bluuebunny/crossref_metadata_2025_split huggingface dataset:
A self‐amplifying NO‐H2S loop mediates melatonin‐induced CBF‐responsive pathway and cold tolerance in watermelon
Authors: Guo Yanliang , Li Jiayue , Liu Lingling , Liu Jiahe , Yang Wanbang , Chen Yi , Li Chao , Yuan Li , Wei Chunhua , Ma Jianxiang , Zhang Yong , Yang Jianqiang , Luan Feishi , Zhang Xian , Li Hao 
Published: February 2025

SUMMARYMelatonin is a pivotal bioactive molecule that enhances plant cold stress tolerance, but the precise mechanisms remain enigmatic. Here, we have discovered that overexpressing melatonin biosynthetic gene ClCOMT1 or applying exogenous melatonin activates the C‐repeat binding factor (CBF)‐responsive pathway and enhances watermelon cold tolerance. This enhancement is accompanied by elevated levels of nitric oxide (NO) and hydrogen sulfide (H2S), along with upregulation of nitrate reductase 1 (ClNR1) and L‐cysteine desulfhydrase (ClLCD) genes involved in NO and H2S generation respectively. Conversely, knockout of ClCOMT1 exhibits contrasting effects compared to its overexpression. Furthermore, application of sodium nitroprusside (SNP, a NO donor) and NaHS (a H2S donor) promotes the accumulation of H2S and NO, respectively, activating the CBF pathway and enhancing cold tolerance. However, knockout of ClNR1 or ClLCD abolished melatonin‐induced H2S or NO production respectively and abrogated melatonin‐induced CBF pathway and cold tolerance. Conversely, supplementation with SNP and NaHS restored the diminished cold response caused by ClCOMT1 deletion. Additionally, deletion of either ClNR1 or ClLCD eliminated NaHS‐ or SNP‐induced cold response, respectively. Overall, these findings suggest a reciprocal positive‐regulatory loop between ClNR1‐mediated NO and ClLCD‐mediated H2S, which plays a crucial role in mediating the melatonin‐induced enhancement of cold tolerance.
How Much Will a Pig Organ Transplant Cost? A Preliminary Estimate of the Cost of Xenotransplantation Versus Allotransplantation in the USA
Authors: Vasudev Krish , Cooper David Kempton Cartwright 
Published: February 2025

ABSTRACTWe reviewed the costs of organ allotransplantation and attempted to estimate the potential costs of xenotransplantation (based on the premise that, when clinically established, the results of pig organ xenotransplantation would be at least equal to those of allotransplantation). The care of patients with end‐stage organ failure waiting for an allograft is expensive, particularly if chronic dialysis or mechanical support is required. Xenotransplantation has the potential to eliminate wait times for organ transplants, significantly reduce certain management costs, for example, chronic dialysis, and enable early transplantation before comorbidities develop or increase. The cost of the surgical procurement of a pig organ and its transplantation will be similar to that of allotransplantation, as will the cost of immunosuppressive therapy. The major “unknown” is the cost of purchasing a gene‐edited pig organ, which is likely to be considerable. We conclude that there will be significant cost savings for the pretransplant care of an individual patient, but these may be offset by the cost of the gene‐edited pig organ. However, the ready availability of an unlimited organ supply will greatly increase the number of transplants carried out each year, thus increasing the overall expenditure on transplantation.
A new upper bound for the growth factor in Gaussian elimination with complete pivoting
Authors: Bisain Ankit , Edelman Alan , Urschel John 
Published: February 2025

AbstractThe growth factor in Gaussian elimination measures how large the entries of an LU factorization can be relative to the entries of the original matrix. It is a key parameter in error estimates, and one of the most fundamental topics in numerical analysis. We produce an upper bound of for the growth factor in Gaussian elimination with complete pivoting — the first improvement upon Wilkinson's original 1961 bound of .
Identification of glyoxalase A in group B
Streptococcus
and its contribution to methylglyoxal tolerance and virulence
Authors: Akbari Madeline S. , Joyce Luke R. , Spencer Brady L. , Brady Amanda , McIver Kevin S. , Doran Kelly S. 
Published: February 2025

