bluuebunny/crossref_metadata_2025 huggingface dataset:
“We try our best to offer them the little that we can” coping strategies of Ghanaian community psychiatric nurses: a qualitative descriptive study
Authors: Opare Frederick Yaw , Aniteye Patience , Afaya Agani , Glover-Meni Nathaniel
Published: June 2020

Introduction

Community psychiatric nurses work in extremely stressful environments with intense patient relationships as they try to prevent self-harm and manage aggressive behaviors. In order to improve their ability to manage the stressful work environments, community psychiatric nurses need to incorporate formal coping strategies into their daily work routines. With evidence-based coping strategies, community psychiatric nurses can effectively manage the stressful situations in their work environment to increase their work longevity. The purpose of this study was to explore the individual coping strategies currently used by community psychiatric nurses in practice in order to develop an intervention strategy for future implementation.

Methods

This was an exploratory qualitative study using an interpretative approach. A purposive sampling method was used to identify participants from the community psychiatric nurses in a region of Ghana. Participants were recruited and interviewed, guided by semi-structured questions, until saturation was reached. The interviews were audio-taped, transcribed verbatim, and analyzed thematically.

Results

A total of 13 participants, 10 women and 3 men ages 26 to 60 years, were interviewed for this study. From the inductive analysis, four coping themes emerged from the data including: 1) self-disguise, 2) reliance on religious faith, 3) self-motivation, and 4) reduction in the number of home visits. The participants described their work environment as stressful, almost to the point of overwhelming. In this regard, they identified the individual coping strategies as critical daily practices for self care to manage their high stress levels.

Conclusion

Individual coping strategies are often used by community psychiatric nurses in daily practice. The participants identified personal coping strategies as critical interventions to manage stress and to decrease their risk for burnout. However, community psychiatric nurses must develop.

personal-mastery in various coping strategies to care for themselves, as well as motivate them despite the challenging working environment. The individual coping strategies adopted by community psychiatric nurses was not only helped them deliver care, but also protected their clients so people would not label them as ‘mental patients.’ Collectively, the four strategies reported in this study need to be developed into a cohesive and comprehensive intervention.
Assessing the quality of care in sick child services at health facilities in Ethiopia
Authors: Getachew Theodros , Abebe Solomon Mekonnen , Yitayal Mezgebu , Persson Lars Åke , Berhanu Della
Published: June 2020

Background

Quality of care depends on system, facility, provider, and client-level factors. We aimed at examining structural and process quality of services for sick children and its association with client satisfaction at health facilities in Ethiopia.

Methods

Data from the Ethiopia Service Provision Assessment Plus (SPA+) survey 2014 were used. Measures of quality were assessed based on the Donabedian framework: structure, process, and outcome. A total of 1908 mothers or caretakers were interviewed and their child consultations were observed. Principal component analysis was used to construct quality of care indices including a structural composite score, a process composite score, and a client satisfaction score. Multilevel mixed linear regression was used to analyze the association between structural and process factors with client satisfaction.

Result

Among children diagnosed with suspected pneumonia, respiratory rate was counted in 56% and temperature was checked in 77% of the cases. A majority of children (92%) diagnosed with fever had their temperature taken. Only 3% of children with fever were either referred or admitted, and 60% received antibiotics. Among children diagnosed with malaria, 51% were assessed for all three Integrated Management of Childhood Illnesses (IMCI) main symptoms, and 4% were assessed for all three general danger signs. Providers assessed dehydration in 54% of children with diarrhea with dehydration, 17% of these children were admitted or referred to another facility, and Oral Rehydration Solution was prescribed for 67% while none received intravenous fluids. The number of basic amenities in the facility was negatively associated with the clients’ satisfaction. Private facilities, when the providers had got training for care of sick children in the past 2 years, had higher client satisfaction. There was no statistical association between structure, process composite indicators and client satisfaction.

Conclusion

The assessment of sick children was of low quality, with many missing procedures when comparing with IMCI guidelines. In spite of this, most clients were satisfied with the services they received. Structural and process composite indicators were not associated with client’s satisfaction. These findings highlight the need to assess other dimensions of quality of care besides structure and process that may influence client satisfaction.
Podoplanin is indispensable for cell motility and platelet-induced epithelial-to-mesenchymal transition-related gene expression in esophagus squamous carcinoma TE11A cells
Authors: Watanabe Nobuo , Kidokoro Masako , Tanaka Makiko , Inoue Shigeaki , Tsuji Tomoatsu , Akatuska Hisako , Okada Chisa , Iida Yumi , Okada Yoshinori , Suzuki Yusuke , Sato Takehito , Yahata Takashi , Hirayama Noriaki , Nakagawa Yoshihide , Inokuchi Sadaki
Published: June 2020

