bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome‐Wide Analysis of the Phospholipase Ds in Perennial Ryegrass Highlights LpABFs‐LpPLDδ3 Cascade Modulated Osmotic and Heat Stress Responses
Authors: Yang Di , Wang Weiliang , Fang Zhengfu , Wu Simin , Chen Lili , Chen Jie , Zhang Wensong , Wang Feilong , Sun Tianxiao , Xiang Lin , Wang Yanping , Luo Hong , Chan Zhulong
Published: October 2024

The phospholipase Ds (PLDs) are crucial for cellular signalling and play roles in plant abiotic stress response. In this study, we identified 12 PLD genes from the genome data of perennial ryegrass (Lolium perenne), which is widely used as forage and turfgrass. Among them, LpPLDδ3 was significantly repressed by ABA treatment, and induced by drought stress and heat stress treatments. The ectopic overexpression (OE) of LpPLDδ3 in Arabidopsis enhanced plant tolerance to osmotic and heat stress as demonstrated by an increased survival rate and reduced malondialdehyde (MDA) accumulation and electrolyte leakage (EL). Arabidopsis endogenous ABA RESPONSIVE ELEMENT BINDING FACTORs (ABFs) and heat stress responsive genes were elevated in LpPLDδ3 OE lines under osmotic and heat stress treatments. Additionally, overexpression of LpPLDδ3 in perennial ryegrass protoplasts could increase heat stress tolerance and elevate expression level of heat stress responsive genes. Moreover, LpABF2 and LpABF4 depressed the LpPLDδ3 expression by directly binding to its ABRE core‐binding motif of promoter region. In summary, LpPLDδ3 was repressed by LpABF2 and LpABF4 and positively involved in perennial ryegrass osmotic and heat stress responses.
HPV Vaccination Stages and Associated Factors Among Children of Immigrant Women
Authors: Lee Ja‐yin , Lee Hyeonkyeong , Kim Sue , Park Sohee , Chae Duckhee , Hong Hye Chong
Published: October 2024

Objective

This study aimed to identify key determinants by stage of implementation of human papillomavirus (HPV) vaccination among children of immigrant women in South Korea.

Design

Cross‐sectional descriptive study.

Sample

The sample comprised 262 Chinese, Vietnamese, and Korean‐Chinese women with children living in South Korea.

Methods

The survey was conducted using self‐report questionnaires. The HPV vaccination levels in children were classified into four transition stages. Sequential logistic regression analysis was conducted to identify the factors affecting the transition of HPV vaccination status.

Results

Social norms had the greatest influence on the intention to vaccinate. Perceived barriers were a significant factor associated with intention or initiation of vaccination, whereas perceived severity and susceptibility were associated with the intention and initiation stages, respectively. Upon the initiation of HPV vaccination, low perception of discrimination in healthcare was associated with continued vaccination.

Conclusion

Given the importance of completing multiple doses of the HPV vaccine within a given timeframe, it is important to provide culturally appropriate interventions in stages to prevent dropouts.
Nursing and Social Justice—A Scoping Review
Authors: Tind Anitha M. , Hoeck Bente , Andersen Helle Elisabeth , Qvistgaard Laura Wacher , Delmar Charlotte
Published: October 2024

Background

Nursing is historically, ethically, and theoretically mandated to champion social justice.

Objective

To investigate how the concept of “social justice” has been explored in nursing research regarding extent, range, and nature.

Methods

The five‐stage framework by Arksey and O'Malley was adopted, and JBI and PRISMA guidelines further informed the study. The search strategy comprised three steps: an initial search, a systematic search in several databases, and finally, a reference, citation, and gray literature search. A total of 55 studies meeting the inclusion criteria were included in the analysis.

Results

Almost all the included studies were authored in the English‐speaking world. Most studies were published from 2014 onward, and qualitative methods were by far the most prominent. A total of 13 specific definitions or understandings of social justice were identified. Five themes were identified across the included studies: (1) education, (2) concept, (3) theory, (4) public health and community nursing, and (5) maternal and child health.

Conclusion

The literature on social justice and nursing is limited, albeit growing. The conceptualization of social justice within nursing is becoming broader and more nuanced. Only a few studies have focused on specific patient groups or specialties.
Cost‐Utility Analysis of Teledermatology Units in Primary Care Centers Versus Face‐to‐Face Dermatology Consultations in the Hospital
Authors: Lopez‐Villegas Antonio , Bautista‐Mesa Rafael Jesus , Lopez‐Liria Remedios , Perez‐Heredia Mercedes , Hernandez‐Montoya Carlos Javier , Gutierrez‐Maldonado Maria Gador , Leal‐Costa Cesar , Peiro Salvador
Published: October 2024

Objective

To perform an economic evaluation to determine whether or not teledermatology (TD) units in primary care (PC) centers offer an alternative in terms of cost‐utility and cost per quality‐adjusted life years (QALYs) to conventional dermatology consultations (face‐to‐face dermatology [F‐F/D]) at the hospital from the perspective of the Public Health System (PHS) and the patients.

