bluuebunny/crossref_metadata_2025_split huggingface dataset:
S309-CAR-NK cells bind the Omicron variants
in vitro
and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice
Authors: Ma Minh Tuyet , Jiang Qingkui , Chen Chih-Hsiung , Badeti Saiaditya , Wang Xuening , Zeng Cong , Evans Deborah , Bodnar Brittany , Marras Salvatore A. E. , Tyagi Sanjay , Bharaj Preeti , Yehia Ghassan , Romanienko Peter , Hu Wenhui , Liu Shan-Lu , Shi Lanbo , Liu Dongfang 
Published: May 2024

ABSTRACT

Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein
in vitro
. In this study, we further demonstrate that the S309-CAR-NK cells can bind to different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants
in vitro
. We also show that S309-CAR-NK cells reduce virus loads in the NOD/SCID gamma (NSG) mice expressing the human angiotensin-converting enzyme 2 (hACE2) receptor challenged with SARS-CoV-2 wild-type (strain USA/WA1/2020). Our study demonstrates the potential use of S309-CAR-NK cells for inhibiting infection by SARS-CoV-2 and for the potential treatment of COVID-19 patients unresponsive to otherwise currently available therapeutics.

IMPORTANCE
Chimeric antigen receptor (CAR)-NK cells can be “off-the-shelf” products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA/WA1/2020) in the lungs of NOD/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.
Kaposi sarcoma-associated herpesvirus complement control protein (KCP) and glycoprotein K8.1 are not required for viral infection
in vitro
or
in vivo
Authors: Muniraju Murali , Mutsvunguma Lorraine Z. , Reidel Ivana G. , Escalante Gabriela M. , Cua Simeon , Musonda Webster , Calero-Landa Jonathan , Farelo Mafalda A. , Rodriguez Esther , Li Zhou , Ogembo Javier Gordon 
Published: May 2024

ABSTRACT

Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causal agent of Kaposi sarcoma, a cancer that appears as tumors on the skin or mucosal surfaces, as well as primary effusion lymphoma and KSHV-associated multicentric Castleman disease, which are B-cell lymphoproliferative disorders. Effective prophylactic and therapeutic strategies against KSHV infection and its associated diseases are needed. To develop these strategies, it is crucial to identify and target viral glycoproteins involved in KSHV infection of host cells. Multiple KSHV glycoproteins expressed on the viral envelope are thought to play a pivotal role in viral infection, but the infection mechanisms involving these glycoproteins remain largely unknown. We investigated the role of two KSHV envelope glycoproteins, KSHV complement control protein (KCP) and K8.1, in viral infection in various cell types
in vitro
and
in vivo
. Using our newly generated anti-KCP antibodies, previously characterized anti-K8.1 antibodies, and recombinant mutant KSHV viruses lacking KCP, K8.1, or both, we demonstrated the presence of KCP and K8.1 on the surface of both virions and KSHV-infected cells. We showed that KSHV lacking KCP and/or K8.1 remained infectious in KSHV-susceptible cell lines, including epithelial, endothelial, and fibroblast, when compared to wild-type recombinant KSHV. We also provide the first evidence that KSHV lacking K8.1 or both KCP and K8.1 can infect human B cells
in vivo
in a humanized mouse model. Thus, these results suggest that neither KCP nor K8.1 is required for KSHV infection of various host cell types and that these glycoproteins do not determine KSHV cell tropism.

IMPORTANCE

Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human gamma-herpesvirus associated with the endothelial malignancy Kaposi sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. Determining how KSHV glycoproteins such as complement control protein (KCP) and K8.1 contribute to the establishment, persistence, and transmission of viral infection will be key for developing effective anti-viral vaccines and therapies to prevent and treat KSHV infection and KSHV-associated diseases. Using newly generated anti-KCP antibodies, previously characterized anti-K8.1 antibodies, and recombinant mutant KSHV viruses lacking KCP and/or K8.1, we show that KCP and K8.1 can be found on the surface of both virions and KSHV-infected cells. Furthermore, we show that KSHV lacking KCP and/or K8.1 remains infectious to diverse cell types susceptible to KSHV
in vitro
and to human B cells
in vivo
in a humanized mouse model, thus providing evidence that these viral glycoproteins are not required for KSHV infection.
An mRNA-LNP-based Lassa virus vaccine induces protective immunity in mice
Authors: Hashizume Mei , Takashima Ayako , Iwasaki Masaharu 
Published: May 2024