Background

The transmembrane glycoprotein podoplanin (PDPN) is upregulated in some tumors and has gained attention as a malignant tumor biomarker. PDPN molecules have platelet aggregation-stimulating domains and, are therefore, suggested to play a role in tumor-induced platelet activation, which in turn triggers epithelial-to-mesenchymal transition (EMT) and enhances the invasive and metastatic activities of tumor cells. In addition, as forced PDPN expression itself can alter the propensity of certain tumor cells in favor of EMT and enhance their invasive ability, it is also considered to be involved in the cell signaling system. Nevertheless, underlying mechanisms of PDPN in tumor cell invasive ability as well as EMT induction, especially by platelets, are still not fully understood.

Methods

Subclonal TE11A cells were isolated from the human esophageal squamous carcinoma cell line TE11 and the effects of anti-PDPN neutralizing antibody as well as PDPN gene knockout on platelet-induced EMT-related gene expression were measured. Also, the effects of PDPN deficiency on cellular invasive ability and motility were assessed.

Results

PDPN-null cells were able to provoke platelet aggregation, suggesting that PDPN contribution to platelet activation in these cells is marginal. Nevertheless, expression of platelet-induced EMT-related genes, including vimentin, was impaired by PDPN-neutralizing antibody as well as PDPN deficiency, while their effects on TGF-β-induced gene expression were marginal. Unexpectedly, PDPN gene ablation, at least in either allele, engendered spontaneous N-cadherin upregulation and claudin-1 downregulation. Despite these seemingly EMT-like alterations, PDPN deficiency impaired cellular motility and invasive ability even after TGF-β-induced EMT induction.

Conclusions

These results suggested that, while PDPN seems to function in favor of maintaining the epithelial state of this cell line, it is indispensable for platelet-mediated induction of particular mesenchymal marker genes as well as the potentiation of motility and invasion capacity.
Exploring TCGA database for identification of potential prognostic genes in stomach adenocarcinoma
Authors: Zhou Lin , Huang Wei , Yu He-Fen , Feng Ya-Juan , Teng Xu
Published: June 2020

Background

Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer in the world and ranks third among cancer-related deaths worldwide. The tumour microenvironment (TME) plays an important role in tumorigenesis, development, and metastasis. Hence, we calculated the immune and stromal scores to find the potential prognosis-related genes in STAD using bioinformatics analysis.

Methods

The ESTIMATE algorithm was used to calculate the immune/stromal scores of the STAD samples. Functional enrichment analysis, protein–protein interaction (PPI) network analysis, and overall survival analysis were then performed on differential genes. And we validated these genes using data from the Gene Expression Omnibus database. Finally, we used the Human Protein Atlas (HPA) databases to verify these genes at the protein levels by IHC.

Results

Data analysis revealed correlation between stromal/immune scores and the TNM staging system. The top 10 core genes extracted from the PPI network, and primarily involved in immune responses, extracellular matrix, and cell adhesion. There are 31 genes have been validated with poor prognosis and 16 genes were upregulated in tumour tissues compared with normal tissues at the protein level.

Conclusions

In summary, we identified genes associated with the tumour microenvironment with prognostic implications in STAD, which may become potential therapeutic markers leading to better clinical outcomes.
In silico analysis for factors affecting anti-malarial penetration into red blood cells
Authors: Pornputtapong Natapol , Suriyapakorn Bovornpat , Satayamapakorn Anchisa , Larpadisorn Kanidsorn , Janviriyakul Pariyachut , Khemawoot Phisit
Published: June 2020

Background

Malaria is a parasitic disease that produces significant infection in red blood cells. The objective of this study is to investigate the relationships between factors affecting the penetration of currently available anti-malarials into red blood cells.

Methods

Fifteen anti-malarial drugs listed in the third edition of the World Health Organization malaria treatment guidelines were enrolled in the study. Relationship analysis began with the prioritization of the physicochemical properties of the anti-malarials to create a multivariate linear regression model that correlates the red blood cell penetration.

Results

It was found that protein binding was significantly correlated with red blood cell penetration, with a negative coefficient. The next step was repeated analysis to find molecular descriptors that influence protein binding. The coefficients of the number of rotating bonds and the number of aliphatic hydrocarbons are negative, as opposed to the positive coefficients of the number of hydrogen bonds and the number of aromatic hydrocarbons. The p-value was less than 0.05.