ABSTRACT

Group B
Streptococcus
(GBS) is a Gram-positive pathobiont that commonly colonizes the gastrointestinal and lower female genital tracts but can cause sepsis and pneumonia in newborns and is a leading cause of neonatal meningitis. Despite the resulting disease severity, the pathogenesis of GBS is not completely understood, especially during the early phases of infection. To investigate GBS factors necessary for bloodstream survival, we performed a transposon (Tn) mutant screen in our bacteremia infection model using a GBS
mariner
transposon mutant library previously developed by our group. We identified significantly underrepresented mutations in 623 genes that contribute to survival in the blood, including those encoding known virulence factors such as capsule, the β-hemolysin, and inorganic metal ion transport systems. Most of the underrepresented genes have not been previously characterized or studied in GBS, including
gloA
and
gloB,
which are homologs for genes involved in methylglyoxal (MG) detoxification. MG is a byproduct of glycolysis and a highly reactive toxic aldehyde that is elevated in immune cells during infection. Here, we observed MG sensitivity across multiple GBS isolates and confirmed that
gloA
contributes to MG tolerance and invasive GBS infection. We show specifically that
gloA
contributes to GBS survival in the presence of neutrophils and depleting neutrophils in mice abrogates the decreased survival and infection of the
gloA
mutant. The requirement of the glyoxalase pathway during GBS infection suggests that MG detoxification is important for bacterial survival during host-pathogen interactions.

IMPORTANCE

A transposon-mutant screen of group B
Streptococcus
(GBS) in a bacteremia mouse model of infection revealed virulence factors known to be important for GBS survival such as the capsule, β-hemolysin/cytolysin, and genes involved in metal homeostasis. Many uncharacterized factors were also identified including genes that are part of the metabolic pathway that breaks down methylglyoxal (MG). The glyoxalase pathway is the most ubiquitous metabolic pathway for MG breakdown and is only a two-step process using glyoxalase A (
gloA
) and B (
gloB
) enzymes. MG is a highly reactive byproduct of glycolysis and is made by most cells. Here, we show that in GBS, the first enzyme in the glyoxalase pathway, encoded by
gloA
, contributes to MG resistance and blood survival. We further demonstrate that GloA contributes to GBS survival against neutrophils
in vitro
and
in vivo
and, therefore, is an important virulence factor required for invasive infection.
Seneca Valley virus infection exploits DNA damage response to facilitate viral replication
Authors: Song Jiangwei , Li Zijian , Yang Jingjing , Ma Ruiyi , Wang Dan , Quan Rong , Wen Xuexia , Liu Jue 
Published: February 2025

ABSTRACT

Seneca Valley virus (SVV) is an emerging pathogen that causes severe vesicular diseases in swine, posing a significant threat to the global pork industry. DNA and RNA viruses manipulate the host DNA damage response (DDR) to modulate cellular machinery and facilitate their life cycles. However, the interaction between the host DDR and SVV infection remains unexplored. Here, we aimed to comprehensively investigate the DDR and DNA repair signaling pathways during SVV infection. We found that SVV infection causes DNA damage and triggers distinct DDR signaling pathways, including ataxia telangiectasia-mutated (ATM) kinase, ATM-Rad3-related kinase, and DNA-dependent protein kinase. However, it failed to induce the formation of γH2AX and 53BP1 foci, resulting in unrepaired DNA damage. Furthermore, we found that SVV 2B and 2C proteins can activate DDR signaling pathways and impair DNA repair. SVV-induced DDR triggered NF-κB signaling accompanied by upregulation of pro-inflammatory cytokines, as evidenced by the inhibition of ATM kinase, abolished SVV-induced NF-κB activation. Inhibition of the ATM pathway attenuated SVV replication. These findings expand our understanding of host DDR manipulation during viral infection and provide crucial insights into a novel mechanism exploited by SVV to regulate the inflammatory response for efficient replication.

IMPORTANCE
DDR is a cellular machinery that senses and repairs host DNA lesions to maintain genome integrity. Viruses have evolved diverse strategies to manipulate host DDR for replicative efficiency. SVV is an emerging virus that causes vesicular diseases in pigs and severely threatens the swine industry. However, the interaction between SVV and DDR remains unclear. Here, we found that SVV modulates host DDR pathways to facilitate viral replication. Our results demonstrated that SVV infection causes DNA damage, activates ATM-mediated DNA double-strand break response, and impedes DNA repair. SVV 2B and 2C proteins induced DNA damage and activated the DDR pathway while impairing repair mechanisms. This study revealed a fine-tuned molecular mechanism of SVV-modulated DDR that contributes to viral replication, facilitating deeper insight into SVV replication.
Clade 2.3.4.4b H5N1 neuraminidase has a long stalk, which is in contrast to most highly pathogenic H5N1 viruses circulating between 2002 and 2020
Authors: Hermann Enikő , Krammer Florian 
Published: February 2025