ABSTRACT

The mammarenavirus Lassa virus (LASV) causes the life-threatening hemorrhagic fever disease, Lassa fever. The lack of licensed medical countermeasures against LASV underscores the urgent need for the development of novel LASV vaccines, which has been hampered by the requirement for a biosafety level 4 facility to handle live LASV. Here, we investigated the efficacy of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), in mice. Two doses of LASgpc- or LCMnp-mRNA-LNP administered intravenously (i.v.) protected C57BL/6 mice from a lethal challenge with a recombinant (r) LCMV expressing a modified LASgpc (rLCMV/LASgpc
2m
) inoculated intracranially. Intramuscular (i.m.) immunization with two doses of LASgpc- or LCMnp-mRNA-LNP significantly reduced the viral load in C57BL/6 mice inoculated i.v. with rLCMV/LASgpc
2m
. High levels of viremia and lethality were observed in CBA mice inoculated i.v. with rLCMV/LASgpc
2m
, which were abrogated by i.m. immunization with two doses of LASgpc-mRNA-LNP. The protective efficacy of two i.m. doses of LCMnp-mRNA-LNP was confirmed in a lethal hemorrhagic disease model of FVB mice i.v. inoculated with wild-type rLCMV. In all conditions tested, negligible and high levels of LASgpc- and LCMnp-specific antibodies were detected in mRNA-LNP-immunized mice, respectively, but robust LASgpc- and LCMnp-specific CD8
+
T cell responses were induced. Accordingly, plasma from LASgpc-mRNA-LNP-immunized mice did not exhibit neutralizing activity. Our findings and surrogate mouse models of LASV infection, which can be studied at a reduced biocontainment level, provide a critical foundation for the rapid development of mRNA-LNP-based LASV vaccines.

IMPORTANCE

Lassa virus (LASV) is a highly pathogenic mammarenavirus responsible for several hundred thousand infections annually in West African countries, causing a high number of lethal Lassa fever (LF) cases. Despite its significant impact on human health, clinically approved, safe, and effective medical countermeasures against LF are not available. The requirement of a biosafety level 4 facility to handle live LASV has been one of the main obstacles to the research and development of LASV countermeasures. Here, we report that two doses of mRNA-lipid nanoparticle-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of lymphocytic choriomeningitis virus (LCMV), a mammarenavirus genetically closely related to LASV, conferred protection to recombinant LCMV-based surrogate mouse models of lethal LASV infection. Notably, robust LASgpc- and LCMnp-specific CD8
+
T cell responses were detected in mRNA-LNP-immunized mice, whereas no virus-neutralizing activity was observed.
Complete genome sequence of the linezolid-resistant clinical
Enterococcus faecalis
N23-3408 linked to a livestock lineage in Switzerland
Authors: Nüesch-Inderbinen Magdalena , Biggel Michael , Wehrli Marianne , Fischer Andreas Hans , Stephan Roger 
Published: May 2024

ABSTRACT

Here, we report the complete genome of human clinical linezolid-resistant
Enterococcus faecalis
N23-3408. N23-3408 harbored a 59.5 kb plasmid with antimicrobial resistance genes
cat
,
erm
(B),
fexA
,
optrA
,
tet
(L), and
tet
(M). Closely related
E. faecalis
harboring this plasmid was previously obtained from livestock animals and pet food in Switzerland.
Complete genome sequence of potential plant growth-promoting
Bacillus altitudinis
strain AIMST-CREST03 isolated from paddy field bulk soil
Authors: Sivaprakasam Sumitra , Mohd Azim Khan Nur Arisa , Yee Fan Tan , Kumarasan Yukgehnaish , Sicheritz-Pontén Thomas , Petersen Bent , Mohd Hata Erneeza , Vadamalai Ganesan , Parimannan Sivachandran , Rajandas Heera 
Published: May 2024

ABSTRACT

We present the complete genome of a potential plant growth-promoting bacteria
Bacillus altitudinis AIMST-CREST03
isolated from a high-yielding paddy plot. The genome is 3,669,202 bp in size with a GC content of 41%. Annotation predicted 3,327 coding sequences, including several genes required for plant growth promotion.
Draft genome sequence of
Methylobacterium
sp. 37f isolated from forest soil
Authors: Uttarotai Toungporn , McGenity Terry J. , Sutheeworapong Sawannee , Chitov Thararat 
Published: May 2024

ABSTRACT

In this study, we report the draft genome sequence data of
Methylobacterium
sp. 37f, isolated from soil beneath
Quercus semiserrata
Roxb. in Thailand. The genome consists of 5,305,449 base pairs, with a GC content of 67.5%.
Ecological and evolutionary processes involved in shaping microbial habitat generalists and specialists in urban park ecosystems
Authors: Li Shuzhen , Yan Xue , Abdullah Al Mamun , Ren Kexin , Rensing Christopher , Hu Anyi , Tsyganov Andrey N. , Mazei Yuri , Smirnov Alexey , Mazei Natalia , Yang Jun 
Published: May 2024