Methods

This is a randomized, controlled, nonblinded, and multicenter study. During 6 months, data from 450 patients (TD: 225 vs. F‐F/D: 225) were collected. From both perspectives, costs, quality of life, and costs per QALYs were analyzed. The QALY scores were estimated from the EuroQol‐5D‐5L (EQ5D‐5L) questionnaire responses.

Results

From the perspective of the PHS, the cost per patient was 53.04% lower in the TD group (p < 0.001). Hospital visits decreased by 72.43% in the TD group (p < 0.001). From the patients’ perspective, TD reduced costs per patient by 77.59% (p < 0.001). The cost per QALY was 63.34% higher in the F‐F/D group (p < 0.001). The TD group's total costs were 56.34% lower (p < 0.001). Furthermore, patients in the TD group gained 0.05 QALYs more than those in the F‐F/D group (p = 0.004).

Conclusions

This study shows that TD units in PC represent a significant cost‐effective alternative to conventional hospital follow‐up. To enhance TD in PC, it is important to introduce remote consultation platforms incorporating artificial intelligence for prediagnosis. This will enable general practitioners and nurses to make more accurate initial assessments. It is also crucial to provide thorough training to healthcare personnel using these technologies to ensure more efficient and personalized care. Public health nurses will benefit from gaining new skills in managing digital tools, which will help in the early identification of dermatological diseases and reduce unnecessary referrals to specialists. This will optimize resources and improve response times for patients.
Social Media Addiction and Cognitive Behavioral Physical Activity Among Adolescent Girls: A Cross‐Sectional Study
Authors: Sönmez Sari Ebru , Terzi Handan , Şahin Didem
Published: October 2024

Objective

To measure a multivariate analysis of social media addiction and cognitive‐behavioral physical activity associated with several sociodemographic characteristics in adolescent girls.

Design and Methods

A cross‐sectional study. The sample consisted of adolescent girls studying in a vocational high‐school in the Middle‐Black‐Sea region in Türkiye (n = 333). A questionnaire, Social Media Addiction Scale‐for‐Adolescents (SMAS‐A), and Cognitive‐Behavioral Physical Activity Questionnaire (CBPAQ) were used to collect the data.

Results

The mean age was 15.35 (SD = 1.15), and 29.4% were the ninth‐class students. Of the adolescent girls, 85.9% were social‐media users, 59.8% used the internet 2‐hours‐or‐more/daily, 67.9% declared themselves as moderately‐active. The mean scores of the SMAS‐A and the CBPAQ were 3.40 (SD = 1.61) and 21.03 (SD = 7.64), respectively. There was a significantly‐negative correlation between cognitive‐behavioral physical activity and social‐media addiction levels. The One‐Way MANOVA results showed significant differences in the academic level, family income, mother education, and physical activity measurement application usage affected to cognitive‐behavioral physical activity. Social media usage habit affected to the social media addiction level.

Conclusions

Daily internet usage time and self‐declared physical activity level were the mutually affected factors. School nurses should act to improve healthy social media usage habits to promote well‐being and encourage the positive attitudes towards regular physical activity in this population.
Socio‐Healthcare for Older People in the Mediterranean Basin: An Integrative Review and Quality Appraisal
Authors: Porcel‐Gálvez Ana María , Allande‐Cussó Regina , Fadden Isotta Mac , Ferentinou Eleni , Zafiropoulou Maria , Lima‐Serrano Marta
Published: October 2024

Objectives

The aging Mediterranean Basin population presents complex challenges for healthcare systems, which require innovative care approaches. The study aimed to critically assess 19 socio‐healthcare practices in the Mediterranean Basin that target the elderly population by analyzing their theoretical foundations, integration of care services, ethical considerations, gender‐specific approaches, and use of technology.

Design

An integrative literature review was conducted using a structured methodology.

Sample

Diverse sources across multiple languages were searched, with the inclusion criteria focusing on the alignment of socio‐healthcare practices with the components of the nursing metaparadigm, the incorporation of transversal values, and relevance to the elderly population.

Results

The socio‐healthcare practices exhibited common themes, such as person‐centered care, interdisciplinary collaboration, and incorporation of technology for coordinated care delivery. Ethical principles of autonomy, dignity, and respect were central, with some socio‐healthcare practices addressing gender‐specific care needs. Evidence‐based findings emphasized holistic care, integration, ethics, and innovation in elderly socio‐healthcare.

