bluuebunny/crossref_metadata_2025 huggingface dataset:
Professional advice for primary healthcare workers in Ethiopia: a social network analysis
Authors: Sabot Kate , Blanchet Karl , Berhanu Della , Spicer Neil , Schellenberg Joanna
Published: June 2020

Background

In an era of increasingly competitive funding, governments and donors will be looking for creative ways to extend and maximise resources. One such means can include building upon professional advice networks to more efficiently introduce, scale up, or change programmes and healthcare provider practices. This cross-sectional, mixed-methods, observational study compared professional advice networks of healthcare workers in eight primary healthcare units across four regions of Ethiopia. Primary healthcare units include a health centre and typically five satellite health posts.

Methods

One hundred sixty staff at eight primary healthcare units were interviewed using a structured tool. Quantitative data captured the frequency of healthcare worker advice seeking and giving on providing antenatal, childbirth, postnatal and newborn care. Network and actor-level metrics were calculated including density (ratio of ties between actors to all possible ties), centrality (number of ties incident to an actor), distance (average number of steps between actors) and size (number of actors within the network). Following quantitative network analyses, 20 qualitative interviews were conducted with network study participants from four primary healthcare units. Qualitative interviews aimed to interpret and explain network properties observed. Data were entered, analysed or visualised using Excel 6.0, UCINET 6.0, Netdraw, Adobe InDesign and MaxQDA10 software packages.

Results

The following average network level metrics were observed: density .26 (SD.11), degree centrality .45 (SD.08), distance 1.94 (SD.26), number of ties 95.63 (SD 35.46), size of network 20.25 (SD 3.65). Advice networks for antenatal or maternity care were more utilised than advice networks for post-natal or newborn care. Advice networks were typically limited to primary healthcare unit staff, but not necessarily to supervisors. In seeking advice, a colleague’s level of training and knowledge were valued over experience. Advice exchange primarily took place in person or over the phone rather than over email or online fora. There were few barriers to seeking advice.

Conclusion

Informal, inter-and intra-cadre advice networks existed. Fellow primary healthcare unit staff were preferred, particularly midwives, but networks were not limited to the primary healthcare unit. Additional research is needed to associate network properties with outcomes and pilot network interventions with central actors.
Cost objects: How is your ED performing?
Authors: Fuentes-Cáceres Verónica , Neriz Liliana , Núñez-Mondaca Alicia , Mateo Ricardo
Published: June 2020

Background

The aim of this study is to a propose a standardized methodology to identify a list of cost objects that can be used by any ED to compute costs considering that the resulting data must facilitate unit management by improving the information available for decision-making.

Methods

This study considers two stages, first, we analyzed the case-mix of two hospitals collecting their data to define and diagram their processes, activities and to obtain their cost objects, second, we used four additional hospitals to validate our initial findings.

Results

We recognized 59 cost objects. Hospitals may have all these cost objects or just a subset of them depending on the services they provide.

Conclusions

Among the main benefits of our cost objects definition are: the possibility of tracing the processes generated by the services delivered by EDs, the economic sense in its grouping, the chance of using any costing methodology, the flexibility with other classification systems such as DRGs and ICDs, and the opportunity of costing for both diseases and treatments. Furthermore, cost comparison among hospitals using our final 59 cost objects list is more accurate and based on comparable units. In different EDs, each cost object will be the result of a similar combination of activities performed. We also present the results of applying this cost objects list to a particular ED. A total of 53 out of 59 cost objects were identified for that particular unit within a calendar year.
Medical insurance and health equity in health service utilization among the middle-aged and older adults in China: a quantile regression approach
Authors: Fan Guorui , Deng Zhaohua , Wu Xiang , Wang Yang
Published: June 2020

Background

China has achieved nearly universal coverage of the Social Basic Medical Insurance (SBMI), which aims to reduce the disease burden and improve the utilization of health services. We investigated the association between China’s health insurance schemes and health service utilization of middle-aged and older adults at different quantiles, and then explored whether the SBMI could help reduce the underutilization of health services among the middle-aged and older adults in China.

Methods

Survey data of middle-aged and older adults were drawn from the China Health and Retirement Longitudinal Study (CHARLS). A linear quantile mixed regression model was utilized to provide a comprehensive understanding of the relationship between SBMI and health service utilization, which was measured by the total medical expenditure. We took the New Rural Cooperative Medical Scheme (NCMS) as the reference level and examined the associations of the Urban Employee Basic Medical Insurance (UEBMI) and the Urban Resident Basic Medical Insurance (URBMI) with health service utilization.

