bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro investigation of metabolic fate of α-mangostin and gartanin via skin permeation by LC-MS/MS and in silico evaluation of the metabolites by ADMET predictor™
Authors: Rukthong P. , Sereesongsang N. , Kulsirirat T. , Boonnak N. , Sathirakul K.
Published: November 2020

Background

Mangosteen, Garciniam angostana L., is a juicy fruit commonly found in Thailand. The rinds of Garciniam angostana L.have been used as a traditional medicine for the treatment of trauma, diarrhea and skin infection. It is also used in dermatological product such as in cosmetics. The mangosteen pericarp can be used to extract valuable bioactive xanthone compounds such as α-mangostin and gartanin. This study is aimed to predict the metabolism of α-mangostin and gartanin using in silico and in vitro skin permeation strategies.

Methods

Based on their 2D molecular structures, metabolites of those compounds were predicted in silico using ADMET Predictor™. The Km and Vmax, for 5 important recombinant CYP isozymes 1A2, 2C9, 2C19, 2D6 and 3A4 were predicted. Moreover, the in vitro investigation of metabolites produced during skin permeation using human epidermal keratinocyte cells, neonatal (HEKn cells) was performed by LC-MS/MS.

Results

It was found that the results derived from in silico were in excellent alignment with those obtained from in vitro studies for both compounds. The prediction referred that gartanin and α-mangostin were the substrate of CYP1A2, 2C9, 2C19 and 3A. In the investigation of α-mangostin metabolites by LC-MS/MS system, the MW of the parent compound was increased from 411.200 to 459.185 Da. Therefore, α-mangostin might be metabolized via tri-oxidation process. The increased molecular weight of parent compound (397.200 to 477.157 Da) illustrated that gartanin might be conjugated to sulfated derivatives.

Conclusions

In all the studies, α-mangostin and gartanin were predicted to be.

metabolized via phase I and phase II metabolism (sulfation), respectively.
A scoping review of cohort studies assessing traditional Chinese medicine interventions
Authors: Duan Yuting , Xu Zhirui , Deng Jingjing , Lin Yanjia , Zheng Yan , Chen Juexuan , Tang Xiaoyu , Zhang Xuan , Tang Chunzhi , Miao Jiangxia , Bian Zhaoxiang
Published: November 2020

Backgrounds

Identifying topics and assessing the reporting quality of Traditional Chinese Medicine (TCM) cohort studies.

Methods

A scoping review of the literature was performed. A descriptive approach to summarize the core study characteristics was prepared, along with structured tables and figures to identify salient points of differences noted across studies. The reporting quality of TCM cohort studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-cohort checklist.

Results

A total of 199 TCM cohort studies were included. The largest number of TCM cohort studies was conducted in Mainland China (70.9%). The TCM cohort study was first published in 2003. The top three diseases studied were Acquired Immune Deficiency Syndrome (AIDS), Stroke, and Asthma. As for the intervention methods, Chinese herbal medicine formulas (60.3%), acupuncture (14.1%) and single herbs (12.6%) accounted for the majority, followed by moxibustion (4.0%) and qigong (2.0%). The overage sufficient reporting rate of included TCM cohort studies according to the STROBE-cohort checklist was 42.9%. Comparing with Chinese literature, the reporting rates of English literature in most items were higher.

Conclusion

For the application of cohort studies to inform the effects of TCM interventions, the interventions assessed and conditions studied were diverse, the reporting quality was unsatisfied.
Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy
Authors: Zhang Qiqiang , Ye Qing , Huang Xiaohui , Xu Ajing , Liu Yan , Qi Jia , Zhang Hai , Zhang Jian
Published: November 2020

Background

Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown.

Methods

To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot.

Results

Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK.

Conclusion

Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1.

Graphical abstract
Electives in the medical curriculum – an opportunity to achieve students’ satisfaction?
Authors: Ramalho Ana Rita , Vieira-Marques P. M. , Magalhães-Alves C. , Severo M. , Ferreira M. A. , Falcão-Pires I.
Published: November 2020

Background

Electives are perceived by medical students as a valuable, highly regarded experience, allowing them to customize learning experiences and enabling them to early differentiate during medical training. The present work aims to uncover students’ major determinants of satisfaction and how they interfere with their future elective choices in order to identify the best approach to implement electives in medical curricula.

