bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility of common family Anatidae bird species to clade 2.3.4.4e H5N6 high pathogenicity avian influenza virus: an experimental infection study
Authors: Soda Kosuke , Tomioka Yukiko , Hidaka Chiharu , Matsushita Mayu , Usui Tatsufumi , Yamaguchi Tsuyoshi
Published: April 2022

Background

There were large outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4e H5N6 viruses in the winter of 2016–2017 in Japan, which caused large numbers of deaths among several endangered bird species including cranes, raptors, and birds in Family Anatidae. In this study, susceptibility of common Anatidae to a clade 2.3.4.4e H5N6 HPAI virus was assessed to evaluate their potential to be a source of infection for other birds. Eurasian wigeons (Mareca penelope), mallards (Anas platyrhynchos), and Northern pintails (Anas acuta) were intranasally inoculated with 106, 104, or 102 50% egg infectious dose (EID50) of clade 2.3.4.4e A/teal/Tottori/1/2016 (H5N6).

Results

All birds survived for 10 days without showing any clinical signs of infection. Most ducks inoculated with ≥ 104 EID50 of virus seroconverted within 10 days post-inoculation (dpi). Virus was mainly shed via the oral route for a maximum of 10 days, followed by cloacal route in late phase of infection. Virus remained in the pancreas of some ducks at 10 dpi. Viremia was observed in some ducks euthanized at 3 dpi, and ≤ 106.3 EID50 of virus was recovered from systemic tissues and swab samples including eyeballs and conjunctival swabs.

Conclusions

These results indicate that the subject duck species have a potential to be a source of infection of clade 2.3.4.4e HPAI virus to the environment and other birds sharing their habitats. Captive ducks should be reared under isolated or separated circumstances during the HPAI epidemic season to prevent infection and further viral dissemination.
Combined immunization with inactivated vaccine reduces the dose of live B. abortus A19 vaccine
Authors: He Chuan-Yu , Zhang Yu-Zhuo , Liu Meng-Zhi , Zhao Hai-Long , Ren Li-Song , Liu Bao-Shan , He Sun , Chen Ze-Liang
Published: April 2022

Background

Brucella spp. is an important zoonotic pathogen responsible for brucellosis in humans and animals.Brucella abortusA19 strain is a widespread vaccine in China. However, it has a drawback of residual virulence in animals and humans.

Methods

In this study, the BALB/c mice were inoculated with either 100 μL PBS(control group, C group), 109 CFU/mL inactivatedB. abortusA19 strain (I group), 105 CFU/mL (low-dose group, L group) 106 CFU/mL liveB. abortusA19 strain (high-dose group, H group), or 105 CFU/mL liveB. abortusA19 strain combined with 109 CFU/mL inactivatedB. abortusA19 strain (LI group). Mice were challenged withB. abortusstrain 2308 at 7 week post vaccination. Subsequently, the immune and protective efficacy of the vaccines were evaluated by measuring splenic bacterial burden, spleen weight, serum IgG, interferon-gamma (IFN-γ), interleukin-4 (IL-4) percentage of CD4 + and CD8 + T cells of mice via bacterial isolation, weighing, ELISA and flow cytometry, respectively.

Results

The splenic bacterial burden and spleen weight of the mice in group LI were mostly equivalent to the mice of group H. Moreover,Brucella-specific serum IgG, IFN-γ, IL-4, and the percentage of CD4+and CD8+T cells of the LI group mice were similar to those of the H group. In the subsequent challenge test, both vaccines conferred protective immunity to wild-type (WT) 2308 strain. In addition, the levels of IL-4 and IFN-γ, CD4+and CD8+T cells in these mice were similar to those of the mice in the H group.

Conclusions

Combined immunization with low dose live vaccine and inactivated vaccine allowed to reduce the liveB. abortusA19 vaccine, dose with an equivalent protection of the high-dose live vaccine.
Development of a droplet digital PCR assay to detect bovine alphaherpesvirus 1 in bovine semen
Authors: Yu Zhichao , Zhao Zhiguo , Chen Linjun , Yan Han , Cui Qiang , Ju Xianghong , Yong Yanhong , Liu Xiaoxi , Ma Xingbin , Zhang Guanhua
Published: April 2022

Background

Infectious bovine rhinotracheitis (IBR) caused by bovine alphaherpesvirus 1 (BoHV-1) is one of the most important contagious diseases in bovine. This is one of the most common infectious disease of cattle. This has led to high economic losses in the cattle farming industry. BoHV-1 can potentially be transmitted via semen during natural or artificial insemination (AI). Therefore, testing methods for the early diagnosis of BoHV-1 infection are urgently needed for international trade of ruminant semen. In this study, we developed a novel droplet digital PCR (ddPCR) assay for the detection of BoHV-1 DNA in semen samples.

Results

The ddPCR results showed that the detection limit was 4.45 copies per reaction with high reproducibility. The established method was highly specific for BoHV-1 and did not show cross-reactivity with specify the organisms (BTV, BVDV, Brucella, M . bovis). The results of clinical sample testing showed that the positivity rate of ddPCR (87.8%) was higher than that of qPCR (84.1%).