ABSTRACT

Since 2020, H5N1 highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4b have been rapidly spreading in wild birds but have also caused a large number of mammalian infections and more than 70 known human cases. Importantly, this H5N1 clade has also crossed the species barrier into dairy cattle in the US in late 2023/early 2024. The neuraminidase (NA) protein of the N1 subtype can feature truncations in its stalk domain, which have been identified as putative virulence factors in poultry but seem to have a negative impact on transmission in mammals. Since its emergence, the vast majority of HPAI H5N1 A/goose/Guangdong/1/1996-lineage isolates have featured this truncated version of the NA stalk domain. Here, we report that this changed with the 2020 expansion of clade 2.3.4.4b H5N1 and that the majority of isolates—including the strains circulating in dairy cattle—feature a long NA stalk domain.

IMPORTANCE
While the truncated version of the N1 neuraminidase stalk domain may be associated with increased virulence in poultry, the long version of the stalk domain has been associated with increased transmissibility in mammals. The vast majority of highly pathogenic H5N1 of clade 2.3.4.4b that is currently circulating globally features the long stalk version of the neuraminidase, which may increase the risk for these viruses to become human-to-human transmissible.
Antibodies with specificity to glycan motifs that decorate OMV cargo proteins
Authors: Kim Hyun Young , Rothenberger Christina M. , Davey Mary E. , Yu Manda 
Published: February 2025

ABSTRACT

Porphyromonas gingivalis
is a major etiological agent of periodontal disease, and infections with this bacterium are associated with systemic pathologies, including atherosclerosis, rheumatoid arthritis, and Alzheimer’s disease.
P. gingivalis
has a variety of immune evasion mechanisms and exhibits highly variable cell surface characteristics that are strain dependent, complicating the development of effective vaccines and therapeutics. Here, we show that a subset of immunoglobulin M (IgM) antibodies in antiserum raised against
P. gingivalis
strain W83 selectively recognize the outer membrane vesicles (OMVs). Pre-adsorption with a mutant strain lacking an OMV-specific lipoprotein (PG1881) that has been shown to be glycosylated significantly enhanced IgM specificity toward PG1881 and the OMVs. In addition, the IgM reactivity against the OMVs derived from a mutant lacking enzymes required for O-glycosylation was markedly reduced, indicating that the IgM targets the glycan motifs on proteins carried on OMVs. Importantly, the IgM exhibited specific recognition of OMVs from both
P. gingivalis
and
Porphyromonas endodontalis
, while showing low reactivity toward other genera belonging to the phylum Bacteroidetes. This study revealed a potential host evasion strategy and highlights the potential for utilizing O-glycans in vaccine development and OMV-targeted antibodies in therapeutic interventions to combat
P. gingivalis
infections.

IMPORTANCE

O-glycosylation of cell surface proteins by bacteria is known to play a role in various functions including colonization and immune evasion. This study highlights the identification of IgM antibodies that specifically recognize O-glycosylated proteins that are selectively carried on outer membrane vesicles (OMVs). The findings suggest a potential host evasion mechanism and open new avenues for using OMVs in vaccine development and targeting O-glycans with antibodies as a therapeutic strategy against the subgingival pathobiont
P. gingivalis
.
Association between maternal sociodemographic characteristics and exclusive mother’s own milk feeding in preterm infants: a cohort study using data from the National Neonatal Research Database
Authors: Ryan Melissa-Sue , Szatkowski Lisa , Doubatty Arrisonia , Ojha Shalini 
Published: February 2025

