bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction treatments with and without addition of one dose anthracycline to all-trans retinoid acid and arsenic in pediatric non-high-risk acute promyelocytic leukemia: study protocol for a randomized controlled trial
Authors: Fan Zhong , Huang Xiu-Ya , Huang Dan-Ping , Luo Jie-Si , Su Jia-Yin , Zhang Xiao-Li , Li Yu , Wang Li-Na , Liang Cong , Luo Xue-Qun , Huang Li-Bin , Tang Yan-Lai 
Published: December 2024

Abstract
Background
The treatment of all-trans retinoic acid (ATRA) and arsenical agent has revolutionarily improved the prognosis of acute promyelocytic leukemia (APL) both in adults and children. Nevertheless, coagulation disorder and differentiation syndrome (DS) are the main causes of early death in APL patients. Early chemotherapy to reduce leukocytes during induction is an important measure to reduce complications and mortality. However, the incidence of hyperleukocytosis (WBC > 10 × 109/L) was significantly higher in pediatric patients without chemotherapy than in adults. Although ATRA plus arsenic is the standard therapy for non-high-risk adult patients, it remains controversial whether chemotherapy is necessary for induction therapy in pediatric APL.

Methods
This study was designed as a multicenter randomized controlled trial. Children with APL were randomly assigned into experimental group (ATRA-RIF plus chemotherapy) and control group (ATRA-RIF). The experimental group was treated with ATRA-RIF plus chemotherapy for induction, while the control group was treated with ATRA-RIF alone. In addition, both groups received the same regimen of ATRA-RIF plus chemotherapy for consolidation and maintenance.

Discussion
This trial aims to compare the efficacy of ATRA-RIF plus chemotherapy versus ATRA-RIF in pediatric non-high-risk patients with APL to demonstrate that chemotherapy during induction therapy can reduce the incidence of complications such as hyperleukocytosis and DS, thereby reducing mortality.

Trial registration
Chinese Clinical Trials Registry, ID: ChiCTR2000038877. Registered on October 8, 2020, https://www.chictr.org.cn/showproj.html?proj=60733. V1.0 date 08/01/2020.
Immune modulation of buffalo peripheral blood mononuclear cells by two asparaginyl endopeptidases from Fasciola gigantica
Authors: Wu Dong-Qi , Guo Yan-Feng , Zou Yu , Tang Xiao-Ting , Zhang Wei-Yu , Di Wen-Da 
Published: December 2024

Abstract
Background
Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica, which poses a serious threat to global public health and livestock farming. Fasciola gigantica secretes and excretes various components to manipulate the immune response, thereby enhancing its invasion, migration, and survival in vivo. However, the roles of specific components in immune modulation, such as asparagine endopeptidase, remain unknown.

Methods
The transcriptional abundance of members of the asparagine endopeptidase family (also known as the legumain family) from F. gigantica was analyzed. Two highly transcribed asparagine endopeptidases in metacercariae, juveniles and adults were cloned, and their recombinant proteins—recombinant F. gigantica legumain (rFgLGMN-1) and (rFgLGMN-2)—were expressed in prokaryotic expression system. Their regulatory effects on buffalo peripheral blood mononuclear cells (PBMCs), including proliferation, migration, total nitric oxide (NO) production, cytokine secretion, and phagocytosis were explored in vitro.

Results
Ten members of the legumain family were detected in F. gigantica, among of which FgLGMN-1 and FgLGMN-2 exhibited high transcription levels in juveniles and adults. The isolation of sequences indicated that FgLGMN-1 encodes 409 amino acids, while FgLGMN-2 encodes 403 amino acids. Both recombinant FgLGMN-1 (rFgLGMN-1) and rFgLGMN-2 were recognized by serum from buffaloes infected with F. gigantica. Both rFgLGMN-1 and rFgLGMN-2 inhibited the proliferation of PBMCs, and rFgLGMN-1 also inhibited the migration of PBMCs. While rFgLGMN-1 increased the production of total NO, rFgLGMN-2 decreased NO production. Both rFgLGMN-1 and rFgLGMN-2 increased the transcription of the cytokines interleukin-10 and transforming growth factor β. The effect of rFgLGMN-1 and rFgLGMN-2 on the phagocytosis of PBMCs varied depending on their concentrations.