Conclusions

The ddPCR assay showed good accuracy for mixed samples and could be a new added diagnostic tool for detecting BoHV-1.
Retro-protein XXA is a remarkable solubilizing fusion tag for inclusion bodies
Authors: Xie Xi , Wu Pei , Huang Xiaochen , Bai WenFeng , Li Bowen , Shi Ning
Published: April 2022

Background

Producing large amounts of soluble proteins from bacteria remains a challenge, despite the help of current various solubilizing fusion tags. Thus, developing novel tags is necessary. Antifreeze protein (AFP) has excellent solubility and hydrophilicity, but there are no current reports on its use as a solubilizing fusion tag. Additionally, there is no precedent for using retro-proteins (reverse sequence) as solubilizing fusion tags. Therefore, we selected the antifreeze protein AXX and obtained its retro-protein XXA by synthesizing the XXA gene for the development of a new solubilizing fusion tag.

Results

XXA exhibits better stability and ease of expression than AXX; hence, we focused the development of the solubilizing fusion tag on XXA. XXA fused with the tested inclusion bodies, significantly increasing the soluble expression compared with commonly used solubilizing fusion tags such as GST, Trx, Sumo, MBP, and NusA. The tested proteins became soluble after fusion with the XXA tag, and they could be purified. They maintained a soluble form after XXA tag removal. Finally, we used enzymatic digestion reaction and western blot experiments to verify that bdNEDP1 and NbALFA, which were soluble expressed by fusion with XXA, were active.

Conclusion

We developed the novel solubilizing fusion tag XXA, which could more effectively facilitate the soluble expression of inclusion bodies compared with current commonly used tags. XXA could function at both low and high temperatures, and its moderate molecular weight has a limited impact on the output. These properties make XXA an ideal fusion tag for future research and industrial production. Moreover, for the first time, we highlighted the broad potential of antifreeze protein as a solubilizing fusion tag, bringing retro-protein into practical application.
A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: with a special focus on the oxidant, apoptotic, and anti-inflammatory activities
Authors: Moutabian Hossein , Majdaeen Mehrsa , Ghahramani-Asl Ruhollah , Yadollahi Masoumeh , Gharepapagh Esmaeil , Ataei Gholamreza , Falahatpour Zahra , Bagheri Hamed , Farhood Bagher
Published: April 2022

Purpose

5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorectal cancer treatment. Nevertheless, its toxicity to normal tissues and the development of tumor resistance are the main obstacles to successful cancer chemotherapy and hence, its clinical application is limited. The use of resveratrol can increase 5-FU-induced cytotoxicity and mitigate the unwanted adverse effects. This study aimed to review the potential therapeutic effects of resveratrol in combination with 5-FU against colorectal cancer.

Methods

According to the PRISMA guideline, a comprehensive systematic search was carried out for the identification of relevant literature in four electronic databases of PubMed, Web of Science, Embase, and Scopus up to May 2021 using a pre-defined set of keywords in their titles and abstracts. We screened 282 studies in accordance with our inclusion and exclusion criteria. Thirteen articles were finally included in this systematic review.

Results

The in vitro findings showed that proliferation inhibition of colorectal cancer cells in the groups treated by 5-FU was remarkably higher than the untreated groups and the co-administration of resveratrol remarkably increased cytotoxicity induced by 5-FU. The in vivo results demonstrated a decrease in tumor growth of mice treated by 5-FU than the untreated group and a dramatic decrease was observed following combined treatment of resveratrol and 5-FU. It was also found that 5-FU alone and combined with resveratrol could regulate the cell cycle profile of colorectal cancer cells. Moreover, this chemotherapeutic agent induced the biochemical and histopathological changes in the cancerous cells/tissues and these alterations were synergized by resveratrol co-administration (for most of the cases), except for the inflammatory mediators.

Conclusion

The results obtained from this systematic review demonstrated that co-administration of resveratrol could sensitize the colorectal cancer cells to 5-FU treatment via various mechanisms, including regulation of cell cycle distribution, oxidant, apoptosis, anti-inflammatory effects.
Plasmodium falciparum multiplicity of infection and pregnancy outcomes in Congolese women from southern Brazzaville, Republic of Congo
Authors: Massamba Jean Erick , Djontu Jean Claude , Vouvoungui Christevy Jeannhey , Kobawila Charles , Ntoumi Francine
Published: April 2022

Background

Investigating whether the multiplicity of Plasmodium falciparum infection (MOI) is related to pregnancy outcomes, is of interest in sub-Saharan area where malaria is highly endemic. The present study aimed to characterize the genetic diversity of P. falciparum in women at delivery from Southern Brazzaville, and investigate whether the MOI is associated with maternal anaemia, preterm delivery, or low birth weight.

Methods

This was a cross sectional study carried out with samples collected between March 2014 and April 2015 from 371 women recruited at delivery at a Health Centre in southern Brazzaville, Republic of Congo. Matched peripheral, placental, and cord blood collected from each of the women at delivery were used for the detection of P. falciparum microscopic and submicroscopic parasitaemia, and parasite DNA genotyping by nested PCR.

