bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient and family burden in pediatric atopic dermatitis and its treatment pattern in Japan
Authors: Otsuka Atsushi , Wang Chaochen , Torisu‐Itakura Hitoe , Matsuo Takashi , Isaka Yoshitaka , Anderson Peter , Piercy James , Austin Jenny , Marwaha Simran , Tanaka Akio
Published: May 2024

Background

This study evaluated the level of burden in pediatric and adolescent atopic dermatitis (AD) patients in Japan, the associated burden on caregivers/families, and whether this burden varied with age.

Methods

Data were drawn from the Adelphi Pediatric AD Disease Specific Programme (DSP)™, a cross‐sectional survey of physicians and their patients conducted in Japan between July and December 2022. Physicians reported patient demographics, clinical characteristics, disease burden, and current/previous therapies. Patients and/or caregivers reported perceived disease severity and impact of AD, including the Children's Dermatology Life Quality Index (CDLQI) and Dermatitis Family Impact questionnaire (DFI).

Results

Overall, 55 physicians provided data for 537 AD patients aged ≤17. Mean (SD) overall scores for CDLQI, POEM, and DFI were 9.3 (6.3), 8.3 (6.8), and 11.7 (7.2), respectively. Age was associated with higher patient and/or caregiver‐reported CDLQI scores, which increased by 0.543 points per year of age (P = 0.01). Patients with severe disease reported a more significant impact on quality of life factors compared with mild patients (P < 0.001). Age was associated with higher caregiver‐reported burden, with DFI scores increasing by 0.325 per year (P = 0.01). Physician‐reported impact on caregivers showed that age was significantly associated with increased burden on sleep, daily activities, work, and mood (P < 0.05), with disease severity associated with impact across all factors (P < 0.01).

Conclusions

Both increasing age and disease severity were associated with the increased impact of AD on patients and their caregivers. Disease control/modification through appropriate therapeutic intervention at a younger age may relieve the burden of pediatric AD on patients and their families.
Validation of the Persian version of the attitudes toward intellectual disability
Authors: Khalili R. , Asgari Z. , Kamrani A. , Morin D.
Published: May 2024

Background

Attitudes toward individuals with intellectual disability (ID) are the most important factor affecting their social integration and can cause them to experience a sense of achievement or discrimination. The present study aimed to evaluate the latent factor structure and validity of the Persian version of the Attitudes toward Intellectual Disability (ATTID) Short‐Form questionnaire.

Methods

The latent factor structure of the Persian version of the ATTID Short‐Form was established in a convenient sample of the general population (N = 280) in Iran. The structural validity and temporal reliability, internal consistency and confirmatory factor analysis were evaluated. Data analysis was done with SPSS v23 Windows edition and R v4.2.1.

Results

The Persian version of the ATTID Short‐Form was shown to have a five‐factor structure: discomfort, knowledge of capacity, interaction, sensitivity and knowledge of cause. The structure was appropriately fit according to the fit indices (χ2(485) = 530.12), (P‐value = 0.077). All the subscales had good temporal reliability.

Conclusions

Findings suggest that the Persian version of the Short‐Form of ATTID is a brief, valid and reliable measure that can be used in research and clinical practice.
Urinary syndecan‐1 in dogs anesthetized with isoflurane or sevoflurane: A randomized, prospective study
Authors: Harris Stephanie , Gerken Katherine , Clark‐Price Stuart , Hung Ellan , Jukier Tom , Yanke Amy , Kuo Kendon , McMichael Maureen
Published: May 2024

Background

Syndecan‐1 (SDC1) is an established marker of endothelial glycocalyx shedding. Most research on SDC1 has focused on plasma or serum concentrations, and little is known about urine concentrations.

Objectives

Measure urinary SDC1 concentrations in dogs undergoing anesthesia with either sevoflurane or isoflurane and assess the effects of anesthesia duration and IV crystalloids on urinary SDC1 concentrations.

Animals

Thirty‐one client‐owned dogs undergoing anesthesia for magnetic resonance imaging (MRI) with or without surgery for suspected intervertebral disk disease (IVDD) were used.

Methods

Dogs with suspected IVDD were randomized to undergo anesthesia with either sevoflurane or isoflurane. Urine was collected before and immediately after anesthesia for the analysis of SDC1. Urinary creatinine concentrations also were measured, and the ratio of urinary SDC1 to urinary creatinine (USCR) was used to account for dilution.

Results

Median (range) USCR was significantly higher after anesthesia compared with baseline for all groups combined (P < .05). No significant difference was found between the groups for age, sex, weight, and type of anesthesia. Multiple regression analysis of the effect of the independent variables inhalant type, age, weight, sex, anesthesia time, surgery, and quantity of IV fluids on the dependent variable SDC1 found that only the quantity of IV fluids significantly predicted a change (P < .001).

