bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Hsp20 gene family in Malus domestica and functional characterization of Hsp20 class I gene MdHsp18.2b
Authors: Zhang Fu‐Jun , Li Zhao‐Yang , Zhang De‐En , Ma Ning , Wang Yong‐Xu , Zhang Ting‐Ting , Zhao Qiang , Zhang Zhenlu , You Chun‐Xiang , Lu Xiao‐Yan
Published: April 2024

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome‐wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo‐ or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.
Exploring provider preference and provision of abortion methods and stigma: Secondary analysis of a United Kingdom provider survey
Authors: Footman Katy , Bright Suzanna , Kavanagh Jayne , Parnham Emma , Bury Louise , Hoggart Lesley
Published: April 2024

Introduction

Method choice is an important component of quality abortion care and qualitative research suggests that abortion stigma can influence provider preference and provision of abortion methods. This study is the first to explore the relationships between abortion providers' method preferences, their provision of medication or instrumentation abortion or both methods, and abortion stigma.

Methods

We conducted secondary analysis of a survey of United Kingdom (UK) abortion providers (N = 172) to describe and compare providers' self‐reported method preferences and provision. We used multinomial logistic regression to assess the association between method preference and provider experiences of abortion stigma (measured using a revised Abortion Provider Stigma Scale (APSS)), adjusting for relevant provider and facility characteristics.

Results

Almost half (52%) of providers reported that they only provided medication abortion care, while 5% only provided instrumentation abortion care and 43% provided both methods. Most (62%) preferred to provide both methods while 32% preferred to provide only medication abortion and 6% only instrumentation abortion. There was no significant difference in revised APSS scores by provider method preference or provision.

Discussion

Most surveyed UK abortion providers prefer to offer both methods, but over half only provide medication abortion. This may reflect patients' preferences for medication abortion, and health system and legal constraints on instrumentation abortion. Addressing these systemic constraints on method provision could expand patient choice. Providers' method preference was not significantly associated with provider stigma but future research should consider the influence of structural stigma on method provision at the health system level.
A prospective study of sexual risk patterns associated with delinquency and justice involvement among child welfare system‐involved male adolescents in the United States
Authors: Grant Nickholas , Merrin Gabriel J. , April Keisha , April‐Sandars Ayana , Arora Ishita , Gordon Derrick
Published: April 2024

Introduction

Early sexual activity and teen pregnancy are known risk factors for delinquency and justice involvement among male adolescents. However, less is known about these patterns among child welfare system (CWS)‐involved boys who face significant social barriers and past/current traumatic experiences.

Methods

We prospectively examined these associations among male adolescents who identified as low and high risk for child‐maltreatment via a secondary data analysis of the Longitudinal Studies of Child Abuse and Neglect dataset—a large scale assessment of children, their parents, and their teachers in the United States to understand issues of child abuse and neglect. We extracted and examined data from 657 boys who were identified as at‐risk for maltreatment or with histories of substantiated maltreatment at ages 6, 8, 12, 14, and 16. We used structural equation modeling to examine the relationship between sexual activity (i.e., age of sexual debut, actively having sex, and sex resulting in a child) and changes in delinquency and justice involvement.

Results

Male adolescents who have engaged in sex and/or have fathered a child had greater increases in delinquency over time compared to those who have not had sex. Further, fathering a child was significantly associated with justice involvement, especially for the high‐risk group.

Conclusion

Results indicate that greater efforts should be taken to ascertain CWS‐involved male adolescents' sexual health practices and parenting status. Male adolescents in the CWS require support with accessing developmentally appropriate sexual health education and family services.
Input legitimacy of bottom‐up fishery governance: Lessons from community‐led local development in two Nordic EU countries
Authors: Svels Kristina , Thuesen Annette Aagaard
Published: April 2024

In European Union member states, the community‐led local development (CLLD) approach implemented through Fisheries Local Action Groups (FLAGs) represents different social organisational and democratic traditions. Hence, FLAGs operate and apply local development strategies and strengthen the role of fishing communities and the fishing industry under the influence of nationally contingent factors. Based on document analysis and mixed methods data, this article addresses the role of input legitimacy in FLAGs in Denmark and Finland. The findings show that Danish FLAGs demonstrate input legitimacy, while the fishery sector's interests are relatively weakly represented on FLAG boards. In Finland, the FLAG institutional system is perceived to be more flexible, demonstrating a lower level of input legitimacy, while the fishery sector's interests are substantially represented on FLAG boards. The comparison provides an analytical basis for member states financing CLLD through EMFAF and paves the way for reflexion on the FLAG governance system based on different programming periods and institutional contexts.
The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study
Authors: Xin Yu , Yuan Tao , Wang Jun
Published: April 2024

Background

Atopic dermatitis ranks among the prevalent skin disorders. Research has indicated a potential association with brain cancer. Yet, establishing a direct causal relationship between atopic dermatitis and brain cancer continues to be challenging.

