bluuebunny/crossref_metadata_2025_split huggingface dataset:
SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway
Authors: Ding Guofei , Li Yingchao , Li Dexin , Dou Mingyu , Fu Chaolun , Chen Ting , Cui Xinyu , Zhang Qin , Yang Pingping , Hou Yanmeng , Liu Sidang , Xiao Yihong 
Published: November 2024

ABSTRACT

Porcine reproductive and respiratory syndrome viru
s
(PRRSV) is the cause of porcine reproductive and respiratory syndrome (PRRS); a disease of pigs, which results in great economic losses in the pork industry. The non-structural protein 4 (Nsp4), a 3C-like serine protease responsible for most non-structural protein processing, plays an essential role in PRRSV infection. We used label-free quantitative proteomics to elucidate the Nsp4 interactome and SRCAP was identified as one of the interactors. SRCAP facilitated PRRSV infection by activating non-canonical Notch signaling. The ATPase I–IV domain in SRCAP and the
122
VITEA
126
in Nsp4 were identified as the interacting sites. The infection of recovered mutant rTA-12/5A (
122
AAAAA
126
) could not activate Notch signaling. The results indicated that
122
VITEA
126
in Nsp4 were key sites to determine the function of SRCAP and their interaction. A function of Nsp4 in activating the Notch signaling pathway was discovered. Block Notch signaling pathway could inhibit PRRSV infection both
in vitro
and
in vivo
which may lead to the development of novel therapeutic antiviral strategies.

IMPORTANCE

In the present study, the interactome of the NSP4 originating from PRRSV was studied and SRCAP was confirmed as one of the interactors. Mechanism study showed the interaction of Nsp4 and SRCAP was found to facilitate PRRSV infection by activating non-canonical Notch signaling. ATPase Ⅰ–Ⅳ domain in SRCAP and the
122
VITEA
126
in Nsp4 were identified as the interacting sites that demined the activating of Notch signaling. Block Notch signaling pathway could inhibit PRRSV infection
in vitro
and
in vivo
which may be a new target for antiviral drug development.
Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs
Authors: Li Chong , Culhane Marie R. , Schroeder Declan C. , Cheeran Maxim C-J. , Galina Pantoja Lucina , Jansen Micah L. , Torremorell Montserrat 
Published: November 2024

ABSTRACT

Global evolutionary dynamics of influenza A virus (IAV) are fundamentally driven by the extent of virus diversity generated, transmitted, and shaped in individual hosts. How vaccination affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs is unknown. To evaluate the effect of vaccination on the transmission of genetically distinct IAV variants and their diversity after transmission in pigs, we examined the whole genome of IAV recovered from the nasal cavities of pigs vaccinated with different influenza immunization regimens after being infected simultaneously by H1N1 and H3N2 IAVs using a seeder pig model. We found that the seeder pigs harbored more diversified virus populations than the contact pigs. Among contact pigs, H3N2 and H1N1 viruses recovered from pigs vaccinated with a single dose of an unmatched modified live vaccine generally accumulated more extensive genetic mutations than non-vaccinated pigs. Furthermore, the non-sterilizing immunity elicited by the single-dose-modified live vaccine may have exerted positive selection on H1 antigenic regions as we detected significantly higher nonsynonymous but lower synonymous evolutionary rates in H1 antigenic regions than non-antigenic regions. In addition, we observed that the vaccinated pigs shared significantly less proportion of H3N2 variants with seeder pigs than unvaccinated pigs. These results indicated that vaccination might reduce the impact of transmitted influenza variants on the overall diversity of IAV populations harbored in recipient pigs and that within-host genetic selection of IAV is more likely to occur in pigs vaccinated with improperly matched vaccines.

IMPORTANCE
Understanding how vaccination shapes the diversity of influenza variants that transmit and propagate among pigs is essential for designing effective IAV surveillance and control programs. Current knowledge about the transmission of IAV variants has primarily been explored in humans during natural infection. However, how immunity elicited by improperly matched vaccines affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs at the whole-genome level is unknown. We analyzed IAV sequences from samples collected daily from experimentally infected pigs vaccinated with various protocols in a field-represented IAV co-infection model. We found that vaccine-induced non-sterilizing immunity might promote genetic variation on the IAV genome and drive positive selection at antigenic sites during infection. In addition, a smaller proportion of H3N2 viral variants were shared between seeder pigs and vaccinated pigs, suggesting the influence of vaccination on shaping the virus genomic diversity in recipient pigs during the transmission events.
Contrasting patterns of
Asaia
association with
Plasmodium falciparum
between field-collected
Anopheles gambiae
and
Anopheles coluzzii
from Cameroon
Authors: Tatsinkou Maffo Claudine Grâce , Sandeu Maurice Marcel , Tchoupo Micareme , Dondji Kamga Fleuriane Metissa , Mugenzi Leon M. J. , Njiokou Flobert , Hughes Grant L. , Wondji Charles S. 
Published: November 2024