Conclusions
rFgLGMN-1 and rFgLGMN-2 modulate several cellular and immunological functions of PBMCs, and exhibited distinct regulatory effects on these in vitro, which indicated that they may play roles in immune modulation and facilitate fluke development. However, due to uncertainties associated with in vitro experiments, further studies are necessary to elucidate the precise functions of these legumains.

Graphical Abstract
Preventive efficacy of six monthly doses of NexGard® PLUS or Simparica Trio® against a macrocyclic lactone-resistant isolate (JYD-34) of Dirofilaria immitis and of a single dose of NexGard PLUS against a susceptible isolate
Authors: Prullage Joseph , Frost Justin , DiCosty Utami , Martin Elizabeth , Dumont Pascal , Yoon Stephen , Süssenberger Ricarda 
Published: December 2024

Abstract
Background
Two studies were conducted assessing the efficacy of NexGard® PLUS (NP) in preventing heartworm disease. Study 1 evaluated the efficacy of six monthly doses of NP or Simparica Trio® (ST) against a macrocyclic lactone-resistant isolate of heartworm, Dirofilaria immitis, and study 2 evaluated the efficacy of a single dose of NP against a susceptible isolate.

Methods
In two studies, dogs that were negative for heartworms by antigen test and modified Knott’s test were used. In study 1, dogs were randomly allocated into three treatment groups (n = 6/group): negative control, NP per label instructions, and ST per label instructions. Dogs were inoculated with 50 third-stage D. immitis larvae (JYD-34 isolate) on day −30. NP and ST were administered orally on days 0, 30, 60, 90, 120, and 150. A necropsy was performed on day 180 for adult heartworm recovery. In study 2, dogs were randomly allocated into two treatment groups (n = 10/group): negative control and NP. Dogs were inoculated with 50 third-stage larvae (SC-20 isolate) on day −30. NP was administered orally once on day 0 to target the minimum moxidectin label dose. A necropsy was performed on day 120 for adult heartworm recovery.

Results
For study 1, all control dogs had adult heartworms at necropsy (geometric mean, 39.7; range, 28–48). Two of the NP-treated dogs had one live worm, and one of the ST-treated dogs had one live worm. Both treated groups were significantly different from the control group with an efficacy of 99.5% for NP and 99.8% for ST (P < 0.0001). There was no significant difference (P = 0.8797) between the groups treated with NP and ST. For study 2, all control dogs had adult heartworms (geometric mean, 34.5; range 26–43). None of the dogs treated with NP had live adult worms (efficacy of 100%, P < 0.0001).

Conclusions
The results of study 1 demonstrated that NexGard® PLUS and Simparica Trio® administered at the label dose provided comparable efficacy against a macrocyclic lactone-resistant isolate of D. immitis. The results of study 2 demonstrated that NexGard® PLUS administered once near the minimum label dose was 100% effective against a susceptible isolate.

Graphical Abstract
Epigenetic regulation on left atrial function and disease recurrence after catheter ablation in atrial fibrillation
Authors: Han Mi-Ryung , Jeong Joo Hee , Kim Yun Gi , Yang Hyun-Ho , Seo Chang-Ok , Kim Yeji , Lee Hyoung Seok , Shim Jaemin , Kim Young-Hoon , Choi Jong-Il 
Published: December 2024

Abstract
Background
Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). The influence of epigenetic modification on AF remains to be elucidated. We investigated the role of DNA methylation in the etiology of AF. Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples. The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage.

Results
The four most significantly methylated genes were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: AF patients with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines.

