bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes
Authors: Taya Naohiro , Katakami Naoto , Mita Tomoya , Okada Yosuke , Wakasugi Satomi , Yoshii Hidenori , Shiraiwa Toshihiko , Otsuka Akihito , Umayahara Yutaka , Ryomoto Kayoko , Hatazaki Masahiro , Yasuda Tetsuyuki , Yamamoto Tsunehiko , Gosho Masahiko , Shimomura Iichiro , Watada Hirotaka
Published: May 2021

Background

The association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages.

Methods

We conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics.

Results

Among 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, β = − 5.822; 95% CI − 8.875 to − 2.768, P < 0.001), glucose coefficient of variation (β = − 0.418; − 0.685 to − 0.151, P = 0.002), mean amplitude of glycemic excursion (β = − 1.689; − 2.567 to − 0.811, P < 0.001), mean of daily differences (β = − 6.500; − 9.758 to − 3.241, P < 0.001), and interquartile range (β = − 4.289; − 6.964 to − 1.614, P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT.

Conclusions

Continuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.
Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double‐blind placebo‐controlled clinical trials
Authors: Yokote Koutaro , Yamashita Shizuya , Arai Hidenori , Araki Eiichi , Matsushita Mitsunori , Nojima Toshiaki , Suganami Hideki , Ishibashi Shun
Published: May 2021

Background

Increased risk of cardiovascular events is associated not only with dyslipidemias, but also with abnormalities in glucose metabolism and liver function. This study uses pooled analysis to explore the in-depth effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα) already known to decrease elevated triglycerides, on glucose metabolism and liver function in patients with hypertriglyceridemia.

Methods

We performed a post-hoc analysis of six phase 2 and phase 3 Japanese randomized double-blind placebo-controlled trials that examined the effects of daily pemafibrate 0.1 mg, 0.2 mg, and 0.4 mg on glucose metabolism markers and liver function tests (LFTs). Primary endpoints were changes in glucose metabolism markers and LFTs from baseline after 12 weeks of pemafibrate treatment. All adverse events and adverse drug reactions were recorded as safety endpoints.

Results

The study population was 1253 patients randomized to placebo (n = 298) or pemafibrate 0.1 mg/day (n = 127), 0.2 mg/day (n = 584), or 0.4 mg/day (n = 244). Participant mean age was 54.3 years, 65.4 % had BMI ≥ 25 kg/m2, 35.8 % had type 2 diabetes, and 42.6 % had fatty liver. Fasting glucose, fasting insulin, and HOMA-IR decreased significantly in all pemafibrate groups compared to placebo. The greatest decrease was for pemafibrate 0.4 mg/day: least square (LS) mean change from baseline in fasting glucose − 0.25 mmol/L; fasting insulin − 3.31 µU/mL; HOMA-IR − 1.28. ALT, γ-GT, ALP, and total bilirubin decreased significantly at all pemafibrate doses vs. placebo, with the greatest decrease in the pemafibrate 0.4 mg/day group: LS mean change from baseline in ALT − 7.6 U/L; γ-GT − 37.3 U/L; ALP − 84.7 U/L; and total bilirubin − 2.27 µmol/L. Changes in HbA1c and AST did not differ significantly from placebo in any pemafibrate groups in the overall study population. The decreases from baseline in LFTs and glucose metabolism markers except for HbA1c were notable among patients with higher baseline values. FGF21 increased significantly in all pemafibrate groups compared to placebo, with the greatest increase in the pemafibrate 0.4 mg/day group. Adverse event rates were similar in all groups including placebo.

Conclusions

In patients with hypertriglyceridemia, pemafibrate can improve glucose metabolism and liver function, and increase FGF21, without increasing adverse event risk.
Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice
Authors: Gao Tong , Ren Yi , Li Shuangqin , Lu Xin , Lei Han
Published: May 2021

Background

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic.

Results

We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model.