Materials and Methods

We extracted single nucleotide polymorphisms (SNPs) significantly associated with atopic dermatitis (sample size = 382 254) at a genome‐wide level from a large Finnish Genome‐Wide Association Study (GWAS) dataset (n cases = 15 208, n controls = 367 046). Summary data for 372 622 cases of brain cancer (n cases = 606, n controls = 372 016) were obtained via the IEU Open GWAS database. We employed the Inverse Variance Weighted (IVW) method as our primary analytical approach for Mendelian Randomization (MR) analysis. Additionally, heterogeneity was measured using Cochran's Q value, and horizontal pleiotropy was evaluated using MR‐Egger 、Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave‐one‐out analyses.

Results

The risk of brain cancer increases with the presence of atopic dermatitis, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs),(OR = 1.0005; 95% CI = 1.0001, 1.0009; p = 0.0096). However, when conducting the analysis in reverse, no significant link was observed.

Conclusion

The findings from our study indicate a causative link between atopic dermatitis and brain cancer, highlighting the importance of conducting broader clinical investigations into their potential association going forward.
The Value of Master's Degree Programmes in Health Professions Education: A Scoping Review
Authors: O'Callaghan Charlotte , Sandars John , Brown Jeremy , Sherratt Cathy
Published: April 2024

Introduction

There are increasing numbers of Master's Degree Programmes in Health Professions Education (MHPE), and the value to their students and graduates is not well understood. We conducted a scoping review to explore what is known about the value of MHPE programmes to their students and graduates.

Methods

A scoping review was conducted using Arksey and O'Malley's five‐stage framework. PubMed, CINAHL, Cochrane, BEI, ERIC and EThOs databases were searched in addition to cited reference searching. Original research with an evaluation and published in the English language were included.

Results

Nineteen studies were included. Studies were based in a variety of locations on five continents, and included in‐person, distance and blended learning. Students and graduates of MHPE programmes self‐reported development of their pedagogical knowledge, confidence and credibility in their role as an educator, and educational scholarship. Enhanced career opportunities and opportunities for collegial interactions and networks were also reported. Important barriers included struggling with the time and financial commitments required for studying on a MHPE programme.

Conclusions

There are a variety of dimensions of value of MHPE programmes to their students and graduates. Important practical recommendations for MHPE programme providers and employers include providing opportunities for the development of networks and supporting the time and financial commitments required for studying.
U‐Pb carbonate dating reveals long‐lived activity of proximal margin extensional faults during the Alpine Tethys rifting
Authors: Rocca M. , Zanchetta S. , Gasparrini M. , Mangenot X. , Berra F. , Deschamps P. , Guihou A. , Zanchi A.
Published: April 2024

Syn‐rift extensional faults play a significant role during the early stage of rifting. Constraining the age of faulting, and how and when deformation shifts from the proximal to the distal margin areas, is crucial for the reconstruction of the rifting process. Previous assessments of the structural and temporal evolution of rift‐related faults of the Adria proximal margin have primarily relied on indirect biostratigraphic evidence. Additionally, the majority of rift‐related faults underwent tectonic inversion during the Alpine orogeny. In this study, in‐situ U‐Pb geochronology was applied on syn‐kinematic calcites to unravel the activity of the Amora Fault, a remarkable example of a Jurassic growth fault unaffected by the Alpine orogeny. The obtained ages, spanning from Hettangian to Callovian, extend the AF activity beyond the previously established Early Jurassic time. This chrono‐structural model has significant implications on the role of major extensional faults in focusing deformation throughout the rift system's evolution.
Genome editing of a recalcitrant wine grape genotype by lipofectamine‐mediated delivery of CRISPR/Cas9 ribonucleoproteins to protoplasts
Authors: Gambino Giorgio , Nuzzo Floriana , Moine Amedeo , Chitarra Walter , Pagliarani Chiara , Petrelli Annalisa , Boccacci Paolo , Delliri Andrea , Velasco Riccardo , Nerva Luca , Perrone Irene
Published: April 2024