Results

From 371 recruited women, 27 were positive to microscopic malaria parasitaemia while 223 women harboured submicroscopic parasitaemia. All msp-1 block 2 family allelic types (K1, MAD20 and RO33) were observed in all the three compartments of blood, with K1 being most abundant. K1 (with 12, 10, and 08 alleles in the peripheral, placental, and cord blood respectively) and MAD20 (with 10, 09, and 06 alleles in the respective blood compartments) were more diverse compared to RO33 (with 06, 06, and 05 alleles in the respective blood compartments). From the 250 women with microscopic and/or submicroscopic parasitaemia, 38.5%, 30.5%, and 18.4% of peripheral, placental and cord blood sample, respectively, harboured more than one parasite clone, and polyclonal infection was more prevalent in the peripheral blood of women with microscopic parasitaemia (54.5%) compared to those with submicroscopic parasitaemia (36.7%) (p = 0.02). The mean multiplicity of genotypes per microscopic and submicroscopic infection in peripheral blood was higher in anemic women (2.00 ± 0.23 and 1.66 ± 0.11, respectively) than in non-anaemic women (1.36 ± 0.15 and 1.45 ± 0.06, respectively) (p = 0.03 and 0.06). In logistic regression, women infected with four or more clones of the parasite were 9.4 times more likely to be anaemic than women harbouring one clone. This association, however, was only observed with the peripheral blood infection. No significant association was found between the MOI and low birth weight or preterm delivery.

Conclusions

These results indicate that the genetic diversity of P. falciparum is high in pregnant women from southern Brazzaville in the Republic of Congo, and the multiplicity of the infection might represent a risk for maternal anaemia.
Could a culturally and age-appropriate song contribute towards malaria prevention in primary school learners?
Authors: Anderson Chad M. , Eloff Irma , Kruger Taneshka
Published: April 2022

Background

Although it is a preventable disease, malaria continues to present one of the major global health challenges. The disease is especially deadly to children under the age of 5 years. This is partly due to the fact that they have yet to build up an immune system to help protect them against malaria. As a prevention strategy, music is one way of communicating knowledge to young children and could therefore potentially be used to change children’s behaviour in order to avoid getting sick from malaria. This exploratory study aimed to compare intervention strategies designed to educate and improve knowledge growth about malaria and its prevention in Grade 3 learners in a high-risk malaria region in Vhembe District, Limpopo Province, South Africa.

Methods

Various intervention strategies were employed and evaluated to determine the most effective intervention method. The study was split into two Phases. Phase 1 used a culturally and age-appropriate song as an intervention, along with a drama piece, a song and drama piece combination, and a control group. The most effective intervention strategy determined during Phase 1 was then subjected to Phase 2, against a control group to validate its efficacy. Questionnaires were used during pre-intervention and post-intervention interviews to evaluate the knowledge growth, if any, of the learners of selected primary schools in two different areas in Vhembe District. Pre-intervention interviews were followed by a specific intervention, based on the respective study groups. After 6 weeks, the post-intervention interviews were done to determine how much learners managed to learn and retain from the intervention received.

Results

The study found that the group that had only the song as intervention was the most effective learning intervention method in both Phases 1 and 2. Both phases showed that there was statistical significance in almost all of the nine questions asked on the questionnaires.

Conclusions

The study concluded that a culturally and age-appropriate song can play a significant role in developing behavioural changes and spreading awareness against disease in a high-risk malaria region.
Accuracy of a rapid diagnosis test, microscopy and loop-mediated isothermal amplification in the detection of asymptomatic Plasmodium infections in Korhogo, Northern Côte d’Ivoire
Authors: Benié Edjronké M. A. , Silué Kigbafori D. , Ding Xavier C. , Yeo Issa , Assamoi J. B. , Tuo Karim , Gnagne Akpa P. , Esso Lasme J. C. E. , Coulibaly Jean T. , Assi Serge-Brice , Bonfoh Bassirou , Yavo William , N’Goran Eliézer K.
Published: April 2022

Background

Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d’Ivoire, using nested polymerase chain reaction (nPCR) as reference.

Methods

A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference.

Results

The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8–5.3), 5.2% (95% CI 3.9–6.6) and 18.8% (95% CI 16.4–21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1–29.4) and 100% for RDT, 20.0% (95% CI 7.8–32) and 100% for microscopy, and 93.3% (95% CI 85.7–100) and 95.4% (95% CI 92.2–100) for LAMP.

Conclusion

In Northern Côte d’Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections.
Using the Ghana malaria indicator survey to understand the difference between female and male-headed households and their prevention and testing for malaria among children under 5
Authors: Iddrisu Daniel , Moyer Cheryl A.
Published: April 2022

Background

Globally, 94% of malaria deaths occur in sub-Saharan Africa, and children under age 5 account for 70% of malaria-related mortality in the region. This study sought to examine differences between female-headed households (FHHs) and male-headed households (MHHs) with regard to malaria prevention and testing among children under age 5 (U5) in Ghana.