ABSTRACT

Microbiomes are integral to ecological health and human well-being; however, their ecological and evolutionary drivers have not been systematically investigated, especially in urban park ecosystems. As microbes have different levels of tolerance to environmental changes and habitat preferences, they can be categorized into habitat generalists and specialists. Here, we explored the ecological and evolutionary characteristics of both prokaryotic and microeukaryotic habitat generalists and specialists from six urban parks across five habitat types, including moss, soil, tree hole, water, and sediment. Our results revealed that different ecological and evolutionary processes maintained and regulated microbial diversity in urban park ecosystems. Under ecological perspective, community assembly of microbial communities was mainly driven by stochastic processes; however, deterministic processes were higher for habitat specialists than generalists. Microbial interactions were highly dynamic among habitats, and habitat specialists played key roles as module hubs in intradomain networks. In aquatic interdomain networks, microeukaryotic habitat specialists and prokaryotic habitat specialists played crucial roles as module hubs and connectors, respectively. Furthermore, analyzing evolutionary characteristics, our results revealed that habitat specialists had a much higher diversification potential than generalists, while generalists showed shorter phylogenetic branch lengths as well as larger genomes than specialists. This study broadens our understanding of the ecological and evolutionary features of microbial habitat generalists and specialists in urban park ecosystems across multi-habitat.

IMPORTANCE
Urban parks, as an important urban greenspace, play essential roles in ecosystem services and are important hotspots for microbes. Microbial diversity is driven by different ecological and evolutionary processes, while little is currently known about the distinct roles of ecological and evolutionary features in shaping microbial diversity in urban park ecosystems. We explored the ecological and evolutionary characteristics of prokaryotic and microeukaryotic habitat generalists and specialists in urban park ecosystems based on a representative set of different habitats. We found that different ecological and evolutionary drivers jointly maintained and regulated microbial diversity in urban park microbiomes through analyzing the community assembly process, ecological roles in hierarchical interaction, and species diversification potential. These findings significantly advance our understanding regarding the mechanisms governing microbial diversity in urban park ecosystems.
Evaluation of systemic medications associated with diabetic retinopathy: a nested case–control study from the UK Biobank
Authors: Jin Guangming , Ma Yiyuan , Zheng Danying , Jin Ling , Young Charlotte Aimee , Shen Yanyu , Tan Yuan , Jin Jiaxin , Zhang Xinyu , Wu Yue , Liu Zhenzhen 
Published: May 2024

AimsThis study aims to investigate the associations between commonly used systemic medications and diabetic retinopathy (DR).MethodsIndividuals with linked primary care prescription data from the UK Biobank were included. Cases were defined as individuals with a Hospital Episode Statistics-coded or primary care recorded diagnosis of DR or self-reported DR. Controls were matched for age, sex, glycosylated haemoglobin, duration of diabetes mellitus (DM), hypertension status and cardiovascular disease status. ORs and 95% CIs were calculated using conditional univariate and multivariable logistic regression models.ResultsA total of 3377 case subjects with DR were included in the study and matched with 3377 control subjects. In multivariable logistic regression, increased odds of incident DR were observed for exposure to short-acting insulins (OR 1.63; 95% CI 1.22 to 2.18), medium-acting insulins (OR 2.10; 95% CI 1.60 to 2.75), sulfonylureas (OR 1.30; 95% CI 1.16 to 1.46). Instead, the use of fibrates (OR 0.71; 95% CI 0.53 to 0.94) and Cox-2 inhibitors (OR 0.68; 95% CI 0.58 to 0.79) was associated with decreased odds of incident DR. Dose–response relationships were observed for all five drug categories (all p<0.05).ConclusionsThis study comprehensively investigated the associations between systemic medication use and DR and found significant associations between the use of short-acting insulins, medium-acting insulins and sulfonylureas with increased odds of incident DR. In contrast, fibrates and Cox-2 inhibitors were associated with decreased odds of incident DR. These findings may provide valuable insights into DM medication management and serve as a reference for the prevention of DR in patients with DM.
Vibration of effects resulting from treatment selection in mixed-treatment comparisons: a multiverse analysis on network meta-analyses of antidepressants in major depressive disorder
Authors: Vinatier Constant , Palpacuer Clement , Scanff Alexandre , Naudet Florian 
Published: May 2024

Objective
It is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact on effect estimates of selecting different treatment combinations (ie, network geometries) for inclusion in NMAs.

Design
Multiverse analysis, covering all possible NMAs on different combinations of treatments.