Conclusions
Epigenetic profiling revealed that epigenetic modification might affect important characteristics of AF. Our results suggest that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation.
Identification of Brucella RS15060 as a novel type IV secretion system effector associated with bacterial virulence
Authors: Yin Yi , Tian Mingxing , Zhang Guangdong , Hu Hai , Ding Chan , Yu Shengqing 
Published: December 2024

AbstractBrucella is an intracellular parasitic pathogen that causes the worldwide zoonotic disease brucellosis. The type IV secretion system (T4SS) is utilized to secrete various effectors to help Brucella form Brucella-containing vacuoles within the cell and accomplish intracellular trafficking and replication. Brucella has fewer recognized effector proteins than other intracellular parasites in the Proteobacteria, indicating that Brucella may contain a large number of unidentified effector proteins. In this study, the optimal conditions for inducing protein secretion from Brucella were screened, and the secreted proteins of 2308 and the T4SS-deficient mutant SV123 under optimal conditions were collected for comparative proteomics analysis. By label-free quantitative proteomics, we identified 15 differential proteins. Through the β-lactamase TEM1 assay and indirect immunofluorescence assay, we identified RS15060 and RS10635 as novel T4SS effectors. Furthermore, by constructing mutation strains and performing cell/mouse infection experiments, we found that deletion of the rs15060 gene reduced the capacity of Brucella to replicate in cells and cause chronic infection in mice. In conclusion, a novel Brucella T4SS effector protein, RS15060, was identified to be associated with virulence in this study, and the discovery of effector proteins is conducive to a more comprehensive elucidation of T4SS function as well as to uncovering the cryptic strategies of Brucella survival in cells.
Insights into genetic determinants of piglet survival during a PRRSV outbreak
Authors: Tarrés Joaquim , Jové-Juncà Teodor , Hernández-Banqué Carles , González-Rodríguez Olga , Ganges Llilianne , Gol Sofia , Díaz Marta , Reixach Josep , Pena Ramona N. , Quintanilla Raquel , Ballester Maria 
Published: December 2024

AbstractBreeding animals to produce more robust and disease-resistant pig populations becomes a complementary strategy to the more conventional methods of biosecurity and vaccination. The objective of this study was to explore the ability of a panel of genetic markers and immunity parameters to predict the survival rates during a natural PRRSV outbreak. Ten-week-old female Duroc pigs (n = 129), obtained from 61 sows and 20 boars, were naturally infected with a highly pathogenic PRRSV genotype 1 strain. Prior to infection, piglets were screened for immunity parameters (IgG levels in plasma and SOX13 mRNA expression in blood) and genetic markers previously associated to PRRSV immune response and immunity traits. Additionally, the 20 boars were genotyped with a panel of 132 single nucleotide polymorphisms (SNPs). Survival analysis showed that mortality was significantly higher for animals with low basal IgG levels in plasma and/or high SOX13 mRNA expression in blood. The genotypes of sires for SNPs associated with IgG plasma levels, CRP in serum, percentage of γδ T cells, lymphocyte phagocytic capacity, total number of lymphocytes and leukocytes, and MCV and MCH were significantly associated with the number of surviving offspring. Furthermore, CD163 and GBP5 markers were also associated to piglet survival. The effects of these SNPs were polygenic and cumulative, survival decreased from 94 to 21% as more susceptible alleles were accumulated for the different markers. Our results confirmed the existence of genetic variability in survival after PRRSV infection and provided a set of genetic markers and immunity traits associated with PRRS resistance.
Revealing novel and conservative CD8+T-cell epitopes with MHC B2 restriction on ALV-J
Authors: Li Xueqing , Li Ziwei , Ma Mulin , Yang Na , Du Shanyao , Liao Ming , Dai Manman 
Published: December 2024