Conclusions

Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.
Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments
Authors: Chang Xiaoying , Li Dan , Liu Chang , Zhang Zhe , Wang Tao
Published: May 2021

Background

Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers.

Methods

GSE18520 and GSE26712 were downloaded from the GEO database. The “limma” and “WGCNA” packages were used to explore hub genes. The Kaplan–Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples.

Results

In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients.

Conclusions

In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
Sugar-sweetened beverage consumption and bone health: a systematic review and meta-analysis
Authors: Ahn Hyejin , Park Yoo Kyoung
Published: May 2021

Background

Current evidence demonstrate that sugar-sweetened beverages (SSBs) and bone health are related; however, there has been only a few reviews on the link between SSBs and bone health. A systematic review and meta-analysis was performed to investigate the association between SSBs consumption and bone health in chidren and adults.

Methods

Relevant studies of SSBs and bone health published up to 15 March 2021 were searched using PubMed, the Web of Science, Cochrane Library, and a reference search. A random-effects meta-analysis was conducted to estimate the standardized mean difference (SMD). Subgroup analyses were performed to identify whether effects were modified by age, sex, measured skeletal sites, type of SSBs, and SSBs intake questionnaire.

Results

Twenty-six publications including 124,691 participants were selected on the review. The results from this meta-analysis showed a significant inverse association between SSBs intake and bone mineral density (BMD) in adults (ES: -0.66, 95% CI: − 1.01, − 0.31, n = 4312). Eighteen of the 20 studies included in the qualitative-only review in children and adults supported the findings from the meta-analysis. When subgroup analysis was performed according to skeletal site, a large effect was found on whole body BMD (ES: -0.97, 95% CI: − 1.54, − 0.40). There was a moderate effect on BMD in females (ES: -0.50, 95% CI: − 0.87, − 0.13). There was a moderate or large effect on BMD in individuals aged under 50 years (under 30 years: ES: -0.57, 95% CI: − 0.97, − 0.17; 30 to 50 years: ES: -1.33, 95% CI: − 1.72, − 0.93). High consumption of carbonated beverages had a moderate effect on BMD (ES: -0.73, 95% CI: − 1.12, − 0.35).

Conclusion

The meta-analysis showed that SSBs consumption such as carbonated beverages were inversely related to BMD in adults. Qualitative review supported the results of meta-analysis.

Trial registration

This review was registered in the PROSPERO database under identifier CRD42020164428.
Research on developing environmental ethics in pharmacists’ activities
Authors: Toma Alexandra , Crişan Ofelia
Published: May 2021

Background

Authors of various backgrounds are preoccupied with the meaning of environmental ethics, which refers to specific values, norms, attitudes, and practices with respect to all beings and elements of nature. Many international organizations have adopted important documents proclaiming the ethical obligation to protect the environment in all professional activities. At the national level, professional associations should include and develop this obligation in their codes of conduct. This study aimed to analyze and compare elements of environmental protection included in codes of conduct for pharmacists, to find ways to integrate environmental ethics into their activities.

Methods

Seven codes of conduct for pharmacists were analyzed using the comparative method and methods of legal interpretation. Based on acknowledged values and principles of environmental ethics, a framework model for developing environmental protection in pharmacists’ activities was created via an iterative process of reflection and discussion.

Results

Explicit provisions for environmental ethics were found in codes in force in three countries and in a Romanian project. These provisions refer, in general, to an ethical duty of environmental protection in pharmacists’ activities. Regarding the other codes, the study could only interpret stipulations of public health ethics to deduce an ethical environmental obligation. Considering the need for developing such provisions, an ethical framework was proposed as a model for professional associations of pharmacists.