ObjectiveTo ascertain the sociodemographic and geographical determinants of exclusive and no mother’s own milk (MOM) feeding for infants <34 weeks’ gestational age (GA) in England and Wales.Study designRetrospective cohort study using the National Neonatal Research Database (2016–2022). We calculated unadjusted and mutually adjusted ORs for exclusive and no MOM feeding throughout an infant’s neonatal stay, by maternal age group, ethnicity and deprivation quintile. Neonatal Operational Delivery Network and unit were included as random effects, and the adjusted models included other potential confounders such as gestational age and mode of delivery.ResultsAmong the 90 730 infants, 11 962 (13.2%) were exclusively MOM fed, while 9018 (9.9%) never received MOM. The odds of exclusive MOM feeding increased with decreasing maternal social deprivation (OR for least deprived vs most deprived quintile 2.16, 95% CI 2.01 to 2.33), while the odds of no MOM decreased (OR 0.33, 95% CI 0.30 to 0.36). The odds of exclusive MOM feeding were lower for Asian/Asian-British mothers compared with white mothers (OR 0.88, 95% CI 0.82 to 0.95). The odds of never receiving MOM were lower for Black, Asian and mixed ethnicities compared with white mothers. Infants of mothers aged 26–35 years had the highest odds of exclusive MOM feeding. There was a geographical variation in feeding practices with a north-south divide in the prevalence of never receiving MOM. There was a significant variation in feeding practices between neonatal units.ConclusionProvision of MOM to preterm infants in England and Wales is associated with maternal sociodemographic characteristics.
Impact of sleep on postpartum health outcomes: a systematic review and meta-analysis
Authors: Khan-Afridi Zain , Ruchat Stephanie-May , Jones Paris A T , Ali Muhammad Usman , Matenchuk Brittany A , Leonard Sierra , Jantz Andrew WE , Vander Leek Kier , Maier Lauren E , Osachoff Laura , Hayman Melanie J , Forte Milena , Sivak Allison , Davenport Margie H 
Published: February 2025

ObjectiveTo examine the impact of postpartum sleep interventions and postpartum sleep on maternal health outcomes.DesignSystematic review with random-effects meta-analysis. Online databases were searched on 12 January 2024.Study eligibility criteriaStudies of all designs (except case studies and reviews) in all languages were eligible if they contained information on the population (individuals up to 1-year post partum), sleep interventions/exposures including (type, duration, frequency, alone or in combination with other components), comparator (control or different duration, frequency or type of sleep intervention) and outcomes: mental health, cardio-metabolic, postpartum weight retention (PPWR), low back pain and pelvic girdle pain, breastfeeding and urinary incontinence.Results60 studies (n=20 684) from 14 countries were included. ‘High’ certainty of evidence showed that sleep interventions were associated with a greater decrease in depressive symptom severity compared with no intervention (five randomised controlled trials; n=992; standardised mean difference −0.27, 95% CI −0.40 to –0.14; small effect). Sleep interventions had no impact on the odds of developing depression (‘moderate’ certainty of evidence) or anxiety or anxiety symptom severity (‘low’ certainty of evidence). Additionally, ‘low’ certainty of evidence demonstrated no effect on cardiometabolic outcomes (systolic blood pressure, diastolic blood pressure, mean arterial pressure), anthropometric measures (maternal weight, body mass index) or prevalence of exclusive breastfeeding. ‘Low’ certainty of evidence from observational studies found that high-quality sleep reduces the odds of developing anxiety and reduces the severity of depression and anxiety symptoms. ‘Low’ and ‘very low’ certainty of evidence from observational studies found that shorter sleep duration is associated with greater PPWR.ConclusionsPostpartum sleep interventions reduced the severity of depression symptoms.
Telehealth Programme for the Education and Enrichment of Relational Skills (PEERS) for adolescents with acquired and congenital brain injuries: a protocol for mixed-methods randomised trial
Authors: Sakzewski Leanne , Gilmore Rose , Hilton Nicola , Goodman Sarah , Whittingham Koa , Barfoot Jacqui , Thompson Bianca , Keramat Afroz , Boyd Roslyn N 
Published: February 2025