ABSTRACT

The widespread prevalence of
Asaia
in mosquitoes makes it a potential candidate for paratrangenic control in
Anopheles
. To better understand whether this bacterium could be used for malaria control, we quantified
Asaia
in
An. gambiae s.l
populations in malaria endemic regions examining co-infection with
Plasmodium falciparum
. Adult
Anopheles
mosquitoes were collected across two different eco-geographical localities in Cameroon, during both the dry and wet seasons. DNA was extracted from whole individual mosquitoes, and real time-qPCR amplification of the
16S ribosomal
RNA was used to quantify
Asaia
in both
An. gambiae
and
An. coluzzii
samples. We also detected and quantified
P. falciparum
infection in the same mosquitoes. The density of
Asaia
was successfully quantified in a total of 864 field mosquitoes, comprising of 439
An. gambiae
from Bankeng and 424
An. coluzii
collected from Gounougou. Interestingly, a higher prevalence of
Asaia
in
An. gambiae
(88.3%) compared to
An. coluzzii
(80.9%) was observed. Moreover, the density of
Asaia
in both species was significantly affected by seasonal changes in the two localities. Furthermore, a significant difference between the infection densities of
Asaia
and the
Plasmodium
infection status in the two species was recorded. However, no correlation was observed between the number of
Asaia
and
P. falciparum
infections. This study provides evidence that naturally occurring
Asaia
infection is not correlated to
P. falciparum
development within
An. gambiae
and
An. coluzzii
. Nevertheless, further studies incorporating experimental infections are required to better investigate the correlation between
Anopheles
mosquitoes,
Asaia,
and
Plasmodium
.

IMPORTANCE

The symbiont
Asaia
has emerged as a promising candidate for paratransgenic control of malaria, but further analysis of its biology and genetics across Africa is necessary. In this study, we investigated and quantified the influence of
Asaia
in naturally infected
An. gambiae s.l
. populations with the malaria parasite
Plasmodium falciparum
. Genomic DNA was extracted from whole individual mosquitoes collected from two localities, and
Asaia
was quantified using real-time qPCR by amplification of the 16S ribosomal RNA gene. We also detected and quantified
Plasmodium falciparum
infection in the same mosquitoes and established the correlation between
Asaia
and
Plasmodium
coinfection. This study provides evidence that naturally occurring
Asaia
infection is not correlated with
P. falciparum
development within
An. gambiae
and
An. coluzzii
mosquitoes.
Genotypic and phylogeographic insights into a pre-epidemic variant of Wesselsbron virus detected in sylvatic
Aedes mcintoshi
from Semuliki Forest, Uganda
Authors: Eibner Georg Joachim , Graff Selina Laura , Hieke Christian , Ochieng James Robert , Kopp Anne , Drosten Christian , Lutwama Julius , Rwego Innocent Bidason , Junglen Sandra 
Published: November 2024

ABSTRACT

Wesselsbron virus (WSLV) is a neglected mosquito-borne virus within the yellow fever subgroup in the genus
Orthoflavivirus
of the
Flaviviridae
family. Despite being primarily a veterinary pathogen able to cause stillbirths, congenital malformations, and mortality in ruminants, WSLV also infects humans, causing a usually self-limiting febrile illness, or may lead to neurological complications in rare cases. WSLV causes sporadic outbreaks in Southern Africa, but findings in mosquitoes from other African countries suggest a wider distribution. Here, we report the detection and isolation of WSLV from an
Aedes mcintoshi
mosquito collected in a pristine ecosystem within Semuliki National Park, western Uganda. The detected strain M5937-UG-2018 was impaired in infectivity, replication, and production of infectious particles in cell lines derived from different hosts compared to an epidemic reference strain, SA H177. Full-genome sequencing by next-generation sequencing from the mosquito homogenate revealed a maximum nucleotide identity of 98.1% to a WSLV isolate from a human sample collected in South Africa in 1996. M5937-UG-2018 grouped in phylogenetic analyses with strains from South Africa and Senegal. Reconstruction of the temporal and spatial dispersal of WSLV across Africa estimated a likely origin of WSLV in South Africa in the early 19th century and spread in Southern Africa in the following decades. Long-distance movement toward Western and Eastern Africa was modeled to have occurred in the early 21st century. However, displacing the origin of M5937-UG-2018 did not decrease the likelihood of the model supporting the hypothesis that WSLV is widely distributed in Africa.