AbstractMHC B2 haplotype chickens have been reported to induce strong immune response against various avian pathogens. However, little is known about the CD8+T-cell epitope with MHC B2-restricted on subgroup J avian leukosis virus (ALV-J). In this study, we explored the ALV-J-induced cellular immune response in B2 haplotype chickens in vivo. We found that ALV-J infection significantly increased the proportion of CD8+T cells in chickens and up-regulated the expression of cytotoxic genes like Granzyme A and antiviral genes like IFIT5 at 14 days post-infection (dpi). We selected 32 candidate peptides based on the peptide-binding motif and further identified three MHC B2-restricted CD8+T epitopes on ALV-J, including Pol652−660, Gag374−382, and Gag403−411 which induced significant levels of chicken IFN-γ production in splenocytes from ALV-J infected chickens using the ELISpot assay. In addition, we also verified that the three identified epitopes stimulated memory splenocytes elevating TNF-α and IL-2 protein expression. Importantly, we found that the three positive peptides were highly conserved among ALV-A, ALV-B, ALV-E, ALV-J, and ALV-K. Taken together, we identified three MHC B2-restricted CD8+T cell epitopes on ALV-J, providing a foundation for developing effective T cell epitope vaccines targeting conserved internal viral proteins.
The predominant role of FliC contributes to the flagella-related pathogenicity of ST34 S. Typhimurium monophasic variant
Authors: Hong Yaming , Hou Qilong , Liu Hui , Wang Xiaojie , Gu Jiaojie , Wang Zhenyu , Jiao Xinan , Li Qiuchun 
Published: December 2024

AbstractOver the past two decades, the monophasic variant of Salmonella enterica serovar Typhimurium (S. Typhimurium) has rapidly emerged and increased worldwide. This upsurge is especially true for the European clone of the ST34 S. Typhimurium monophasic variant. The key distinction between ST34 S. Typhimurium and its monophasic variant is that the genes that encode for second-phase flagellin (FljB) and the regions around it have been replaced with various multidrug resistance cassettes. To determine if the loss of fljB or the retention of fliC,-the gene coding for first-phase flagellin (FliC)-, would impact its pathogenicity, we constructed various mutations, including deletions of fljB, fliC, fliC/fljB, and strains where fliC was replaced with fljB. Our results showed that the loss of fljB in ST34 S. Typhimurium and its monophasic variant does not affect bacterial motility, cell infection ability, survival in macrophages, induced pro-inflammatory cytokines secretion, virulence, or persistent infection in mice. However, the deletion of fliC caused a significant decrease in these outcomes for both strains, while the replacement of fliC with fljB only partially restored these capabilities. Consequently, we determined that FliC is predominant in the flagellar expression of ST34 S. Typhimurium other than FljB. This finding demonstrates that replacing the fljB gene with various resistance regions in ST34 S. Typhimurium monophasic variants can enhance bacterial survival under specific antibiotic farming practices and spread globally.
Leveraging Lactobacillus plantarum probiotics to mitigate diarrhea and Salmonella infections in broiler chickens
Authors: Mirsalami Seyed Mehrdad , Mirsalami Mahsa 
Published: December 2024

AbstractAnaerobic bacteria, such as Lactobacillus plantarum (LP), are known to play a significant role in maintaining gut health and protecting against enteric pathogens in animals. The present study aimed to develop a safe, affordable, and eco-friendly method for producing LP-based probiotics and evaluate their efficacy in mitigating Salmonella-induced diarrhea in broiler chickens. The study employed three different culture media (MRS, TSB, and Baird Parker) to grow LP, which was then dried using a spray-drying technique to produce a stable probiotic formulation. When administered to broiler chickens, the LP probiotic derived from the MRS medium significantly improved body weight gain (4.147-fold increase over 4 weeks) compared to the other two culture conditions. Importantly, the LP probiotic treatment could substantially reduce the diarrhea index in broilers, with up to an 86.45% improvement in Salmonella-induced enteric infections. The beneficial effects were attributed to the ability of LP to modulate the gut microbiome, enhance the integrity of the intestinal mucosa, and mitigate the pathogenic effects of Salmonella. These findings demonstrate the potential of anaerobic Lactobacillus plantarum as a safe and effective probiotic intervention for controlling enteric diseases and improving production outcomes in poultry farming. The developed method provides a sustainable approach to harness the beneficial properties of this anaerobic bacterium for animal health and welfare.
Graphical abstract
Gender-based opportunity structure in the energy sector: a literature review on women’s networking and mentoring
Authors: Lazoroska Daniela , Palm Jenny , Kojonsaari Anna-Riikka 
Published: December 2024