Conclusions

Anti-malarials with a small number of hydrogen bonds and aromatic hydrocarbons, together with a high number of rotatable bonds and aliphatic hydrocarbons, may have a higher tendency to penetrate the red blood cells.
Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether–lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania: a randomized controlled trial
Authors: Mhamilawa Lwidiko E. , Ngasala Billy , Morris Ulrika , Kitabi Eliford Ngaimisi , Barnes Rory , Soe Aung Paing , Mmbando Bruno P. , Björkman Anders , Mårtensson Andreas
Published: June 2020

Background

Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa.

Methods

Standard 3-day treatment with artemether–lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1–65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan–Meier survival analyses were done for both parasite clearance and recurrence.

Results

A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p = 0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p = 0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p = 0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitaemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p = 0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitaemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and haematological safety was high and similar in both arms.

Conclusion

Extended 6-day artemether–lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe. Thus, extended artemether–lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum, to prolong the therapeutic lifespan of ACT in Africa.

Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017 https://clinicaltrials.gov/show/NCT03241901
Aquatic habitats of the malaria vector Anopheles funestus in rural south-eastern Tanzania
Authors: Nambunga Ismail H. , Ngowo Halfan S. , Mapua Salum A. , Hape Emmanuel E. , Msugupakulya Betwel J. , Msaky Dickson S. , Mhumbira Nicolaus T. , Mchwembo Karim R. , Tamayamali Gerald Z. , Mlembe Slyakus V. , Njalambaha Rukiyah M. , Lwetoijera Dickson W. , Finda Marceline F. , Govella Nicodem J. , Matoke-Muhia Damaris , Kaindoa Emmanuel W. , Okumu Fredros O.
Published: June 2020

Background

In rural south-eastern Tanzania, Anopheles funestus is a major malaria vector, and has been implicated in nearly 90% of all infective bites. Unfortunately, little is known about the natural ecological requirements and survival strategies of this mosquito species.

Methods

Potential mosquito aquatic habitats were systematically searched along 1000 m transects from the centres of six villages in south-eastern Tanzania. All water bodies were geo-referenced, characterized and examined for presence of Anopheles larvae using standard 350 mLs dippers or 10 L buckets. Larvae were collected for rearing, and the emergent adults identified to confirm habitats containing An. funestus.

Results

One hundred and eleven habitats were identified and assessed from the first five villages (all < 300 m altitude). Of these, 36 (32.4%) had An. funestus co-occurring with other mosquito species. Another 47 (42.3%) had other Anopheles species and/or culicines, but not An. funestus, and 28 (25.2%) had no mosquitoes. There were three main habitat types occupied by An. funestus, namely: (a) small spring-fed pools with well-defined perimeters (36.1%), (b) medium-sized natural ponds retaining water most of the year (16.7%), and (c) slow-moving waters along river tributaries (47.2%). The habitats generally had clear waters with emergent surface vegetation, depths > 0.5 m and distances < 100 m from human dwellings. They were permanent or semi-permanent, retaining water most of the year. Water temperatures ranged from 25.2 to 28.8 °C, pH from 6.5 to 6.7, turbidity from 26.6 to 54.8 NTU and total dissolved solids from 60.5 to 80.3 mg/L. In the sixth village (altitude > 400 m), very high densities of An. funestus were found along rivers with slow-moving clear waters and emergent vegetation.

Conclusion

This study has documented the diversity and key characteristics of aquatic habitats of An. funestus across villages in south-eastern Tanzania, and will form an important basis for further studies to improve malaria control. The observations suggest that An. funestus habitats in the area can indeed be described as fixed, few and findable based on their unique characteristics. Future studies should investigate the potential of targeting these habitats with larviciding or larval source management to complement malaria control efforts in areas dominated by this vector species.
Household factors associated with access to insecticide-treated nets and house modification in Bagamoyo and Ulanga districts, Tanzania
Authors: Odufuwa Olukayode G. , Ross Amanda , Mlacha Yeromin P. , Juma Omary , Mmbaga Selemani , Msellemu Daniel , Moore Sarah
Published: June 2020

Background

Insecticide-treated nets (ITNs) and house modifications are proven vector control tools, yet in most regions, full coverage has not been achieved. This study investigates household factors associated with access to ITNs and house modification in Tanzania.

Methods

Baseline cross-sectional survey data from previous studies on spatial repellants and indoor residual spray evaluation was analysed from 6757 households in Bagamoyo (60 km north of Dar es Salaam) and 1241 households in Ulanga (a remote rural area in southeast Tanzania), respectively. Regression models were used to estimate the associations between the outcomes: population access to ITNs, access to ITN per sleeping spaces, window screens and closed eaves, and the covariates household size, age, gender, pregnancy, education, house size, house modification (window screens and closed eaves) and wealth.