Conclusions

The studied codes demonstrate a preoccupation of the professional associations with environmental protection in pharmacists’ activities, with different degrees of interest in developing environmental ethics. To this end, the codes of conduct for pharmacists should include environmental values, principles, and ethics guidelines. Those guidelines should indicate the ethical attitude in relation to the environment for each activity. Further research is needed to stimulate, shape, and develop an environmental ethical behavior in pharmacists’ practice.
Development of the gait outcomes assessment list for lower-limb differences (GOAL-LD) questionnaire: a child and parent reported outcome measure
Authors: Dermott Jennifer A. , Wright F. Virginia , Salbach Nancy M. , Narayanan Unni G.
Published: May 2021

Background

To develop a priority-based patient/parent reported outcome measure for children with lower-limb differences (LD) by adapting the Gait Outcomes Assessment List (GOAL) questionnaire.

Methods

Guided by a conceptual framework of patient priorities, the GOAL questionnaire was iteratively modified and its sensibility evaluated by field-testing it on children with LD, and their parents. Cognitive interviews were conducted with a subgroup of these children, and an e-survey administered to a multidisciplinary group of health care professionals with expertise in paediatric LD. Findings were integrated to create the final version of the GOAL-LD.

Results

Twenty-five children (9–18 years), 20 parents, and 31 healthcare professionals evaluated the content and sensibility of the GOAL, with an emphasis on the relevance and importance of the items to patients’ health related quality of life (HRQL). This resulted in the retention of 26 of the original 50 items, elimination of 12, modification of 12, and addition of seven new items. The new 45-item GOAL-LD questionnaire was shown to be sensible, and its content deemed important.

Conclusions

The GOAL-LD questionnaire has a high level of face and content validity, and sensibility. It comprehensively captures the HRQL goals and outcomes that matter to children with LD and their parents. Following further psychometric evaluation, the GOAL-LD may serve as a much needed patient and parent reported outcome measure for this population.
Meta-analysis of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Authors: Lin Huaqin , Wang Lei , Zhong Xiaohong , Zhang Xueqing , Shao Lingdong , Wu Junxin
Published: May 2021

Background and purpose

With the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.

Materials and methods

Eligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).

Results

Six studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).

Conclusion

We concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.
Construct validity and reliability of the physical activity parenting questionnaire for children (PAP-C)
Authors: Laukkanen Arto , Aunola Kaisa , Korhonen Elisa , Barnett Lisa M. , Sääkslahti Arja
Published: May 2021

Background

Children’s perception of parenting is hypothesised to significantly affect their physical activity (PA). This study aimed to examine construct validity, factorial invariance and reliability of a new tool: Physical Activity Parenting questionnaire for Children (PAP-C).

Methods

PAP-C comprised 22 items hypothesised to cover 3 theory-guided factors of physical activity parenting (PAP)—namely, structure for activity, autonomy support and involvement. Construct validity and internal consistency of PAP-C were tested using confirmatory factor analysis (CFA) and composite reliability in a sample of Finnish first, second- and third graders (n = 456; mean age 8.77 ± 0.84 years, girls 51.1%). Factorial invariance of PAP-C across grade levels was investigated using sequential multigroup CFA. Intra-class correlation (ICC) coefficients of the sum factors were calculated in a sample of children who completed a 4-week PAP-C retest (n = 450; mean age 8.83 ± 0.87 years, girls 48.0%).

Results

A first-order 3-factor model of the structure for activity, autonomy support and involvement, with 20 items (two items removed), showed an acceptable fit. The model demonstrated configural, metric, and scalar invariance across grade levels. Composite reliabilities indicated moderate-to-good internal consistency (from .74 to .87) for the factors. ICCs (from .494 to .750, p < .001) showed moderate to excellent test–retest stability for all grade levels.

Conclusions

PAP-C can be considered to be a promising tool for investigating 7–10-year-old children’s perceptions of PAP.
Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa
Authors: Farinre Omotayo , Gounder Kamini , Reddy Tarylee , Tongo Marcel , Hare Jonathan , Chaplin Beth , Gilmour Jill , Kanki Phyllis , Mann Jaclyn K. , Ndung’u Thumbi
Published: May 2021

Background

The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.