IMPORTANCE

WSLV is a neglected mosquito-borne virus causing teratogenicity in ruminants and febrile illness in humans. WSLV is mainly endemic to Southern Africa, but findings in other regions suggest a wider distribution on the continent. Knowledge of the distribution of WSLV is impaired as differential diagnostics are rarely performed in livestock and humans presenting with symptoms compatible with WSLV infection. Our work investigating viral infections in mosquitoes from a remote tropical rainforest region demonstrates that WSLV is endemic in Uganda. The isolated virus was less infective and showed lower replication ability
in vitro
compared to an epidemic isolate from South Africa. Phylogeographic reconstruction of spatial and temporal movements, along with the displacement of the origin of the newly detected strain
,
suggests that WSLV may be widely distributed across Africa. Our data show that the geographic distribution of WSLV and its impact on human and animal health are likely underestimated.
The PdxR-PdxKU locus involved in vitamin B
6
salvage is important for group A streptococcal resistance to neutrophil killing and survival in human blood
Authors: Davis Sarah E. , Hart Meaghan T. , Braza Rezia Era D. , Perry Aolani A. , Vega Luis A. , Le Breton Yoann S. , McIver Kevin S. 
Published: November 2024

ABSTRACT

Streptococcus pyogenes
(Group A
Streptococcus
, GAS) is a Gram-positive bacterium that inflicts both superficial and life-threatening diseases on its human host. Analysis of fitness using a transposon mutant library revealed that genes predicted to be involved in vitamin B
6
acquisition are associated with fitness in whole human blood. Vitamin B
6
is essential for all life and is important for many cellular functions. In several streptococcal species, it has been shown that mutants in B
6
acquisition exhibited reduced virulence phenotypes and were attenuated during infection. In GAS, B
6
acquisition is believed to be controlled by the
pdxR-pdxKU
locus, where PdxR is a positive regulator of
pdxKU
, which encodes for a B
6
-substrate kinase and permease, respectively. Mutants in the regulator (Δ
pdxR
) and salvage machinery (Δ
pdxKU
) both exhibited modest growth defects when grown in oxygenated conditions with limited vitamin B
6
precursors. ∆
pdxR
and ∆
pdxKU
mutants also exhibited an impaired ability to survive when challenged with whole human or mouse blood. This defect was characterized by reduced survival in the presence of human neutrophil-like HL60s, primary polymorphonuclear leukocytes, and antimicrobial peptide LL-37. Promoter analysis showed that PdxR is an autoregulator and activated
pdxKU
in the absence of B
6
. Interestingly, ∆
pdxR
and ∆
pdxKU
mutants were not attenuated in mouse models of infection, suggesting a species-specific impact on virulence. Overall, it appears that
pdxR-pdxKU
is associated with GAS vitamin B
6
metabolism as well as pathogen survival during encounters with the human innate immune system.

IMPORTANCE

Bacterial pathogens such as
Streptococcus pyogenes
(Group A
Streptococcus
, GAS) must be able to obtain needed nutrients in their human host. Vitamin B
6
or pyridoxal 5’ phosphate is essential for all life and is important for many cellular functions. In other streptococcal pathogens, B
6
acquisition has been shown to be important for their ability to cause disease. Here, we show that loss of the putative vitamin B
6
salvage pathway locus
pdxR-pdxKU
affects GAS pathogenesis when encountering innate immune responses from phagocytic neutrophils and antimicrobial peptides within the host.
pdxR-
pdxKU may contribute to oxygen tolerance through B
6
; however, there appear to be other mechanisms for salvaging vitamin B
6
. Overall,
pdxR-pdxKU
is associated with GAS resistance to the human innate immune response and oxygen tolerance and contributes modestly to B
6
metabolism.
Macronutrient concentrations in human milk beyond the first half year of lactation: a cohort study
Authors: Muts Jacqueline , Lukowski Juliette I A , Twisk Jos W R , Schoonderwoerd Anne , van Goudoever Johannes B , van Keulen Britt J , Van Den Akker Chris H P 
Published: November 2024