The main bottleneck in the application of biotechnological breeding methods to woody species is due to the in vitro regeneration recalcitrance shown by several genotypes. On the other side, woody species, especially grapevine (Vitis vinifera L.), use most of the pesticides and other expensive inputs in agriculture, making the development of efficient approaches of genetic improvement absolutely urgent. Genome editing is an extremely promising technique particularly for wine grape genotypes, as it allows to modify the desired gene in a single step, preserving all the quality traits selected and appreciated in elite varieties. A genome editing and regeneration protocol for the production of transgene‐free grapevine plants, exploiting the lipofectamine‐mediated direct delivery of CRISPR–Cas9 ribonucleoproteins (RNPs) to target the phytoene desaturase gene, is reported. We focused on Nebbiolo (V. vinifera), an extremely in vitro recalcitrant wine genotype used to produce outstanding wines, such as Barolo and Barbaresco. The use of the PEG‐mediated editing method available in literature and employed for highly embryogenic grapevine genotypes did not allow the proper embryo development in the recalcitrant Nebbiolo. Lipofectamines, on the contrary, did not have a negative impact on protoplast viability and plant regeneration, leading to the obtainment of fully developed edited plants after about 5 months from the transfection. Our work represents one of the first examples of lipofectamine use for delivering editing reagents in plant protoplasts. The important result achieved for the wine grape genotype breeding could be extended to other important wine grape varieties and recalcitrant woody species.
Challenges and Strategies of Higher Vocational Education in China with the New Demographics-Based on the Data Analysis of China’s Seventh National Census
Authors: Wang Shijie
Published: April 2024

There is an important connection between the development of higher vocational education and the national demographics. According to the data of the seventh national census, China is facing a population reality with negative growth, an inverted pyramid structure, expanding migration, and stable quality improvement. The change in demographics sets out new requirements for the goal, types, structure and quality of higher vocational education. To develop higher vocational education, we should constantly optimize development planning, expand development types, optimize resource allocation and improve development quality.
Plasma confinement by an optoelectronic system
Authors: Tsukazaki Ryuta , Naito Haruhiro , Koga Hisashi , Fukuda Akito , Kato Naoki , Watanabe Takayuki , Takabayashi Susumu
Published: April 2024

Plasma confinement was succeeded by an optoelectronic system with the aid of a vacuum ultraviolet (VUV) light source, called the photoemission-assisted plasma system. The photoemission-assisted plasma was generated by utilizing photoelectrons from the substrate cathode. The photoelectrons were emitted from the substrate by external VUV irradiation via the photoelectric effect and then worked as initial electrons triggering the plasma generation. The photoemission-assisted plasma was confined with bright luminescence in an argon atmosphere by controlling the flow rate and pressure. The plasma confinement survived at up to 6400 Pa, which was much higher than the pressure estimated from the current–voltage characteristics. These results suggested that the area exhibiting luminescence dominated by the γ regime becomes small as the argon flow rate increases; however, the area does not vanish because the VUV-excited photoelectrons are sufficiently supplied. The residual area is dominated by the α regime without luminescence. Thus, the photoemission-assisted plasma seems to be confined on the balance between α and γ regimes. Because the current in the α-regime area is one hundredth in magnitude compared with that in the γ-regime area, the actual current density results in over 40 times with strong luminescence. This confined plasma with certain voltage and current condition may be expected for developing a new plasma reaction system and for application in semiconductor engineering.
Statistical physics of frictional grains: Some simple applications of the Edwards statistics
Authors: Bertin Eric
Published: April 2024

Granular matter like sand is composed of a large number of interacting grains and is, thus, expected to be amenable to a statistical physics treatment. Yet, the frictional properties of grains make the statistical physics of granular matter significantly different from the equilibrium statistical physics of atomic or molecular systems. We use three simple models to illustrate some of the key concepts of the statistical physics introduced by Edwards and co-workers more than 30 years ago to describe shaken granular piles: non-interacting frictional grains attached to a wall by a spring, a chain of frictional grains connected by springs, and a simplified mean-field model of a granular packing. We observe that a chain of frictional grains connected by springs exhibits a critical point at an infinite effective temperature (i.e., infinitely strong shaking) at odds with the zero-temperature critical point generically found in one-dimensional systems at thermal equilibrium in the presence of local interactions.
The Born rule: Axiom or result?
Authors: Lawrence Jay
Published: April 2024

The Born rule is part of the collapse axioms in the standard version of quantum theory, as presented by most textbooks on the subject. We show here that its signature quadratic dependence on the initial wavefunction's projection onto the measured outcome state follows from a single additional assumption beyond the other axioms. We give two examples of such an assumption, with a separate derivation for each, and we discuss their relationship with existing derivations. Our presentation is suitable for advanced undergraduates or graduate students who have taken a standard course in quantum theory. It does not depend on any particular interpretation of the theory.
Effects of general relativistic post-Newtonian approximations on the configuration space properties of elliptical orbital trajectories
Authors: Bose Prasenjit
Published: April 2024