Methods

A cross-sectional study was conducted through a written evaluation survey concerning the electives available in the academic year 2015–2016. Our institution provides 106 electives to students from the 2nd to the 5th year. Students’ satisfaction was assessed through a validated questionnaire with eight sentences expressing opinions related to electives global satisfaction. Data from 538 inquiries from 229 students were analyzed quantitatively using regression and correlation models, and qualitatively through phenomenography.

Results

Quantitative analysis of the questionnaires allowed to establish both: 1) The determinants of students’ satisfaction with electives, which were Agreement with teaching and learning methodologies, followed by Agreement with assessment methodologies employed, Perception of the workload demanded and Requirement for continuous work and 2) The predictors of students preferences in the following years, namely, Agreement with assessment methodologies employed, Classes attendance and Ranking of the allocated elective established in the previous year. Qualitative analysis of questionnaires revealed that students consider electives as being innovative and interesting, claiming that some, for their relevant content, could be integrated into the medical core curriculum.

Conclusions

Our work raises awareness on the best practices when it comes to electives’ organization to meet students’ satisfaction. We can conclude that medical schools should measure students satisfaction as a tool to organize and predict future needs of electives and placements when designing and implementing this alternative student-centred curriculum or even to improve the existing practices regarding electives in medical courses.
Levelling the playing field: students’ motivations to contribute to an amnesty of assessment materials
Authors: Gondhalekar Anjali R , Rees Eliot L , Ntuiabane Daniel , Janjua Osman , Choa George , Eboreime Oziegbe , Sturrock Alison
Published: November 2020

Background

‘Exam recall’ is a recognised phenomenon whereby students recall and record questions after leaving the examination hall. This poses two main problems. First, as these questions are only available to peers of the students who recall the questions, these individuals have an unfair advantage. Secondly, the distribution of these recalled questions poses a threat to the validity and defensibility of assessments.

To address the first of these problems, we developed an amnesty enabling students to submit assessment material to an on-line site. This study sought to explore which factors influence students’ contributions to an amnesty of assessment material.

Methods

We conducted a qualitative study using semi-structured focus groups. We used convenience sampling and recruited participants from all years of our undergraduate medical programme. The focus groups were facilitated by a medical student peer to reduce the power imbalance and encourage participants to discuss candidly. The focus groups were audio recorded and transcribed verbatim.

Two researchers independently analysed all transcripts using thematic analysis and the research team met regularly to discuss emergent findings. Nvivo was used to assist with thematic analysis of the transcripts.

Results

Twenty-six individuals participated in six focus groups. Six themes were identified through the analysis, which were categorised into motivating factors and de-motivating factors.

Motivating factors were a perception that this would overcome inequity, a fear of repercussions, and the perceived usefulness of resources. Factors that prevented students contributing were a culture of competition, a lack of incentives, and mistrust of the medical school.

Conclusions

The establishment of an amnesty was acceptable to students and they were motivated to contribute materials. The competitive nature of medical careers and the stakes of summative assessments meant that students felt that some peers might still not contribute their materials. Students felt that the school were listening to their concerns and this led to a better dialogue between students and faculty.
Physicians’ attitudes in relation to end-of-life decisions in Neonatal Intensive Care Units: a national multicenter survey
Authors: Chatziioannidis Ilias , Iliodromiti Zoi , Boutsikou Theodora , Pouliakis Abraham , Giougi Evangelia , Sokou Rozeta , Vidalis Takis , Xanthos Theodoros , Marina Cuttini , Iacovidou Nicoletta
Published: November 2020

Background

End-of-life decisions for neonates with adverse prognosis are controversial and raise ethical and legal issues. In Greece, data on physicians’ profiles, motivation, values and attitudes underlying such decisions and the correlation with their background are scarce. The aim was to investigate neonatologists' attitudes in Neonatal Intensive Care Units and correlate them with self-reported practices of end-of-life decisions and with their background data.

Methods

A structured questionnaire was distributed to all 28 Neonatal Intensive Care Units in Greece. One hundred and sixty two out of 260 eligible physicians answered anonymously the questionnaire (response rate 66%). Demographic and professional characteristics, self-reported practices and opinions were included in the questionnaire, along with a questionnaire of 12 items measuring physicians’ attitude and views ranging from value of life to quality of life approach (scale 1–5).