Conclusions

New eldercare frameworks should integrate these aspects, which offer a comprehensive approach to addressing the complex needs of elderly patients. Managers should design systems prioritizing patient well‐being, whereas policymakers should develop equitable and high‐quality care policies that collectively improve the well‐being of the elderly population in the Mediterranean Basin.
Carbon border adjustments or climate clubs: Impacts on African agricultural sectors under different cooperative scenarios
Authors: Bassi Andrea M. , Calciolari Francesco , Costantini Valeria , D'Angeli Mariagrazia , Paglialunga Elena
Published: October 2024

Despite the rapid acceleration of climate change, international climate negotiations have yet to implement effective mitigation action. This failure can be attributed to the phenomenon of free‐riding behaviours and the adverse effects of unilateral abatement policies, such as carbon leakage. The introduction of a Carbon Border Adjustment Mechanism (CBAM), as planned by the EU and the creation of climate clubs represent two potential solutions. However, both present uncertainties regarding their trade impacts, effectiveness and equity implications, particularly for developing countries. The outcome of these alternative unilateral or cooperative solutions is analysed using a dynamic CGE model, with a particular focus on the EU‐Africa relations and the agricultural sector. The results indicate that the effectiveness of CBAM in preventing carbon leakage and supporting EU climate goals depends on foreign partners implementing domestic carbon pricing mechanisms. Conversely, for African regions, domestic mitigation efforts and exemption from CBAM can enhance export competitiveness on EU markets while reducing global carbon leakage. Overall, the establishment of climate clubs, coupled with the transfer of technology and the diffusion of best practices in agriculture, can support developing countries and facilitate an inclusive and environmentally beneficial development transition.
Characterisation of Antimicrobial Resistance in Special‐Fed Veal Production Environments
Authors: Dunmyre Alexander , Vinayamohan Poonam , Locke Samantha R. , Cheng Ting‐Yu , Schaffner Victoria , Habing Greg
Published: October 2024

Introduction

Antimicrobial resistance (AMR) is one of the leading public health threats globally. AMR genes can be transferred between bacteria through lateral gene transfer, and AMR organisms can spread through environments by contaminated water, agriculture and animals. Thus, widespread environmental dissemination of bacteria and lateral gene transfer facilitate AMR transmission pathways. Farm environments in dairy and calf production are known to harbour AMR bacteria that pose a risk for food contamination and to workers in direct or indirect contact with animals. Escherichia coli is present in farm environments and is known to participate in lateral gene transfer, providing a good marker of resistance genes in each environment.

Methods

In this study, E. coli from nine cohorts of calves was isolated at different time points from nine barns, nine trailers and one slaughterhouse environment in a single special‐fed veal calf production facility. The antimicrobial susceptibility to 15 antimicrobials, classified as highly or critically important by the World Health Organization, was characterised for E. coli isolates using Kirby–Bauer disk diffusion.

Results

The highest proportion of isolates showing multidrug resistance was present in barn environments (51.7%), where calves were housed from their arrival at < 2 weeks of age until they were transported to slaughter. Additionally, 15 E. coli isolates were resistant to 11 of the 15 antimicrobials tested. Trailer and slaughterhouse environments had greater prevalence of resistance after accommodating calves, including resistance to third‐generation cephalosporins.

Conclusion

These data highlight the importance of calf environments in the dissemination of resistant bacteria and gives insight into where interventions could be most effective in combatting antimicrobial‐resistant bacteria that could infect humans and livestock.
Fruit Wastes and Crop Residues as Nutrient Sources for Bacterial Nanocellulose Production: A Review
Authors: Mathivanan Yamunathevi , Shahir Shafinaz , Ibrahim Zaharah , Nik Malek Nik Ahmad Nizam
Published: October 2024

Nanocellulose has been developed and used as a bio-based advanced material in modern biotechnology. Lately, bacterial nanocellulose (BNC) emerged as a prominent biopolymer because of its multi-functional application in various industries, such as food, biomedical, cosmetics, and environmental. The emerging concern for large-scale BNC production is the high fermentation costs, low productivity, and expensive culture medium. To minimise this issue, agro-industrial wastes can be used as feedstock. Recently, many studies have investigated the utilization of agro-industrial wastes as potential nutrient sources for BNC production. However, a comprehensive review of BNC production from fruit wastes and crop residues is lacking. To address this gap, the current review focuses on the utilization of fruit wastes and crop residues for BNC production, including its advantages and disadvantages. This study contributes to the scientific community by (a) providing an insight into fruit waste and crop residue utilization for BNC synthesis (b) an overview on its advantages and disadvantages (c) providing recommendations and future perspectives on BNC production from agro-industrial waste utilization. The sustainable concept of BNC production utilizing agro-industrial wastes opens a way for industries to produce BNC on a larger scale.
Hydrothermal Liquefaction of Microalgae to Bio-oil Using Zeolite Catalysts
Authors: Ramli Anita , Fakhruldin Afeefah , Azmi Adam , Khairul Anuar Nur Akila Syakida Idayu
Published: October 2024