Results

Population access to ITNs (households with one ITN per two people that stayed in the house the previous night of the survey) was 69% (n = 4663) and access to ITNs per sleeping spaces (households with enough ITNs to cover all sleeping spaces used the previous night of the survey) was 45% (n = 3010) in Bagamoyo, 3 years after the last mass campaign. These findings are both lower than the least 80% coverage target of the Tanzania National Malaria Strategic Plan (Tanzania NMSP). In Ulanga, population access to ITNs was 92% (n = 1143) and ITNs per sleeping spaces was 88% (n = 1093), 1 year after the last Universal Coverage Campaign (UCC). Increased household size was significantly associated with lower access to ITNs even shortly after UCC. House modification was common in both areas but influenced by wealth. In Bagamoyo, screened windows were more common than closed eaves (65% vs 13%), whereas in Ulanga more houses had closed eaves than window screens (55% vs 12%).

Conclusion

Population access to ITNs was substantially lower than the targets of the Tanzania NMSP after 3 years and lower among larger households after 1 year following ITN campaign. House modification was common in both areas, associated with wealth. Improved access to ITNs and window screens through subsidies and Behaviour Change Communication (BCC) strategies, especially among large and poor households and those headed by people with a low level of education, could maximize the uptake of a combination of these two interventions.
Excess free fructose, apple juice, high fructose corn syrup and childhood asthma risk – the National Children’s Study
Authors: DeChristopher Luanne R. , Tucker Katherine L.
Published: June 2020

Background

Recent research provides consistent evidence that the unexplained doubling of childhood asthma prevalence (1980–1995), its continued climb and 2013 plateau, may be associated with the proliferation of high-fructose-corn-syrup (HFCS) in the US food supply. The HFCS used in soft drinks has been shown to contain a higher fructose-to-glucose ratio than previously thought. This coincides with a preference shift from orange to apple juice among young children. Apple juice naturally contains a high (≥2:1) fructose-to-glucose ratio. Thus, children have received high excess-free-fructose doses, the fructose type associated with fructose malabsorption. Unabsorbed excess-free-fructose in the gut may react with dietary proteins to form immunogens that bind asthma mediating receptors, and/or alter the microbiota towards a profile linked to lung disorders. Studies with longitudinal childhood data are lacking. Therefore, we tested the hypothesis that excess-free-fructose intake is associated with childhood asthma risk.

Methods

Cox regression models were used to analyze prospective early childhood data (12–30 months of age) from the National Children’s Study. Intake frequencies for soda/sports/fruit drinks, and 100% juices were used for analyses.

Results

Greater consumption of 100% juice, soda/sports/fruit drinks, and any combination, was associated with ~two (P = 0.001), ~ 2.5 (P = 0.001), and ~ 3.5 times (P < 0.0001) higher asthma incidence.

Conclusions

Given these results, prior research and case-study evidence, it is reasonable to suggest that the two-fold higher asthma risk associated with 100% juice consumption is due to apple juice’s high fructose-to-glucose ratio, and that the ~ 2.5/~ 3.5 times higher risk associated with soda/sports/fruit drinks intake is with the excess-free-fructose in HFCS.
The genetic and pharmacogenomic landscape of snoRNAs in human cancer
Authors: Liu Yaoming , Ruan Hang , Li Shengli , Ye Youqiong , Hong Wei , Gong Jing , Zhang Zhao , Jing Ying , Zhang Xiulan , Diao Lixia , Han Leng
Published: June 2020

Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno (http://hanlab.uth.edu/GPSno), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.
Sensitization to storage proteins in peanut and hazelnut is associated with higher levels of inflammatory markers in asthma
Authors: Johnson Jennifer , Malinovschi Andrei , Lidholm Jonas , Petersson Carl Johan , Nordvall Lennart , Janson Christer , Alving Kjell , Borres Magnus P.
Published: June 2020

Background

Sensitization to peanuts and hazelnuts is common among young asthmatics and can be primary or a result of cross-reactivity. Sensitization as a result of cross-reactivity to birch pollen is typically associated to tolerance or mild and local symptoms upon intake of peanut or hazelnut.

Aim

The aim of this study was to investigate relationships between IgE antibody responses against peanut and hazelnut components, airway and systemic inflammation markers, lung function parameters and reported food hypersensitivity in a cohort of asthmatic children and young adults.

Methods

A population of 408 asthmatic individuals aged 10–35 years were investigated. Information on hypersensitivity symptoms upon intake of peanut or hazelnut were recorded in a standardized questionnaire. Fraction of exhaled nitric oxide (FeNO), blood eosinophil count (B-Eos), spirometry, methacholine challenge outcome and IgE antibodies to peanut and hazelnut allergens were measured by standard clinical and laboratory methods.