Results

Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.

Conclusions

Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies.
Training and expertise in undertaking assisted vaginal delivery (AVD): a mixed methods systematic review of practitioners views and experiences
Authors: Feeley Claire , Crossland Nicola , Betran Ana Pila , Weeks Andrew , Downe Soo , Kingdon Carol
Published: May 2021

Background

During childbirth, complications may arise which necessitate an expedited delivery of the fetus. One option is instrumental assistance (forceps or a vacuum-cup), which, if used with skill and sensitivity, can improve maternal/neonatal outcomes. This review aimed to understand the core competencies and expertise required for skilled use in AVD in conjunction with reviewing potential barriers and facilitators to gaining competency and expertise, from the point of view of maternity care practitioners, funders and policy makers.

Methods

A mixed methods systematic review was undertaken in five databases. Inclusion criteria were primary studies reporting views, opinions, perspectives and experiences of the target group in relation to the expertise, training, behaviours and competencies required for optimal AVD, barriers and facilitators to achieving practitioner competencies, and to the implementation of appropriate training. Quality appraisal was carried out on included studies. A mixed-methods convergent synthesis was carried out, and the findings were subjected to GRADE-CERQual assessment of confidence.

Results

31 papers, reporting on 27 studies and published 1985–2020 were included. Studies included qualitative designs (3), mixed methods (3), and quantitative surveys (21). The majority (23) were from high-income countries, two from upper-middle income countries, one from a lower-income country: one survey included 111 low-middle countries. Confidence in the 10 statements of findings was mostly low, with one exception (moderate confidence). The review found that AVD competency comprises of inter-related skill sets including non-technical skills (e.g. behaviours), general clinical skills; and specific technical skills associated with particular instrument use. We found that practitioners needed and welcomed additional specific training, where a combination of teaching methods were used, to gain skills and confidence in this field. Clinical mentorship, and observing others confidently using the full range of instruments, was also required, and valued, to develop competency and expertise in AVD. However, concerns regarding poor outcomes and litigation were also raised.

Conclusion

Access to specific AVD training, using a combination of teaching methods, complements, but does not replace, close clinical mentorship from experts who are positive about AVD, and opportunities to practice emerging AVD skills with supportive supervision. Further research is required to ascertain effective modalities for wider training, education, and supportive supervision for optimal AVD use.
Predictors of mortality rate among adult HIV-positive patients on antiretroviral therapy in Metema Hospital, Northwest Ethiopia: a retrospective follow-up study
Authors: Workie Kefale Lejadiss , Birhan Tilahun Yemanu , Angaw Dessie Abebaw
Published: May 2021

Background

Globally Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is an ongoing public health issue associated with high morbidity and mortality. Efforts have been made to reduce HIV/AIDS-related morbidity and mortality by delivering antiretroviral therapy. However, the incidence and predictors of mortality in border areas like Metema were not investigated. This study aimed to assess predictors of mortality rate among adult HIV-positive patients on antiretroviral therapy at Metema Hospital.

Methods

Retrospective follow-up study was employed among ART patients from January 1, 2013, to December 30, 2018. Data were entered in Epi-data 3.1 and exported to STATA 14 for analysis. Kaplan–Meier and Log-Rank test was used to compare survival differences among categories of different variables. In bi-variable analysis p-values < 0.20 were entered into a multivariable analysis. Multivariate Weibull model was used to measure the risk of death and identify the significant predictors of death. Variables that were statistically significant at p-value < 0.05 were concluded as predictors of mortality.