Post-Newtonian approximations have been successful in describing various astronomical phenomena that classical Newtonian gravity could not. One such phenomenon is the precession of the periapsis of elliptical orbits. Einstein originally solved the problem in 1916 and since then others have been applying the technique to numerous complex systems. However, not much attention has been given to studying the changes in the configuration space when switching from Newtonian to post-Newtonian mechanics. Here, we compare the sizes and topologies of the configuration spaces of both these approaches and further explore the likelihood of planetary collisions in other star systems when configuration space expansion due to general relativity is taken into account.
Arduino cavity controller for LIGO analogy lab [Am. J. Phys. 87, 44 (2019)]
Authors: Ugolini Dennis
Published: April 2024

The LIGO analogy lab [Am. J. Phys. 87, 44 (2019)] includes a complicated pair of circuits to sense and control the length of an optical cavity. This Note describes an alternate, Arduino-based controller that is significantly less complex and easier to troubleshoot.
Omega-3 Status Evaluation in Australian Female Rugby League Athletes: Ad Libitum Fish Oil Provision Results in a Varied Omega-3 Index
Authors: Anthony Ryan , Jaffrey Nicola , Byron Caitlin , Peoples Gregory E. , Macartney Michael J.
Published: April 2024

Optimal omega-3 status, influenced by increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is vital for physiological health. This study investigated the impact of ad libitum fish oil supplementation on the omega-3 status of female athletes in a professional rugby league team during a competitive season. Twenty-four (n = 24) athletes participated, and their omega-3 status was assessed using the Omega-3 Index (O3I) and arachidonic acid (AA) to EPA ratio through finger-prick blood samples taken at the start and end of the season. They were given access to a fish oil supplement (PILLAR Performance, Australia) with a recommended daily dose of four capsules per day (2,160 mg EPA and 1,440 mg docosahexaenoic acid). At the beginning of the season, the group mean O3I was 4.77% (95% confidence interval [CI: 4.50, 5.04]) and the AA to EPA ratio was 14.89 (95% CI [13.22, 16.55]). None of the athletes had an O3I exceeding 8%. By the season’s end, the O3I was a significantly increased to 7.28% (95% CI [6.64, 7.93], p < .0001) and AA to EPA ratio significantly decreased to a mean of 6.67 (95% CI [5.02, 8.31], p < .0001), driven primarily by the significant increase in EPA of +1.14% (95% CI [0.77, 1.51], p < .0001). However, these changes were varied between the athletes and most likely due to compliance. This study has demonstrated that using the objective O3I feedback scale is possible with elite female rugby athletes, but individual strategies will be required to achieve daily intake targets of EPA + DHA.
“You Are Not Wrong About Getting Strong:” An Insight Into the Impact of Age Group and Level of Competition on Strength in Spanish Football Players
Authors: Soriano Marcos A. , Paredes Víctor , Comfort Paul , Jiménez-Ormeño Ester , Areces-Corcuera Francisco , Giráldez-Costas Verónica , Gallo-Salazar César , Alonso-Aubín Diego A. , Menchén-Rubio María , McMahon John J.
Published: April 2024

Objective: This study aimed to compare the maximum and rapid force production of Spanish football players and explore the differences between age group and level of competition. Methods: A cross-sectional study was developed to evaluate the peak force (PF), relative PF, and rate of force development over 250 ms (RFD0−250) during the isometric midthigh pull between groups of football players based on age group (senior vs junior) and level of competition (national vs regional). Using a portable isometric rig, 111 football players performed 2 isometric midthigh-pull trials on a force plate. Two-way analysis of variance with Bonferroni post hoc correction was applied, and statistical significance was set at P ≤ .05. The PF, relative PF, and RFD0−250 0, 25, 50, 75, and 100 percentiles were also calculated and descriptively reported, separated by age group and level of competition. Results: The analysis of variance revealed a significant main effect of the level of competition for the PF (P < .001), relative PF (P = .003), and RFD0−250 (P < .001). There was a significant main effect of age group for the PF (P < .001). There was a significant interaction effect of the age group × level of competition for relative PF (P = .014). National players were stronger than regional players on the PF and RFD0−250 (P < .001). Senior players were stronger than junior players for the PF (P < .001). Conclusions: Maximum and rapid force production are crucial for Spanish football players as they progress in both level of competition and age group. Practitioners should encourage young football players to prioritize strength development to improve their athletic performance.
Impact of operational conditions on drinking water biofilm dynamics and coliform invasion potential
Authors: Waegenaar Fien , García-Timermans Cristina , Van Landuyt Josefien , De Gusseme Bart , Boon Nico
Published: April 2024