Results

The quantile regression analysis revealed a significant positive association between URBMI and health service utilization at the 0.75 (β = 1.608, p < 0.01), 0.8 (β = 1.578, p < 0.01), 0.85 (β = 1.473, p < 0.01), 0.9 (β = 1.403, p < 0.01) and 0.95 (β = 1.152, p < 0.01) quantiles, and also a significant positive association between UEBMI and health service utilization at the 0.85 (β = 1.196, p < 0.01), 0.9 (β = 1.070, p < 0.01) and 0.95 (β = 0.736, p < 0.01) quantiles. Results showed that URBMI was significantly associated with an improvement in inpatient health service utilization of the middle-aged and older adults, and a significant positive association between UEBMI and inpatient health service utilization was observed at 0.1 (β = 0.559, p < 0.01), 0.25 (β = 0.420, p < 0.05), 0.5 (β = 0.352, p < 0.05), and 0.75 (β = 0.306, p < 0.05) quantiles.

Conclusions

Inequity in health service utilization exists among the middle-aged and older adults across urban and rural Chinese areas, and it can be explained by the different reimbursement benefits of SBMI types.
Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma
Authors: Guo Lingyun , Wang Zhenjiang , Du Yuanyuan , Mao Jie , Zhang Junqiang , Yu Zeyuan , Guo Jiwu , Zhao Jun , Zhou Huinian , Wang Haitao , Gu Yanmei , Li Yumin
Published: June 2020

Background

Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients.

Methods

We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients’ database, and obtained the data and results of immunohistochemistry.

Results

We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis.

Conclusion

Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.
Long non-coding RNA SNHG22 facilitates the malignant phenotypes in triple-negative breast cancer via sponging miR-324-3p and upregulating SUDS3
Authors: Fang Xuan , Zhang Jin , Li Chunyan , Liu Jinjin , Shi Zhendong , Zhou Peng
Published: June 2020

Background

Increasing evidence has indicated the important role of long non-coding RNAs (lncRNAs) in regulating the development and progression of cancers, including triple-negative breast cancer (TNBC). Small nucleolar RNA host gene 22 (SNHG22) is a novel lncRNA that has been identified as tumor-contributor in ovarian carcinoma. However, its function has not been explored in TNBC.

Methods

qRT-PCR was used to identify gene expression at mRNA level while western blot was utilized to analyze the protein level. Functional assays were implemented to identify changes on the proliferation, apoptosis and motility of TNBC cells under different conditions. Additionally, mechanistic assays, such as RIP assay, RNA pull down assay and luciferase reporter assay, were applied to assess relationships between molecules.

Results

SNHG22 represented a high expression level in TNBC tissues and cells. Besides, SNHG22 silencing restrained the proliferation, migration and invasion of TNBC cells. Furthermore, miR-324-3p that was lowly expressed in TNBC cells was conformed to be sponged by SNHG22. Moreover, upregulated miR-324-3p inhibited cell proliferation and motility in TNBC. Subsequently, we identified that SUDS3, a tumor-facilitator with elevated expression in TNBC, was the downstream target of SNHG22/miR-324-3p axis. Of note, miR-324-3p repression or SUDS3 overexpression could rescue the anti-tumor effect of SNHG22 silencing on the malignant phenotypes of TNBC cells.

Conclusion

LncRNA SNHG22 facilitated cell growth and motility in TNBC via sponging miR-324-3p and upregulating SUDS3, highlighting a new promising road for TNBC treatment development.
Arsenic trioxide potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK-mediated endoplasmic reticulum stress
Authors: Hu Xiaoli , Cai Jiayi , Zhu Jianyi , Lang Wenjing , Zhong Jihua , Zhong Hua , Chen Fangyuan
Published: June 2020

Background

Acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have a high relapse rate and poor prognosis. This study aims to explore the underlying mechanism of combining Gilteritinib with ATO at low concentration in the treatment of FLT3-ITD positive leukemias.

Methods

We used both in vitro and in vivo studies to investigate the effects of combination of Gilteritinib with ATO at low concentration on FLT3-ITD positive leukemias, together with the underlying molecular mechanisms of these processes.

Results

Combination of Gilteritinib with ATO showed synergistic effects on inhibiting proliferation, increasing apoptosis and attenuating invasive ability in FLT3-ITD-mutated cells and reducing tumor growth in nude mice. Results of western blot indicated that Gilteritinib increased a 160KD form of FLT3 protein on the surface of cell membrane. Detection of endoplasmic reticulum stress marker protein revealed that IRE1a and its downstream signal phosphorylated JNK were suppressed in Gilteritinib-treated FLT3-ITD positive cells. The downregulation of IRE1a induced by Gilteritinib was reversed with addition of ATO. Knockdown of IRE1a diminished the combinatorial effects of Gilteritinib plus ATO treatment and combination of tunicamycin (an endoplasmic reticulum pathway activator) with Gilteritinib achieved the similar effect as treatment with Gilteritinib plus ATO.

Conclusions

Thus, ATO at low concentration potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK signal pathway, targeting IRE1a to cooperate with Gilteritinib may serve as a new theoretical basis on FLT3-ITD mutant AML treatment.
DNA methylation-based classification and identification of bladder cancer prognosis-associated subgroups
Authors: Tian Zijian , Meng Lingfeng , Long Xingbo , Diao Tongxiang , Hu Maolin , Wang Miao , Liu Ming , Wang Jianye
Published: June 2020

Background

Bladder cancer (BCA) is the most common urinary tumor, but its pathogenesis is unclear, and the associated treatment strategy has rarely been updated. In recent years, a deeper understanding of tumor epigenetics has been gained, providing new opportunities for cancer detection and treatment.