Result

A total of 542 study participants were included. The overall incidence rate was 6.7 (95% CI: 5.4–8.4) deaths per 100 person-years of observation. Being male (HR = 2.4; 95% CI: 1.24–4.62), STAGE IV (HR = 5.64; 95% CI: 2.53–12.56), stage III (HR = 3.31; 95% CI: 1.35–8.10), TB-coinfection (HR = 3.71; 95% CI: 1.59–8.64), low hemoglobin (HR = 4.14; 95% CI: 2.18–7.86), BMI ≤ 15.4 kg/m2 (HR = 2.45; 95% CI: 1.17–5.10) and viral load > 1000 copy/ml (HR = 6.70; 95% CI: 3.4–13.22) were found to be a significant predictor for mortality among HIV patients on ART treatment.

Conclusion

The incidence of death was high. Being male, viral load, those with advanced STAGE (III & IV), TB co-infected, low BMI, and low hemoglobin were at a higher risk of mortality. Special attention should be given to male patients and high public interventions needed among HIV patients on ART to reduce the mortality rate.
Development of an indirect ELISA to specifically detect antibodies against African swine fever virus: bioinformatics approaches
Authors: Gao Zhan , Shao Jun-Jun , Zhang Guang-Lei , Ge Su-Dan , Chang Yan-Yan , Xiao Lei , Chang Hui-Yun
Published: May 2021

Background

African swine fever (ASF), characterized by acute, severe, and fast-spreading, is a highly lethal swine infectious disease caused by the African swine fever virus (ASFV), which has caused substantial economic losses to the pig industry worldwide in the past 100 years.

Methods

This study started with bioinformatics methods and verified the epitope fusion protein method's reliability that does not rely on traditional epitope identification. Meanwhile, it will also express and purify the constructed genes through prokaryotic expression and establish antibody detection methods.

Results

The results indicated that the protein had good reactivity and did not cross-react with other swine diseases. The receiver-operating characteristic analysis was performed to verify the determination. The area under the receiver-operating characteristic curve was 0.9991 (95% confidence interval 0.9973 to 1.001).

Conclusions

It was proved that the recombinant protein is feasible as a diagnostic antigen to distinguish ASFV and provides a new idea for ASFV antibody detection.
Anterior hybrid construction of multilevel cervical disc disease and spondylotic spinal stenosis: surgical results and factors affecting adjacent segment problems
Authors: Yilmaz Murat , Yucesoy Kemal , Erbayraktar Resat S. , Altinag Rıfat S.
Published: May 2021

Objective

We aimed to evaluate reliability, radiological outcomes, and the impacts of anterior cervical hybrid construction on the adjacent segments for the multilevel cervical degenerative disc disease (mCDDD) and spondylotic spinal stenosis (SSS).

Methods

A retrospective analysis was performed using data extracted from the medical files of 195 patients (105 males, 90 females; mean age: 47.7 years). From 2008 to 2018, these patients underwent anterior cervical hybrid construction for symptomatic contiguous at least 2-level cervical degenerative disc diseases and cervical spondylosis. Clinical and radiological data including Neck Disability Index (NDI), visual analogue scale (VAS), local cervical degenerative disk disease in adjacent segments on magnetic resonance imaging (MRI) views, and complications were reviewed.

Results

The mean clinical and radiological follow-up was 45.2 months (range 24 to 102). Radiculopathy and/or myelopathy were the main clinical problems in all patients. The mean VAS scores of HC for arm pain were 7.4 ± 0.8 preoperatively; 2.8 ± 0.6, 1 month after surgery; 2.3 ± 0.6, 6 months after surgery; 1.8 ± 0.6, 12 month after surgery; and 1.6 ± 0.6, 24 months after surgery. The mean NDI scores (mean ± SD) of HC significantly improved after surgery (on admission, 57.2 ± 5.5%; 1 month after surgery, 27.35 ± 5.3%; 6 month after surgery, 21.43 ± 2.8%; 12 months after surgery, 21.9 ± 2.3%; 24 months after surgery, 20.6 ± 2.6%, p = 0.006). Hoarseness and dysphagia were the most common complications and osteophyte formation was the most frequent radiographic change.

Conclusion

Anterior cervical hybrid construction appears to be an acceptable option in the management of multilevel cervical degenerative disc diseases and spondylotic spinal stenosis.
Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value
Authors: Liu Hua , Qin Guangzhen , Ji Yanan , Wang Xiaojian , Bao Hailin , Guan Xiaojun , Wei Aichun , Cai Zhigang
Published: May 2021

Background

Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value.

Methods

Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature.

Results

According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis.

Conclusions

In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.
Dynamic exacerbation in inflammation and oxidative stress during the formation of peritendinous adhesion resulted from acute tendon injury
Authors: Li Pengfei , Zhou Haiying , Tu Tian , Lu Hui
Published: May 2021

Background

Peritendinous adhesion is among the common complications after tendon injury. Numerous studies have been carried out to prevent its formation, including modifications of surgical procedures, postoperative cares, application of medicines, etc. This study dynamically monitored fluctuations of inflammation, state of oxidative stress, and histopathologic changes around injured tendon to provide theoretical basis for further exploration in mechanisms of peritendinous adhesion formation.

Methods

Eighteen mature Sprague-Dawley male rats were randomly allocated into 6 equal groups. Compared with control and sham group, every rat’s right hind Achilles tendon in experimental groups was cut and repaired by the modified Kessler technique. Besides control and sham group, samples of tendon margin and serum were collected at different time points after the surgery. Content of TNF-α, IL-1β, and TGF-β were assayed in harvested serum. Reactive oxygen species (ROS) were detected, expression levels of related genes (IL-1β, IL-6, SOD1, SOD2, COL1, HIF1A) were quantified by qPCR, and various histopathological evaluations were performed.

Results

Indicators (TNF-α, IL-1β, TGF-β1, ROS) were noticed to have a similar trend of significant rising 24 h after the surgery except TGF-β which was rising 72 h later. So were the expression trends of IL-1β, IL-6, SOD1, SOD2, and COL1. HIF1A, inversely correlated with SOD2, showed the progressive relief of regional tissue hypoxia. Histological evaluation showed the same tendency that fibrosis and inflammation were getting serious 48 h later after the surgery.

Conclusions

Inflammation, oxidative stress in injured tendon resulted from acute trauma, would be getting intense in 24 h. Peritendinous adhesion emerges and aggravates after 48 h. Thus, prompt efficient measures are advised to be taken after the injury as soon as possible.
Initial forest age distribution may generate computational sinks or sources of carbon: A generic approach to test assumptions underlying the EU LULUCF forest reference levels
Authors: Vauhkonen Jari , Mutanen Antti , Packalen Tuula , Asikainen Antti
Published: May 2021

Background

The current EU LULUCF regulation calls for member state-specific Forest Reference Levels (FRLs) for benchmark in the accounting of greenhouse gas emissions and removals of managed forest land during the compliance period (2021–2030). According to the technical guidance on developing and reporting the FRLs, it could be actualized by projecting a ratio of harvested to total available biomass. We tested how the initial age distribution may affect the aforementioned ratio by simulating the continuation of forest management based on several descriptive shapes of forest age class distribution.

Results

Our simulations suggest that when the FRLs are prepared by employing the harvest ratio and forest management is assumed strictly age dynamics driven, the shape of the initial forest age class distribution gives rise to computational sinks or sources of carbon in managed forest land. Harvests projected according to the ratio corresponded those resulting from the age dynamics only in the case of uniform age distribution.

Conclusions

The result calls for a better consideration of variation in initial states between countries when determining the future LULUCF regulation. Our exercise demonstrates how generic simulations in a standardized modeling framework could help in ex-ante impact assessment of proposed changes to the LULUCF regulation.
Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations
Authors: Stephenson Kirk A. J. , Zhu Julia , Wynne Niamh , Dockery Adrian , Cairns Rebecca M. , Duignan Emma , Whelan Laura , Malone Conor P. , Dempsey Hilary , Collins Karen , Routledge Shana , Pandey Rajiv , Crossan Elaine , Turner Jacqueline , O’Byrne James J. , Brady Laura , Silvestri Giuliana , Kenna Paul F. , Farrar G. Jane , Keegan David J.
Published: May 2021

Introduction

Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, manifesting variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interventions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective pathway for assessment and management is required.

Methods

Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service (Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis, functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors) reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing interventions, and novel therapies/clinical trials.

Results and discussion

Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/support services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000 allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding has transferred from charitable sources to government resources.

Conclusion

Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model could be used to develop similar IRD programmes in small/medium-sized nations.
Genome-wide histone acetylation analysis reveals altered transcriptional regulation in the Parkinson’s disease brain
Authors: Toker Lilah , Tran Gia T. , Sundaresan Janani , Tysnes Ole-Bjørn , Alves Guido , Haugarvoll Kristoffer , Nido Gonzalo S. , Dölle Christian , Tzoulis Charalampos
Published: May 2021

Background

Parkinson’s disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD is strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic dysregulation and specifically altered histone acetylation. Nevertheless, and despite the emerging role of epigenetics in age-related brain disorders, the question of whether aberrant histone acetylation is involved in PD remains unresolved.

Methods

We studied fresh-frozen brain tissue from two independent cohorts of individuals with idiopathic PD (n = 28) and neurologically healthy controls (n = 21). We performed comprehensive immunoblotting to identify histone sites with altered acetylation levels in PD, followed by chromatin immunoprecipitation sequencing (ChIP-seq). RNA sequencing data from the same individuals was used to assess the impact of altered histone acetylation on gene expression.

Results

Immunoblotting analyses revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. ChIP-seq analysis further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data from the same individuals revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Strikingly, this decoupling was most pronounced among nuclear-encoded mitochondrial genes, corroborating the notion that impaired crosstalk between the nucleus and mitochondria is involved in the pathogenesis of PD. Our findings independently replicated in the two cohorts.

Conclusions

Our findings strongly suggest that aberrant histone acetylation and altered transcriptional regulation are involved in the pathophysiology of PD. We demonstrate that PD-associated genes are particularly prone to epigenetic dysregulation and identify novel epigenetic signatures associated with the disease.
“We do not know how to screen and provide treatment”: a qualitative study of barriers and enablers of implementing perinatal depression health services in Ethiopia
Authors: Dadi Abel Fekadu , Miller Emma R. , Azale Telake , Mwanri Lillian
Published: May 2021

Background

Qualitative studies evaluating maternal mental health services are lacking in Ethiopia, and the available evidence targets severe mental illnesses in the general population. We conducted a qualitative study to explore barriers to, enablers of, or opportunities for perinatal depression health services implementations in Ethiopia.

Methods

We conducted a total of 13 face to face interviews with mental and maternal health service administrators from different levels of the Ethiopian healthcare system. We interviewed in Amharic (a local language), transcribed and translated into English, and imported into NVivo. We analysed the translated interviews inductively using thematic framework analysis.

Results

The study identified: (i) health administrators’ low literacy about perinatal depression as individual level barriers; (ii) community low awareness, health-seeking behaviours and cultural norms about perinatal depression as socio-cultural level barriers; (iii) lack of government capacity, readiness, and priority of screening and managing perinatal depression as organisational level barriers; and (iv) lack of mental health policy, strategies, and healthcare systems as structural level barriers of perinatal mental health implementation in Ethiopia. The introduction of the new Mental Health Gap Action Programme (mhGap), health professionals’ commitment, and simplicity of screening programs were identified enablers of, or opportunities for, perinatal mental health service implementation.