Mesoporous zeolite silica-alumina catalysts were investigated for their impact on the hydrothermal liquefaction (HTL) to convert Nannochloropsis oculata into bio-oil. The commercial catalysts were characterized using characterization instruments which are XRD, SAP, and TPD-NH3 analysis, revealing distinctive structural and physicochemical properties. The catalytic screening was conducted at varied reaction temperatures (160–240 °C), durations (60–120 min), and catalyst loadings (1–5 wt.%). The result revealed that ZSM-5 demonstrates effectiveness as a catalyst for the HTL of Nannochloropsis oculata, yielding high bio-oil production under optimized conditions. Strong acid sites and high surface area density are highlighted as the key factors contributing to the catalyst's enhanced performance in promoting valuable bio-oil components.
The Influence of Advertising Strategies on Purchase Intention of Beauty Products on RED
Authors: Lin Kehan , Liang Shizhen , Wen Haowei , Yang Mengfan
Published: October 2024

With the popularity of social media platforms in China, research on social media advertising is increasing. Prior research has shown that the value perception given to consumers by social media advertising affects the purchase intention of consumers. However, its internal logic and behavioral mechanism have not been well investigated. In view of this, this research is designed to examine the direct effects of interactivity and aesthetic appeal of beauty product advertisements on perceived advertising value on RED and to explore the influence of perceived advertising value on consumers’ purchase intentions. Based on questionnaire analysis, bivariate regression analysis, and univariate regression analysis, we found the significant influence of interactivity and aesthetic appeal on advertising value as well as the influence of advertising value on consumers’ purchase intention. The chain behavior generation mechanism of consumers’ purchase decisions was also elaborated. This paper provides enlightenment for theoretical research, especially in enriching the SOR model. Also, the result has practical implications for enterprise practice, pointing out important directions for enterprises to design their advertisements.
A Cross-Regional Study on the Public's Channel Preferences for Accessing Information
Authors: Chen Jia , Wang Lin
Published: October 2024

In this study, an online questionnaire was administered simultaneously in Beijing and Seoul to investigate the public's channel preferences for air quality index (AQI) information and risk perception of air pollution in order to comparatively analyze the public's information acquisition behaviors in different media environments. As people become more aware of the health risks of air pollution, the AQI has become routine information released when there is a need to warn of health hazards, and many countries are releasing it to the public through a variety of information channels to ensure that the public can perceive the risks and take appropriate measures in a timely manner. This study, through a comparative cross-regional analysis, found that public preferences for accessing AQI information varied across regions with differing media environments. In addition, the correlation between air pollution risk perceptions and information access behaviors varied across regions.
Boundary-Element Analysis of the Noise Scattering for Urban Aerial Mobility Vehicles: Solver Development and Assessment
Authors: Deng Yuanyuan , Wang Zhaohuan , Zhou Teng , Wu Jiafeng , Jiang Hanbo
Published: October 2024

Urban aerial mobility (UAM) vehicles with multipropeller configurations have attracted considerable attention in recent years. However, previous investigations have mainly focused on the aerodynamic noise from individual propellers, with limited focus on the fuselage’s sound scattering effects which can alter the far-field noise directivity. In this work, an efficient boundary element solver for sound scattering was developed to fill this gap. The solver employs hierarchical matrices to save computational cost. The benchmark examples showed high accuracy and good scalability. A representative vehicle model was then chosen, and the propeller noise was simulated using rotating sources. Results show that the shielding effect in the fuselage/propeller configuration can produce an apparent noise reduction and redirect sound energy distribution, suggesting the importance of considering the fuselage in low-noise UAM development.
Revisiting the sound absorption mechanisms of a finite flexible perforated panel absorber using a numerical approach
Authors: Li Jiaxing , Zhao Peidong , Wang Peng , Yang Cheng
Published: October 2024

This study investigates the sound absorption mechanisms of a finite flexible perforated panel absorber. Different from existing work where the mechanisms were often investigated by comparing the sound absorption coefficient curves of different absorber configurations, a numerical approach, called virtual impedance tube (VIT) technique, is developed and used for the analysis. One advantage of this technique is the vast dataset generated can be used to investigate the sound absorption mechanisms from an energy standpoint. The developed VIT technique is first validated using the impedance tube test, where a proportion-integration-differentiation control algorithm is developed to maintain the incident sound at a desired sound pressure level. Then, the sound absorption mechanisms at three absorption peaks, i.e., hole-cavity controlled, panel-cavity controlled, and panel controlled, are investigated and the dominant energy dissipation mechanism at different sound pressure levels (SPLs) is revealed. Finally, an impedance model that takes account of the panel vibration and is applicable to various SPLs is proposed and validated.
“One Day . . . It Won’t Be a Big Story”: Analyzing the Media Response to Female National Football League Coaches
Authors: Taylor Katie
Published: October 2024