IntroductionFor adolescents with brain injury, challenges with social function often persist into adulthood, impacting social participation and quality of life. The Programme for the Education and Enrichment of Relational Skills (PEERS) is a manualised group-based intervention with preliminary evidence demonstrating improved social knowledge and participation for adolescents with acquired brain injury or cerebral palsy when delivered face to face. The recent COVID-19 pandemic and challenges for families living outside metropolitan centres to access the programme suggest a telehealth delivered PEERS should be explored. This study aims to compare telehealth PEERS to usual care in a mixed-methods randomised waitlist-controlled trial to determine preliminary efficacy to improve social functioning and secondarily to determine acceptability, feasibility, cost and contextual factors impacting the implementation.Methods and analysisIn this single-centre mixed-methods randomised waitlist-controlled trial, 32 adolescents with brain injury, aged 11–17 years attending mainstream high school and their caregivers will be randomised to receive either (a) telehealth PEERS once/week for 1.5 hours for 14 weeks or (b) usual care (UC). UC is highly variable in Australia but often comprises fortnightly occupational therapy, physiotherapy or speech therapy. The waitlist group will then receive PEERS following the 26-week retention time point. Measures will be administered at baseline, 14 weeks (immediately post) and then 26 and 52 weeks post baseline. The primary outcome is self-reported performance and satisfaction with social goals on the Canadian Occupational Performance Measure at 14 weeks. Secondary outcomes include self and parent-reported social competence, frequency of get-togethers with peers, self-report knowledge of social skills, frequency of peer victimisation and quality of life. An implementation evaluation will be done to determine acceptability, feasibility, cost and identify barriers and facilitators in the implementation of the intervention and map these against the Consolidated Framework for Implementation Research. This study will assess the unit costs of implementing the PEERS from an Australian health system perspective.Ethics and disseminationThe Children’s Health Queensland Hospital and Health Service and The University of Queensland Human Research Ethics Committees have approved this study. Findings will be disseminated in peer-reviewed journals and conference presentations.Trial registration numberACTRN1263000082606.
Prioritisation of functional needs for ICU intelligent robots in China: a consensus study based on the national survey and nominal group technique
Authors: Cui Zhen , Yan Yufeng , Wang Hao , Bai Ying , Zhang Liu , Yu Miaomiao , Zhang Fan , Yuan Xin , Wang Shuya , Ouyang Bo , Wu Xinbao 
Published: February 2025

ObjectiveThis study aims to define the prioritisation of the needs for an intelligent robot’s functions in the intensive care unit (ICU) from a clinical perspective.DesignThis study introduces a nominal group technique.SettingThis study uses national setting.ParticipantsThis study includes a total of 851 respondents from 34 provinces in China who participated in the survey. A nominal group of 12 members was organised by the research group; there were seven experts with a background in critical care, two junior attending physicians with a background in critical care and three experienced nurses.ResultsA total of 50 needed intelligent robot functions in ICUs were obtained from the questionnaire data. Through three rounds of nominal group voting and discussion, a consensus was reached on 44 items, which were categorised into 29 high-priority needs, 13 medium-priority needs and two low-priority needs. The functionalities in areas such as ‘sleep and pain assessment,’ ‘monitoring of sedation, agitation, and delirium,’ and ‘robot-assisted rehabilitation and physical therapy’ were particularly favoured by the ICU medical and nursing staff.ConclusionsThis study has defined the functional needs and priorities for ICU intelligent robots from the perspective of ICU clinical medical and nursing staff. It has been concluded that ‘disease assessment function’ and ‘rehabilitation and physical therapy’ are most needed by clinical doctors and nurses. The results presented in this study could serve as a useful reference for future research and development of medical robots.
All the voices we cannot hear: a taxonomy of why some populations’ experiences are missing from health and care quality evidence and the Toolkit for Assessing Under Representation in User Surveys (TAURUS)
Authors: Graham Chris , King Jenny , Lerway Clare , Poots Alan J 
Published: February 2025

BackgroundPatient and public voices are vital for understanding the quality of health and care. However, many healthcare providers, commissioners, decision-makers and researchers cannot hear the voices of all people within diverse populations, with different groups excluded from patient experience data collections and analyses for a variety of causes—some of which are overlooked or misunderstood. Exclusion and under-representation can be particularly problematic for disadvantaged people and marginalised communities, and risk exacerbating existing inequalities.Key messagesWe posit a taxonomy of causes of exclusion and under-representation in research involving patient and public voice: (1) Non-access: people are excluded because they cannot or do not access a service in the first place. (2) Non-invitation: health research and feedback programmes may not include invitations for some groups, despite being eligible, or use language that is inappropriate. (3) Non-response: some communities are less likely to respond to requests for feedback. (4) Non-identification: sometimes the structure and content of data do not allow the identification of distinct groups in data collections. (5) Non-review: sometimes data are available and yet not analysed. We provide aToolkit for Assessing Under Representation in User Surveysto prompt conversations.ConclusionsThese causes result in under-representation that creates knowledge gaps for quality and equity. Overcoming this requires strategic approaches with a commitment to equity and inclusion, supported by resources in collecting and using data with an appropriate range of methodologies. Providers should undertake equalities impact assessments around new data collections, using the taxonomy to identify and minimise potential sources of under-representation and ensure that voices are heard and acted on.