Methods

We identified prognostic methylation sites based on DNA methylation profiles of BCA in the TCGA database and constructed a specific prognostic subgroup.

Results

Based on the consistent clustering of 402 CpGs, we identified seven subgroups that had a significant association with survival. The difference in DNA methylation levels was related to T stage, N stage, M stage, grade, sex, age, stage and prognosis. Finally, the prediction model was constructed using a Cox regression model and verified using the test dataset; the prognosis was consistent with that of the training set.

Conclusions

The classification based on DNA methylation is closely related to the clinicopathological characteristics of BCA and determines the prognostic value of each epigenetic subtype. Therefore, our findings provide a basis for the development of DNA methylation subtype-specific therapeutic strategies for human bladder cancer.
Determining a critical threshold for G6PD activity below which red blood cell response to oxidative stress is poor
Authors: Swastika Maria , Harahap Alida R. , Panggalo Lydia V. , Jusman Sri Widia A. , Satyagraha Ari W.
Published: June 2020

Background

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine, which has a long half-life, screening for G6PD deficiency becomes a necessity where those with < 70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.

Methods

RBC models were developed to analyse the effect of oxidant on RBC oxidative markers namely total glutathione (GSH)and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from two G6PD heterozygous women with different G6PD activities were also analysed for comparison.

Results

There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, the CuCl RBC model showed that in low G6PD activities (10–30%) cells, the MDA level is lower compared to the rest of the models (p < 0.05). The ex vivo models however were in line with the hypothesis, although the result was not significant (p = 0.5). There was a significant difference between RBC with < 60% and those with > 80% G6PD activities in CuCl RBC model, but not in ex vivo RBC (p = 0.5). Genotyping heterozygous subjects showed G6PDViangchan variant with 2.97 U/gHb (33% activity) and 6.58 U/gHb (74% activity).

Conclusions

The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old World Health Organization threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex vivo model.
Malaria infection, disease and mortality among children and adults on the coast of Kenya
Authors: Kamau Alice , Mtanje Grace , Mataza Christine , Mwambingu Gabriel , Mturi Neema , Mohammed Shebe , Ong’ayo Gerald , Nyutu Gideon , Nyaguara Amek , Bejon Philip , Snow Robert W.
Published: June 2020

Background

Malaria transmission has recently fallen in many parts of Africa, but systematic descriptions of infection and disease across all age groups are rare. Here, an epidemiological investigation of parasite prevalence, the incidence of fevers associated with infection, severe hospitalized disease and mortality among children older than 6 months and adults on the Kenyan coast is presented.

Methods

A prospective fever surveillance was undertaken at 6 out-patients (OPD) health-facilities between March 2018 and February 2019. Four community-based, cross sectional surveys of fever history and infection prevalence were completed among randomly selected homestead members from the same communities. Paediatric and adult malaria at Kilifi county hospital was obtained for the 12 months period. Rapid Diagnostic Tests (CareStart™ RDT) to detect HRP2-specific to Plasmodium falciparum was used in the community and the OPD, and microscopy in the hospital. Crude and age-specific incidence rates were computed using Poisson regression.

Results

Parasite prevalence gradually increased from childhood, reaching 12% by 9 years of age then declining through adolescence into adulthood. The incidence rate of RDT positivity in the OPD followed a similar trend to that of infection prevalence in the community. The incidence of hospitalized malaria from the same community was concentrated among children aged 6 months to 4 years (i.e. 64% and 70% of all hospitalized and severe malaria during the 12 months of surveillance, respectively). Only 3.7% (12/316) of deaths were directly attributable to malaria. Malaria mortality was highest among children aged 6 months–4 years at 0.57 per 1000 person-years (95% CI 0.2, 1.2). Severe malaria and death from malaria was negligible above 15 years of age.

Conclusion

Under conditions of low transmission intensity, immunity to disease and the fatal consequences of infection appear to continue to be acquired in childhood and faster than anti-parasitic immunity. There was no evidence of an emerging significant burden of severe malaria or malaria mortality among adults. This is contrary to current modelled approaches to disease burden estimation in Africa and has important implications for the targeting of infection prevention strategies based on chemoprevention or vector control.
Transthoracic echocardiography monitoring during ASD closure using an artificial hand system
Authors: Fu Yun-Ching , Tsai Shen Kou , Jian Wen-Yen , Shyu Tsung-Cheng , Chuang Chieh-Mao , Hwang Betau
Published: June 2020

Aim

Continuous real-time echocardiographic monitoring is essential for guidance during ASD closure. However, transthoracic echocardiography (TTE) can only be implemented intermittently during fluoroscopy. We evaluate a novel approach to provide real-time imaging during the entire procedure.