In 2015, Dr. Jen Welter became the first woman to coach in the National Football League (NFL). Other female coaches followed. Yet, sports-studies scholars know little about the media’s response to these football pioneers. This paper presents critical themes on how popular media discussed female coaches by analyzing the hiring announcements of four women who coach or have coached in the NFL. Utilizing a critical feminist lens, this paper demonstrates that media outlets reproduced conventional media tropes by reassuring readers that women have the requisite knowledge, trivializing women’s achievements, underscoring the need for male player support, emphasizing appearance, and permitting sexist comments. However, it is evident that online publishers are simultaneously making progress. In most cases, the articles represented the coaches in ways that differ from how female athletes have been historically depicted. This research reveals nonlinear and incremental progress toward gender equality in football.
Development of a safe and broad-spectrum attenuated PEDV vaccine candidate by S2 subunit replacement
Authors: Zhang Ding , Xie Yunfei , Liao Qi , Jiao Zhe , Liang Rui , Zhang Jintao , Zhang Yu , Tan Yubei , Wang Huanbin , Zhang Wanpo , Xiao Shaobo , Peng Guiqing , Shi Yuejun
Published: October 2024

Porcine epidemic diarrhea (PED) has caused serious economic losses to the swine livestock industry. Due to the rapid variation in the PEDV) genome, especially the spike (S) protein, the cross-protection ability of antibodies between different vaccine strains is weakened. Hence, the rapid development of safe, broad-spectrum and highly effective attenuated PEDV vaccine still needs further research. Here, we found that the replacement of the S2 subunit had little effect on S protein immunogenicity. Moreover, the chimeric virus (YN-S2
DR13
), the S protein of the YN strain was replaced by the DR13 S2 subunit, which lost its trypsin tropism and increased its propagation ability (approximately 1 titer) in Vero cells. Then, the pathogenesis of YN-S2
DR13
was evaluated in neonatal piglets. Importantly, quantitative real-time PCR, histopathology, and immunohistochemistry confirmed that the virulence of YN-S2
DR13
was significantly reduced compared with that of YN. Immunization with YN-S2
DR13
induced neutralizing antibodies against both YN and DR13 in weaned piglets.
In vitro
passaging data also showed that YN-S2
DR13
had good genetic stability. Collectively, these results suggest that YN-S2
DR13
has significant advantages as a novel vaccine candidate, including a capacity for viral propagation to high titers with no trypsin requirement and the potential to provide protection against both PEDV G1 and G2 strains infections. Our results also suggests that S2 subunit replacement using reverse genetics can be a rapid strategy for the rational design of live attenuated vaccines for PEDV.

IMPORTANCE

Emerging highly virulent porcine epidemic diarrhea virus (PEDV) G2 strains has caused substantial economic losses worldwide. Vaccination with a live attenuated vaccine is a promising method to prevent and control PED because it can induce a strong immune response (including T- and B-cell immunity). Previous studies have demonstrated that the S2 subunit of the PEDV spike (S) protein is the determinant of PEDV trypsin independence. Here, we evaluated the pathogenicity, tissue tropism, and immunogenicity of the chimeric virus (YN-S2
DR13
) via animal experiments. We demonstrated that YN-S2
DR13
strain, as a trypsin independent strain, increased intracellular proliferation capacity, significantly reduced virulence, and induced broad-spectrum neutralization protection against PEDV G1 and G2 strains.
In vitro
passaging data also validated the stability of YN-S2
DR13
. Our results showed that generating a chimeric PEDV strain that is trypsin-independent by replacing the S2 subunit is a promising approach for designing a live attenuated vaccine for PEDV in the future.
Pan-flavivirus analysis reveals sfRNA-independent, 3′ UTR-biased siRNA production from an insect-specific flavivirus
Authors: Besson Benoit , Overheul Gijs J. , Wolfinger Michael T. , Junglen Sandra , van Rij Ronald P.
Published: October 2024

RNA interference (RNAi) plays an essential role in mosquito antiviral immunity, but it is not known whether viral small interfering RNA (siRNA) profiles differ between mosquito-borne and mosquito-specific viruses. A pan-Orthoflavivirus analysis in
Aedes albopictus
cells revealed that viral siRNAs were evenly distributed across the viral genome of most representatives of the
Flavivirus
genus. In contrast, siRNA production was biased toward the 3′ untranslated region (UTR) of the genomes of classical insect-specific flaviviruses (cISF), which was most pronounced for Kamiti River virus (KRV), a virus with a unique, 1.2 kb long 3′ UTR. KRV-derived siRNAs were produced in high quantities and almost exclusively mapped to the 3′ UTR. We mapped the 5′ end of KRV subgenomic flavivirus RNAs (sfRNAs), products of the 5′−3′ exoribonuclease XRN1/Pacman stalling on secondary RNA structures in the 3′ UTR of the viral genome. We found that KRV produces high copy numbers of a long, 1,017 nt sfRNA1 and a short, 421 nt sfRNA2, corresponding to two predicted XRN1-resistant elements. Expression of both sfRNA1 and sfRNA2 was reduced in
Pacman
-deficient
Aedes albopictus
cells; however, this did not correlate with a shift in viral siRNA profiles. We suggest that cISFs, particularly KRV, developed a unique mechanism to produce high amounts of siRNAs as a decoy for the antiviral RNAi response in an sfRNA-independent manner.