Results

Continuation of treatment in neonates with adverse prognosis without adding further therapeutic interventions was the most commonly reported EoL practice, when compared to withdrawal of mechanical ventilation. Physicians with a high attitude score (indicative of value of quality-of-life) were more likely to limit, while those with a low score (indicative of value of sanctity-of-life) were more likely for continuation of intensive care. Physicians’ educational level (p:0.097), involvement in research (p:0.093), religion (p:0.024) and position on the existing legal framework (p < 0.001) were factors that affected the attitude score.

Conclusions

Physicians presented with varying end-of-life practices. Limiting interventions in neonates with poor prognosis was strongly related to their attitudes. The most important predictors for physicians' attitudes were religiousness and belief for Greek legal system reform.
Defining culturally safe primary care for people who use substances: a participatory concept mapping study
Authors: Urbanoski Karen , Pauly Bernadette , Inglis Dakota , Cameron Fred , Haddad Troy , Phillips Jack , Phillips Paige , Rosen Conor , Schlotter Grant , Hartney Elizabeth , Wallace Bruce
Published: November 2020

Background

People who use substances experience high levels of substance-related stigma, both within and outside of health care settings, which can prevent people from help-seeking and contribute further to health inequities. Recognizing and respecting how political, social, economic, and historical conditions influence health and health care, cultural safety, with origins in addressing Indigenous racism, is a potential strategy for mitigating stigma and marginalization in health care. Using a participatory research approach, we applied the concept of cultural safety to develop a model of safe primary care from the perspective of people who use substances.

Methods

People who use or used substances were involved in all phases of the research and led data collection. Study participants (n = 75) were 42.5 years old on average; half identified as female and one quarter as Indigenous. All were currently using or had previous experience with substances (alcohol and/or other drugs) and were recruited through two local peer-run support agencies. Concept mapping with hierarchical cluster analysis was used to develop the model of safe primary care, with data collected over three rounds of focus groups.

Results

Participants identified 73 unique statements to complete the focus prompt: “I would feel safe going to the doctor if …” The final model consisted of 8 clusters that cover a wide range of topics, from being treated with respect and not being red-flagged for substance use, to preserving confidentiality, advocacy for good care and systems change, and appropriate accommodations for anxiety and the effects of poverty and criminalization.

Conclusions

Developing a definition of safe care (from the patient perspective) is the necessary first step in creating space for positive interactions and, in turn, improve care processes. This model provides numerous concrete suggestions for providers, as well as serving as starting point for the development of interventions designed to foster system change.
Use of the supportive care framework to explore haematological cancer survivors’ unmet needs: a qualitative study
Authors: Herrmann Anne , Mansfield Elise , Tzelepis Flora , Lynagh Marita , Hall Alix
Published: November 2020

Background

Some sub-types of haematological cancers are acute and require intensive treatment soon after diagnosis. Other sub-types are chronic, relapse over many years and require life-long cycles of monitoring interspersed with bouts of treatment. This often results in significant uncertainty about the future, high levels of depression and anxiety, and reduced quality of life. Little is known about how to improve care for haematological cancer survivors. This study explored qualitatively, in a sample of haematological cancer survivors, (i) their unmet needs experienced as a result of their disease and treatment; and (ii) strategies that may help address these needs.

Methods

Semi-structured interviews were conducted with 17 adult haematological cancer survivors. Data was analysed using qualitative content analysis. The Supportive Care Framework guided data collection and analysis.

Results

Participants had a mean age of 57 years (SD 13). Most were male (n = 10, 59%). Five themes emerged from the data: (i) changes in unmet needs across the care trajectory (with greatest unmet needs experienced soon after diagnosis, at discharge from hospital and with cancer recurrence); (ii) informational unmet needs requiring improved patient-centred communication; (iii) uncertainty about treatment and the future; (iv) coordinated, tailored and documented post-treatment care planning as a strategy for optimal care delivery; and (v) ongoing support services to meet psychosocial and practical unmet needs by involving peer support, less bureaucratic transport services and flexible work arrangements.