Finding

We developed a custom-made TTE monitoring apparatus using artificial hand (AH-TTE) that enables real-time TTE images during atrial septal defect (ASD) closure. Thirty-two patients underwent successful device implantation using AH-TTE monitoring without complications. The median duration for real-time AH-TTE monitoring was 22 min and the median fluoroscopy time was 7.2 min. One case of pericardial effusion and one of transient bradycardia event due to air embolism was detected. All patients had uneventful recoveries.

Conclusions

Our simple and novel monitoring technique with AH-TTE provides TEE-like monitoring and may be a new alternative method for ASD closure. It gives real-time stable TTE images and minimizes radiation exposure for the interventional team during fluoroscopy.
Clinical efficacy of enhanced recovery after surgery (ERAS) program in patients undergoing radical prostatectomy: a systematic review and meta-analysis
Authors: Zhao Yurong , Zhang Shaobo , Liu Bianjiang , Li Jie , Hong Hanxia
Published: June 2020

Background

Enhanced recovery after surgery (ERAS) protocol has been identified to be beneficial in the amount of operations such as gastrointestinal surgery. However, the efficacy and safety in robot-assisted laparoscopic prostatectomy/laparoscopic radical prostatectomy (RALP/LRP) still remain controversial.

Method

We searched randomized controlled trials and retrospective cohort studies comparing ERAS versus conventional care for prostate cancer patients who have undergone RALP/LRP. ERAS-related data were extracted, and quality of included studies was assessed using the Newcastle-Ottawa quality assessment scale and the Jadad scale.

Result

As a result, seven trials containing 784 prostate cancer patients were included. ERAS was observed to be significantly associated with shorter length of hospital stay (SMD − 2.55, 95%CI − 3.32 to − 1.78, P < 0.05), shorter time to flatus (SMD − 1.55, 95%CI − 2.26 to − 0.84, P < 0.05), shorter time to ambulate (SMD − 6.50, 95%CI − 10.91 to − 2.09, P < 0.05), shorter time to defecate (SMD − 2.80, 95%CI − 4.56 to − 1.04, P < 0.05), and shorter time to remove drainage tube (SMD − 2.72, 95%CI − 5.31 to − 0.12, P < 0.05). Otherwise, no significant difference was reported in other measurements.

Conclusions

In conclusion, ERAS can reduce length of hospital stay, time to flatus, time to defecate, time to ambulate, and time to remove drainage tube in prostate cancer patients who have undergone RALP/LRP compared with conventional care.
Effectiveness of jejunostomy for enteral nutrition during complete thoracoscopic and laparoscopic Ivor-Lewis esophagectomy in thoracic segment esophageal carcinoma
Authors: Tian Jieyong , Mei Xinyu , Guo Mingfa , Xiong Ran , Sun Xiangxiang
Published: June 2020

Background

Although jejunostomy is widely used in complete thoracoscopic and laparoscopic minimally invasive Ivor-Lewis esophagectomy, its clinical effectiveness remains undefined. This study aimed to assess the therapeutic and side effects of jejunostomy in patients undergoing Ivor-Lewis esophagectomy for thoracic segment esophageal carcinoma.

Methods

A total of 1400 patients with esophageal carcinoma who underwent minimally invasive esophagectomy in the Thoracic Surgery of our hospital from 2015 to 2018 were retrospectively evaluated. Of these, 356 and 1044 were treated with nasojejunal feeding tubes (Nasojejunal group) and by jejunostomy (Jejunostomy group), respectively. Clinicopathologic factors, postoperative complications and tubule-related complications between the two groups were compared.

Results

Both groups were well-balanced for clinicopathological data, except tumor location, which was significantly different (P < 0.001). Operation time (208.8 ± 53.5 min vs. 218.1 ± 43.2 min) was shorter in the Jejunostomy group compared with the Nasojejunal group, while intraoperative (26.6 ± 10.4 min vs 18.4 ± 9.1 min) and postoperative (38.6 ± 6.9 min vs 18.5 ± 7.6 min) indwelling times of nutrition tubes were prolonged (all P < 0.05). Postoperative pulmonary infection (17.0% vs 22.2%), incision infection (0.2% vs 1.1%), nutrient tube slippage (0.2% vs 5.1%) and nutrient reflux 1 (0.1% vs 5.6%) rates were reduced in the Jejunostomy group compared with the Nasojejunal group (P < 0.05). Meanwhile, ileus rates perioperatively (1.7% vs 0.3%) and at 3 postoperative months (1.7% vs 0.3%) were both higher in the Jejunostomy group compared with the Nasojejunal group.