Setting
Data from a previously published NMA exploring the comparative effectiveness of 22 treatments (21 antidepressants and a placebo) for the treatment of acute major depressive disorder.

Participants
Cipriani
et al
explored a dataset of 116 477 patients included in 522 randomised controlled trials.

Main outcome measures
For each possible treatment selection, we performed an NMA to estimate comparative effectiveness on treatment response and treatment discontinuation for the treatments included (231 between-treatment comparisons). The distribution of effect estimates of between-treatment comparisons across NMAs was computed, and the direction, magnitude and statistical significance of the 1st and 99th percentiles were compared.

Results
4 116 254 different NMAs concerned treatment response. Among possible network geometries, 172/231 (74%) pairwise comparisons exhibited opposite effects between the 1st and 99th percentiles, 57/231 (25%) comparisons exhibited statistically significant results in opposite directions, 118 of 231 (51%) comparisons derived results that were both significant and non-significant at 5% risk and 56/231 (24%) treatment pairs obtained consistent results with only significant differences (or only non-significant differences) at 5% risk. Comparisons based on indirect evidence only were associated with greater variability in effect estimates. Comparisons with small absolute values observed in the complete NMA more frequently obtained statistically significant results in opposite directions. Similar results were observed for treatment discontinuation.

Conclusion
In this multiverse analysis, we observed that the selection of treatments to be included in an NMA could have considerable consequences on treatment effect estimations.

Trial registration

https://osf.io/mb5dy
.
Joint RCEM and NPIS best practice guideline: assessment and management of acute opioid toxicity in adults in the emergency department
Authors: Blundell Matthew , Gill Rupinder , Thanacoody Ruben , Humphries Christopher , Wood David M , Dargan Paul I 
Published: May 2024

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy’s and St Thomas’ NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence.
Familial aggregation of traffic risky behaviours among pedestrians: a cross-sectional study in northwestern Iran
Authors: Davtalab Esmaeili Elham , Ghaffari Alireza , R. Kalankesh Leila , Zeinalzadeh Ali Hossein , Dastgiri Saeed 
Published: May 2024

ObjectiveThis study aims to assess the familial aggregation of traffic risky behaviours among pedestrians and describe the sociodemographic profile of pedestrians in northwestern Iran.MethodsA cross-sectional study was conducted among 933 pedestrians in 2023. Participants were selected using stratified random sampling. Traffic risky behaviour was measured using a validated instrument among heads of households and their first relatives. The generalised estimating equations were computed to estimate the adjusted OR and 95% CI for familial aggregation of traffic risky behaviours.ResultsOf the total sample, 52.2% and 27.7% of the participants were male and aged 41–50, respectively. The majority of respondents were categorised in middle socioeconomic class (36.9%). The OR for familial aggregation of traffic risky behaviours was 1.42 (95% CI 1.07 to 1.89), indicating that the presence of traffic risky behaviours in at least one family member increased the likelihood of similar behaviour in other members. Fathers showing violation behaviours were associated by 1.98-fold increase in violation behaviours among their offspring. Similarly, the existence of violation behaviour in one sibling increased the odds of violation behaviour among other siblings (OR 1.99, 95% CI 1.18 to 3.73).ConclusionsThis study revealed the familial aggregation of traffic risky behaviours of pedestrians, with father-offspring and sibling aggregations emerging as prominent components of familial aggregation. The findings suggested that family-based prevention programmes may yield greater effectiveness than individual-based approaches. As such, implementing targeted interventions focusing on family might have a substantial impact on reducing pedestrian traffic risky behaviours.
Content analysis of succession planning in nursing management: a qualitative study
Authors: Ashghali-Farahani Mansoureh , Salehi Tahmine , Mirzaee Mohammadsaeed 
Published: May 2024

AimThe identification and development of managerial talents for nursing manager succession in the future should be a concern for organisations, as the concept of succession planning has not been seriously addressed in nursing. This study aimed to explore managers’ perceptions of the concept of succession planning in nursing management.DesignThis qualitative study used a conventional content analysis approach.MethodsParticipants included 15 nursing managers, who were purposively selected based on predetermined inclusion and exclusion criteria. After obtaining ethical approval, data were collected through semistructured interviews. MAXQDA software was used for data management, and data analysis was performed using the seven-stage method by Graneheim and Lundman. The credibility and dependability of the data were assessed using Guba and Lincoln’s criteria.ResultsThe main categories identified in this study were barriers to succession planning, facilitators, succession planning requirements, contextualisation, succession planning cycle, the dynamism of the successor organisation and consequences of lack of succession planning. Based on the findings of this study, it is recommended that organisations plan and adopt policies to develop qualified personnel management in nursing organisations and appoint these individuals to critical managerial positions.