Conclusions and Clinical Importance

The total volume of lactated Ringer's solution administered to anesthetized dogs may affect USCR. Further investigations are warranted to evaluate the relationship between IV fluids and SDC1.
Strategic advertising in the aftermath of a corporate scandal
Authors: Andina‐Díaz Ascensión , Campos Javier , Jiménez Juan‐Luis , Perdiguero Jordi
Published: May 2024

This paper contributes to the literature on how firms change their advertising strategies after a corporate scandal by providing both a theoretical model and an empirical evaluation based on the idea that advertising acts as a signal of the product quality that is modulated by the number of competing substitutes in the market. This result is new to the literature and helps to explain cases in which, possibly counter‐intuitively, a firm affected by a corporate scandal may optimally decide to reduce its advertising expenditures, rather than increase it, in an attempt to restore its reputation as quickly as possible. We find empirical support for this result in the Volkswagen Group's response to the Dieselgate scandal.
Adhesive and biofilm‐forming Candida glabrata Lebanese hospital isolates harbour mutations in subtelomeric silencers and adhesins
Authors: Fattouh Nour , Husni Rola , Finianos Marc , Bitar Ibrahim , Khalaf Roy A.
Published: May 2024

Background

The prevalence of Candida glabrata healthcare‐associated infections is on the rise worldwide and in Lebanon, Candida glabrata infections are difficult to treat as a result of their resistance to azole antifungals and their ability to form biofilms.

Objectives

The first objective of this study was to quantify biofilm biomass in the most virulent C. glabrata isolates detected in a Lebanese hospital. In addition, other pathogenicity attributes were evaluated. The second objective was to identify the mechanisms of azole resistance in those isolates.

Methods

A mouse model of disseminated systemic infection was developed to evaluate the degree of virulence of 41 azole‐resistant C. glabrata collected from a Lebanese hospital. The most virulent isolates were further evaluated alongside an isolate having attenuated virulence and a reference strain for comparative purposes. A DNA‐sequencing approach was adopted to detect single nucleotide polymorphisms (SNPs) leading to amino acid changes in proteins involved in azole resistance and biofilm formation. This genomic approach was supported by several phenotypic assays.

Results

All chosen virulent isolates exhibited increased adhesion and biofilm biomass compared to the isolate having attenuated virulence. The amino acid substitutions D679E and I739N detected in the subtelomeric silencer Sir3 are potentially involved— in increased adhesion. In all isolates, amino acid substitutions were detected in the ATP‐binding cassette transporters Cdr1 and Pdh1 and their transcriptional regulator Pdr1.

Conclusions

In summary, increased adhesion led to stable biofilm formation since mutated Sir3 could de‐repress adhesins, while decreased azole susceptibility could result from mutations in Cdr1, Pdh1 and Pdr1.
Tree richness affects ground‐ant diversity and seed dispersal in a tropical biodiversity–ecosystem function experiment
Authors: Dantas Anderson , Dantas Thais A. Vitoriano , Ganade Gislene , Fonseca Carlos Roberto
Published: May 2024

The global loss of plant diversity is expected to have reverberating effects on other trophic levels, affecting the structure and functioning of ecosystems. To understand such effects, biodiversity–ecosystem function (BEF) experiments that manipulate tree diversity have been established around the world. In a BEF experiment carried out since 2016 in a seasonally dry tropical forest, we examined the effects of tree diversity, facilitation and density of trees with extrafloral nectaries on the abundance, richness, functional diversity and phylogenetic diversity of ground ants. Also, we used artificial seeds to test seed dispersal efficiency of ants within the experiment. Generalized linear mixed models (GLMM) showed that tree richness positively affects ant abundance, richness, functional diversity and phylogenetic diversity. Also, tree richness had a strong positive effect on the proportion of dispersed seeds, as well as their dispersal distance. Contrary to our expectations, facilitation and the number of trees with extrafloral nectaries did not affect ground ants and their functions. Our results indicate that the global impoverishment of tree communities can affect several dimensions of ant diversity and their ecosystem functions, including forest regeneration processes.
Innovative change not as yet fully integrated in pediatric anesthesia
Authors: Lauder Gillian , Kuttner Leora
Published: May 2024

Pediatric hypnosis is an extremely valuable adjuvant therapeutic tool to reduce pain and ameliorate anxiety in children undergoing procedures and pediatric anesthesia. This perspective summarises; why Integrating hypnosis into practice has this potential, some techniques that are particularly useful in this setting, the training oppurtunities to learn more, and recommendations for future pediatric anesthesia hypnotic research. There is definite capacity for change by Integrating hypnosis into our practice. Not only will this ensure more capable, confident children who present for peri‐operative care but also reduce costs and the environmental impact of the pharmaceutical agents we currently employ for sedation and anxiolysis.
“We had a lot of fun”: Psychological rewards of white supremacy group membership
Authors: Munden Hanna Paalgard , Morrison John
Published: May 2024