IMPORTANCE

The
Flavivirus
genus contains diverse mosquito viruses ranging from insect-specific viruses circulating exclusively in mosquito populations to mosquito-borne viruses that cause disease in humans and animals. Studying the mechanisms of virus replication and antiviral immunity in mosquitoes is important to understand arbovirus transmission and may inform the development of disease control strategies. In insects, RNA interference (RNAi) provides broad antiviral activity and constitutes a major immune response against viruses. Comparing diverse members of the
Flavivirus
genus, we found that all flaviviruses are targeted by RNAi. However, the insect-specific Kamiti River virus was unique in that small interfering RNAs are highly skewed toward its uniquely long 3′ untranslated region. These results suggest that mosquito-specific viruses have evolved unique mechanisms for genome replication and immune evasion.
The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir
Authors: Dinh Tung , Tber Zahira , Rey Juan S. , Mengshetti Seema , Annamalai Arun S. , Haney Reed , Briganti Lorenzo , Amblard Franck , Fuchs James R. , Cherepanov Peter , Kim Kyungjin , Schinazi Raymond F. , Perilla Juan R. , Kim Baek , Kvaratskhelia Mamuka
Published: October 2024

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into phase 2a clinical trials. Previous cell culture-based viral breakthrough assays identified the HIV-1
(Y99H/A128T IN)
variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. Although both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect the direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor-mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCD
Y99H/A128T
+ PIR complex. Consequently, full-length IN
Y99H/A128T
was substantially less susceptible to the PIR-induced hyper-multimerization than the WT protein, and HIV-1
(Y99H/A128T IN)
conferred >150-fold resistance to the inhibitor compared with the WT virus. By rationally modifying PIR, we have developed its analog EKC110, which readily induced hyper-multimerization of IN
Y99H/A128T
in vitro
and was ~14-fold more potent against HIV-1
(Y99H/A128T IN)
than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.

IMPORTANCE

Antiretroviral therapies save the lives of millions of people living with HIV (PLWH). However, the evolution of multi-drug-resistant viral phenotypes is a major clinical problem, and there are limited or no treatment options for heavily treatment-experienced PLWH. Allosteric HIV-1 integrase inhibitors (ALLINIs) are a novel class of antiretroviral compounds that work by a unique mechanism of binding to the non-catalytic site on the viral protein and inducing aberrant integrase multimerization. Accordingly, ALLINIs potently inhibit both wild-type HIV-1 and all drug-resistant viral phenotypes that have so far emerged against currently used therapies. Pirmitegravir, a highly potent and safe investigational ALLINI, is currently advancing through clinical trials. Here, we have elucidated the structural and mechanistic bases behind the emergence of HIV-1 integrase mutations in infected cells that confer resistance to pirmitegravir. In turn, our findings allowed us to rationally develop an improved ALLINI with substantially enhanced potency against the pirmitegravir-resistant virus.
Complete genome sequence of a lumpy skin disease virus isolate from a 2021 outbreak of disease in Bangladesh
Authors: Samad Mohammed A. , Hossen Anowar , Karim Md. Rezaul , Uddin A. S. M. Ashab , Roy Dipu , Shithi Khairun Nahar , Akter Mst Nazia , Das Taposh Kumar , Selleck Paul W. , Bulach Dieter M. , Bowden Timothy R.
Published: October 2024

Lumpy skin disease (LSD) is an economically devasting and vector-borne transboundary disease of cattle caused by lumpy skin disease virus (LSDV). Here, we report the complete genome sequence of an outbreak isolate of LSDV from Bangladesh. Bangladesh LSD-29 was detected in skin nodule samples of an LSD-infected bovine in 2021.
Draft genome sequencing of multidrug-resistant
Pseudomonas putida
strains, isolated from dairy cows with clinical mastitis and their farm environment
Authors: Mallick Tima Tisa , Siddique Naim , Rahman Md. Morshedur , Shuvo Khaled Hassan , Das Ziban Chandra , Hoque M. Nazmul
Published: October 2024

We sequenced the genomes of three multidrug-resistant
Pseudomonas putida
strains namely 11CM-M1, 11CM-F1, and 11CM-S1, isolated from milk, feces, and farm soil samples collected from dairy cows with clinical mastitis. The assembled draft genomes of these
P. putida
strains were approximately 5.6 Mbp, with a GC content of 62.4%.
Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis
Authors: Nishimori Asami , Andoh Kiyohiko , Matsuura Yuichi , Okagawa Tomohiro , Konnai Satoru
Published: October 2024

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in eight genes,
TP53
,
KMT2D
,
CREBBP
,
KRAS
,
PTEN
,
NOTCH1
,
MYD88
, and
CARD11
. In addition,
TP53
gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to high impact mutations affecting protein translation and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylcytosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.

