bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for cranial cruciate ligament rupture in dogs participating in canine agility
Authors: Sellon Debra C. , Marcellin-Little Denis J. 
Published: January 2022

AbstractBackgroundCranial cruciate ligament rupture (CCLR) is one of the most common causes of pelvic limb lameness in dogs. Risk factors for CCLR include breed (especially large and giant breeds), body weight, gender and spay/neuter status, and age. Few studies have evaluated physical activity and fitness indicators, however, as risk factors for disease. This study used an online questionnaire distributed primarily via social media to assess risk factors for CCLR in dogs actively engaged in agility training or competition to determine demographic and physical activity factors associated with rupture.ResultsData from 260 dogs with CCLR were compared to similar data from 1006 dogs without CCLR. All dogs were actively training or competing in agility at the time of CCLR or the time of data submission, respectively. Physical characteristics associated with increased risk of CCLR included younger age, spayed female sex, greater body weight, and greater weight to height ratio. Agility activities associated with increased odds ratios included competition in events sponsored by the North American Dog Agility Council (NADAC), competing at novice and intermediate levels, and competing in fewer than 10 events/year. Odds ratios were lower in dogs that competed in events sponsored by United Kingdom Agility International (UKI). Other activities associated with increased odds ratio for CCLR included involvement in flyball activities and short walks or runs over hilly or flat terrain on a weekly basis. Activities associated with decreased odds ratio included involvement in dock diving, barn hunt, nosework, or lure coursing/racing activities and participation in core balance and strength exercises at least weekly.ConclusionsThese results are consistent with previous studies demonstrating that body weight and spay/neuter status are risk factors for CCLR in dogs. This is the first report to demonstrate that risk of CCLR in agility dogs is decreased in dogs that engage in regular core strengthening exercises, compete more frequently, compete at higher levels, and compete in more athletically challenging venues.
Analysis of genetic variants in myeloproliferative neoplasms using a 22-gene next-generation sequencing panel
Authors: Tan Jaymi , Chow Yock Ping , Zainul Abidin Norziha , Chang Kian Meng , Selvaratnam Veena , Tumian Nor Rafeah , Poh Yang Ming , Veerakumarasivam Abhi , Laffan Michael Arthur , Wong Chieh Lee 
Published: January 2022

Abstract
Background
The Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF), are a group of chronic clonal haematopoietic disorders that have the propensity to advance into bone marrow failure or acute myeloid leukaemia; often resulting in fatality. Although driver mutations have been identified in these MPNs, subtype-specific markers of the disease have yet to be discovered. Next-generation sequencing (NGS) technology can potentially improve the clinical management of MPNs by allowing for the simultaneous screening of many disease-associated genes.

Methods
The performance of a custom, in-house designed 22-gene NGS panel was technically validated using reference standards across two independent replicate runs. The panel was subsequently used to screen a total of 10 clinical MPN samples (ET n = 3, PV n = 3, PMF n = 4). The resulting NGS data was then analysed via a bioinformatics pipeline.

Results
The custom NGS panel had a detection limit of 1% variant allele frequency (VAF). A total of 20 unique variants with VAFs above 5% (4 of which were putatively novel variants with potential biological significance) and one pathogenic variant with a VAF of between 1 and 5% were identified across all of the clinical MPN samples. All single nucleotide variants with VAFs ≥ 15% were confirmed via Sanger sequencing.

Conclusions
The high fidelity of the NGS analysis and the identification of known and novel variants in this study cohort support its potential clinical utility in the management of MPNs. However, further optimisation is needed to avoid false negatives in regions with low sequencing coverage, especially for the detection of driver mutations in MPL.
Securin overexpression correlates with the activated Rb/E2F1 pathway and histone H3 epigenetic modifications in raw areca nut-induced carcinogenesis in mice
Authors: Boruah Nabamita , Singh Chongtham Sovachandra , Swargiary Pooja , Dkhar Hughbert , Chatterjee Anupam 
Published: January 2022

Abstract
Background
Raw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). An association of Securin/PTTG1 upregulation and gastric cancer in human was also demonstrated earlier. Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene.

Methods
Six groups of mice were used, and in the treated group, each mouse consumed 1 mg of RAN extract with lime per day ad libitum in the drinking water for 60 days, after which the dose was increased by 1 mg every 60 days. Histopathological evaluation of stomach tissues was performed and securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions.

Results
All mice developed gastric cancer with securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 lysine 4 and acetylation of H3 lysine 9 and 18 both globally and in the promoter region of the securin gene were observed by increasing the levels of lysine-N-methyltransferase 2A, lysine-acetyltransferase, EP-300 and PCAF after RAN treatment. ChIP-qPCR data revealed that the quantity of DNA fragments retrieved from the immunoprecipitated samples was maximum in the -83 to -192 region than further upstream and the downstream of the promoter for H3K4Me3, H3K9ac, H3K18ac and H3K9me3.

Conclusions
RAN-mediated pRb-inactivation induced securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region, which led to transcriptional activation and subsequent development of chromosomal instability. Therefore, present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, securin overexpression and subsequent elevation of chromosomal instability is probably byproducts of inactivation of the pRb pathway.
The Prognostic value of the Fibrinogen to pre-albumin ratio in malignant tumors of the digestive system: a systematic review and meta-analysis
Authors: Li Baibei , Deng Huachu , Zhou Ziyan , Tang Bo 
Published: January 2022

AbstractBackgroundIn recent years, the Fibrinogen to pre-albumin ratio (FPR) has been reported in many studies to be significantly associated with the prognosis of various cancers. This systematic review and meta-analysis aimed to investigate the prognostic value of FPR in malignant tumors of the digestive system based on available evidence.MethodsThe relevant articles published before July 1, 2021, were systematically retrieved from electronic databases to evaluate the effect of Fibrinogen to pre-albumin ratio (FPR) on the prognosis of patients with malignant digestive system tumors and calculate the hazard ratio (HR) and the corresponding 95% confidence interval (CI).ResultThirteen articles, all from China, including 15 cohort studies and a total of 5116 cases, were included in this study. A high FPR was associated with poor overall survival (HR = 1.88, 95%CI 1.53–2.32, P < 0.001), recurrence-free survival (HR = 2.29, 95%CI 1.91–2.76, P < 0.001), progression-free survival (HR = 1.96, 95%CI: 1.33–2.90, P = 0.001), complications (HR = 1.78, 95%CI: 1.06–3.00, P = 0.029), disease-free survival (HR = 1.46, 95%CI: 1.08–1.97, P = 0.013) was significantly associated with cancer-specific survival (HR = 1.44, 95%CI: 1.15–1.79, P = 0.001). Even though intergroup differences were present, FPR was strongly associated with overall and relapse-free survival, and sensitivity analysis suggested that our results were stable.ConclusionFPR can be used as a valuable indicator to predict the prognosis of patients with malignant digestive system tumors.
SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma
Authors: Zhang Xin , Zhang Hongwei , Liao Zhibin , Zhang Jiacheng , Liang Huifang , Wang Weixing , Yu Jia , Dong Keshuai 
Published: January 2022

Abstract
Background
The Src homology and collagen 4 (SHC4) is an important intracellular adaptor protein that has been shown to play a pro-cancer role in melanoma and glioma. However, the biological function and detailed mechanisms of SHC4 in hepatocellular carcinoma progression are unclear. This study aimed to evaluate the potential prognostic and treatment value of SHC4 in patients with HCC.

Methods
The expression status of SHC4 in HCC tissues were investigated by immunohistochemistry and western blotting. Clinical significance of SHC4 was evaluated in a large cohort of HCC patients. The effects of SHC4 repression or overexpression on migration, invasion, and tumor growth were detected by colony formation assay, wound healing, transwell assays, and xenograft assay. Cell cycle and EMT-related proteins were detected by western blotting and immunofluorescence. In addition, the molecular regulation between SHC4 and STAT3 signaling in HCC were discovered by western blotting, immunofluorescence and xenograft assay.

Results
SHC4 was overexpressed in HCC compared to adjacent normal liver tissues and increased SHC4 expression was associated with high AFP level, incomplete tumor encapsulation, poor tumor differentiation and poor prognosis. SHC4 was shown to enhance cell proliferation, colony formation, cells migration and invasion in vitro, and promotes cell cycle progression and EMT process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of SHC4 in tumorigenicity in nude mice. Moreover, activation of STAT3 signaling was found in the SHC4 overexpressed HCC cells and HCC tissues. Further intervention of STAT3 confirmed STAT3 as an important signaling pathway for the oncogenic role of SHC4 in HCC.

Conclusions
Together, our results reveal that SHC4 activates STAT3 signaling to promote HCC progression, which may provide new clinical ideas for the treatment of HCC.
MiR-937-3p promotes metastasis and angiogenesis and is activated by MYC in lung adenocarcinoma
Authors: Ma Zijian , Chen Ganyi , Chen Yiqian , Guo Zizhang , Chai Hao , Tang Yu , Zheng Lin , Wei Ke , Pan Chunfeng , Ma Zhifei , Xia Yang , Zhang Aiping 
Published: January 2022

Abstract
Background
Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear.

Methods
miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA.

Result
In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3′-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region.

Conclusions
Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.
hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway
Authors: Zhang Wei , Wang Bo , Lin Yilin , Yang Yang , Zhang Zhen , Wang Quan , Zhang Haoran , Jiang Kewei , Ye Yingjiang , Wang Shan , Shen Zhanlong 
Published: January 2022

Abstract
Background
Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. In this study, we explored the role of hsa_circ_0000231 and its downstream pathway in CRC.

Methods
The expression profile of circRNAs in 5 pairs of CRC tissues and adjacent normal tissues were analyzed by Microarray. Quantitative real-time PCR and in situ hybridization and Base Scope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, functional experiments in vitro and in vivo were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and IGF2BP3 or has_miR-375.

Results
We acquired data through circRNA microarray profiles, showing that the expression of hsa_circ_0000231 was upregulated in CRC primary tissues compared to adjacent normal tissues, which was indicated poor prognosis of patients with CRC. Functional analysis indicated that inhibition of hsa_circ_0000231 in CRC cell lines could suppress CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation.

Conclusions
The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that hsa_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC.
Molecular identification and anti-malarial drug resistance profile of Plasmodium falciparum from patients attending Kisoro Hospital, southwestern Uganda
Authors: Manirakiza Godfrey , Kassaza Kennedy , Taremwa Ivan Mugisha , Bazira Joel , Byarugaba Fredrick 
Published: January 2022

Abstract
Background
The evolution of malaria infection has necessitated the development of highly sensitive diagnostic assays, as well as the use of dried blood spots (DBS) as a potential source of deoxyribonucleic acid (DNA) yield for polymerase chain reaction (PCR) assays. This study identified the different Plasmodium species in malaria-positive patients, and the anti-malarial drug resistance profile for Plasmodium falciparum using DBS samples collected from patients attending Kisoro Hospital in Kisoro district, Southwestern Uganda.

Methods
The blood samples were prospectively collected from patients diagnosed with malaria to make DBS, which were then used to extract DNA for real-time PCR and high-resolution melting (HRM) analysis. Plasmodium species were identified by comparing the control and test samples using HRM-PCR derivative curves. Plasmodium falciparum chloroquine (CQ) resistance transporter (pfcrt) and kelch13 to screen the samples for anti-malarial resistance markers. The HRM-PCR derivative curve was used to present a summary distribution of the different Plasmodium species as well as the anti-malarial drug profile.

Results
Of the 152 participants sampled, 98 (64.5%) were females. The average age of the participants was 34.9 years (range: 2 months–81 years). There were 134 samples that showed PCR amplification, confirming the species as Plasmodium. Plasmodium falciparum (N = 122), Plasmodium malariae (N = 6), Plasmodium ovale (N = 4), and Plasmodium vivax (N = 2) were the various Plasmodium species and their proportions. The results showed that 87 (71.3%) of the samples were sensitive strains/wild type (CVMNK), 4 (3.3%) were resistant haplotypes (SVMNT), and 31 (25.4%) were resistant haplotypes (CVIET). Kelch13 C580Y mutation was not detected.

Conclusion
The community served by Kisoro hospital has a high Plasmodium species burden, according to this study. Plasmodium falciparum was the dominant species, and it has shown that resistance to chloroquine is decreasing in the region. Based on this, molecular identification of Plasmodium species is critical for better clinical management. Besides, DBS is an appropriate medium for DNA preservation and storage for future epidemiological studies.
Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy
Authors: Zhang Chi , Zhang Wei , Zhu Dashuai , Li Zhenhua , Wang Zhenzhen , Li Junlang , Mei Xuan , Xu Wei , Cheng Ke , Zhong Biao 
Published: January 2022

Abstract
Background
Osteoporosis is a chronic condition affecting patients’ morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity.

Results
Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C–X–C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis.

Conclusions
In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats.

Graphical Abstract
Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection
Authors: Pi Jiang , Zhang Zhiyi , Yang Enzhuo , Chen Lingming , Zeng Lingchan , Chen Yiwei , Wang Richard , Huang Dan , Fan Shuhao , Lin Wensen , Shen Hongbo , Xu Jun-Fa , Zeng Gucheng , Shen Ling 
Published: January 2022

AbstractTuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)’s uptake and the following processing/presentation for better anti-TB protective immunity. Here, we engineered BCG protoplasts into nanoscale membraned BCG particles, termed as “BCG-Nanocage” to enhance the anti-TB vaccination efficiency and safety. BCG-Nanocage could readily be ingested/taken by APC macrophages selectively; BCG-Nanocage-ingested macrophages exhibited better viability and developed similar antimicrobial responses with BCG-infected macrophages. BCG-Nanocage, like live BCG bacilli, exhibited the robust capability to activate and expand innate-like T effector cell populations of Vγ2+ T, CD4+ T and CD8+ T cells of rhesus macaques in the ex vivo PBMC culture. BCG-Nanocage immunization of rhesus macaques elicited similar or stronger memory-like immune responses of Vγ2Vδ2 T cells, as well as Vγ2Vδ2 T and CD4+/CD8+ T effectors compared to live BCG vaccination. BCG-Nanocage- immunized macaques developed rapidly-sustained pulmonary responses of Vγ2Vδ2 T cells upon Mtb challenge. Furthermore, BCG- and BCG-Nanocage- immunized macaques, but not saline controls, exhibited undetectable Mtb infection loads or TB lesions in the Mtb-challenged lung lobe and hilar lymph node at endpoint after challenge. Thus, the current study well justifies a large pre-clinical investigation to assess BCG-Nanocage for safe and efficacious anti-TB vaccination, which is expected to further develop novel vaccines or adjuvants.
Graphical Abstract
Implementing healthy food environment policies in New Zealand: nine years of inaction
Authors: Mackay Sally , Gerritsen Sarah , Sing Fiona , Vandevijvere Stefanie , Swinburn Boyd 
Published: January 2022

Abstract
Background
The INFORMAS [International Network for Food and Obesity/Non-communicable Diseases (NCDs) Research, Monitoring and Action Support] Healthy Food Environment Policy Index (Food-EPI) was developed to evaluate the degree of implementation of widely recommended food environment policies by national governments against international best practice, and has been applied in New Zealand in 2014, 2017 and 2020. This paper outlines the 2020 Food-EPI process and compares policy implementation and recommendations with the 2014 and 2017 Food-EPI.

Methods
In March–April 2020, a national panel of over 50 public health experts participated in Food-EPI. Experts rated the extent of implementation of 47 “good practice” policy and infrastructure support indicators compared to international best practice, using an extensive evidence document verified by government officials. Experts then proposed and prioritized concrete actions needed to address the critical implementation gaps identified. Progress on policy implementation and recommendations made over the three Food-EPIs was compared.

Results
In 2020, 60% of the indicators were rated as having “low” or “very little, if any” implementation compared to international benchmarks: less progress than 2017 (47%) and similar to 2014 (61%). Of the nine priority actions proposed in 2014, there was only noticeable action on one (Health Star Ratings). The majority of actions were therefore proposed again in 2017 and 2020. In 2020 the proposed actions were broader, reflecting the need for multisectoral action to improve the food environment, and the need for a mandatory approach in all policy areas.

Conclusions
There has been little to no progress in the past three terms of government (9 years) on the implementation of policies and infrastructure support for healthy food environments, with implementation overall regressing between 2017 and 2020. The proposed actions in 2020 have reflected a growing movement to locate nutrition within the wider context of planetary health and with recognition of the social determinants of health and nutrition, resulting in recommendations that will require the involvement of many government entities to overcome the existing policy inertia. The increase in food insecurity due to COVID-19 lockdowns may provide the impetus to stimulate action on food polices.