Conclusions

Jejunostomy is a reliable enteral nutrition method in Ivor-Lewis esophagectomy for thoracic segment esophageal carcinoma.
The effect of low- versus normal-pressure pneumoperitoneum during laparoscopic colorectal surgery on the early quality of recovery with perioperative care according to the enhanced recovery principles (RECOVER): study protocol for a randomized controlled study
Authors: Albers Kim I. , Polat Fatih , Panhuizen Ivo F. , Snoeck Marc M. J. , Scheffer Gert-Jan , de Boer Hans D. , Warlé Michiel C.
Published: June 2020

Background

There is increasing evidence for the use of lower insufflation pressures during laparoscopic surgery. Deep neuromuscular blockade allows for a safe reduction in intra-abdominal pressure without compromising the quality of the surgical field. While there is considerable evidence to support superior surgical conditions during deep neuromuscular blockade, there is only a limited amount of studies investigating patient outcomes. Moreover, results are not always consistent between studies and vary between different types of laparoscopic surgery. This study will investigate the effect of low-pressure pneumoperitoneum facilitated by deep NMB on quality of recovery after laparoscopic colorectal surgery.

Methods

The RECOVER study is a multicenter double-blinded randomized controlled trial consisting of 204 patients who will be randomized in a 1:1 fashion to group A, low-pressure pneumoperitoneum (8 mmHg) facilitated by deep neuromuscular blockade (post tetanic count of 1–2), or group B, normal-pressure pneumoperitoneum (12 mmHg) with moderate neuromuscular blockade (train-of-four response of 1–2). The primary outcome is quality of recovery on postoperative day 1, quantified by the Quality of Recovery-40 questionnaire.

Discussion

Few studies have investigated the effect of lower insufflation pressures facilitated by deep neuromuscular blockade on patient outcomes after laparoscopic colorectal procedures. This study will identify whether low pressure pneumoperitoneum and deep neuromuscular blockade will enhance recovery after colorectal laparoscopic surgery and, moreover, if this could be a valuable addition to the Enhanced Recovery After Surgery guidelines.

Trial registration

EudraCT 2018-001485-42. Registered on April 9, 2018. Clinicaltrials.govNCT03608436. Registered on July 30, 2018.
Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum
Authors: Liu Hui , Cui Xin-Yu , Xu Dan-Dan , Wang Fei , Meng Lin-Wen , Zhao Yue-Meng , Liu Meng , Shen Shi-Jun , He Xiao-Hui , Fang Qiang , Tao Zhi-Yong , Jiang Ci-Zong , Zhang Qing-Feng , Gu Liang , Xia Hui
Published: June 2020

Background

Malaria caused by Plasmodium spp. is still a major threat to public health globally. The various approaches to developing new antimalarial agents rely on the understanding of the complex regulatory mechanisms of dynamic gene expression in the life-cycle of these malaria parasites. The nuclear members of the evolutionarily conserved actin-related protein nuclear (ARP) superfamily are the major components of nucleosome remodelling complexes. In the human malaria parasite Plasmodium falciparum, bioinformatics analysis has predicted three ARP orthologues: PfArp1, PfArp4 and PfArp6. However, little is known about the biological functions of putative PfArp4. In this study, we aimed to investigate the function and the underlying mechanisms of PfArp4 gene regulation.

Methods

A conditional gene knockdown approach was adopted by incorporating the glucosamine-inducible glmS ribozyme sequence into the 3’ UTR of the PfArp4 and PfArp6 genes. The transgenic parasites PfArp4-Ty1-Ribo, PfArp6-Ty1-Ribo and pL6-PfArp4-Ty1::PfArp6-HA were generated by the CRISPR-Cas9 technique. The knockdown effect in the transgenic parasite was measured by growth curve assay and western blot (WB) analysis. The direct interaction between PfArp4 and PfArp6 was validated by co-IFA and co-IP assays. The euchromatic gene expression mediated through H2A.Z (histone H2A variant) deposition and H3K9ac modification at promoters and regulated by PfArp4, was determined by RNA-seq and ChIP-seq.

Results

The inducible knockdown of PfArp4 inhibited blood-stage development of P. falciparum. PfArp4 and PfArp6 were colocalized in the nucleus of P. falciparum parasites. PfArp4 gene knockdown altered the global transcriptome. PfArp4 protein colocalized with the histone variant H2A.Z and euchromatic marker H3K9ac in intergenic regions. The inducible downregulation of PfArp4 resulted in the depletion of H2A.Z and lower H3K9ac levels at the upstream regions of eukaryotic genes, thereby repressing the transcriptional abundance of H2A.Z-dependent genes.

Conclusions

Our findings suggest that PfArp4 regulates the cell cycle by controlling H2A.Z deposition and affecting centromere function, contributing to the understanding the complex epigenetic regulation of gene expression and the development of P. falciparum.
G9a regulates tumorigenicity and stemness through genome-wide DNA methylation reprogramming in non-small cell lung cancer
Authors: Pangeni Rajendra P. , Yang Lu , Zhang Keqiang , Wang Jinhui , Li Wendong , Guo Chao , Yun Xinwei , Sun Ting , Wang Jami , Raz Dan J.
Published: June 2020

Background

Eukaryotic histone methyltransferases 2 (EHMT2 or G9A) has been regarded as a potential target for non-small cell lung cancer (NSCLC) therapy. This study investigated the regulatory roles of G9A in tumorigenesis and stemness in NSCLC. We isolated and enriched tumor-initiating cells (TIC) from surgically resected NSCLC tissues by FACS and sphere formation assays. We then knocked down G9A using shRNA and carried out genome-wide 850K methylation array and RNA sequencing analyses. We carried out in vivo tumorigenecity asssay using mice xenografts and examined G9A interactions with its novel target using chromatin Immunoprecipitation (ChIP).