White supremacist organizations pose a serious and growing threat to democracy and public safety. This article analyzes nonideological ways in which these groups attract and maintain membership. The primary data comprises interviews with 15 former white supremacist group members. Each was asked about their experience of group participation and exit. Interview data were analyzed via thematic analysis. Five distinct themes emerged: belonging, perceived importance, empowerment, emotional intensity, and long‐term psychological rewards. Based on the analysis, it is argued that group membership maintenance can be partially explained by psychologically rewarding experiences that may, for them, seem difficult to attain elsewhere. The analysis is consistent with the assumptions of the good lives model, a strength‐based approach to the rehabilitation of criminal offenders. This model provides a theoretical way forward in the understanding and prevention of (re)engagement through the promotion of prosocial ways of achieving the psychological rewards that are important to the individual and that membership of white supremacy groups offers.
Does having a family member with dementia affect health beliefs about changing lifestyle and health behaviour for dementia risk reduction?
Authors: Şener Melek , Küçükgüçlü Özlem , Akyol Merve Aliye
Published: May 2024

Background

Dementia is a worldwide public health concern. Implementing lifestyle changes that target modifiable risk factors is crucial for reducing the risk of dementia. The aim of this study was to investigate the effect of having family members with dementia on individuals' health beliefs and tendencies towards adopting healthier lifestyles and behaviours.

Methods

A cross‐sectional, comparative study was conducted with 338 people aged 40 years and older, of whom 168 have the experience of having family members with dementia, and 170 have no such experience. Data were collected using a characteristics form, the Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction scale, and the modified Charlson comorbidity index. Descriptive statistics, Pearson's chi‐square and independent t‐tests, were used.

Results

Those with family members with dementia were more likely to have greater motivation to modify their lifestyle (perceived susceptibility, severity, benefits, and cues to action) to reduce their risk of developing dementia. Additionally, they had greater perceived barriers to gain by adopting a healthy lifestyle, in contrast to those without such family members.

Conclusion

The presence of family members with dementia could be an important factor to consider when designing initiatives targeting health beliefs related to dementia prevention behaviours and lifestyle changes.
Linking topography, soil variability, and early successional vegetation in abandoned gold mines in the tropical rainforest of Colombia's Chocó Biogeographic region
Authors: Valois‐Cuesta Hamleth , Martínez‐Ruiz Carolina , Valoyes Zulay Q.
Published: May 2024

Soil fertility heterogeneity is one of the main factors affecting early recovery and plant succession toward a target plant community. This study examined the influence of topography on the diversity and composition of plant communities established in areas degraded by opencast mining in Chocó, Colombia. Soil fertility and plant community were characterized in the four topographic formations identified in the abandoned mines: plains (PL), slopes (SLP), floodplains (FP), and sand and gravel mounds (SGM). Topographic formations did not result in significant differences in soil properties. However, a gradient of fertility and vegetation cover was observed: from the SGM, with less fertile soils and little vegetation, to the PL, SLP, and FP, with the most fertile soils and greater vegetation cover and density. The species composition found in PL, SLP, and FP was similar but differed from that of SGM. These results suggest that the SGM does not promote early revegetation in the mines. However, experimental studies are necessary to determine how topographic formations and soil conditions resulting from mining should be managed to facilitate the early recovery of vegetation and the ecological restoration of areas affected by mining.
Under pressure: assessment of chemical stress on restored river sections using effect‐based methods
Authors: Hörchner Sarah , Moulinec Ariane , Sundermann Andrea , Oehlmann Jörg , Oetken Matthias
Published: May 2024

Aquatic ecosystems are affected by multiple stressors, including hydrological and morphological degradation, high nutrient loading, and chemical pollution. To improve freshwater habitats, hydromorphological restorations have been increasingly implemented. However, follow‐up assessments often show little to no improvement in ecological status, even years after restoration measures have been implemented. The success of restoration projects can be compromised by other stressors, such as insufficient water and sediment quality, which often receive less attention compared to nonchemical stressors. In this study, the impact of chemical stress on the outcome of five river restorations was evaluated ecologically, chemically, and ecotoxicologically. Overall, the habitat structure was considerably improved through the restoration measures, whereas the species communities did not show a consistent trend toward an improved ecological status. Effect‐based methods were used for an integrative assessment of the exposure to chemical mixtures in water and sediment samples of restored stream sections. Differences in toxicity between restored and non‐restored sections were found but did not show a consistent trend among the applied assays. In contrast, the chemical analysis showed that the sections of the same stream were similar in their chemical composition, and differences within a stream were primarily due to sediment contamination. The results of this study suggest that chemical pollution is a relevant factor preventing the success of restoration measures and, ultimately, the improvement of the ecological status of rivers. They also demonstrate the applicability of EBMs in water quality monitoring to detect mixture toxicity in streams and link chemical and ecological assessment.
Does the frequency of using Internet entertainment affect happiness? Evidence from China
Authors: Lin Yunyuan
Published: May 2024

Objective

In the context of rapid Internet development, studying individual happiness holds significant practical and academic value.