Results

Subjects sensitized to any of the peanut (Ara h 1, 2 or 3) or hazelnut (Cor a 9 or 14) storage proteins were significantly younger (17.6 vs 21.2 years), had higher levels of FeNO (23.2 vs 16.7 ppb) and B-Eos (340 vs 170 cells/mcl) than those displaying only pollen-related cross-reactive sensitization. Levels of FeNO correlated with levels of IgE to storage proteins in children, but not in adults. Levels of B-Eos correlated with levels of IgE to all allergen components investigated in children, but only to levels of IgE to storage proteins in adults. Anaphylaxis and skin reactions upon intake of peanuts or hazelnuts were more often reported among subjects sensitized to the respective storage proteins than among those with only pollen-related cross-reactive sensitization. As compared to peanut, hazelnut was more often reported to cause gastrointestinal symptoms and less often oral cavity symptoms.

Conclusions

Sensitization to peanut and hazelnut storage proteins was associated with higher levels of inflammation markers and food hypersensitivity symptoms in this population of subjects with asthma.
Associations between perceived environmental pollution and health-related quality of life in a Chinese adult population
Authors: Han Bingxue
Published: June 2020

Background

Health-related quality of life (HRQoL) measures are being used in increasingly diverse populations. However, there have no known studies to date to examine the associations between perceived environmental pollution and HRQoL in a Chinese population. This study aimed to report the associations between air, water, noise pollution and HRQoL among Chinese adult population.

Methods

A cross-sectional survey data was used from East Asian Social Survey 2010 with a sample of 3866 Chinese populations regarding environmental pollution. HRQoL was computed by SF-12 and reflected by physical and mental component summary score (PCS & MCS). Ordinary least regression analyses were used to examine associations between perceived environmental pollution and PCS and MCS scores. Models in SPSS PROCESS were selected to demonstrate the moderating and mediating effects.

Results

Only considering one pollutant, perceived air pollution and perceived water pollution had significant associations with PCS and MCS scores. Perceived noise pollution had significant associations with PCS scores. Perceived air×noise, air×water, noise×water, and air×noise×water pollution had significant associations with PCS and MCS scores. Conditional (moderated) mediation showed that there were no moderating effects and mediating effects of perceived one pollutant on another pollutant.

Conclusions

Co-occurring perceived environmental pollution were mainly associated with progressive increase in PCS and MCS scores among the Chinese adult population. These results suggested that some effective policies should be carried out to improve environmental quality in Chinese adult population.
Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases
Authors: Konishi Takanori , Yoshidome Hiroyuki , Shimizu Hiroaki , Yoshitomi Hideyuki , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Takano Shigetsugu , Miyazaki Masaru , Ohtsuka Masayuki
Published: June 2020

Background

Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection.

Methods

We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed.

Results

A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration.

Conclusions

Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.
FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1
Authors: Shi Weidong , Feng Lanyun , Dong Shu , Ning Zhouyu , Hua Yongqiang , Liu Luming , Chen Zhen , Meng Zhiqiang
Published: June 2020

Background

Heat shot protein 90 (HSP90) AA1 functions as an onco-protein to regulate the assembly, manipulation, folding and degradation of its client proteins, including c-MYC. However, little is known about the mechanism of HSP90AA1 regulation.

Methods

Transcriptome RNA-sequencing data of hepatocellular carcinoma (HCC) samples were used to detect the mRNA expression of FBXL6. Immunoprecipitation/Mass Spectrum (IP/MS) method was used to identify the interacting proteins of FBXL6. The co-immunoprecipitation assay was used to determine the interaction between FBXL6 and HSP90AA1. The in vivo ubiquitination assay was performed to determine the regulation of HSP90AA1 by FBXL6. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to determine the transcriptional regulation of FBXL6 by c-MYC. Immunohistochemical (IHC) staining was performed to study the correlation of FBXL6 and HSP90AA1 protein expression in 87 HCC samples. Cell counting and colony formation assays were implemented to detect the biological effects of FBXL6 on the growth of HCC cells in vitro. The effect of FBXL6 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice.

Results

Here, we identified the orphan F-box protein FBXL6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin ligase for HSP90AA1. FBXL6 promoted K63-dependent ubiquitination of HSP90AA1 to stabilize it. Through analysis of the TCGA dataset, we found that FBXL6 was significantly increased in HCC tissues and positively correlated with c-MYC pathway. FBXL6 accumulation in HCC causes the stabilization and activation of c-MYC by preventing HSP90AA1 degradation. The activated c-MYC directly binds to the promoter region of FBXL6 to induce its mRNA expression.