Methods

This cross-sectional study used publicly available data from the 2019 Ghana Malaria Indicator Survey (GMIS). Frequencies and descriptive statistics were calculated for all key variables. Bivariate analyses comparing FHHs and MHHs were conducted using t tests and Chi-square analysis. A P value of 0.05 was taken for statistical significance.

Results

Five thousand one hundred and eighty one household were identified, of which 1938 (37.4%) were female-headed and 3243 (62.6%) were male-headed. 51.7% of FHHs included a child U5, whereas 67.8% of MHHs included a child U5. MHHs were significantly more likely to own an ITN than FHHs (83.1% vs. 78.3%, P < 0.001), whereas FHHs were more likely to report taking malaria prevention steps such as spraying the house with insecticide, filling in stagnant puddles, and keeping surroundings clear (all significant at P < 0.001). U5 children in MHHs were more likely to sleep under a bed net the night preceding the survey (51.0%) than U5 children in FHHs (44.8%), although the finding was not statistically significant. The rates of fevers in the previous two weeks among children U5 were similar across MHH and FHH (24.2% vs. 22.3%), and the rates of testing for malaria among those who experienced a febrile episode were also similar across MHHs and FHHs (39.0% vs. 41.3%). Of those tested, the percentage of U5 children who tested positive for malaria was also similar across MHHs and FHHs (63.9% vs. 63.0%).

Conclusions

Both FHHs and MHHs in Ghana make a concerted effort to prevent and test for malaria among children U5 in their households. Despite differences in malaria prevention strategies, there were no significant difference in febrile episodes, malaria testing, and rates of positivity, suggesting that malaria prevention is challenging for all households in Ghana. In the face of a newly-developed malaria vaccine, future research is warranted to ensure adequate uptake across all households.
A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma
Authors: Duan Jin-Ling , Chen Wei , Xie Juan-Juan , Zhang Mao-Lei , Nie Run-Cong , Liang Hu , Mei Jie , Han Kai , Xiang Zhi-Cheng , Wang Feng-Wei , Teng Kai , Chen Ri-Xin , Deng Min-Hua , Yin Yi-Xin , Zhang Nu , Xie Dan , Cai Mu-Yan
Published: April 2022

Background

Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC.

Methods

CircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC.

Results

We found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin–proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients.

Conclusions

CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance.

Graphical Abstract

CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.
Eradication of Helicobacter pylori alleviates lipid metabolism deterioration: a large-cohort propensity score-matched analysis
Authors: Wang Zeyu , Wang Weijun , Gong Rui , Yao Hailing , Fan Mengke , Zeng Junchao , Xu Sanping , Lin Rong
Published: April 2022

Background

The impact of Helicobacter pylori (H. pylori) eradication on metabolism of lipid and the potential predictor of such changes remain unclear.

Methods

This study retrospectively included subjects who underwent at least two 13C urea breath tests between 2015 and 2019 at Wuhan Union Hospital. Based on two H. pylori13C examination results, subjects were divided into propensity score-matched persistently negative (HPN), persistently positive (HPP), and eradication (HPE) groups. The changes in lipid measurements from before to after H. pylori eradication, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides, were compared within and between groups. Forty-two candidate factors were tested for their ability to predict lipid metabolism changes after H. pylori eradication.

Results

After propensity score matching, 3412 matched cases were analyzed. Within-group comparisons showed significantly decreased HDL (P <  0.001) and increased LDL (P <  0.001) at the second examination in both the HPE and HPP groups. Between-group comparisons showed that the HDL decrease of the HPE group was significantly larger and smaller when compared with the HPN (P = 0.001) and HPP (P = 0.004) group, respectively. Uni- and multivariate analyses showed that low diastolic blood pressure (DBP) (P = 0.002) and high mean platelet volume (MPV) (P = 0.001) before eradication were associated with increased HDL after eradication. Low total protein (TP) (P <  0.001) was associated with decreased LDL after eradication.

Conclusions

Compared with sustained H. pylori infectious states, H. pylori eradication alleviated the lipid metabolism deterioration but did not restore it to the uninfected level within 1.5 years after eradication. Patients with low DBP, high MPV, and low TP may reap a greater lipid-metabolism benefit from H. pylori eradication.
The dose-response relationship of serum uric acid with Dyslipidaemia and its components: a cross-sectional study of a Chinese multi-ethnic cohort
Authors: Peng Lian , Liu Leilei , Ma Nana , Yang Fan , Nie Chan , Yang Tingting , Zeng Qibing , Wang Ziyun , Xu Degan , Ma Lu , Xu Yuyan , Hong Feng
Published: April 2022

Background

The association between serum uric acid (SUA) and the components of dyslipidaemia and their dose-response relationships have not been thoroughly explored. This study assessed the relationship between SUA and each dyslipidaemia component in Dong, Miao, and Bouyei populations in Guizhou by sex and ethnicities and investigated the dose-response relationship.