Methods

This article employs ordinary least squares to examine the impact of the frequency of Internet entertainment usage on happiness using data from the China Family Panel Studies spanning 2014 to 2018.

Results

The empirical results demonstrate a significant positive effect of the frequency of Internet entertainment usage on happiness. Specifically, each additional instance of using Internet entertainment is associated with a 4.2 percent increase in happiness. This finding remains robust after controlling for other variables, annual, and provincial fixed effects. To address potential endogeneity issues, the perceived importance of Internet entertainment to residents is used as an instrumental variable. Heterogeneity analysis reveals that the frequency of Internet entertainment usage significantly affects happiness across different genders, ages, education levels, and employment statuses.

Conclusion

The implications of this study suggest that governments should focus on the development of Internet entertainment, explore its beneficial potentials further, minimize its drawbacks, and enhance the overall happiness of residents through their engagement with Internet entertainment, thereby allowing the Internet to better serve the populace.
Seeing double: two different homospermidine oxidases are involved in pyrrolizidine alkaloid biosynthesis in different organs of comfrey (Symphytum officinale)
Authors: Zakaria Mahmoud M. , Kruse Lars H. , Engelhardt Annika , Ober Dietrich
Published: May 2024

Pyrrolizidine alkaloids (PAs) are toxic specialized metabolites produced in several plant species and frequently contaminate herbal teas or livestock feed. In comfrey (Symphytum officinale, Boraginaceae), they are produced in two different organs of the plant, the root and young leaves. In this study, we demonstrate that homospermidine oxidase (HSO), a copper‐containing amine oxidase (CuAO) responsible for catalyzing the formation of the distinctive pyrrolizidine ring in PAs, is encoded by two individual genes. Specifically, SoCuAO1 is expressed in young leaves, while SoCuAO5 is expressed in roots. CRISPR/Cas9‐mediated knockout of socuao5 resulted in hairy roots (HRs) unable to produce PAs, supporting its function as HSO in roots. Plants regenerated from socuao5 knockout HRs remained completely PA‐free until the plants began to develop inflorescences, indicating the presence of another HSO that is expressed only during flower development. Stable expression of SoCuAO1 in socuao5 knockout HRs rescued the ability to produce PAs. In vitro assays of both enzymes transiently expressed in Nicotiana benthamiana confirmed their HSO activity and revealed the ability of HSO to control the stereospecific cyclization of the pyrrolizidine backbone. The observation that the first specific step of PA biosynthesis catalyzed by homospermidine synthase requires only one gene copy, while two independent paralogs are recruited for the subsequent homospermidine oxidation in different tissues of the plant, suggests a complex regulation of the pathway. This adds a new level of complexity to PA biosynthesis, a system already characterized by species‐specific, tight spatio‐temporal regulation, and independent evolutionary origins in multiple plant lineages.
Abscisic acid controls sugar accumulation essential to strawberry fruit ripening via the FaRIPK1‐FaTCP7‐FaSTP13/FaSPT module
Authors: Chen Xuexue , Gao Jiahui , Shen Yuanyue
Published: May 2024

Strawberry is considered as a model plant for studying the ripening of abscisic acid (ABA)‐regulated non‐climacteric fruits, a process in which sugar plays a fundamental role, while how ABA regulates sugar accumulation remains unclear. This study provides a direct line of physiological, biochemical, and molecular evidence that ABA signaling regulates sugar accumulation via the FaRIPK1‐FaTCP7‐FaSTP13/FaSPT signaling pathway. Herein, FaRIPK1, a red‐initial protein kinase 1 previously identified in strawberry fruit, not only interacted with the transcription factor FaTCP7 (TEOSINTE BRANCHEN 1, CYCLOIDEA, and PCF) but also phosphorylated the critical Ser89 and Thr93 sites of FaTCP7, which negatively regulated strawberry fruit ripening, as evidenced by the transient overexpression (OE) and virus‐induced gene silencing transgenic system. Furthermore, the DAP‐seq experiments revealed that FvTCP7 bound the motif “GTGGNNCCCNC” in the promoters of two sugar transporter genes, FaSTP13 (sugar transport protein 13) and FaSPT (sugar phosphate/phosphate translocator), inhibiting their transcription activities as determined by the electrophoretic mobility shift assay, yeast one‐hybrid, and dual‐luciferase reporter assays. The downregulated FaSTP13 and FaSPT transcripts in the FaTCP7‐OE fruit resulted in a reduction in soluble sugar content. Consistently, the yeast absorption test revealed that the two transporters had hexose transport activity. Especially, the phosphorylation‐inhibited binding of FaTCP7 to the promoters of FaSTP13 and FaSPT could result in the release of their transcriptional activities. In addition, the phosphomimetic form FaTCP7S89D or FaTCP7T93D could rescue the phenotype of FaTCP7‐OE fruits. Importantly, exogenous ABA treatment enhanced the FaRIPK1–FaTCP7 interaction. Overall, we found direct evidence that ABA signaling controls sugar accumulation during strawberry fruit ripening via the “FaRIPK1‐FaTCP7‐FaSTP13/FaSPT” module.
On the Smith–Thom deficiency of Hilbert squares
Authors: Kharlamov Viatcheslav , Răsdeaconu Rareş
Published: May 2024