Conclusion

Collectively, our data revealed an unknown FBXL6-HSP90AA1-c-MYC axis which might contribute to the oncogenesis of HCC, and we propose that inhibition of FBXL6 might represent an effective therapeutic strategy for HCC treatment.
A novel collision tumour of myofibroblastoma and low-grade adenosquamous carcinoma in breast
Authors: Yang Guang-Zhi , Liang Shang-Hua , Shi Xiao-Hong
Published: June 2020

Background

Myofibroblastoma (MFB) and low-grade adenosquamous carcinoma (LGASC) are rare tumours in the breast, respectively. However, a collision tumour of the two types has never been reported.

Case presentation

A 42-year-old female presented with a palpable mass in diameter of about 2.5 cm in the left breast. Morphologically, the lesion was predominately composed of bland spindle cells admixed with some islands of mature adipocytes and a few epithelial elements dispersing in infiltrating way which formed both tubule and solid structures. The mass showed low positive index of Ki-67. The spindle cells were strongly and diffusely positive for CD34, SMA, desmin, ER and PR. The epithelial elements were positive for CK and EMA, and negative for ER and PR completely. CK5/6 and P63 were positive in the outer-layer of the tubules and nearly all the cells of the solid nests.

Conclusions

A collision tumour of MFB and LGASC in breast is extremely rare and either component is supposed to be not overlooked. Excision and close follow-up are advised.
Clinical effect of intramuscular calcitonin compared with oral celecoxib in the treatment of knee bone marrow lesions: a retrospective study
Authors: Zhou Jiaming , Xiong Wuyi , Gou Pengguo , Chen Zhao , Guo Xing , Huo Xiaoyang , Xue Yuan
Published: June 2020

Background

Bone marrow lesions (BMLs) are a common finding in patients with osteoarthritis (OA), which are predictors of progression and pain related to cartilage damage in OA. The objective of the present research was to compare the short-term clinical effect of intramuscular calcitonin and oral celecoxib in treating knee BMLs.

Patients and methods

Between January 2016 and December 2018, the medical records of patients with knee BMLs treated by intramuscular calcitonin or oral celecoxib were reviewed. Visual analog scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used to assess knee pain and function, respectively. BMLs were assessed by MRI scans and were scored by the modified Whole-Organ MRI Score (WORMS). The safety of these two medications was also evaluated.

Results

A total of 123 eligible patients who received calcitonin treatment (n = 66) or celecoxib treatment (n = 57) were included. All patients were followed up clinically and radiographically for 3 months. The VAS and WOMAC scores were lower statistically in calcitonin group than celecoxib group at 4-week and 3-month follow-up. For BMLs, the WORMS scores in the calcitonin group were significantly lower than the celecoxib group. Besides, statistically higher MRI improvement rates were found in the calcitonin group compared with the celecoxib group at 4-week follow-up (21.21% vs. 7.01%; P = 0.039) and 3-month follow-up (37.88% vs. 15.79%; P = 0.006).

Conclusion

Intramuscular calcitonin 50 IU once daily demonstrated a better short-term effect for knee BML patients compared with oral celecoxib 200 mg twice per day.
Locking plate versus external fixation in the treatment of displaced femoral supracondylar fracture in children
Authors: Li Jin , Guo Xikai , Wang Hai Qiang , Yue Changjie , Chen Kailei , Ma Jiewen , Wang Jing , Tang Xin
Published: June 2020

Background

Displaced supracondylar femoral fractures (SFF) are difficult injuries to treat in children. Several techniques have been widely used but few studies have compared the merits and drawbacks of each surgical intervention in order to analyze clinical values. The aim of this study was to (1) evaluate postoperative and functional conditions after treatments with locking plate (LP) or external fixation (EF), (2) observe adverse events associated with these two techniques, and (3) evaluate the clinical value of these two techniques.

Methods

Twenty-eight patients less than 14 years of age were included in this study with supracondylar femoral fractures. They underwent locking plate or external fixation in authors’ hospital. The postoperative healing and functional outcome were elevated according to radiographic and clinical measures, including American Knee Society Score (KSS). Fisher’s exact test and independent samplesttest were used for statistical analysis.

Results

All fractures healed without delayed union. The KSS scoring results of locking plate and external fixation groups were both excellent. The alignment of lower limbs was acceptable with knee valgus less than 2° for all involved patients. In addition, leg length discrepancy was less than 1 cm. No acute or severe complications were noted. There was significant difference in union time (p= 0.03), operating time (p< 0.001), intraoperative blood loss (p< 0.001), and limb length discrepancy (p= 0.04) between LP group and EF group.

Conclusions

External fixation is superior than locking plate in terms of union, operation time phrases, and intraoperative blood loss. EF techniques are better options for treating displaced supracondylar femoral fracture in children.