Methods

In total, 16,092 participants aged 30–79 years from The China Multi-Ethnic Cohort (CMEC) Study were examined. Multivariable logistic regression models were applied to explore the relationship between SUA and each dyslipidaemia component by sex and three ethnicities. The dose-response associations between SUA and various dyslipidaemias were investigated using restricted cubic spline regression.

Results

After controlling for confounding factors, the SUA level in total participants positively correlated with each dyslipidaemia component, and women had higher odds ratios (ORs) for each dyslipidaemia component than men (Pfor trend < 0.001). At the SUA level > 6.37 mg/dL, ORs (95% CI) for dyslipidaemia in the Dong, Miao and Bouyei were 2.89 (2.00–4.19), 2.43 (1.70–3.48), and 3.26 (2.23–4.78), respectively. When the SUA concentration increased by 1 mg/dL, the ORs (95% CI) for total dyslipidaemia was 1.31 (1.24–1.37). A positive dose-response but nonlinear association was found between SUA and total dyslipidaemia, high total cholesterol, and low HDL, whereas an inverse U-shaped association was found between SUA and high LDL-C (P-nonlinear< 0.0001).

Conclusion

The SUA level was positively correlated with each dyslipidaemia component in Dong, Miao, and Bouyei adults, and sex and ethnic differences were also found. A nonlinear dose-response relationship was found between SUA levels and dyslipidaemia and its components. Further research is warranted to investigate the causal link between SUA levels and dyslipidaemia incidence.
Identification and evaluation of circulating small extracellular vesicle microRNAs as diagnostic biomarkers for patients with indeterminate pulmonary nodules
Authors: Zheng Di , Zhu Yuming , Zhang Jiyang , Zhang Wei , Wang Huizhen , Chen Hao , Wu Chunyan , Ni Jian , Xu Xiaoya , Nian Baoning , Chen Sheng , Wang Beibei , Li Xiaofang , Zhang Yanan , Zhang Jiatao , Zhong Wenzhao , Xiong Lei , Li Fugen , Zhang Dadong , Xu Jianfang , Jiang Gening
Published: April 2022

Background

The identification of indeterminate pulmonary nodules (IPNs) following a low-dose computed tomography (LDCT) is a major challenge for early diagnosis of lung cancer. The inadequate assessment of IPNs’ malignancy risk results in a large number of unnecessary surgeries or an increased risk of cancer metastases. However, limited studies on non-invasive diagnosis of IPNs have been reported.

Methods

In this study, we identified and evaluated the diagnostic value of circulating small extracellular vesicle (sEV) microRNAs (miRNAs) in patients with IPNs that had been newly detected using LDCT scanning and were scheduled for surgery. Out of 459 recruited patients, 109 eligible patients with IPNs were enrolled in the training cohort (n = 47) and the test cohort (n = 62). An external cohort (n = 99) was used for validation. MiRNAs were extracted from plasma sEVs, and assessed using Small RNA sequencing. 490 lung adenocarcinoma samples and follow-up data were used to investigate the role of miRNAs in overall survival.

Results

A circulating sEV miRNA (CirsEV-miR) model was constructed from five differentially expressed miRNAs (DEMs), showing 0.920 AUC in the training cohort (n = 47), and further identified in the test cohort (n = 62) and in an external validation cohort (n = 99). Among five DEMs of the CirsEV-miR model, miR-101-3p and miR-150-5p were significantly associated with better overall survival (p = 0.0001 and p = 0.0069). The CirsEV-miR scores were calculated, which significantly correlated with IPNs diameters (p < 0.05), and were able to discriminate between benign and malignant PNs (diameter ≤ 1 cm). The expression patterns of sEV miRNAs in the benign, adenocarcinoma in situ/minimally invasive adenocarcinoma, and invasive adenocarcinoma subgroups were found to gradually change with the increase in aggressiveness for the first time. Among all DEMs of the three subgroups, five miRNAs (miR-30c-5p, miR-30e-5p, miR-500a-3p, miR-125a-5p, and miR-99a-5p) were also significantly associated with overall survival of lung adenocarcinoma patients.

Conclusions

Our results indicate that the CirsEV-miR model could help distinguish between benign and malignant PNs, providing insights into the feasibility of circulating sEV miRNAs in diagnostic biomarker development.

Trial registration: Chinese Clinical Trials: ChiCTR1800019877. Registered 05 December 2018, https://www.chictr.org.cn/showproj.aspx?proj=31346.

Graphical Abstract
Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo
Authors: Chen Zhou , Hu Yue , Mao Xinggang , Nie Dan , Zhao Hui , Hou Zheng , Li Mingkai , Meng Jingru , Luo Xiaoxing , Xue Xiaoyan
Published: April 2022

Background

Outbreaks of infection due to multidrug-resistant (MDR) bacteria, especially Gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by MDR bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity.

Results

Here, we designed a series of dendritic poly-peptides (DPP1 to DPP12) to encapsulate ASOs to form DSPE-mPEG2000 decorated ASOs/DPP nanoparticles (DP-AD1 to DP-AD12) and observed that amphipathic DP-AD2, 3, 7 or 8 with a positive charge ≥ 8 showed great efficiency to deliver ASOs into bacteria, but only the two histidine residues contained DP-AD7 and DP-AD8 significantly inhibited the bacterial growth and the targeted gene expression of tested bacteria in vitro. DP-AD7anti-acpP remarkably increased the survival rate of septic mice infected by ESBLs-E. coli, exhibiting strong antibacterial effects in vivo.