IMPORTANCE

Enzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.
Marine biofilms: cyanobacteria factories for the global oceans
Authors: Zhong Cheng , Yamanouchi Shun , Li Yingdong , Chen Jiawei , Wei Tong , Wang Ruojun , Zhou Kun , Cheng Aifang , Hao Weiduo , Liu Hongbin , Konhauser Kurt O. , Iwasaki Wataru , Qian Pei-Yuan
Published: October 2024

Marine biofilms were newly revealed as a giant microbial diversity pool for global oceans. However, the cyanobacterial diversity in marine biofilms within the upper seawater column and its ecological and evolutionary implications remains undetermined. Here, we reconstructed a full picture of modern marine cyanobacteria habitats by re-analyzing 9.3 terabyte metagenomic data sets and 2,648 metagenome-assembled genomes (MAGs). The abundances of cyanobacteria lineages exclusively detected in marine biofilms were up to ninefold higher than those in seawater at similar sample size. Analyses revealed that cyanobacteria in marine biofilms are specialists with strong geographical and environmental constraints on their genome and functional adaption, which is in stark contrast to the generalistic features of seawater-derived cyanobacteria. Molecular dating suggests that the important diversifications in biofilm-forming cyanobacteria appear to coincide with the Great Oxidation Event (GOE), “boring billion” middle Proterozoic, and the Neoproterozoic Oxidation Event (NOE). These new insights suggest that marine biofilms are large and important cyanobacterial factories for the global oceans.

IMPORTANCE

Cyanobacteria, highly diverse microbial organisms, play a crucial role in Earth’s oxygenation and biogeochemical cycling. However, their connection to these processes remains unclear, partly due to incomplete surveys of oceanic niches. Our study uncovered significant cyanobacterial diversity in marine biofilms, showing distinct niche differentiation compared to seawater counterparts. These patterns reflect three key stages of marine cyanobacterial diversification, coinciding with major geological events in the Earth's history.
Role of blood metabolites in mediating the effect of gut microbiota on chronic gastritis
Authors: Liu Tianying , Chen Zhian , Sun Li , Xiong Lihui
Published: October 2024

Exploring the link between gut microbiota and chronic gastritis (CG), and assessing the potential mediating influence of blood metabolites. Using aggregated data from genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to explore the genetic links between gut microbiota (412 types) and CG (623,822 cases). Furthermore, we utilized a two-step MR approach to measure the extent to which blood metabolites (1,400 types) mediate the impact of gut microbiota on CG. Through MR, we identified that three genetically predicted gut microbiota increased the risk of CG: the ubiquinol-8 biosynthesis pathway (OR 1.149, 95%CI 1.022–1.291),
Odoribacter
from the Porphyromonadaceae family (OR 1.260, 95%CI 1.044–1.523), and
Coprococcus
from the Lachnospiraceae family (OR 1.125, 95%CI 1.010–1.253). Currently, there is no evidence to suggest that genetically predicted CG affects the risk of gut microbiota. Four blood metabolites mediated the proportionate changes in genetically predicted gut microbiota: levels of 4-hydroxyphenylacetate levels by 14.9% (95% CI −0.559%, 30.3%), palmitoleate (16:1n7) levels, and the phosphate to alanine ratio together mediated the same microbiota by 6.97% (95% CI −1.61%, 15.6%) and 7.91% (95% CI −1.67%, 17.5%), while the phosphate to alanine ratio and X-12839 levels together mediated the same microbiota by 8.48% (95% CI −2.87%, 19.8%) and 10.7% (95% CI 0.353%, 21.1%). In conclusion, our research has confirmed a causal link between gut microbiota, blood metabolites, and CG. Metabolites such as 4-hydroxyphenylacetate levels, palmitoleate (16:1n7) levels, the phosphate to alanine ratio, and X-12839 levels have relatively significant mediating roles between gut microbiota and CG. These metabolites may influence the occurrence and development of CG by regulating inflammatory responses, energy metabolism, and gut barrier function. However, the majority of the influence of gut microbiota on CG remains unclear, necessitating further research into other potential mediating risk factors. Clinically, it is crucial to focus on patients suffering from CG who exhibit dysbiosis of gut microbiota.