ObjectiveHuman milk composition is dynamic. While extensive research has focused on its macronutrient concentrations during the first 6 months of lactation, limited research exists for extended lactation periods. This study aims to examine the nutritional composition of human milk during these longer lactation phases.DesignA retrospective longitudinal cohort study performed within the National Dutch Human Milk Bank.ParticipantsWe selected donors who had provided milk donations at least once after the 6-month postpartum mark.Main outcome measuresThe Miris Human Milk Analyser was used to analyse macronutrient concentrations in the milk samples. Linear mixed models were used for longitudinal analysis of these concentrations, factoring in time variables established for six sequential lactation periods.ResultsWe analysed 820 milk samples from 86 women, collected between 5 weeks and 28 months postpartum. Initially, milk protein concentrations dropped over the first 8 months of lactation (diff = −0.19 g/dL, p<0.001) and stabilised between 8 and 18 months before increasing again by 0.21 (95% CI 0.06–0.21) g/dL. Carbohydrate concentrations remained steady throughout the study period. Fat concentrations were stable for the first 8 months but saw an increase afterwards. Post 18 months, the fat content saw a rise of 1.90 (95% CI 1.59–2.21) g/dL. The caloric density mirrored the pattern of the fat concentrations.ConclusionThe nutritional content of human milk does not decrease after 6 months of lactation. Therefore, human milk banks may accept donations from mothers up to 2 years post-birth.
(Intravascular) papillary endothelial hyperplasia or Masson’s tumour of the axilla in a patient with a history of breast cancer
Authors: Van Houdt Maxime , Fidlers Tom , Neven Patrick , Han Sileny 
Published: November 2024

Intravascular papillary endothelial hyperplasia, or Masson’s tumour, is a benign lesion of the subcutaneous tissue and skin, characterised by a reactive proliferation of endothelial cells within a vessel. Although this pathology can occur at various sites, it is generally rare. Differential diagnosis with other benign lesions or malignancies can be challenging, and since its circumscribed nature is impossible to recognise with a biopsy, excision is frequently required.We present the case of a female patient with a history of bilateral breast cancer, treated with surgery, chemotherapy and radiotherapy, who developed a slowly growing, large bulging mass in the right axilla. Biopsies were benign, and the positron emission tomography–CT showed no hypermetabolism of the mass. However, due to the debilitating bleeding from the fragile mass and uncertainty about its biological behaviour, excision was performed. Pathological examination revealed an intravascular lesion with a central thrombus, characteristic of intravascular papillary endothelial hyperplasia.
Identifying important and feasible primary care structures and processes in the US healthcare system: a modified Delphi study
Authors: Albert Stephanie L , Kwok Lorraine , Shelley Donna R , Paul Maggie M , Blecker Saul B , Nguyen Ann M , Harel Daphna , Cleland Charles M , Weiner Bryan J , Cohen Deborah J , Damschroder Laura , Berry Carolyn A 
Published: November 2024

ObjectiveTo identify primary care structures and processes that have the highest and lowest impact on chronic disease management and screening and prevention outcomes as well as to assess the feasibility of implementing these structures and processes into practice.DesignA two-round Delphi study was conducted to establish consensus on the impact and feasibility of 258 primary care structures and processes.Participants29 primary care providers, health system leaders and health services researchers in the USA.OutcomesPrimary outcomes were (1) consensus on the impact of each structure and process on chronic disease management and screening and prevention outcomes, separately and (2) consensus on feasibility of implementation by primary care practices.ResultsConsensus on high impact and feasibility of implementation was reached on four items for chronic disease management: ‘Providers use motivational interviewing to help patients set goals’, ‘Practice has designated staff to manage patient panel’, ‘Practice has onsite providers or staff that speak the most dominant, non-English language spoken by patients’ and ‘Practice includes mental health providers and/or behavioural health specialists in care team’ and seven items for screening and prevention: ‘Practice utilizes standing protocols and orders’, ‘Practice generates reports to alert clinicians to missed targets and to identify gaps in care, such as overdue visits, needed vaccinations, screenings or other preventive services’, ‘Practice has designated staff to manage patient panel’, ‘Practice sets performance goals and uses benchmarking to track quality of care’, ‘Practice uses performance feedback to identify practice-specific areas of improvement’, ‘Practice builds quality improvement activities into practice operations’ and ‘Pre-visit planning data are reviewed during daily huddles’. Only ‘Practice has designated staff to manage patient panel’ appeared on both lists.ConclusionFindings suggest that practices need to focus on implementing mostly distinct, rather than common, structures and processes to optimise chronic disease and preventive care.
Pilot study protocol evaluating the impact of telerobotics interactions with autistic children during a Denver intervention on communication skills using single-case experimental design
Authors: Fournier Carole , Michelon Cécile , Granit Véronique , Audoyer Paul , Bernardot Arielle , Picot Marie-Christine , Kheddar Abderrahmane , Baghdadli Amaria 
Published: November 2024