We give an expression for the Smith–Thom deficiency of the Hilbert square of a smooth real algebraic variety in terms of the rank of a suitable Mayer– Vietoris mapping in several situations. As a consequence, we establish a necessary and sufficient condition for the maximality of in the case of projective complete intersections, and show that with a few exceptions, no real nonsingular projective complete intersection of even dimension has maximal Hilbert square. We also provide new examples of smooth real algebraic varieties with maximal Hilbert square.
Bifurcation and Chaos Analysis of a Supersonic Slipper–Track System
Authors: Dang Tianjiao , Liu Zhen , Morandini Marco , Ma Linjie , Masarati Pierangelo
Published: May 2024

The slipper is the critical component of a supersonic rocket sled that is in contact with the track. Due to clearance and contact effects, the supersonic slipper–track system displays pronounced nonlinearities. A comprehensive analysis, including bifurcation and chaos detection, is conducted on this system to predict the nonlinear behavior of the slipper. Kinematic and dynamic models of the system are established using the generalized coordinate and Lagrange multiplier methods. This model accounts for slipper–track clearances, track irregularities, and normal contact forces. The dynamic response of the slipper is examined both in time and frequency domain. The bifurcation analysis encompasses various parameters such as slipper velocity and length, and slipper–track clearance. Chaos identification is employed for both qualitative and quantitative assessments, utilizing phase diagrams, Poincaré sections, the trajectory of the slipper's center, and the largest Lyapunov exponent (LLE). The findings revealed significant nonlinear phenomena, including self-excited vibrations, superharmonic responses, jumping phenomena, strange attractors, and combined frequencies. Notably, this study demonstrated the potential for leveraging chaotic response to mitigate the contact forces on the slipper. These insights contribute to the rationalization of control parameters and the optimization of slipper and track design.
Heinrich event ice discharge and the fate of the Atlantic Meridional Overturning Circulation
Authors: Zhou Yuxin , McManus Jerry F.
Published: May 2024

During Heinrich events, great armadas of icebergs episodically flooded the North Atlantic Ocean and weakened overturning circulation. The ice discharges of these episodes constrain the sensitivity of overturning circulation to iceberg melting. We reconstructed these ice discharges to be as high as 0.13 sverdrup (Sv) (1 Sv = 1 million cubic meters per second) during Heinrich event 4 and to average 0.029 Sv over all episodes. The present-day Greenland Ice Sheet calving of icebergs is comparable to that of a mid-range Heinrich event. As the future Greenland Ice Sheet recedes from marine-terminating outlets, its iceberg calving likely will not persist long enough for icebergs alone to cause catastrophic disruption to the Atlantic overturning circulation, although the accelerating Greenland runoff and continued global warming remain threats to the circulation stability.
Supersharers of fake news on Twitter
Authors: Baribi-Bartov Sahar , Swire-Thompson Briony , Grinberg Nir
Published: May 2024

Governments may have the capacity to flood social media with fake news, but little is known about the use of flooding by ordinary voters. In this work, we identify 2107 registered US voters who account for 80% of the fake news shared on Twitter during the 2020 US presidential election by an entire panel of 664,391 voters. We found that supersharers were important members of the network, reaching a sizable 5.2% of registered voters on the platform. Supersharers had a significant overrepresentation of women, older adults, and registered Republicans. Supersharers’ massive volume did not seem automated but was rather generated through manual and persistent retweeting. These findings highlight a vulnerability of social media for democracy, where a small group of people distort the political reality for many.
No new fossil fuel projects: The norm we need
Authors: Green Fergus , Bois von Kursk Olivier , Muttitt Greg , Pye Steve
Published: May 2024

A social-moral norm against new fossil fuel projects has strong potential to contribute to achieving global climate goals
In Science Journals
Authors: Smith Jesse , Lavine Marc S. , Szuromi Phil , Vignieri Sacha , Grocholski Brent , Olingy Claire , Simonti Corinne , Yashinski Melisa , Maroso Mattia , Nusinovich Yevgeniya , Uzogara Ekeoma , Osborne Ian S. , Malo Courtney , Wong Wei
Published: May 2024

Highlights from the
Science
family of journals
Mysterious sea urchin plague is spreading rapidly
Authors: Cummings Sean
Published: May 2024

Pathogen that kills victims within days leaps from Caribbean to Red Sea
Theory of sleep as a brain cleanser challenged
Authors: Reardon Sara
Published: May 2024