Conclusions

For the first time, we designed DPP as a potent carrier to deliver ASOs for combating MDR bacteria and demonstrated the essential features, namely, amphipathicity, 8–10 positive charges, and 2 histidine residues, that are required for efficient DPP based delivery, and provide a novel approach for the development and research of the antisense antibacterial strategy.

Graphical Abstract
Quality of life and mental health in emerging adults with cerebral palsy compared to the general population
Authors: Schmidt Silke , Markwart Henriette , Rapp Marion , Guyard Audrey , Arnaud Catherine , Fauconnier Jérôme , Thyen Ute , Hahm Stefanie , Vidart d’Egurbide Bagazgoïtia Nicolas , Muehlan Holger
Published: April 2022

Background

While evidence concerning Quality of Life (QoL) in youth with cerebral palsy (CP) in comparison to the general population has been accumulating, there is a lack of studies exploring differences on a wider range of positive and negative mental health outcomes in emerging adults.

Methods

This binational case control study is part of the SPARCLE cohort study on QoL and participation of youth with CP. QoL (WHOQOL-BREF), depression (PHQ-9), anxiety (GAD-7) and self-efficacy (GSE) were assessed in 198 emerging adults with CP and 593 emerging adults from the general population, matched for country of residence, age and gender. ANCOVAs with impairment and pain as covariates were run.

Results

Similar levels of QoL were found in both samples, except for the environmental domain, with better QoL for emerging adults with CP compared to the general population. There were significant descriptive differences regarding depression with worse levels in the CP sample, however, also worse levels of self-efficacy. Pain as a covariate had a significant negative impact on all measures, leading to poorer self-efficacy while worsening depression and anxiety; impairment had a significant worsening impact on physical QoL and self-efficacy only.

Conclusion

Similar expressions of mental health outcomes in emerging adults with CP and the general population indicate the high adaptive capability of emerging adults with CP.
Adaptation and validation of the HIV Knowledge Questionnaire-18 for the general population of Indonesia
Authors: Arifin Bustanul , Rokhman M. Rifqi , Zulkarnain Zulkarnain , Perwitasari Dyah Aryani , Manggau Marianti , Rauf Saidah , Noor Rasuane , Padmawati Retna Siwi , Postma Maarten J. , Massi Muhammad Nasrum , van der Schans Jurjen
Published: April 2022

Background

Despite a global decline in new HIV/AIDS cases in low-middle countries, cases are increasing in Indonesia. Low knowledge about the disease among the general population is one of the major factors responsible for this trend. Indonesia does not have a validated instrument to assess HIV/AIDS knowledge. The HIV Knowledge Questionnaire-18 (HIV-KQ-18) has been translated into several languages and is one of the most extensively used instruments for assessing HIV/AIDS knowledge. This paper describes the process of adapting and validating the HIV-KQ-18, an instrument to assess the level of HIV/AIDS knowledge in the general population of Indonesia.

Methods

In the adaptation phase, feedback for the initial Bahasa Indonesia version was gathered from two HIV activists, an obstetrician, two general practitioners, and 60 pilot participants. At the validation stage, we distributed the instrument link via Google Form to 6 major regions in Indonesia. Validity was measured using known-group validity and construct validity. The construct validity was assessed using an exploratory factor analysis (EFA) with a polychoric correlation matrix. Cronbach’s alpha was used to analyze the internal consistency.

Results

Based on the findings in the adaptation phase, additional descriptions (namely synonyms or examples) were added to 6 items to make them more understandable. In the validation phase, 1,249 participants were recruited. The a priori hypothesis in known-group validity was supported. We also found three items that did not meet the construct validity. Based on the acceleration factor approach to interpret the scree tree in the factor analysis, using only two factors was preferable. Cronbach's alpha values were 0.75 and 0.71 representing good internal reliability.

Conclusion

The HIV-KQ-18 Bahasa Indonesia is considered a valid and reliable instrument to assess the level of HIV/AIDS knowledge in Indonesia.
Sense of coherence moderates the relationship between social capital and oral health‑related quality of life in schoolchildren: a 10-year cohort study
Authors: Knorst Jessica Klöckner , Vettore Mario Vianna , Brondani Bruna , Emmanuelli Bruno , Tomazoni Fernanda , Ardenghi Thiago Machado
Published: April 2022

Background

This study aimed to evaluate the moderating effect of sense of coherence (SOC) on the relationship between social capital and oral health-related quality of life (OHRQoL) among schoolchildren.

Methods

A cohort study was conducted in the city of Santa Maria, Brazil, involving children aged 1–5 years at baseline who were reassessed after 10 years in adolescence (11–15 years-old). Social capital was assessed at baseline and follow-up through social networks and social trust. Sense of coherence scale (SOC-13) and the short form of the Child Perceptions Questionnaire 11–14 (CPQ11–14) were measured at 10-years follow-up. Demographic and socioeconomic characteristics, and dental caries were also evaluated. Moderating effect of SOC on the relationship between social capital and OHRQoL was tested using multilevel adjusted Poisson regression analysis and simple slope test.