Results

We identified 67 genes hypomethylated and 143 genes upregulated following G9A knockdown of which 43 genes were both hypomethylated and upregulated. We selected six genes (CDYL2, DPP4, SP5, FOXP1, STAMBPL1, and ROBO1) for validation. In addition, G9A expression was higher in TICs and targeting G9a by shRNA knockdown or by selective inhibitor UNC0642 significantly inhibited the expression of cancer stem cell markers and sphere forming capacity, in vitro proliferation, and in vivo growth. Further, transient overexpression of FOXP1, a protein may promote normal stem cell differentiation, in TICs resulted in downregulation of stem cell markers and sphere forming capacity and cell proliferation in vitro indicating that the genes we identified are directly regulated by G9A through aberrant DNA methylation and subsequent expression. Similarly, ChIP assay has shown that G9a interacts with its target genes through H3K9me2 and downregulation of H3K9me2 following G9a knockdown disrupts its interaction with its target genes.

Conclusions

These data suggest that G9A is involved in lung cancer stemness through epigenetic mechanisms of maintaining DNA methylation of multiple lung cancer stem cell genes and their expression. Further, targeting G9A or its downstream genes could be a novel therapeutic approach in treating NSCLC patients.
Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
Authors: Gao Chao , Wang Xiaodong , Lu Jian , Li Zhilin , Jia Haowen , Chen Minghao , Chang Yuchen , Liu Yanhong , Li Peiyuan , Zhang Baotong , Du Xuezhi , Qi Feng
Published: June 2020

Background

Mesenchymal stem cells (MSCs) have become a promising candidate for cell-based immune therapy for acute rejection (AR) after heart transplantation due to possessing immunomodulatory properties. In this study, we evaluated the efficacy of soluble fibronectin-like protein 2 (sFgl2) overexpressing mesenchymal stem cells (sFgl2-MSCs) in inhibiting AR of heart transplantation in mice by regulating immune tolerance through inducing M2 phenotype macrophage polarization.

Methods and results

The sFgl2, a novel immunomodulatory factor secreted by regulatory T cells, was transfected into MSCs to enhance their immunosuppressive functions. After being co-cultured for 72 h, the sFgl2-MSCs inhibited M1 polarization whereas promoted M2 of polarization macrophages through STAT1 and NF-κB pathways in vitro. Besides, the sFgl2-MSCs significantly enhanced the migration and phagocytosis ability of macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Further, the application potential of sFgl2-MSCs in AR treatment was demonstrated by heterotopic cardiac transplantation in mice. The tissue damage and macrophage infiltration were evaluated by H&E and immunohistochemistry staining, and the secretion of inflammatory cytokines was analyzed by ELISA. The results showed that sFgl2-MSCs injected intravenously were able to locate in the graft, promote the M2 polarization of macrophages in vivo, regulate the local and systemic immune response, significantly protect tissues from damaging, and finally prolonged the survival time of mice heart grafts.

Conclusion

sFgl2-MSCs ameliorate AR of heart transplantation by regulating macrophages, which provides a new idea for the development of anti-AR treatment methods after heart transplantation.
Correction to: MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells
Authors: Wang Hongtao , Wang Mengge , Wang Yu , Wen Yuqi , Chen Xiaoyuan , Wu Dan , Su Pei , Zhou Wen , Shi Lihong , Zhou Jiaxi
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Climate change implications for the distribution of the babesiosis and anaplasmosis tick vector, Rhipicephalus (Boophilus) microplus
Authors: Marques Roberta , Krüger Rodrigo F. , Peterson A. Townsend , de Melo Larissa F. , Vicenzi Natália , Jiménez-García Daniel
Published: June 2020

Climate change ranks among the most important issues globally, affecting geographic distributions of vectors and pathogens, and inducing losses in livestock production among many other damaging effects. We characterized the potential geographic distribution of the ticksRhipicephalus(Boophilus)microplus, an important vector of babesiosis and anaplasmosis globally. We evaluated potential geographic shifts in suitability patterns for this species in two periods (2050 and 2070) and under two emissions scenarios (RCPs 4.5 and 8.5). Our results anticipate increases in suitability worldwide, particularly in the highest production areas for cattle. The Indo-Malayan region resulted in the highest cattle exposure under both climate change projections (2050), with increases in suitability of > 30%. This study illustrates how ecological niche modeling can be used to explore probable effects of climate change on disease vectors, and the possible consequences on economic dimensions.
Crosstalk between Neospora caninum and the bovine host at the maternal-foetal interface determines the outcome of infection
Authors: Jiménez-Pelayo Laura , García-Sánchez Marta , Collantes-Fernández Esther , Regidor-Cerrillo Javier , Horcajo Pilar , Gutiérrez-Expósito Daniel , Espinosa José , Benavides Julio , Osoro Koldo , Pfarrer Christiane , Ortega-Mora Luis Miguel
Published: June 2020