Biofilms within drinking water distribution systems serve as a habitat for drinking water microorganisms. However, biofilms can negatively impact drinking water quality by causing water discoloration and deterioration and can be a reservoir for unwanted microorganisms. In this study, we investigated whether indicator organisms for drinking water quality, such as coliforms, can settle in mature drinking water biofilms. Therefore, a biofilm monitor consisting of glass rings was used to grow and sample drinking water biofilms. Two mature drinking water biofilms were characterized by flow cytometry, ATP measurements, confocal laser scanning microscopy, and 16S rRNA sequencing. Biofilms developed under treated chlorinated surface water supply exhibited lower cell densities in comparison with biofilms resulting from treated groundwater. Overall, the phenotypic as well as the genotypic characteristics were significantly different between both biofilms. In addition, the response of the biofilm microbiome and possible biofilm detachment after minor water quality changes were investigated. Limited changes in pH and free chlorine addition, to simulate operational changes that are relevant for practice, were evaluated. It was shown that both biofilms remained resilient. Finally, mature biofilms were prone to invasion of the coliform,
Serratia fonticola
. After spiking low concentrations (i.e., ±100 cells/100 mL) of the coliform to the corresponding bulk water samples, the coliforms were able to attach and get established within the mature biofilms. These outcomes emphasize the need for continued research on biofilm detachment and its implications for water contamination in distribution networks.

IMPORTANCE

The revelation that even low concentrations of coliforms can infiltrate into mature drinking water biofilms highlights a potential public health concern. Nowadays, the measurement of coliform bacteria is used as an indicator for fecal contamination and to control the effectiveness of disinfection processes and the cleanliness and integrity of distribution systems. In Flanders (Belgium), 533 out of 18,840 measurements exceeded the established norm for the coliform indicator parameter in 2021; however, the source of microbial contamination is mostly unknown. Here, we showed that mature biofilms, are susceptible to invasion of
Serratia fonticola
. These findings emphasize the importance of understanding and managing biofilms in drinking water distribution systems, not only for their potential to influence water quality, but also for their role in harboring and potentially disseminating pathogens. Further research into biofilm detachment, long-term responses to operational changes, and pathogen persistence within biofilms is crucial to inform strategies for safeguarding drinking water quality.
Microbial contamination pathways in a poultry abattoir provided clues on the distribution and persistence of
Arcobacter
spp.
Authors: Botta Cristian , Buzzanca Davide , Chiarini Elisabetta , Chiesa Francesco , Rubiola Selene , Ferrocino Ilario , Fontanella Edoardo , Rantsiou Kalliopi , Houf Kurt , Alessandria Valentina
Published: April 2024

The consumption of contaminated poultry meat is a significant threat for public health, as it implicates in foodborne pathogen infections, such as those caused by
Arcobacter
. The mitigation of clinical cases requires the understanding of contamination pathways in each food process and the characterization of resident microbiota in the productive environments, so that targeted sanitizing procedures can be effectively implemented. Nowadays these investigations can benefit from the complementary and thoughtful use of culture- and omics-based analyses, although their application
in situ
is still limited. Therefore, the 16S-rRNA gene-based sequencing of total DNA and the targeted isolation of
Arcobacter
spp. through enrichment were performed to reconstruct the environmental contamination pathways within a poultry abattoir, as well as the dynamics and distribution of this emerging pathogen. To that scope, broiler’s neck skin and caeca have been sampled during processing, while environmental swabs were collected from surfaces after cleaning and sanitizing. Metataxonomic survey highlighted a negligible impact of fecal contamination and a major role of broiler’s skin in determining the composition of the resident abattoir microbiota. The introduction of
Arcobacter
spp. in the environment was mainly conveyed by this source rather than the intestinal content.
Arcobacter butzleri
represented one of the most abundant species and was extensively detected in the abattoir by both metataxonomic and enrichment methods, showing higher prevalence than other more thermophilic Campylobacterota. In particular,
Arcobacter
spp. was recovered viable in the plucking sector with high frequency, despite the adequacy of the sanitizing procedure.