IMPORTANCE

The results indicate that interactions between particular gut microbiota and blood metabolites may significantly contribute to the onset and progression of CG. These findings offer new insights and potential targets for early diagnosis, personalized treatment, and prevention of CG.
Hidden deep sulfide cumulates beneath the Jinchuan Ni–Cu–platinum-group element deposit (China) inferredfrom Ni–Cu isotopes
Authors: Zhao Yun , Wang Shui-Jiong , Xue Chunji , Brzozowski Matthew J.
Published: October 2024

The mechanisms that concentrated metals in the world’s single largest nickel–copper–platinum-group element (Ni–Cu–PGE) sulfide deposit, the Jinchuan deposit in northwestern China, remain enigmatic. Nickel and Cu isotopes are novel isotopic systems that may fill this knowledge gap as they are major constituents of sulfide melt, the main carrier of economically important metals. Sulfide ores in the Jinchuan deposit are characterized by systematically high δ60/58Ni and δ65Cu values, which are positively correlated (r2 = 0.84), and show well-defined correlations with PGEs, S, Ni, and Cu contents, and Ni/Pd, Cu/Pd, and Pd/Ir ratios. The isotopic signatures can be best explained by the early segregation of sulfide melt at depth prior to ascent of the parental magmas, storing isotopically light Ni and Cu in deep magma chambers. Subsequent sulfide melt segregation and fractionation in shallow portions of the magmatic conduit generated the currently explored sulfide ores, with heavy and positively correlated Ni–Cu isotopic signatures. Therefore, hidden deep orebodies are promising targets for further exploration beneath the Jinchuan deposit.
Opening of the North Atlantic Ocean and the rise of Scandinavian mountains
Authors: Makushkina Anna , Tauzin Benoit , Miller Meghan S. , Tkalčić Hrvoje , Thybo Hans
Published: October 2024

Large-scale topography is usually associated with tectonic plate boundaries, but the Scandinavian mountains (Scandes) are located far from any active tectonic setting, and their origin is unknown. We demonstrate that the Precambrian lithospheric structure of Fennoscandia controlled both the Cenozoic ocean opening and mountain rise in the North Atlantic region. Our new seismic receiver function analysis reveals a block of thick continental crust formed by Proterozoic crustal stacking. We propose that this block created a wide continental shelf bounded by two transform fault systems during continental breakup. This geometry resulted in the formation of lithospheric steps at the continental margin on both sides of the stacked crustal structure, coinciding with the highest Southern and Northern Scandes. We propose that edge-driven convection at these steps caused the mountain rise. This study presents a general model for the formation of high elevation behind passive margins.
Supplemental Material: Genetic linkage between parent granite and zoned rare metal pegmatite in the Renli-Chuanziyuan granite-pegmatite system, South China
Authors: Xiong Yi-Qu , Jiang Shao-Yong , al. et
Published: October 2024

Tables S1–S6.
COVID-19 vaccine effectiveness and uptake in a national cohort of English children and young people with life-limiting neurodisability
Authors: Cruz Joana , Harwood Rachel , Kenny Simon , Clark Matthew , Davis Peter J , Draper Elizabeth S , Hargreaves Dougal , Ladhani Shamez N , Luyt Karen , Turner Stephen W , Whittaker Elizabeth , Hardelid Pia , Fraser Lorna K , Viner Russell M , Ward Joseph Lloyd
Published: October 2024

Objective

To investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability.

Design

We undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models.

Patients

CYP aged 5–17 with life-limiting neurodisability.

Results

We identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)).

Conclusions

SARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.
Intermittent sigh breaths during high-frequency oscillatory ventilation in preterm infants: a randomised crossover study
Authors: Hough Judith Leigh , Jardine Luke , Hough Matthew James , Steele Michael , Greisen Gorm , Heiring Christian
Published: October 2024

Objective

To determine if combining high-frequency oscillatory ventilation (HFOV) with additional sigh breaths would improve end-expiratory lung volume (EELV) and oxygenation in preterm infants.

Design

Prospective interventional crossover study.

Setting

Neonatal intensive care unit.

Patients

Ventilated preterm infants <36 weeks corrected gestational age receiving HFOV.

Interventions

Infants were randomly assigned to receive HFOV with sigh breaths followed by HFOV-only (or vice versa) for four alternating periods. Sigh breaths were delivered with an inspiratory time of 1 s, peak inspiratory pressure of 30 cmH20 and frequency of three breaths/min.

Main outcome measures

Electrical impedance tomography measured the effect of sigh breaths on EELV and ventilation distribution. Physiological variables were recorded to monitor oxygenation. Measurements were taken at 30 and 60 min postchange of HFOV mode and compared with baseline.

Results

Sixteen infants (10 males, 6 females) with a median (range) gestational age at birth of 25.5 weeks (23–31), study weight of 950 g (660–1920) and a postnatal age of 25 days (3–49) were included in the study. The addition of sigh breaths resulted in a significantly higher global EELV (mean difference±95% CI) (0.06±0.05; p=0.04), with increased ventilation occurring in the posterior (dependent) and left lung segments, and improved oxygen saturations (3.31±2.10; p<0.01).

Conclusion

Intermittent sigh breaths during HFOV were associated in the short-term with an increased EELV in the posterior and left lungs, and improved oxygen saturations in preterm infants.