Neospora caninumis an apicomplexan cyst-forming parasite that is considered one of the main causes of abortion. The pathogenic mechanisms associated with parasite virulence at the maternal-foetal interface that are responsible for the outcome of infection are largely unknown. Here, utilizing placentomes from cattle experimentally infected with high-virulence (Nc-Spain7) and low-virulence (Nc-Spain1H) isolates, we studied key elements of the innate and adaptive immune responses, as well as components of the extracellular matrix (ECM), at 10 and 20 days post-infection (dpi). The low-virulence isolate elicited a robust immune response characterized by upregulation of genes involved in pathogen recognition, chemokines and pro-inflammatory cytokines, crucial for its adequate control. In addition, Nc-Spain1H triggered the expression of anti-inflammatory cytokines and other mechanisms implicated in the maintenance of ECM integrity to ensure foetal survival. In contrast, local immune responses were initially (10 dpi) impaired by Nc-Spain7, allowing parasite multiplication. Subsequently (20 dpi), a predominantly pro-inflammatory Th1-based response and an increase in leucocyte infiltration were observed. Moreover, Nc-Spain7-infected placentomes from animals carrying non-viable foetuses exhibited higher expression of the IL-8, TNF-α, iNOS and SERP-1 genes and lower expression of the metalloproteases and their inhibitors than Nc-Spain7-infected placentomes from animals carrying viable foetuses. In addition, profound placental damage characterized by an alteration in the ECM organization in necrotic foci, which could contribute to foetal death, was found. Two different host-parasite interaction patterns were observed at the bovine placenta as representative examples of different evolutionary strategies used by this parasite for transmission to offspring.
Ethical dilemmas due to the Covid-19 pandemic
Authors: Robert René , Kentish-Barnes Nancy , Boyer Alexandre , Laurent Alexandra , Azoulay Elie , Reignier Jean
Published: June 2020

The devastating pandemic that has stricken the worldwide population induced an unprecedented influx of patients in ICUs, raising ethical concerns not only surrounding triage and withdrawal of life support decisions, but also regarding family visits and quality of end-of-life support. These ingredients are liable to shake up our ethical principles, sharpen our ethical dilemmas, and lead to situations of major caregiver sufferings. Proposals have been made to rationalize triage policies in conjunction with ethical justifications. However, whatever the angle of approach, imbalance between utilitarian and individual ethics leads to unsolvable discomforts that caregivers will need to overcome. With this in mind, we aimed to point out some critical ethical choices with which ICU caregivers have been confronted during the Covid-19 pandemic and to underline their limits. The formalized strategies integrating the relevant tools of ethical reflection were disseminated without deviating from usual practices, leaving to intensivists the ultimate choice of decision.
Competence perceptions of veterinary nursing students and registered veterinary nurses in Ireland: a mixed methods explanatory study
Authors: Dunne Karen , Brereton Bernadette , Duggan Vivienne , Campion Deirdre P.
Published: June 2020

Background

Veterinary regulators require veterinary nursing students to demonstrate clinical competence prior to registration and practice as a veterinary nurse. However, in common with other medical professions, there is no one broadly accepted definition of competence. Studies in nursing have revealed that practicing nurses may view newly qualified colleagues as lacking competence, leading to disillusionment with nursing training programmes. Similar studies are lacking in veterinary nursing, despite the profession having recently undergone a similar transition from workplace-based training to undergraduate education.

Methods

A mixed methods explanatory study surveyed 66 Irish registered veterinary nurses and 31 first year veterinary nursing students at two Irish third level institutions to obtain their views on what constitutes veterinary nursing competence and when veterinary nurses develop it. The surveys were followed by student focus groups and semi-structured one-on-one interviews with registered veterinary nurses. Content analysis was employed to analyse the surveys, while the focus groups and interview transcripts underwent thematic analysis.

Results

Students perceived competence primarily as the ability to provide patient care, and they expected it to develop close to the time of graduation. RVNs held a broader definition of competence, incorporating leadership skills and confidence as well as patient care provision. RVNs expected it to take approximately two years of workplace-based experience post-graduation for a veterinary nurse to develop competence. In addition, RVNs recognised that anxiety felt by many newly qualified veterinary nurses during this period could be attenuated by mentorship from more experienced colleagues.

