The findings suggest that introducing scramble phases positively impacts intersection safety, notably reducing severe conflicts and total right-turn-on-red violations. These results offer valuable insights for policymakers and researchers working towards safer urban traffic environments.
Changing your perspective: the impact of different visualisation methods on seismic hazard maps
Authors: Yin Yue , Crameri Fabio , Shephard Grace E. , Heron Philip J.
Published: September 2024

A number of widely used colour palettes applied to display critical scientific results not only distort data but are also inaccessible to a proportion of the population. An issue with the rainbow palette (and variants such as “jet”) is that the gradients between the colours are not even. The impact of an uneven colour gradient is that certain colours are highlighted over others, distorting the underlying data. Furthermore, an uneven colour palette like rainbow may be inaccessible for people with colour vision deficiencies or colour blindness. When communicating scientific results, data should always be presented without distortion and be universally accessible. This is particularly important when communicating public-facing and time-critical information such as hazards. Here, we show the impact of changing the visualisation profile of seismic hazard maps on the perception of risk, as well as qualifying the public accessibility of this information. Using Canadian seismic hazard as an example, our results reveal that an uneven colour map applied to seismic hazard data can exaggerate lower hazard values and reduce the perception of extremely high hazard values. Applying an even colour gradient to our sample data not only allows this essential public resource to be universally accessible but was found to lead to the greatest visual change in regions with the most populated cities. The choice of colour map and subsequent data interpretations also holds relevance for considerations such as insurance. We highlight potential next steps to promote inclusiveness in data visualisation and welcome discussion on science communication best practices.
Anisotropic interior models with Kohler–Chao–Tikekar-like complexity factor
Authors: Albalahi Abeer M. , Yousaf Z. , Khan S. , Ali Akbar
Published: September 2024

This work explores the construction of spherically symmetric models of stellar interiors by incorporating the null complexity factor (CF) as an additional constraint. This supplementary condition helps us to close an array of stellar structure equations resulting from the process of gravitational decoupling. By making use of MGD-type gravitational decoupling we analyze the role of gravitational decoupling and its impact on the complexity of static, self-gravitational systems. We begin by considering an anisotropic seed solution described by the Kohler–Chao–Tikekar metric ansatz. We then apply the minimal geometric deformation technique to this seed solution, imposing the constraint that the effective anisotropic factor vanishes. This constraint leads to the generation of an isotropic stellar solution. Furthermore, we construct a second family of solutions in which the CF, remains the same for both the seed solution and its minimally deformed counterpart. Our analysis further investigated the influence of both the deformation parameter and the CF on the structural properties of the static and spherically symmetric stellar objects.
Evolution of the color dipole cross section
Authors: Boroun G. R.
Published: September 2024

Using Laplace transform techniques, we describe the evolution of the color dipole cross section at the leading-order and next-to-leading-order approximations from the Bartels–Golec-Biernat–Kowalski model in a kinematic region of low values of the Bjorken variable x and a wide range of transverse dipole size r. This evolution method shows that the saturation scale and geometric scaling are retained. We derived analytical results for the integrated and unintegrated color dipole gluon distribution functions and compared them with the CJ15 parameterization group and the unintegrated color dipole gluon distribution models, respectively. The Sudakov form factor in the evolution of the unintegrated color dipole gluon distribution is incorporated, and the results are considered at small and large values of $$k_{t}^{2}$$

k

t

2

.
Gauge-invariant quantum fields
Authors: Quadri A.
Published: September 2024

Gauge-invariant quantum fields are constructed in an Abelian power-counting renormalizable gauge theory with both scalar, vector and fermionic matter content. This extends previous results already obtained for the gauge-invariant description of the Higgs mode via a propagating gauge-invariant field. The renormalization of the model is studied in the Algebraic Renormalization approach. The decomposition of Slavnov–Taylor identities into separately invariant sectors is analyzed. We also comment on some non-renormalizable extensions of the model whose 1-PI Green’s functions are the flows of certain differential equations of the homogeneous Euler type, exactly resumming the dependence on a certain set of dim. 6 and dim. 8 derivative operators. The latter are identified uniquely by the condition that they span the mass and kinetic terms in the gauge-invariant dynamical fields. The construction can be extended to non-Abelian gauge groups.
Chromoelectric flux tubes within non-Abelian Proca theory
Authors: Dzhunushaliev Vladimir , Folomeev Vladimir
Published: September 2024

Flux tube solutions within non-Abelian SU(3) Proca theory with external sources are obtained. It is shown that such tubes have a longitudinal chromoelectric field possessing two components (nonlinear and gradient), as well as a transverse chromomagnetic field whose force lines create concentric circles with the center on the axis of the tube. The scenario of a possible relationship between non-Abelian Proca theory and quantum chromodynamics is considered. In such scenario: (a) the components of color fields have different behavior: those which are almost classical, and those which are purely quantum; (b) the second components create a gluon condensate that is a source of the field for the almost classical components of the Proca field; (c) Proca masses may appear as a result of an approximate description of the gluon condensate; (d) the question of gauge invariance is considered. It is shown that the results obtained are in good agreement with the results of lattice calculations. We make an assumption that an approximate description of a flux tube in quantum chromodynamics can be carried out using classical Proca equations but with a mandatory account of a gluon condensate.