Mouse study contradicts landmark finding, but some question its methodology
The interplay of suppressive soil bacteria and plant root exudates determines germination of microsclerotia of
Verticillium longisporum
Authors: Sarenqimuge Sarenqimuge , Wang Yao , Alhussein Mohammad , Koopmann Birger , von Tiedemann Andreas
Published: May 2024

Dormant microsclerotia play a vital role in the survival and spread of
Verticillium longisporum
, as they can stay viable in the soil and maintain their infectivity for many years. In our previous work, we revealed that soil bacterial volatiles are a key inhibitory factor causing microsclerotia dormancy in the soil. In this study, we further demonstrate that root exudates collected from both host and non-host plants can effectively rescue microsclerotia from bacterial suppression and initiate germination. To identify the specific compounds in root exudates responsible for microsclerotia germination, we fractionated the collected root exudates into polar and non-polar compounds. Subsequently, we conducted comprehensive bioassays with each fraction on germination-suppressed microsclerotia. The result revealed a pivotal role of primary metabolites in root exudates, particularly glutamic acid, in triggering microsclerotia germination and overcoming bacterial inhibition. Moreover, our studies revealed a decrease in inhibitory bacterial volatile fatty acids when bacteria were cultured in the presence of root exudates or glutamic acid. This suggests a potential mechanism, by which root exudates set-off bacterial suppression on microsclerotia. Here, we reveal for the first time that plant root exudates, instead of directly inducing the germination of microsclerotia, enact a set-off effect by counteracting the suppressive impact of soil bacteria on the microsclerotia germination process. This nuanced interaction advances our understanding of the multifaceted dynamics governing microsclerotia dormancy and germination in the soil environment.

IMPORTANCE

Our research provides first-time insights into the crucial interaction between plant root exudates and soil bacteria in regulating the germination of
Verticillium longisporum
microsclerotia, a significant structure in the survival and proliferation of this soil-borne pathogen. We describe so far unknown mechanisms, which are key to understand how root infections on oilseed rape can occur. By pinpointing primary metabolites in root exudates as key factors in overcoming bacteria-induced dormancy and promote microsclerotia germination, our study highlights the potential for exploiting plant - as well as soil microbe-derived - compounds to control
V. longisporum
. This work underscores the importance of elucidating the nuanced interactions within the soil ecosystem to devise innovative strategies for managing root infective plant diseases, thereby contributing to the resilience and health of cropping systems.
Unveiling the immune dynamics of
Neisseria
persistent oral colonization
Authors: Alles Mario , Gunasena Manuja , Zia Tauqir , D'Mello Adonis , Bhattarai Saroj , Mulhern Will , Terry Luke , Scherger Trenton , Wijeratne Saranga , Singh Sachleen , Wijeratne Asela J. , Kasturiratna Dhanuja , Tettelin Hervé , Weyand Nathan J. , Liyanage Namal P. M.
Published: May 2024

Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus
Neisseria
, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective but lacks models that study immune responses in the context of long-term persistence.
Neisseria musculi
, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time, we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to
N. musculi
colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from the lung, blood, and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic
Neisseria
.
Isolation and identification of uric acid-dependent
Aciduricibacillus chroicocephali
gen. nov., sp. nov. from seagull feces and implications for hyperuricemia treatment
Authors: Liu Wenxuan , Nan Fulong , Liu Fengjun , Yang Xiaoli , Li Zonghui , Jiang Shasha , Zhang Xianjuan , Li Jun , Yu Meng , Wang Yunyang , Wang Bin
Published: May 2024

Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XB
T
, a uric acid-degrading bacterium, from black-headed gull (
Chroicocephalus ridibundus
) feces. Using a polyphasic taxonomic approach, strain 44XB
T
was identified as a novel genus within the family
Bacillaceae
; subsequently, the name
Aciduricibacillus chroicocephali
was proposed. Strain 44XB
T
had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (
pucL
,
pucM
,
uraD
, and
allB
) were found. Six copies of
pucL
(encoding urate oxidase) were detected. Of these, five
pucL
copies were in a tandem arrangement and shared 70.42%–99.70% amino acid identity.
In vivo
experiments revealed that 44XB
T
reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT.

IMPORTANCE

The increasing disease burden of hyperuricemia highlights the need for new therapeutic drugs and treatment strategies. Our study describes the developmental and application values of natural uric acid-degrading bacteria found in the gut of birds and broadened the source of bacteria with potential therapeutic value. Furthermore, the special physiology characteristics and genomic features of strain 44XB
T
are valuable for further study.
Stratigraphy, eruption, and evolution of the Columbia River Basalt Group
Authors: Soderberg Evan R. , Hart Rachelle , Camp Victor E. , Wolff John A. , Steiner Arron
Published: May 2024