Conclusions

Irish RVNs and veterinary nursing students perceive competence differently, similar to previous findings from the nursing profession. Educators and regulators should provide explicit descriptions of terms such as ‘competence’ to avoid confusion and possible disillusionment amongst veterinary nursing stakeholders.
Singular spectrum analysis-based image sub-band decomposition filter banks
Authors: Evers Julia , Evers Florian , Goppelt Florian , Schmidt-Vollus Ronald
Published: June 2020

This paper presents a novel type of a filter bank for image decomposition that incorporates “singular spectrum analysis” (SSA). SSA is based on “singular value decomposition” (SVD).The presented filter banks provide good directional selectivity. Sub-band images highlight exposed directional features such as 0∘,90∘,+ 45∘, and − 45∘of the input image. The proposed method can be seen as a tool to separate an image into layers or to present an image as a sum of its high-frequency directional components and a low-frequency approximation.
Recognition of cooking activities through air quality sensor data for supporting food journaling
Authors: Gerina Federica , Massa Silvia M. , Moi Francesca , Reforgiato Recupero Diego , Riboni Daniele
Published: June 2020

Unhealthy behaviors regarding nutrition are a global risk for health. Therefore, the healthiness of an individual’s nutrition should be monitored in the medium and long term. A powerful tool for monitoring nutrition is a food diary; i.e., a daily list of food taken by the individual, together with portion information. Unfortunately, frail people such as the elderly have a hard time filling food diaries on a continuous basis due to forgetfulness or physical issues. Existing solutions based on mobile apps also require user’s effort and are rarely used in the long term, especially by elderly people. For these reasons, in this paper we propose a novel architecture to automatically recognize the preparation of food at home in a privacy-preserving and unobtrusive way, by means of air quality data acquired from a commercial sensor. In particular, we devised statistical features to represent the trend of several air parameters, and a deep neural network for recognizing cooking activities based on those data. We collected a large corpus of annotated sensor data gathered over a period of 8 months from different individuals in different homes, and performed extensive experiments. Moreover, we developed an initial prototype of an interactive system for acquiring food information from the user when a cooking activity is detected by the neural network. To the best of our knowledge, this is the first work that adopts air quality sensor data for cooking activity recognition.
Dynamic resource provisioning for cyber-physical systems in cloud-fog-edge computing
Authors: Xu Zhanyang , Zhang Yanqi , Li Haoyuan , Yang Weijing , Qi Quan
Published: June 2020

Cyber-Physical Systems(CPS) serves as an interdisciplinary effort that incorporates cyber vector as well as physical vector. The latter can generate exponentially growing amounts of data. How to process CPS big data systematically and efficiently is the key to the breakthrough of offering prospective and personalized services for each individual user and entity involved. In recent years, much research has been proactively conducted on advancing specific scenario or algorithm. However, few surveys value their integration. For good measure, the synthesis remains a fundamental challenge. Subsequently, we fill the gap in the literature by constructing cloud computing, fog computing and edge computing as a whole to inspire on new architectures and cross utilizations. Moreover, bringing the enthusiasm of traditionally solitude entities into play is crucial. In this exploratory study, we examine definitions of CPS as well as the three aforementioned computing paradigms and then shed new light on comprehensively established frameworks. We also survey on the application level of Cloud-Fog-Edge Computing in CPS respectively and dive into diversified algorithms and strategies to embed big data applications into a more intelligent and convenient society with current deficiencies and future research directions followed.
A novel apidaecin Api-PR19 synergizes with the gut microbial community to maintain intestinal health and promote growth performance of broilers
Authors: Wu Shengru , Wang Jian , Zhu Liqin , Ren Hao , Yang Xiaojun
Published: June 2020

Background

Antibiotic growth promoters (AGPs) have been used as growth promoters to maintain animal intestinal health and improve feed efficiency in broilers by inhibiting pathogen proliferation. In view of the growing emergence of antibiotic-resistant pathogen strains and drug residue issues, novel treatments are increasingly required. This study aimed to compare two antimicrobial approaches for managing pathogen infection and maintaining animal intestinal health in broilers by supplying Apidaecin Api-PR19 and AGPs over 42 d of a feeding trial.

Results

Compared with the broilers that were only fed a corn-soybean basal diet (CON group), supplementation with Api-PR19 and AGP (respectively named the ABP and AGP groups) both increased the feed conversion efficiency. When compared with the AGP group, Api-PR19 supplementation could significantly increase the organ index of the bursa of fabricius and subtype H9 antibody level in broiler chickens. Moreover, when compared with the CON group, the intestinal villus height, intestinal nutrient transport, and intestinal sIgA content were all increased in the Api-PR19 group, while AGP supplementation was harmful to the intestinal villus height and intestinal nutrient transport. By assessing the antibacterial effect of Api-PR19 and antibiotics in vitro and in vivo, we found that Api-PR19 and antibiotics both inhibited the growth of pathogens, including Escherichia coli and Campylobacter jejuni. Furthermore, by using 16S rRNA gene sequencing, the beneficial bacteria and microbiota in broilers were not disturbed but improved by apidaecin Api-PR19, including the genera of Eubacterium and Christensenella and the species of uncultured_Eubacterium_sp, Clostridium_asparagiforme, and uncultured_Christensenella_sp, which were positively related to improved intestinal development, absorption, and immune function.

Conclusion

Apidaecin Api-PR19 treatment could combat pathogen infection and had little negative impact on beneficial bacteria in the gut compared to antibiotic treatment, subsequently improving intestinal development, absorption, and immune function.