IntroductionFor several years, studies have been conducted on the contribution of social robots as an intervention tool for children with autism spectrum disorder (ASD). One of the early intervention models recommended by the French National Authority for Health is the Early Start Denver Model, an individualised, intensive programme based on play activities chosen by the child. While studies published in recent years suggest that robots provide benefits for autistic children in learning social interactions within a clinical setting, there is no scientific consensus on the widespread contribution and maintenance of their effects over time. On the other hand, a robotic solution controlled directly by a practitioner (ie, on-site telepresence system) enables greater adaptability to children’s responses and choices during interventions. We believe that such a solution would enable better assessment of progress in the fundamental skills of expressive communication and imitation as well as greater engagement during interventions.Methods and analysisThis is a prospective, monocentric, descriptive and evaluative pilot study based on single-case experimental design (SCED) methodology. The study will recruit eight children diagnosed with ASD aged between 2 and 5 years. The intervention will take place 15 min after the usual weekly care. The SCED methodology is constructed in three stages: (A) 4 weekly sessions at baseline without the robot, (B) 9 weekly sessions with intervention modification using a social robot as cotherapist and (C) 4 weekly sessions without the robot for follow-up.Ethics and disseminationEthical approval was obtained from the South East IV Ethics Committee (CPP Sud-Est IV) (number: 2023-A00895-40) in France. Explicit consent is required from all legal representatives (parents) of children participating in this study. We aim to disseminate the results of this study through national and international conferences, international peer-reviewed journals and social media.Trial registration numberNCT05991791.
Combination of body mass index and body fat percentage in middle and late pregnancy to predict pregnancy outcomes in patients with gestational diabetes in Wenzhou, China: a single-centre retrospective cohort study
Authors: Chen Bingru , Chen Lanxi , Zhao Xiner , You Tao , Zheng Zhi , Chen Yilin , Zhu Shuoru 
Published: November 2024

ObjectivesThe present study aimed to evaluate whether body mass index (BMI) and body fat percentage (BFP) could be used to predict pregnancy outcomes in patients with gestational diabetes mellitus (GDM).DesignRetrospective cohort study.SettingWenzhou Medical University Affiliated Second Hospital (Zhejiang Province, China). Clinical data were collected from electronic medical records.ParticipantsData from 683 patients with GDM admitted to the Wenzhou Medical University Affiliated Second Hospital between January 2019 and December 2021 were retrospectively analysed.Outcome measuresPregnancy outcomes.ResultsThe results showed that pregnant women with BFP ≥33% were more prone to abnormal amniotic fluid volume, abnormal blood pressure and anaemia (p<0.05). Additionally, these patients were more likely to experience postpartum haemorrhage and macrosomia, as well as risk factors associated with caesarean section at labour (p<0.05). BMI exhibited a strong predictive value for abnormal blood pressure (OR 1.170; 95% CI 1.090 to 1.275), anaemia (OR 1.073; 95% CI 1.016 to 1.134), caesarean section (OR 1.150; 95% CI 1.096 to 1.208) and macrosomia (OR 1.169; 95% CI 1.063 to 1.285). Additionally, classified BFP had a predictive value for abnormal amniotic fluid volume (OR 3.196; 95% CI 1.294 to 7.894), abnormal blood pressure (OR 2.321; 95% CI 1.186 to 4.545), anaemia (OR 1.817; 95% CI 1.216 to 2.714), and caesarean section (OR 1.734; 95% CI 1.270 to 2.367).ConclusionsThe results suggest that patients with GDM with BFP ≥33% were more likely to experience unfavourable pregnancy outcomes, undergo caesarean section and develop macrosomia. The combination of BMI with classified BFP could better predict abnormal blood pressure and caesarean section in patients with GDM during the middle and late stages of pregnancy.