Level of evidence

Retrospective comparative study; level III.
Can we predict patient outcome before extracorporeal membrane oxygenation for refractory cardiac arrest?
Authors: Siao Fu-Yuan , Chiu Chun-Wen , Chiu Chun-Chieh , Chang Yu-Jun , Chen Ying-Chen , Chen Yao-Li , Hsieh Yung-Kun , Chou Chu-Chung , Yen Hsu-Hen
Published: June 2020

Background

Refractory cardiac arrest resistant to conventional cardiopulmonary resuscitation (C-CPR) has a poor outcome. Although previous reports showed that extracorporeal cardiopulmonary resuscitation (E-CPR) can improve the clinical outcome, there are no clinically applicable predictors of patient outcome that can be used prior to the implementation of E-CPR. We aimed to evaluate the use of clinical factors in patients with refractory cardiac arrest undergoing E-CPR to predict patient outcome in our institution.

Methods

This is a single-center retrospective study. We report 112 patients presenting with refractory cardiac arrest resistant to C-CPR between January 2012 and November 2017. All patients received E-CPR for continued life support when a cardiogenic etiology was presumed. Clinical factors associated with patient outcome were analyzed. Significant pre-ECMO clinical factors were extracted to build a patient outcome risk prediction model.

Results

The overall survival rate at discharge was 40.2, and 30.4% of patients were discharged with good neurologic function. The six-month survival rate after hospital discharge was 36.6, and 25.9% of patients had good neurologic function 6 months after discharge. We stratified the patients into low-risk (n = 38), medium-risk (n = 47), and high-risk groups (n = 27) according to the TLR score (low-flow Time, cardiac arrest Location, and initial cardiac arrest Rhythm) that we derived from pre-ECMO clinical parameters. Compared with the medium-risk and high-risk groups, the low-risk group had better survival at discharge (65.8% vs. 42.6% vs. 0%, p < 0.0001) and at 6 months (60.5% vs. 38.3% vs. 0%, p = 0.0001). The low-risk group also had a better neurologic outcome at discharge (50% vs. 31.9% vs. 0%, p = 0.0001) and 6 months after discharge (44.7% vs. 25.5% vs. 0%, p = 0.0003) than the medium-risk and high-risk groups.

Conclusions

Patients with refractory cardiac arrest receiving E-CPR can be stratified by pre-ECMO clinical factors to predict the clinical outcome. Larger-scale studies are required to validate our observations.
Mobilization practices in critically ill children: a European point prevalence study (EU PARK-PICU)
Authors: Ista Erwin , Scholefield Barnaby R. , Manning Joseph C. , Harth Irene , Gawronski Orsola , Bartkowska-Śniatkowska Alicja , Ramelet Anne-Sylvie , Kudchadkar Sapna R. ,   EU PARK-PICU Collaborators, Ritson Paul C. , Nikolaou Filippia , de Neef Marjorie , Kneyber Martin , Penny-Thomas Kate , Linton Christina , Balmaks Reinis , Richter Matthias , Chiusolo Fabrizio , Cecchetti Corrado , Roberti Marco , Di Furia Michela , Grandjean Chantal , Nygaard Bettina , Lopez Yolanda , Koroglu Tolga , Besci Tolga , Mora Roberta Da Rin Della , Agbeko Rachel S. , Borrows Emma , Bochaton Nathalie , Mattsson Janet , Ksellmann Anne , Hero Barbara , Rosada-Kurasinska Jowita , Świder Magdalena , Bonaldi Amabile , Giugni Cristina , Oruganti Siva , Gates Simon , Smith Hazel , van Zwol Annelies , Hills Jenna , Conroy Johanna , Bebbington Mark , Neunhoeffer Felix , Duval Els
Published: June 2020

Background

Early mobilization of adults receiving intensive care improves health outcomes, yet little is known about mobilization practices in paediatric intensive care units (PICUs). We aimed to determine the prevalence of and factors associated with physical rehabilitation in PICUs across Europe.

Methods

A 2-day, cross-sectional, multicentre point prevalence study was conducted in May and November 2018. The primary outcome was the prevalence of physical therapy (PT)- or occupational therapy (OT)-provided mobility. Clinical data and data on patient mobility, potential mobility safety events, and mobilization barriers were prospectively collected in patients admitted for ≥72 h.