Conclusions

This qualitative inquiry identified important barriers and potential opportunities that could be used to address perinatal depression in Ethiopia. Building the capacity of policy makers and planners, strengthening the mental healthcare system and governance should be a priority issue for an effective integration of maternal mental health care with the routine maternal health services in Ethiopia.
When a maternal heterozygous mutation of the CYP24A1 gene leads to infantile hypercalcemia through a maternal uniparental disomy of chromosome 20
Authors: Hureaux Marguerite , Chantot-Bastaraud Sandra , Cassinari Kévin , Martinez Casado Edouard , Cuny Ariane , Frébourg Thierry , Vargas-Poussou Rosa , Bréhin Anne-Claire
Published: May 2021

Background

Infantile hypercalcemia is an autosomal recessive disorder caused either by mutations in the CYP24A1 gene (20q13.2) or in the SLC34A1 gene (5q35.3). This disease is characterized by hypercalcemia, hypercalciuria and nephrocalcinosis in paediatric patients.

Maternal uniparental disomy of chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. UPD(20)mat patients manifest a phenotype similar to that of Silver-Russell syndrome and small for gestational age-short stature.

Case presentation

We report here the genetic and clinical characterization of a male child with a phenotype of infantile hypercalcemia, postnatal growth retardation, and minor dysmorphic features. Genetic analysis using a next generation sequencing panel revealed a homozygous pathogenic variant of CYP24A1. The absence of the variant in the father led to microsatellite segregation analysis, suggestive of UPD. SNP-array revealed a large terminal copy neutral loss of heterozygosity leading to CYP24A1 homozygosity. SNP-array data of parent–child trio confirmed a UPD(20)mat responsible for both infantile hypercalcemia and Silver-Russell syndrome-like traits.

Conclusion

This is the first report of uniparental disomy of chromosome 20 revealed by infantile hypercalcemia related to CYP24A1 biallelic homozygous variants, underlying the importance of controlling allelic segregation in cases of homozygosity.
The effects of citrulline supplementation on meta-inflammation and insulin sensitivity in type 2 diabetes: a randomized, double-blind, placebo-controlled trial
Authors: Abbaszadeh Fatemeh , Azizi Samaneh , Mobasseri Majid , Ebrahimi-Mameghani Mehrangiz
Published: May 2021

Background

This study aimed to examine the effects of l-citrulline (l-CIT) on low-grade inflammation (meta-inflammation) and insulin sensitivity in type 2 diabetes (T2D) patients since it has exhibited hypoglycemic and anti-inflammatory effects in most animal studies.

Methods

In this double-blind, placebo-controlled randomized clinical trial, 54 patients with T2D referred to specialized clinics of Tabriz University of Medical Sciences were assigned to l-CIT group (receiving orally one 3 g sachet of l-CIT daily before breakfast) or placebo group (receiving orally one 3 g sachet of microcrystalline cellulose daily before breakfast) for eight weeks. Serum levels of fasting blood glucose, hemoglobin A1c (HbA1c), CIT, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), and toll-like receptor 4 (TLR-4) were determined. The quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment of β-cell function (HOMA-B) index were estimated at the baseline and post-intervention.

Results

No significant difference was observed between the studied parameters at the baseline. l-CIT supplementation significantly reduced not only serum concentrations of fasting blood glucose but also HbA1c, serum IL-6 and TLR-4 levels in the l-CIT group (p < 0.05). Additionally, at the end of the study serum levels of CIT increased significantly in l-CIT group compared to the baseline and placebo group. Fasting blood glucose concentrations and HbA1c significantly decreased after the intervention compared to the placebo. There was no significant difference in serum IL-6, TLR-4, MCP-1 levels, as well as QUICKI and HOMA-B index between the two groups, even after adjusting for baseline variables and confounders.

Conclusions

Our findings revealed that, although l-CIT supplementation significantly reduced fasting blood glucose concentrations, HbA1c and increased serum levels of CIT. It seems it could not significantly improve insulin sensitivity and meta-inflammation biomarkers. Additional studies with longer duration and different doses of l-CIT are required.

Trial registration The protocol of this clinical trial is registered at the Iranian Registry of Clinical Trials (registration no: IRCT20100209003320N16 at www.irct.ir)