Abstract
Background
While the energy system is recognized as the largest contributor to climate disruption, the bulk of the sustainability-oriented interventions are made through technologies rather than employment equity and social justice issues. Emergent research points to the critical role of increasing the number of women and other minoritized groups in the energy sector, which could have a cultural, economic, and environmental impact. Nevertheless, how inclusion and diversity in the sector are to be achieved is not clear.

Main text
This article is a result of a structured literature review of earlier research focusing on gender in professional networks and mentoring programs within the energy sector. Professional networks and mentoring have been identified as some of the tools employed for increasing gender diversity in the sector. We seek to understand how gender has been integrated, what the main barriers and enablers for women are, and what strategies organizations have applied to achieve gender balance so that men and women face equal opportunities to partake in and influence decisions concerning the energy system.

Conclusion
We found that women’s exclusion is not recognized as a problem that needs to be acknowledged, monitored, or addressed by the energy sector or policymakers. Professional mentoring and networking have largely been employed to fill the career advancement and diversity gaps left untackled by the energy sector or policymakers. Opportunities for women to be meaningfully included in energy systems decision-making are still limited and fragmented. Furthermore, this lack of recognition is mirrored in energy research. We identified a concerning lack of evidence-based findings on the topic of women’s networking and mentoring in the energy sector. We thus call for in-depth, qualitative, and critical examinations of how opportunities for women and other minoritized groups are generated on both the policy and practice level.
Innovations to the ECHO model to enhance reach and network-building among addiction clinicians in Western Canada
Authors: Robinson Samantha , Brohman Isabella , Draanen Jenna van , Kushner Rivka , Fairbairn Nadia , Glegg Stephanie 
Published: December 2024

Abstract
Background
Building capacity for evidence-based treatment and support for people with substance use disorders (SUD) is an urgent priority in the context of the toxic drug poisoning crisis. We implemented the first substance use-focused Project Extension for Community Healthcare Outcomes (ECHO) in Western Canada for health care providers, to enhance their clinical addiction skills and knowledge, facilitate practice change, and foster a supportive community of practice. The aims of this article are to describe our innovations to the Project ECHO model in British Columbia (BC) and Yukon, and present key program outcomes.

Methods
A pragmatic multi-methods program evaluation employed observational records of BC ECHO on Substance Use session attendance, cross-sectional and longitudinal participant surveys, and qualitative interviews with participants to assess satisfaction, relevance, and preparation to use evidence-based approaches, practice change intentions, and actual behaviours.

Results
The 52 ECHO sessions (from June 2019 to July 2022) attracted 2134 unique registrants with 5089 attendances (mean 124/session), 2132 newsletter subscribers, and 5842 podcast downloads. The evaluation included 844 post-session survey respondents and 53 interview participants. The program included ECHO sessions with rolling attendance; widely accessed supplemental formats (e.g., newsletter, podcast, clinical tools, archived presentation recordings); variable, regional hub representation; and evidence-based content developed by medical writers. These features contributed to broad geographic and discipline reach, high-quality program content, and high mean session satisfaction ratings (4.2/5). Key qualitative themes emerged, related to knowledge and skill acquisition, gaining confidence in providing SUD care, facilitating shared decision-making, increasing compassion for patients, consolidating learning and applying it to practice, and reducing isolation through expanded networks.

Conclusions
The ECHO model is an effective way to improve capacity in SUD care for physicians and nurse practitioners, while offering benefits for interprofessional attendees. Our findings can inform innovations in other ECHO programs to enhance reach, engagement, and impact.