The Miocene Columbia River Basalt Group (CRBG) is world famous and the best studied continental flood basalt province on Earth. Decades of field and laboratory study have resulted in a detailed stratigraphy, consisting of seven formations containing more than 350 flows, a well-constrained chronology, and a large geochemical database. Petrogenesis of the flood basalts is constrained by many thousands of major element, trace element, and isotopic analyses of whole rocks and their constituent minerals. There is broad consensus that the province is the product of a deep mantle plume, although the details of plume interaction with North American lithosphere, and the generation, storage, transport, and eruption of flood basalt magma, are the subjects of continuing research. This field trip focuses on basalt flow sequences, dikes, vents, evolution of basaltic magmas through the lifetime of flood lava activity, and their relation to the larger Yellowstone Hotspot Province. The formations to be examined include the Imnaha, Grande Ronde, Wanapum, and Saddle Mountain Basalts. Trip stops are primarily along the Snake and Grande Ronde Rivers located in and adjacent to the canyon country of southeast Washington, western Idaho, and northeast Oregon.
Reconciling devolution with health financing and public financial management: challenges and policy options for the health sector
Authors: Ravishankar Nirmala , Mathauer Inke , Barroy Hélène , Vîlcu Ileana , Chaitkin Michael , Offosse Marie Jeanne , Co Pura Angela , Nakyanzi Angellah , Mbuthia Boniface , Lourenço Salomão , Mardani Halimah , Kutzin Joseph
Published: May 2024

The interplay between devolution, health financing and public financial management processes in health—or the lack of coherence between them—can have profound implications for a country’s progress towards universal health coverage. This paper explores this relationship in seven Asian and African countries (Burkina Faso, Kenya, Mozambique, Nigeria, Uganda, Indonesia and the Philippines), highlighting challenges and suggesting policy solutions. First, subnational governments rely heavily on transfers from central governments, and most are not required to allocate a minimum share of their budget to health. Central governments channelling more funds to subnational governments through conditional grants is a promising way to increase public financing for health. Second, devolution makes it difficult to pool funding across populations by fragmenting them geographically. Greater fiscal equalisation through improved revenue sharing arrangements and, where applicable, using budgetary funds to subsidise the poor in government-financed health insurance schemes could bridge the gap. Third, weak budget planning across levels could be improved by aligning budget structures, building subnational budgeting capacity and strengthening coordination across levels. Fourth, delays in central transfers and complicated procedures for approvals and disbursements stymie expenditure management at subnational levels. Simplifying processes and enhancing visibility over funding flows, including through digitalised information systems, promise to improve expenditure management and oversight in health. Fifth, subnational governments purchase services primarily through line-item budgets. Shifting to practices that link financial allocations with population health needs and facility performance, combined with reforms to grant commensurate autonomy to facilities, has the potential to enable more strategic purchasing.
Evidence of cardiomyopathy associated with Marfan syndrome in children
Authors: Weigand Justin , Stephens-Novy Sara , Sachdeva Shagun , Doan Tam T , Yasso Abigail , Morris Shaine A
Published: May 2024

Objective

Marfan syndrome (MFS)-associated cardiomyopathy, defined as ventricular dilation and dysfunction unexplained by volume loading, is not well defined in children. This study evaluated ventricular size and function in paediatric MFS using cardiac MRI (cMRI).

Methods

This retrospective cohort study examined patients with MFS <19 years old at first cMRI. Left ventricular (LV) ejection fraction (EF) <55% was considered abnormal, as were z-scores >2. Combined mitral and aortic regurgitation indexed to LV stroke volume <20% defined absent/mild volume load. Biventricular volumes and EF on serial cMRI studies were compared with normative paediatric cMRI values, with measures converted to z-scores as appropriate. Longitudinal changes in volumes and EF were evaluated by mixed linear regression. Associations between ventricular, aortic and mitral characteristics were evaluated.

Results

58 patients (60% male) were evaluated. Median age at initial cMRI was 13.6 years (IQR 10.0–15.8 years). Among patients with absent/mild LV volume load at initial cMRI (n=44, 76%), indexed LV end-diastolic volume (EDV) was significantly increased above normative values (median z-score 1.8, IQR 0.6–3.5, p<0.0001) and LVEF was abnormal in 48% (21/44). In the absence of volume loading, mitral valve prolapse (MVP) was associated with larger ventricular volumes and lower LVEF. Among those with serial cMRIs, LVEF and EDV z-scores did not significantly change over a mean follow-up time between cMRI studies of 1.5 years.

Conclusion

Ventricular dilation and reduced EF are common in children with MFS and occur with no/mild LV volume load, suggesting intrinsic cardiomyopathy. MVP may be associated with cardiomyopathy.
Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes
Authors: Levin Noam , Kim Sanghyun P , Marquardt Charles A , Vale Nolan R , Yu Zhiya , Sindiri Sivasish , Gartner Jared J , Parkhurst Maria , Krishna Sri , Lowery Frank J , Zacharakis Nikolaos , Levy Lior , Prickett Todd D , Benzine Tiffany , Ray Satyajit , Masi Robert V , Gasmi Billel , Li Yong , Islam Rafiqul , Bera Alakesh , Goff Stephanie L , Robbins Paul F , Rosenberg Steven A
Published: May 2024

Background

Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment.