Results

From the 639 subjects assessed at baseline, 429 were reassessed at follow-up (cohort retention rate 67.1%). Moderate and high levels of SOC demonstrated a moderating effect on the relationship between social capital and OHRQoL. Among individuals who presented low social capital at baseline and follow-up, those who had high SOC reported, respectively, an impact 63% and 70% lower on OHRQoL when compared to those with low SOC. The greatest margin effect was observed in individuals with low social capital and low SOC at follow-up (24.25; p < 0.05).

Conclusion

Our findings suggest that SOC moderates the negative impact of low social capital on poor OHRQoL in schoolchildren.
Co-production practice and future research priorities in United Kingdom-funded applied health research: a scoping review
Authors: Smith Helen , Budworth Luke , Grindey Chloe , Hague Isabel , Hamer Natalie , Kislov Roman , van der Graaf Peter , Langley Joe
Published: April 2022

Background

Interest in and use of co-production in healthcare services and research is growing. Previous reviews have summarized co-production approaches in use, collated outcomes and effects of co-production, and focused on replicability and reporting, but none have critically reflected on how co-production in applied health research might be evolving and the implications of this for future research. We conducted this scoping review to systematically map recent literature on co-production in applied health research in the United Kingdom to inform co-production practice and guide future methodological research.

Methods

This scoping review was performed using established methods. We created an evidence map to show the extent and nature of the literature on co-production and applied health research, based on which we described the characteristics of the articles and scope of the literature and summarized conceptualizations of co-production and how it was implemented. We extracted implications for co-production practice or future research and conducted a content analysis of this information to identify lessons for the practice of co-production and themes for future methodological research.

Results

Nineteen articles reporting co-produced complex interventions and 64 reporting co-production in applied health research met the inclusion criteria. Lessons for the practice of co-production and requirements for co-production to become more embedded in organizational structures included (1) the capacity to implement co-produced interventions, (2) the skill set needed for co-production, (3) multiple levels of engagement and negotiation, and (4) funding and institutional arrangements for meaningful co-production. Themes for future research on co-production included (1) who to involve in co-production and how, (2) evaluating outcomes of co-production, (3) the language and practice of co-production, (4) documenting costs and challenges, and (5) vital components or best practice for co-production.

Conclusion

Researchers are operationalizing co-production in various ways, often without the necessary financial and organizational support required and the right conditions for success. We argue for accepting the diversity in approaches to co-production, call on researchers to be clearer in their reporting of these approaches, and make suggestions for what researchers should record. To support co-production of research, changes to entrenched academic and scientific practices are needed.

Protocol registration details: The protocol for the scoping review was registered with protocols.io on 19 October 2021: https://dx.doi.org/10.17504/protocols.io.by7epzje.
An assessment of adherence to the WHO-delineated good manufacturing practice by the pharmaceutical companies in Kabul, Afghanistan
Authors: Roien Rohullah , Shrestha Rajeev , Yadav Kashikant , Ozaki Akihiko , Ahmadi M. Bashir , Kaneda Yudai , Kotera Yasuhiro , Sapkota Binaya , Shrestha Sunil
Published: April 2022

Background

Afghanistan, a low-income landlocked country, is continuously suffering from domestic war and conflicts; the country struggles to provide quality healthcare services, including affordable medicinal products in the required quantity. Moreover, the quality standards of domestic pharmaceutical companies have not been established yet. One of the internationally recognized guidelines for monitoring manufacturing processes in pharmaceutical companies is Good Manufacturing Practice (GMP), recommended by World Health Organization (WHO). Therefore, this study aimed to assess whether a pharmaceutical company in Kabul, Afghanistan adheres to the GMP standards established by WHO.

Method

A descriptive cross-sectional study was conducted to assess the WHO-delineated GMP compliance of 25 pharmaceutical companies in Kabul, Afghanistan. The inspection checklist was developed by Afghanistan's National Medicine and Healthcare Products Regulatory Authority (NMHRA) using the WHO-delineated GMP guidelines. In addition, direct observation, interviews with respective delegates, and documentation reviews were conducted to collect research data.

Result

Only 38.33% (1.14 ± 1.08) of GMP contents were complied. Personnel 66.67% (2 ± 1.15) and materials 58.67% (1.76 ± 1.11) were the most commonly complied components, whereas the product recall 12.98% (0.39 ± 0.85), quality assurance 16.44% (0.49 ± 0.81) and quality control laboratory 28.35% (0.85 ± 1.12) were the least complied ones.