IMPORTANCE

Our findings have emphasized the persistence of
Arcobacter
spp. in a modern poultry abattoir and its establishment as part of the resident microbiota in specific environmental niches. Although the responses provided here are not conclusive for the identification of the primary source of contamination, this biogeographic assessment underscores the importance of monitoring
Arcobacter
spp. from the early stages of the production chain with the integrative support of metataxonomic analysis. Through such combined detection approaches, the presence of this pathogen could be soon regarded as hallmark indicator of food safety and quality in poultry slaughtering.
The whole-genome sequence of
Bacillus
sp. KICET-3, isolated from doenjang
Authors: Park Hyojung , Lee Hye Sun , Lee Jin Hyung , Jeon Byoung Seung
Published: April 2024

Bacillus
sp. KICET-3, isolated from doenjang, a traditional Korean fermented food, has a single chromosomal DNA fragment of 4,616,861 bp, and the G+C content is 45.52%. It is estimated to have 4,450 predicted coding DNA sequences, 84 tRNAs, and 24 rRNAs.
A laboratory-based predictive pathway for the development of
Neisseria gonorrhoeae
high-level resistance to corallopyronin A, an inhibitor of bacterial RNA polymerase
Authors: Balthazar Jacqueline T. , Golparian Daniel , Unemo Magnus , Read Timothy D. , Grosse Miriam , Stadler Marc , Pfarr Kenneth , Schiefer Andrea , Hoerauf Achim , Edwards Jennifer L. , Vassylyev Dmitry G. , Shafer William M.
Published: April 2024

The continued emergence of
Neisseria gonorrhoeae
strains that express resistance to multiple antibiotics, including the last drug for empiric monotherapy (ceftriaxone), necessitates the development of new treatment options to cure gonorrheal infections. Toward this goal, we recently reported that corallopyronin A (CorA), which targets the switch region of the β′ subunit (RpoC) of bacterial DNA-dependent RNA polymerase (RNAP), has potent anti-gonococcal activity against a panel of multidrug-resistant clinical strains. Moreover, in that study, CorA could eliminate gonococcal infection of primary human epithelial cells and gonococci in a biofilm state. To determine if
N. gonorrhoeae
could develop high-level resistance to CorA in a single step, we sought to isolate spontaneous mutants expressing any CorA resistance phenotypes. However, no single-step mutants with high-level CorA resistance were isolated. High-level CorA resistance could only be achieved in this study through a multi-step pathway involving over-expression of the MtrCDE drug efflux pump and single amino acid changes in the β and β′ subunits (RpoB and RpoC, respectively) of RNAP. Molecular modeling of RpoB and RpoC interacting with CorA was used to deduce how the amino acid changes in RpoB and RpoC could influence gonococcal resistance to CorA. Bioinformatic analyses of whole genome sequences of clinical gonococcal isolates indicated that the CorA resistance determining mutations in RpoB/C, identified herein, are very rare (≤ 0.0029%), suggesting that the proposed pathway for resistance is predictive of how this phenotype could potentially evolve if CorA is used therapeutically to treat gonorrhea in the future.

IMPORTANCE

The continued emergence of multi-antibiotic-resistant strains of
Neisseria gonorrhoeae
necessitates the development of new antibiotics that are effective against this human pathogen. We previously described that the RNA polymerase-targeting antibiotic corallopyronin A (CorA) has potent activity against a large collection of clinical strains that express different antibiotic resistance phenotypes including when such gonococci are in a biofilm state. Herein, we tested whether a CorA-sensitive gonococcal strain could develop spontaneous resistance. Our finding that CorA resistance could only be achieved by a multi-step process involving over-expression of the MtrCDE efflux pump and single amino acid changes in RpoB and RpoC suggests that such resistance may be difficult for gonococci to evolve if this antibiotic is used in the future to treat gonorrheal infections that are refractory to cure by other antibiotics.
Ling-Gui-Zhu-Gan decoction ameliorates nonalcoholic fatty liver disease via modulating the gut microbiota
Authors: Chen Lu-ping , Zhang Lin-fang , Liu Shuang , Hua Hua , Zhang Lei , Liu Bao-cheng , Wang Rui-rui
Published: April 2024

Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances.