Methods

We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens. An in vitro stimulation method, termed “NeoExpand”, was developed to provide neoantigen-specific stimulation to TILs. 25 consecutive patient TILs from tumors harboring p53 or RAS mutations were subjected to NeoExpand.

Results

We show that neoantigenic stimulation achieved selective expansion of neoantigen-reactive TILs and broadened the neoantigen-reactive CD4+and CD8+TIL clonal repertoire. This allowed the effective isolation of novel neoantigen-reactive TCRs. Out of the 25 consecutive TIL samples, neoantigenic stimulation enabled the identification of 16 unique reactivities and 42 TCRs, while conventional TIL expansion identified 9 reactivities and 14 TCRs. Single-cell transcriptome analysis revealed that neoantigenic stimulation increased neoantigen-reactive TILs with stem-like memory phenotypes expressing IL-7R, CD62L, and KLF2. Furthermore, neoantigenic stimulation improved the in vivo antitumor efficacy of TILs relative to the conventional OKT3-induced rapid TIL expansion in p53-mutated or KRAS-mutated xenograft mouse models.

Conclusions

Taken together, neoantigenic stimulation of TILs selectively expands neoantigen-reactive TILs by frequencies and by their clonal repertoire. NeoExpand led to improved phenotypes and functions of neoantigen-reactive TILs. Our data warrant its clinical evaluation.

Trial registration number

NCT00068003,NCT01174121, andNCT03412877.
Moderators of movement behaviour changes among Canadian toddlers and preschoolers throughout the first 2 years of the COVID-19 pandemic
Authors: Carson Valerie , Zhang Zhiguang , Boyd Madison , Potter Morgan , Li Joshua , Kuzik Nicholas , Hunter Stephen
Published: May 2024

Primary objectives were to examine: (1) changes in movement behaviours (i.e., outdoor play (OP), organized physical activity (PA), screen time (ST), sleep) across the first 2 years of coronavirus disease-2019 (COVID-19) among Canadian toddlers and preschoolers, and (2) intrapersonal, interpersonal, community, and policy moderators of change in movement behaviors. Participants were 341 Canadian parents of children (start of study: 1–4 years; 48% female). Participants completed online questionnaires regarding their children’s movement behaviours and intrapersonal, interpersonal, and community factors at five time-points before and throughout the pandemic (T1–T5). Data from government websites were also used for some community and policy factors. Linear mixed models were conducted. Compared to pre-COVID-19 (T1): OP was on average 30 min/day higher at T2 and T3; organized PA was on average 62, 44, and 37 min/day lower at T2, T3, and T4, respectively; ST was on average 67, 17, 38, and 52 min/day higher at T2, T3, T4, and T5, respectively; and sleep was on average 30, 36, and 82 min/day lower at T3, T4, and T5, respectively. Significant moderating variables were observed for OP (parental education, parental work inside home, COVID-19 restriction severity), organized PA (children’s sex, started kindergarten, nonparental care, parental education, household income, parental employment status, house type, indoor home space and support for PA), ST (nonparental care, parental marital status) and sleep (children’s T1 age group, started kindergarten, parental place of birth, parental employment status). All movement behaviors changed across the first 2 years of COVID-19 but patterns and moderators were behaviour-specific. Children from lower socioeconomic status families had the least optimal patterns.
A toolkit for greater equity, diversity, and inclusion in early-career ecology funding
Authors: Sun Catherine , Granados Alys , Beirne Christopher , Chow-Fraser Gillian , Francis Abraham , Kwong Lian , Soroye Peter , Yip Helen , Miettunen Anita , Bowman Jeff , Burton A. Cole
Published: May 2024

Funding is critical in ecology and related fields, as it enables research and sustains livelihoods. However, early-career researchers (ECRs) from diverse backgrounds are disproportionately underrepresented as funding recipients. To help funding programs self-evaluate progress towards increasing equity, diversity, and inclusion (EDI) in their funding opportunities, we introduce the Stage-based Assessments of Grants for EDI (SAGE) Toolkit. Developed using existing literature, semi-structured interviews, and coauthors’ experiences, the toolkit considers how each funding stage (Advertisement, Application, Review, Awarding) interacts with applicants from racialized and other underrepresented backgrounds. The toolkit offers specific criteria and recommendations, with explanations and examples from funding agencies, to support applicants who have been historically marginalized in ecology and are often left out of equitable funding consideration. Changes in funding mechanisms alone will not reverse the marginalization of communities and peoples in the field of ecology, but advancing EDI must include action throughout the grant process. Efforts to increase EDI must be sustained, and the toolkit allows for additional considerations and evolving best practices. With the SAGE Toolkit, efforts to increase EDI can help to transition away from a transactional dynamic between funder and applicant to instead supportive community and collaboration. The SAGE Toolkit is available online at bit.ly/ediSAGEtoolkit.