Conclusion

None of the GMP components was fully adhered to by the pharmaceutical companies in Kabul, Afghanistan. Quality control and assurance should be implemented immediately, including validation and qualification practices.
Cross-sectional and longitudinal associations of active travel, organised sport and physical education with accelerometer-assessed moderate-to-vigorous physical activity in young people: the International Children’s Accelerometry Database
Authors: Ikeda Erika , Guagliano Justin M. , Atkin Andrew J. , Sherar Lauren B. , Ekelund Ulf , Hansen Bjørge , Northstone Kate , van Sluijs Esther ,   On behalf of the International Children’s Accelerometry Database (ICAD) Collaborators, Salmon Jo , Riddoch Chris , Judge Ken , Cooper Ashley , Griew Pippa , Andersen L. B. , Anderssen S. , Cardon G. , Davey R. , Hallal P. , Jago R. , Janz K. F. , Kriemler S. , Møller N. , Northstone K. , Pate R. , Puder J. J. , Reilly J. , Salmon J. , Sardinha L. B. , van Sluijs E. M. F.
Published: April 2022

Background

Physical activity (PA) declines during childhood. Important sources of PA are active travel, organised sport and physical education (PE), but it is unclear how these domain-specific PA sources contribute to (changes in) daily moderate-to-vigorous PA (MVPA) in young people. This study aimed to examine (1) the cross-sectional association between domain-specific physical activity (i.e., active travel, organised sport and PE) and daily minutes in accelerometer-assessed MVPA; and (2) the longitudinal association between domain-specific physical activity at baseline and change in daily minutes in MVPA.

Methods

Participants (baseline age 11.3 ± .1.2 years) were drawn from three studies in the International Children’s Accelerometry Database. The contribution of self-reported standardised active travel, organised sport and PE to accelerometer-measured daily minutes in MVPA was examined using linear regression. In cross-sectional analyses, MVPA was regressed on each PA domain in separate models, adjusted for study, age, sex, maternal education, season, and monitor wear time. In longitudinal analyses, change in MVPA was regressed on each of the baseline PA domains, additionally adjusting for changes in season and wear time, follow-up duration, and baseline MVPA. R-squared was used to compare variance explained by each PA domain.

Results

In the cross-sectional analyses (n = 3871), organised sport (standardised β = 3.81, 95% confidence interval [95%CI] = 3.06, 4.56) and active travel (β = 3.46, 95%CI = 2.73, 4.19) contributed more to daily MVPA than PE (β = 0.82, 95%CI = -0.02, 1.66). Compared to the base model which included only covariates (R2 = 21.5%), organised sport (absolute change: + 1.9%) and active travel (+ 1.7%) models explained more of the variance than the PE model (± < 0.1%). Associations followed a similar pattern in the longitudinal analyses (n = 2302), but none of the PA domains predicted change in MVPA (organised sport: standardised β = 0.85, 95%CI = -0.03, 1.72; active travel: β = 0.68, 95%CI = -0.14, 1.50; PE: β = 0.02, 95%CI = -0.87, 0.91).

Conclusions

A multi-sectoral approach covering a wide range of PA domains should be promoted to minimise the age-related decline in MVPA during childhood.
Optimizing NK-92 serial killers: gamma irradiation, CD95/Fas-ligation, and NK or LAK attack limit cytotoxic efficacy
Authors: Navarrete-Galvan Lydia , Guglielmo Michael , Cruz Amaya Judith , Smith-Gagen Julie , Lombardi Vincent C. , Merica Rebecca , Hudig Dorothy
Published: April 2022

Background

The NK cell line NK-92 and its genetically modified variants are receiving attention as immunotherapies to treat a range of malignancies. However, since NK-92 cells are themselves tumors, they require irradiation prior to transfer and are potentially susceptible to attack by patients’ immune systems. Here, we investigated NK-92 cell-mediated serial killing for the effects of gamma-irradiation and ligation of the death receptor Fas (CD95), and NK-92 cell susceptibility to attack by activated primary blood NK cells.

Methods

To evaluate serial killing, we used51Cr-release assays with low NK-92 effector cell to target Raji, Daudi or K562 tumor cell (E:T) ratios to determine killing frequencies at 2-, 4-, 6-, and 8-h.

Results

NK-92 cells were able to kill up to 14 Raji cells per NK-92 cell in 8 h. NK-92 cells retained high cytotoxic activity immediately after irradiation with 10 Gy but the cells surviving irradiation lost > 50% activity 1 day after irradiation. Despite high expression of CD95, NK-92 cells maintained their viability following overnight Fas/CD95-ligation but lost some cytotoxic activity. However, 1 day after irradiation, NK-92 cells were more susceptible to Fas ligation, resulting in decreased cytotoxic activity of the cells surviving irradiation. Irradiated NK-92 cells were also susceptible to killing by both unstimulated and IL-2 activated primary NK cells (LAK). In contrast, non-irradiated NK-92 cells were more resistant to attack by NK and LAK cells.

Conclusions

Irradiation is deleterious to both the survival and cytotoxicity mediated by NK-92 cells and renders the NK-92 cells susceptible to Fas-initiated death and death initiated by primary blood NK cells. Therefore, replacement of irradiation as an antiproliferative pretreatment and genetic deletion of Fas and/or NK activation ligands from adoptively transferred cell lines are indicated as new approaches to increase therapeutic efficacy.