IMPORTANCE

Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.
Respiration and growth of
Paracoccus denitrificans
R-1 with nitrous oxide as an electron acceptor
Authors: Zhou Jiaxian , Deng Wenfang , Wu Jiapeng , Xiang Hua , Shen Xiaomei , Lin Jih-Gaw , Hong Yiguo
Published: April 2024

In the nitrogen biogeochemical cycle, the reduction of nitrous oxide (N
2
O) to N
2
by N
2
O reductase, which is encoded by
nosZ
gene, is the only biological pathway for N
2
O consumption. In this study, we successfully isolated a strain of denitrifying
Paracoccus denitrificans
R-1 from sewage treatment plant sludge. This strain has strong N
2
O reduction capability, and the average N
2
O reduction rate was 5.10 ± 0.11 × 10
−9
µmol·h
−1
·cell
−1
under anaerobic condition in a defined medium. This reduction was accompanied by the stoichiometric consumption of acetate over time when N
2
O served as the sole electron acceptor and the reduction can yield energy to support microbial growth, suggesting that microbial N
2
O reduction is related to the energy generation process. Genomic analysis showed that the gene cluster encoding N
2
O reductase of
P. denitrificans
R-1 was composed of
nos
R,
nos
Z,
nos
D,
nos
F,
nos
Y,
nos
L, and
nos
Z, which was identified as that in other strains in clade I. Respiratory inhibitors test indicated that the pathway of electron transport for N
2
O reduction was different from that of the traditional electron transport chain for aerobic respiration. Cu
2+
, silver nanoparticles, O
2
, and acidic conditions can strongly inhibit the reduction, whereas NO
3
-
or NH
4
+
can promote it. These findings suggest that modular N
2
O reduction of
P. denitrificans
R-1 is linked to the electron transport and energy conservation, and dissimilatory N
2
O reduction is a form of microbial anaerobic respiration.

IMPORTANCE

Nitrous oxide (N
2
O) is a potent greenhouse gas and contributor to ozone layer destruction, and atmospheric N
2
O has increased steadily over the past century due to human activities. The release of N
2
O from fixed N is almost entirely controlled by microbial N
2
O reductase activities. Here, we investigated the ability to obtain energy for the growth of
Paracoccus denitrificans
R-1 by coupling the oxidation of various electron donors to N
2
O reduction. The modular N
2
O reduction process of denitrifying microorganism not only can consume N
2
O produced by itself but also can consume the external N
2
O generated from biological or abiotic pathways under suitable condition, which should be critical for controlling the release of N
2
O from ecosystems into the atmosphere.
Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats
Authors: Dib Ferreira Gremião Isabella , Pereira-Oliveira Gabriela Reis , Pereira Sandro Antonio , Corrêa Maria Lopes , Borba-Santos Luana Pereira , Viçosa Alessandra Lifsitch , Garg Ashna , Haranahalli Krupanandan , Dasilva Deveney , Pereira de Sa Nivea , Matos Gabriel S. , Silva Vanessa , Lazzarini Cristina , Fernandes Caroline Mota , Miranda Kildare , Artunduaga Bonilla Jhon Jhamilton , Nunes Anna Letícia , Nimrichter Leonardo , Ojima Iwao , Mallamo John , McCarthy John B. , Del Poeta Maurizio
Published: April 2024

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against
Sporothrix
sp., both
in vitro
and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-
N
′-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by
Sporothrix brasiliensis
. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.

IMPORTANCE

This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
Carbon-rich polyphasic inclusions in postcollisional mafic magmatic rocks from the Dabie Shan, China: Implications for the carbon cycle in continental subduction zones
Authors: Tan Dong-Bo , Xiao Yilin , Wang Yang-Yang , Jin Deshi , Gu Hai-Ou , Sun He , Jiang Lingling
Published: April 2024

Subduction is a fundamental geodynamic process that transfers carbon from Earth’s surface into the mantle. However, current understanding of the migration mechanisms, final storage region, and species involved in carbon recycling from continental crust remains limited. Here, we investigated the compositions of polyphasic inclusions and Mg isotopes in postcollisional mafic magmatic rocks from the Dabie Shan region of China. The main rock-forming minerals contained two distinct types of polyphasic inclusions, which displayed systematic differences in daughter mineral/gaseous phase assemblages, including host-like silicates ± carbonates (magnesite, dolomite, and calcite) + CH4 and carbonates + talc ± SiO2 (aqueous) + CH4, respectively. These inclusions indicate that carbon-rich silicate melts and carbon-rich magmatic fluids were trapped by host minerals during magmatic processes. The abundant carbonates and CH4 in both types of inclusions suggest that the mantle source of these postcollisional mafic magmatic rocks was rich in carbon, most likely existing in the forms of CO2 and CH4. Moreover, the studied postcollisional mafic magmatic rocks have mantle-like Mg isotope compositions, with δ26Mg values ranging from −0.23‰ to −0.16‰. The combined observations of polyphase inclusions and Mg isotopes indicate that a substantial carbon-rich mantle domain arose from the metasomatism of silicate melts derived from subducted continental slabs that had dissolved a certain quantity of CO2 and CH4. We proposed that continental subduction is an efficient pathway for transporting crustal carbon into an orogenic subcontinental lithospheric mantle wedge, where the recycled carbon can be stored for >100 m.y. and eventually released to the surface during postcollisional magmatism.
Supplemental Material: Assessing the geometry of the Main Himalayan thrust in central Nepal: A thermokinematic approach
Authors: Ghoshal S. , al. et
Published: April 2024