Results

Data of 456 children admitted to one of 38 participating PICUs from 15 European countries were collected (456 patient days); 70% were under 3 years of age. The point prevalence of PT- and/or OT-provided mobility activities was 39% (179/456) (95% CI 34.7–43.9%) during the patient days, with significant differences between European regions. Nurses were involved in 72% (924/1283) of the mobility events; in the remaining 28%, PT/OT, physicians, family members, or other professionals were involved. Of the factors studied, family presence was most strongly positively associated with out-of-bed mobilization (aOR 7.83, 95% CI 3.09–19.79). Invasive mechanical ventilation with an endotracheal tube was negatively associated with out-of-bed mobility (aOR 0.28, 95% CI 0.12–0.68). Patients were completely immobile on 25% (115/456) of patient days. Barriers to mobilization were reported on 38% of patient days. The most common reported patient-related barriers were cardiovascular instability (n = 47, 10%), oversedation (n = 39, 9%), and medical contraindication (n = 37, 8%). Potential safety events occurred in 6% of all documented mobilization events.

Conclusion

Therapists are infrequently consulted for mobilization of critically ill children in European PICUs. This study highlights the need for a systematic and interdisciplinary mobilization approach for critically ill children.

Graphical abstract
Whole-genome sequence association analysis of blood proteins in a longitudinal wellness cohort
Authors: Zhong Wen , Gummesson Anders , Tebani Abdellah , Karlsson Max J. , Hong Mun-Gwan , Schwenk Jochen M. , Edfors Fredrik , Bergström Göran , Fagerberg Linn , Uhlén Mathias
Published: June 2020

Background

The human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life.

Methods

We have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with repeated sampling. Analyses of genetic and non-genetic associations related to the variability of blood levels of proteins in these individuals were performed.

Results

The analyses showed that each individual has a unique protein profile, and we report on the intra-individual as well as inter-individual variation for 794 plasma proteins. A genome-wide association study (GWAS) using 7.3 million genetic variants identified by whole-genome sequencing revealed 144 independent variants across 107 proteins that showed strong association (P < 6 × 10−11) between genetics and the inter-individual variability on protein levels. Many proteins not reported before were identified (67 out of 107) with individual plasma level affected by genetics. Our longitudinal analysis further demonstrates that these levels are stable during the 2-year study period. The variability of protein profiles as a consequence of environmental factors was also analyzed with focus on the effects of weight loss and infections.

Conclusions

We show that the adult blood levels of many proteins are determined at birth by genetics, which is important for efforts aimed to understand the relationship between plasma proteome profiles and human biology and disease.
DNA methylation for cervical cancer screening: a training set in China
Authors: Kong Linghua , Wang Linhai , Wang Ziyun , Xiao Xiaoping , You Yan , Wu Huanwen , Wu Ming , Liu Pei , Li Lei
Published: June 2020

Background

Despite rapid improvements in DNA methylation tools for cervical cancer screening, few robust, exploratory studies have been performed using the combination of two host genes, EPB41L3 and JAM3, newly developed assays.

Methods

A review of abnormal liquid-based cytology and/or high-risk human papillomavirus (hrHPV) data from outpatient clinics in the study center from March 2018 to March 2019 was performed. Eligible patients with definitive histological pathology results were included, and their residual cytology samples were assessed for EPB41L3 and JAM3 methylation. The diagnostic accuracies of various screening strategies for definitive pathology and for cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+) were compared.

Results

In total, 306 patients were successfully tested; 301 cases with cervical histological pathology were included in the final analysis, including 118 (39.2%) and 183 (60.8%) cases of inflammation/CIN1 and CIN2+, respectively. Regarding CIN2+ detection, methylation status and hrHPV plus methylation had similar positive predictive values (0.930 and 0.954, respectively, p = 0.395). Additionally, hrHPV, methylation, and hrHPV plus methylation had similar negative predictive values (0.612, 0.679, and 0.655, p = 0.677) that were significantly higher than that of cytology alone (0.250, p values 0.012, 0.001, and 0.001, respectively). For 49 cases with negative hrHPV results, positive methylation alone was able to differentiate CIN2+ from inflammation/CIN1.

Conclusions

Methylation of both EPB41L3 and JAM3 is an accurate and feasible screening method for CIN2+.
Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
Authors: Krug Axel , Wöhr Markus , Seffer Dominik , Rippberger Henrike , Sungur A. Özge , Dietsche Bruno , Stein Frederike , Sivalingam Sugirthan , Forstner Andreas J. , Witt Stephanie H. , Dukal Helene , Streit Fabian , Maaser Anna , Heilmann-Heimbach Stefanie , Andlauer Till F. M. , Herms Stefan , Hoffmann Per , Rietschel Marcella , Nöthen Markus M. , Lackinger Martin , Schratt Gerhard , Koch Michael , Schwarting Rainer K. W. , Kircher Tilo
Published: June 2020

Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N= 677). Paternal age was further positively associated with gray matter volume (VBM,N= 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI,N= 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction.