bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular identification and functional characterization of IRF4 from common carp (Cyprinus carpio. L) in immune response: a negative regulator in the IFN and NF-κB signalling pathways
Authors: Zhu Yaoyao , Yang Guiwen 
Published: March 2022

Abstract
Background
The interferon (IFN) regulatory factors (IRFs) were originally identified as transcription factors playing critical roles in the regulation of IFN-related genes in the signal pathway. In mammals, IRF4 plays a vital role in both the innate and adaptive immune system. This study aims to reveal the molecular characterization, phylogenetic analysis, expression profiles and the regulatory role in the IFN and NF-κB signalling pathways of IRF4 in common carp (Cyprinus carpio. L) (abbreviation, ccIRF4).

Results
Here, ccIRF4 was identified and characterized, it contained a DNA binding domain (DBD) which possess five tryptophans and an IRF-associated domain (IAD). The predicted protein sequence of the ccIRF4 showed higher identities with grass carp (Ctenopharyngodon idella) and zebrafish (Danio rerio). Phylogenetic analysis suggested that ccIRF4 has the closest relationship with zebrafish IRF4. Quantitative real-time PCR analysis showed that ccIRF4 was constitutively expressed in all investigated tissues with the highest expression level in the gonad. Polyinosinic:polycytidylic acid (poly I:C) stimulation up-regulated the ccIRF4 expressions in the liver, spleen, head kidney, skin, foregut and hindgut. Upon Aeromonas hydrophila injection, the expression level of ccIRF4 was up-regulated in all tissues with the exception of spleen. In addition, ccIRF4 was induced by lipopolysaccharide (LPS), peptidoglycan (PGN) and Flagellin in head kidney leukocytes (HKLs). Overexpression of the ccIRF4 gene in epithelioma papulosum cyprini cells (EPC) down regulated the expressions of IFN-related genes and proinflammatory factors. Dual-luciferase reporter assay revealed that ccIRF4 decreased the activation of NF-κB through MyD88.

Conclusions
These results indicate that ccIRF4 participates in both antiviral and antibacterial immune response and negatively regulates the IFN and NF-κB response. Overall, our study on ccIRF4 provides more new insights into the innate immune system of common carp as well as a theoretical basis for investigating the pathogenesis and prevention of fish disease.
Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
Authors: Lei Shizhen , Zhang Yi 
Published: March 2022

Abstract
Purpose
Uveal melanoma (UM) is an aggressive intraocular malignancy, leading to systemic metastasis in half of the patients. However, the mechanism of the high metastatic rate remains unclear. This study aimed to identify key genes related to metastasis and construct a gene-based signature for better prognosis prediction of UM patients.

Methods
Weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression of genes primarily associated with metastasis of UM. Univariate, Lasso-penalized and multivariate Cox regression analyses were performed to establish a prognostic signature for UM patients.

Results
The tan and greenyellow modules were significantly associated with the metastasis of UM patients. Significant genes related to the overall survival (OS) in these two modules were then identified. Additionally, an OS-predicting signature was established. The UM patients were divided into a low- or high-risk group. The Kaplan–Meier curve indicated that high-risk patients had poorer OS than low-risk patients. The receiver operating curve (ROC) was used to validate the stability and accuracy of the final five-gene signature. Based on the signature and clinical traits of UM patients, a nomogram was established to serve in clinical practice.

Conclusions
We identified key genes involved in the metastasis of UM. A robust five-gene‐based prognostic signature was constructed and validated. In addition, the gene signature-based nomogram was created that can optimize the prognosis prediction and identify possible factors causing the poor prognosis of high-risk UM patients.
Development and evaluation of the MAINTAIN instrument, selecting patients suitable for secondary or tertiary preventive manual care: the Nordic maintenance care program
Authors: Eklund Andreas , Palmgren Per J. , Jakobsson Ulf , Axén Iben 
Published: March 2022

Abstract
Background
Chiropractic maintenance care (MC) has been found to be effective for patients classified as dysfunctional by the West Haven-Yale Multidimensional Pain Inventory (MPI). Although displaying good psychometric properties, the instrument was not designed to be used in clinical practice to screen patients for stratified care pathways. The aim was to develop a brief clinical instrument with the intent of identifying dysfunctional patients with acceptable diagnostic accuracy.

Methods
Data from 249 patients with a complete MPI dataset from a randomized clinical trial that investigated the effect and cost-effectiveness of MC with a 12-month follow-up was used in this cross-sectional analysis. A brief screening instrument was developed to identify dysfunctional patients, with a summary measure. Different cut-offs were considered with regards to diagnostic accuracy using the original instrument’s classification of dysfunctional patients as a reference. Very good diagnostic accuracy was defined as an area under the curve (AUC) metric between 0.8 and 0.9. The instrument was then externally validated in 3 other existing datasets to assess model transportability across populations and medical settings.

Results
Using an explorative approach, the MAINTAIN instrument with 10 questions (0–6 Likert responses) capturing 5 dimensions (pain severity, interference, life control, affective distress, and support) was developed, generating an algorithm-based score ranging from − 12 to 48. Reporting a MAINTAIN score of 18 or higher, 146 out of the 249 patients were classified as dysfunctional with 95.8% sensitivity and 64.3% specificity. At a score of 22 or higher, 109/249 were classified as dysfunctional with 81.1% sensitivity and 79.2% specificity. AUC was estimated to 0.87 (95% CI 0.83, 0.92) and Youden’s index was highest (0.70) at a score of 20. The diagnostic accuracy was similar and high across populations with minor differences in optimal thresholds for identifying dysfunctional individuals.

Conclusion
The MAINTAIN instrument has very good diagnostic accuracy with regards to identifying dysfunctional patients and may be used as a decision aid in clinical practice. By using 2 thresholds, patients can be categorized into “low probability (− 12 to 17)”, “moderate probability (18 to 21)”, and “high probability (22 to 48)” of having a good outcome from maintenance care for low back pain.

Trial registration
Clinical trials.gov; NCT01539863; registered February 28, 2012; https://clinicaltrials.gov/ct2/show/NCT01539863.
Baicalin improves the functions of granulosa cells and the ovary in aged mice through the mTOR signaling pathway
Authors: Fan Huiying , He Jiahuan , Bai Yucheng , He Qina , Zhang Tongwei , Zhang Junya , Yang Guang , Xu Ziwen , Hu Jingyi , Yao Guidong 
Published: March 2022

Abstract
Background
The mammalian follicle is the basic functional unit of the ovary, and its normal development is required to obtaining oocytes capable of fertilization. As women get older or decline in ovarian function due to certain pathological factors, the growth and development of follicles becomes abnormal, which ultimately leads to infertility and other related female diseases. Kuntai capsules are currently used in clinical practice to improve ovarian function, and they contain the natural compound Baicalin, which is a natural compound with important biological activities. At present, the role and mechanism of Baicalin in the development of ovarian follicles is unclear.

Methods
Human primary granulosa cells collected from follicular fluid, and then cultured and treated with Baicalin or its normal control, assessed for viability, subjected to RT-PCR, western blotting, flow cytometry, and hormone analyses. The estrus cycle and oocytes of CD-1 mice were studied after Baicalin administration and compared with controls. Ovaries were collected from the mice and subjected to hematoxylin-eosin staining and immunohistochemistry analysis.

Results
We showed that Baicalin had a dose-dependent effect on granulosa cells cultured in vitro. A low concentration of Baicalin (for example, 10 μM) helped to maintain the viability of granulosa cells; however, at a concentration exceeding 50 μM, it exerted a toxic effect. A low concentration significantly improved the viability of granulosa cells and inhibited cell apoptosis, which may be related to the resultant upregulation of Bcl-2 expression and downregulation of Bax and Caspase 3. By constructing a hydrogen peroxide-induced cell oxidative stress damage model, we found that Baicalin reversed the cell damage caused by hydrogen peroxide. In addition, Baicalin increased the secretion of estradiol and progesterone by upregulating P450arom and stAR. The results of the in vivo experiment showed that the intragastric administration of Baicalin to aged mice improved the estrous cycle and oocyte quality. Furthermore, we observed that Baicalin enhanced the viability of granulosa cells through the mTOR pathway, which in turn improve ovarian function.

Conclusion
These results indicate that Baicalin could improve the viability of ovarian granulosa cells and the secretion of steroid hormones and thus could help to improve degenerating ovarian function and delay ovarian aging.
Virulence determinant and antimicrobial resistance traits of Emerging MDR Shiga toxigenic E. coli in diarrheic dogs
Authors: Algammal Abdelazeem M. , El-Tarabili Reham M. , Alfifi Khyreyah J. , Al-Otaibi Amenah S. , Hashem Marwa E. Abo , El-Maghraby Mamdouh M. , Mahmoud Ahmed E. 
Published: March 2022

AbstractShiga-toxigenic Escherichiacoli (STEC) is incriminated in severe hemorrhagic enteritis in dogs, which is considered a veterinary and public health alarm. To investigate the prevalence, antimicrobial resistance patterns, virulence determinants, and distribution of antimicrobial resistance genes in STEC strains isolated from dogs: 80 fecal samples were obtained from diseased dogs suffering from hemorrhagic diarrhea from pet animal clinics in Ismailia governorate, Egypt. The obtained samples were examined bacteriologically. Moreover, the retrieved isolates were tested for serogrouping, Congo-red binding, antimicrobial resistance, and PCR-based determination of virulence and antimicrobial resistance genes. The prevalence of E.coli in the examined diseased dogs was 23.75% (19/80). The serogrouping of the recovered isolates revealed that 84.2% of the tested isolates were distributed into three serogroups: O146 (36.8%), O111 (31.5%), and O26 (15.7%). Meanwhile, three isolates were untypable (15.8%). Moreover, all the tested E.coli serovars were positive for CR-binding. PCR revealed that the prevalence of stx1, eaeA, hlyA, and stx2 virulence genes was 100%, 100%, 100%, and 47.3%, respectively. Our findings revealed that 31.5% of the recovered isolates showed MDR to five antimicrobial classes and harbored blaTEM, blaCTX-M, tetA, tetB, and sul1 genes. Alarmingly, three isolates were carbapenem-resistant. Two strains harbored the blaKPC gene, while one strain carried the blaNDM-1 gene. Concisely, as far as we know, this is the first study that reported the existence of MDR-STEC in dogs in Egypt. The stx1 gene is the most predominant Shiga toxin gene that accompanied the STEC isolated from hemorrhagic enteritis in dogs. The emerging MDR-STEC in dogs commonly harbors blaTEM, blaCTX-M, sul1, tetA, tetB, and qnrA resistance genes. Meropenem, levofloxacin, and tigecycline exhibited talented antimicrobial activity against MDR-STEC isolated from dogs.
Prevalence of domestic violence in a time of catastrophic disease outbreaks including COVID-19 pandemic: a systematic review protocol
Authors: Abraham Gelila , Gelana Beshea , Yitbarek Kiddus , Morankar Sudhakar 
Published: March 2022

Abstract
Background
Domestic violence is a public health issue that has a long-term and irreversible effect on the victims. There are vulnerable groups like children, women, and elders. The problem becomes worse for these populations in the time of catastrophic events including disease pandemics. However, few attempts have been made to systematically review the prevalence and pattern of domestic violence during these times all over the world.

Methods
An initial search of PubMed will be followed by CINAHL, Scopus, Google Scholar, Embase, and ProQuest Health. The titles and abstracts of studies will be reviewed, and full-text articles will be selected if the inclusion criteria are met. Studies that meet the eligibility criteria will then be assessed by two independent reviewers. Full-text articles will be selected if the inclusion criteria are met. A standardized critical appraisal checklist for studies reporting prevalence data will be used to assess the methodological quality, and a standardized data extraction tool will be used. The results from the included studies will be analysed using the JBI SUMARI software.

Discussion
This systematic review will provide solid evidence on the magnitude of domestic violence of any forms during catastrophic disease outbreaks including the current pandemic, COVID-19.

Systematic review registration
PROSPERO CRD42020192255.
On some accelerated optimization algorithms based on fixed point and linesearch techniques for convex minimization problems with applications
Authors: Yatakoat Pornsak , Suantai Suthep , Hanjing Adisak 
Published: March 2022

AbstractIn this paper, we introduce and study a new accelerated algorithm based on forward–backward and SP-algorithm for solving a convex minimization problem of the sum of two convex and lower semicontinuous functions in a Hilbert space. Under some suitable control conditions, a weak convergence theorem of the proposed algorithm based on a fixed point is established. Moreover, we choose the stepsize of our algorithm which is independent on the Lipschitz constant of the gradient of the objective function by using a linesearch technique, and then a weak convergence result of the proposed algorithm is analyzed. As applications, we apply the proposed algorithm for solving the image restoration problems and compare its convergence behavior with other well-known algorithms in the literature. By our experiment, the algorithms have a higher efficiency than the others.
Psychological distress among elderly surgical patients who had their surgery postponed during the COVID-19 pandemic
Authors: Loh Pui San , Chaw Sook Hui , Foong Yi Xian , Ramasamy Dhurgka , Zaki Rafdzah Ahmad , Kuppusamy Shanggar , Ong Teng Aik , See Mee Hoong , Khor Hui Min 
Published: March 2022

Abstract
Background
Many institutions withheld elective lists and triaged surgeries during the peak of coronavirus disease 2019 (COVID-19) pandemic. As a result, older surgical patients have had to wait for rescheduled dates in a long waitlist. This study aimed to identify the psychological impact in these patients when they returned for surgery.

Methods
This was a cross-sectional study which included 153 patients aged ≥ 65 years undergoing elective surgery. Trained interviewers recruited and assessed psychological status pre-operatively with two validated questionnaires - Hospital Anxiety and Depression Scale (HADS) and 36-item Short Form Health Survey (SF-36). Specific questions were asked about their postponed surgeries, appetite and fear.

Results
A total of 36 out of 153 (23.5%) patients had their procedures deferred during the first wave of COVID-19 pandemic. Postponed cases were significantly based on the nature of surgery (p = 0.002), cancer diagnosis (p = 0.006) and surgical specialty (p = 0.023). Median HADS scores were higher for patients who were postponed (2.00 versus 4.00 for anxiety, p = 0.180 and 0.00 versus 1.00 for depression, p = 0.424) although no statistical significance was shown. In the whole study population, anxiety was a significant predictor for depression and vice versa (p < 0.001) with other predictive risk factors for anxiety that were age ≥ 85 years old (odds ratio [OR] 6.14, p = 0.018), female (OR 2.41, p = 0.024), cancer (OR 2.19, p = 0.039) and major surgery (OR 2.39, p = 0.023). Similarly, older patients ≥ 85 years old (OR 10.44, p = 0.003) and female (OR 6.07, p = 0.006) had higher risk for depression. Both anxiety and depression were significant risks for loss of appetite (p = 0.005 and 0.001). Lastly, the fear of disease progression due to rescheduling was more frequent in cancer patients (p = 0.035).

Conclusion
The mental health and disease burden of older surgical patients should be taken into careful consideration when cases need to be postponed in our healthcare system.
Investigating the effects of peptide-based, MOS and protease feed additives on the growth performance and fecal microbial composition of weaned pigs
Authors: Poudel Prakash , Samuel Ryan , Levesque Crystal , St-Pierre Benoit 
Published: March 2022

Abstract
Background
Digestive disorders in weaning pigs remain a major challenge for swine producers. Different types of commercial feed additives have been developed to promote gut health and development in young pigs, but their effects on resident gut microbial communities remain largely unexplored. The aim of this study was to investigate the impact of a peptide-based product (Peptiva) in combination with mannose oligosaccharides (MOS) and an exogenous protease on the performance and fecal microbiome of nursery pigs.

Methods
A total of 1097 weaned pigs were divided into 44 pens (24–26 pigs/pen) with each pen randomly assigned to one of four experimental diets as part of Phase II and Phase III of a standard nursery phase feeding program. Fecal samples collected from representative control and treatment pigs were used to investigate bacterial composition profiles by high throughput sequencing of PCR-generated amplicons targeting the V1-V3 region of the 16S rRNA gene.

Results
Higher gain:feed was observed for pigs fed Peptiva and MOS compared to Controls during the period when experimental diets were fed, but the benefits of supplementation were not maintained after pigs were transitioned to a non-supplemented diet. Three candidate bacterial species, identified as Operational Taxonomic Units (OTUs), were found to have significantly different abundances between control samples and treatment samples during the same phase. In Phase III samples, SD_Ssd-00039, predicted to be a strain of Streptococcus alactolyticus based on nucleotide sequence identity, was the most highly represented of these OTUs with an average abundance in pigs fed Peptiva, MOS and protease that was 3.9 times higher than in Controls. The report also presents evidence of microbial succession that occurred during the trial, with 16 of the 32 most abundant OTUs found to vary between Phase II and Phase III samples for the same dietary treatment.

Conclusions
Dietary supplementation with a combination of a peptide-based product, MOS, and protease increased the growth performance of weaned pigs compared to control animals during the nursery phase, but these benefits were no longer observed within 2 weeks after all animals were transitioned to a non-supplemented diet. Supplementation with these feed additives was found to modulate the composition of the swine gut microbiome during this period.
Trends in Canadian prescription drug purchasing: 2001–2020
Authors: Hofmeister Mark , Sivakumar Ashwinie , Clement Fiona , Hayes Kaleen N. , Law Michael , Guertin Jason R. , Neville Heather L. , Tadrous Mina 
Published: March 2022

Abstract
Background
In 2019, more than $34.5 billion was spent on prescription drugs in Canada. However, little is known about the distribution of this spending across medications and settings (outpatient and inpatient) over time. The objective of this paper is to describe the largest expenditures by medication class over time in inpatient and outpatient settings. This information can help to guide policies to control prescription medication expenditures.

Methods
IQVIA’s Canadian Drugstore and Hospital Purchases Audit data from January 1, 2001, to December 31, 2020, were used. In this dataset, purchasing was stratified by outpatient drugstore and inpatient hospital. Spending trajectories in both settings were compared to total expenditure over time. Total expenditure of the 25 medications with the largest expenditure were compared over time, stratified by setting. Nominal costs were used for all analysis.

Results
In 2001, spending in the outpatient and inpatient settings was greatest on atorvastatin ($467.0 million) and erythropoietin alpha ($91.2 million), respectively. In 2020, spending was greatest on infliximab at $1.2 billion (outpatient) and pembrolizumab at $361.6 million (inpatient). Annual outpatient spending, although increasing, has been growing at a slower rate (5.3%) than inpatient spending (7.0%). In both settings, spending for the top 25 medications has become increasingly concentrated on biologic agents, with a reduction in the diversity of therapeutic classes of agents over time.

Discussion
Identification of the concentration on spending on biologic agents is a key step in managing costs of prescription medications in Canada. Given the increases in spending on biologic agents over the last 20 years, current cost-control mechanisms may be insufficient. Future research efforts should focus on examining the effectiveness of current cost-control mechanisms and identifying new approaches to cost control for biologic agents.
High burden of hypovitaminosis D among the children and adolescents in South Asia: a systematic review and meta-analysis
Authors: Siddiqee Mahbubul H. , Bhattacharjee Badhan , Siddiqi Umme Ruman , Rahman Mohammad Meshbahur 
Published: March 2022

Abstract
Background
Vitamin D is vital for the growth and development of children. While deficiency and/or insufficiency of vitamin D among South Asian children are frequently reported in the literature, the lack of a meta-analysis has left its true extent poorly characterized. In this study, we aimed to conduct a systematic review and perform meta-analyses of the prevalence of hypovitaminosis D among the children of the South Asian countries.

Methods
Two major electronic search engines (PubMed and Scopus) and one database (Google scholar) were used; original studies, conducted among South Asian children and adolescents and published between 1 January 2001 and 31 December 2019. A random-effect meta-analysis was also performed to calculate the pooled prevalence of hypovitaminosis D followed by subgroup analyses for countries and age groups.

Results
After applying inclusion and exclusion criteria, a total of 41 studies with a total population size of 18,233 were finally selected. The overall prevalence of hypovitaminosis D was 61% [95% CI: 46% to 71%] with highly significant heterogeneity (I2 = 99.72%; p < 0.0001). The average level of serum vitamin D ranged from 5 ng/mL to 34 ng/mL, with a weighted mean of 19.15 ng/mL (weighted standard deviation 11.59 ng/mL). Country-wise analysis showed that hypovitaminosis D in Afghanistan was the highest [96.2%; 95% CI: 91% to 99%], followed by Pakistan [94%; 95% CI: 90% to 96%], India [64%; 95% CI: 46% to 79%], Bangladesh [35.48%; 95% CI: 32% to 39%], Nepal [35%; 95% CI: 1% to 83%], and Sri Lanka [25%; 95% CI: 16% to 36%]. Age group analyses revealed that hypovitaminosis D was most prevalent among neonates [85%; 95% CI: 76% to 91%], followed by school-going children [57%; 95% CI: 33% to 80%], and preschool children [55%; 95% CI: 35% to 75%].

Conclusion
This study generates quantitative evidence and specific extent of hypovitaminosis D in the South Asian countries as a public health concern. Being the first systematic review for this region, results from this study will create awareness and will facilitate adopting mitigation strategies by the policymakers and the governments to address this problem.