Text S1 and Figures S1–S4; Tables S1 and S2; and Videos S1–S3.
Nasogastric tube feeding under physical restraint of children and young people with mental disorders: a comprehensive audit and case series across paediatric wards in England
Authors: Fuller Sarah , Sheridan Emerie , Hudson Lee D , Nicholls Dasha
Published: April 2024

Objective

To estimate the number of patients on paediatric wards in England who received nasogastric tube (NGT) feeding under physical restraint from April 2022 to March 2023, identify the demographics and clinical characteristics of these patients, and which personnel facilitated the restraint.

Design

Audit and anonymous case series

Setting

Paediatric wards in England.

Patients

Children and young people receiving this intervention in a 1-year period.

Outcome measures

An online survey was sent to all paediatric wards in England, with the option of submitting anonymous case studies.

Results

136/143 (95.1%) acute paediatric units responded. 144 young people received this intervention across 55 (38.5%) paediatric units. The predominant diagnosis was anorexia nervosa (64.5%), age range 9–18 years (M=14.2, SD=2.1). The duration of NGT feeding under restraint ranged from 1 to 425 days, (M=60.2, SD=80.4). Numerous personnel facilitated the restraints, including mental health nurses, paediatric nurses, security staff, healthcare assistants and parents/carers.

Conclusion

NGT feeding under restraint is a relatively common intervention in acute paediatric units in England. Understanding the demographics of those receiving this intervention may highlight where additional support is needed. Further research is needed to understand when this intervention transitions from a lifesaving intervention to ongoing management.
Food environment and obesity: a systematic review and meta-analysis
Authors: Pineda Elisa , Stockton Jemima , Scholes Shaun , Lassale Camille , Mindell Jennifer S
Published: April 2024

Background

Obesity is influenced by a complex, multifaceted system of determinants, including the food environment. Governments need evidence to act on improving the food environment. The aim of this study was to review the evidence from spatial environmental analyses and to conduct the first series of meta-analyses to assess the impact of the retail food environment on obesity.

Methods

We performed a systematic review and random-effects meta-analyses, focusing on geographical–statistical methods to assess the associations between food outlet availability and obesity. We searched OvidSP-Medline, Scielo, Scopus and Google Scholar databases up to January 2022. The search terms included spatial analysis, obesity and the retail food environment. Effect sizes were pooled by random-effects meta-analyses separately according to food outlet type and geographical and statistical measures.

Findings

Of the 4118 retrieved papers, we included 103 studies. Density (n=52, 50%) and linear and logistic regressions (n=68, 66%) were the main measures used to assess the association of the food environment with obesity. Multilevel or autocorrelation analyses were used in 35 (34%) studies. Fast-food outlet proximity was positively and significantly associated with obesity (OR: 1.15, 95% CI: 1.02 to 1.30, p=0.02). Fresh fruit and vegetable outlet density and supermarket proximity were inversely associated with obesity (OR: 0.93, 95% CI: 0.90 to 0.96, p<0.001; OR: 0.90, 95% CI: 0.82 to 0.98, p=0.02). No significant associations were found for restaurants, convenience stores or any of the body mass index measures.

Conclusions

Food outlets which sell mostly unhealthy and ultra-processed foods were associated with higher levels of obesity, while fruit and vegetable availability and supermarket accessibility, which enable healthier food access, were related to lower levels of obesity. The regulation of food outlets through zoning laws may not be enough to tackle the burden of obesity. Regulations that focus on increasing the availability of healthy food within stores and ensure overall healthy food environments require further attention.

PROSPERO registration number

CRD42018111652.
Efforts to improve the billing accuracy of robotic-assisted thoracic surgery through education, updated procedure cards, and electronic medical record system changes
Authors: Wu Kevin A , Boccaccio Kenneth , Buckles Danielle , Hartwig Matthew G , Klapper Jacob A
Published: April 2024

Precise medical billing is essential for decreasing hospital liability, upholding environmental stewardship and ensuring fair costs for patients. We instituted a multifaceted approach to improve the billing accuracy of our robotic-assisted thoracic surgery programme by including an educational component, updating procedure cards and removing the auto-populating function of our electronic medical record. Overall, we saw significant improvements in both the number of inaccurate billing cases and, specifically, the number of cases that overcharged patients.