Conclusions

To our knowledge, this is the first qualitative investigation using the Supportive Care Framework to explore unmet needs of haematological cancer survivors. Our findings offer fresh insights into this important area of study. Written, take-home care plans which provide simple but tailored guidance on where to seek additional support may help decrease uncertainty and feelings of vulnerability post-treatment for adult haematological cancer survivors. Future research should further develop and test strategies aimed at addressing unmet needs of haematological cancer survivors identified in this study.
Change and improvement 50 years in the making: a scoping review of the use of soft systems methodology in healthcare
Authors: Augustsson Hanna , Churruca Kate , Braithwaite Jeffrey
Published: November 2020

Introduction

Improving the quality of healthcare has proven to be a challenging task despite longstanding efforts. Approaches to improvements that consider the strong influence of local context as well as stakeholders’ differing views on the situation are warranted. Soft systems methodology (SSM) includes contextual and multi-perspectival features. However, the way SSM has been applied and the outcomes of using SSM to stimulate productive change in healthcare have not been sufficiently investigated.

Aim

This scoping review aimed to examine and map the use and outcomes of SSM in healthcare settings.

Method

The review was based on Arksey and O’Malley’s framework. We searched six academic databases to January 2019 for peer-reviewed journal articles in English. We also reviewed reference lists of included citations. Articles were included if they were empirical studies focused on the application of SSM in a healthcare setting. Two reviewers conducted the abstract review and one reviewer conducted the full-text review and extracted data on study characteristics, ways of applying SSM and the outcomes of SSM initiatives. Study quality was assessed using Hawker’s Quality Assessment Tool.

Result

A total of 49 studies were included in the final review. SSM had been used in a range of healthcare settings and for a variety of problem situations. The results revealed an inconsistent use of SSM including departing from Checkland’s original vision, applying different tools and involving stakeholders idiosyncratically. The quality of included studies varied and reporting of how SSM had been applied was sometimes inadequate. SSM had most often been used to understand a problem situation and to suggest potential improvements to the situation but to a lesser extent to implement and evaluate these improvements.

Conclusion

SSM is flexible and applicable to a range of problem situations in healthcare settings. However, better reporting of how SSM has been applied as well as evaluation of different types of outcomes, including implementation and intervention outcomes, is needed in order to appreciate more fully the utility and contribution of SSM in healthcare.
Vegetarian and vegan diets and risks of total and site-specific fractures: results from the prospective EPIC-Oxford study
Authors: Tong Tammy Y. N. , Appleby Paul N. , Armstrong Miranda E. G. , Fensom Georgina K. , Knuppel Anika , Papier Keren , Perez-Cornago Aurora , Travis Ruth C. , Key Timothy J.
Published: November 2020

Background

There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large proportion of non-meat eaters.

Methods

In EPIC-Oxford, dietary information was collected at baseline (1993–2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. Using multivariable Cox regression, we estimated the risks of total (n = 3941) and site-specific fractures (arm,n = 566; wrist,n = 889; hip,n = 945; leg,n = 366; ankle,n = 520; other main sites, i.e. clavicle, rib, and vertebra,n = 467) by diet group over an average of 17.6 years of follow-up.

Results

Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in fish eaters (hazard ratio 1.26; 95% CI 1.02–1.54), vegetarians (1.25; 1.04–1.50), and vegans (2.31; 1.66–3.22), equivalent to rate differences of 2.9 (0.6–5.7), 2.9 (0.9–5.2), and 14.9 (7.9–24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20–1.70), leg (2.05; 1.23–3.41), and other main site fractures (1.59; 1.02–2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment.

Conclusions

Non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.
The first assessment to detect Mycoplasma hyopneumoniae by sampling laryngeal swabs to investigate sow stability in South Korea
Authors: Oh YuSik , Baek JongHyuk , Lee JoongBok , Cho Sun-Hee , Park Changhoon
Published: November 2020

Background

Mycoplasma hyopneumoniae (M. hyopneumoniae), a representative pathogen causing swine enzootic pneumonia, generally infects piglets vertically. However, it is difficult to ascertain theM. hyopneumoniaeinfection state of sows due to limited detection methods. This report investigated sow herd stability by applying nested PCR to laryngeal swabs of suckling pigs, which is reportedly the most sensitive method.

Results

M. hyopneumoniaewas detected in 14 farms (63.6%) and 127 piglets (6.5%). The prevalence of sows likely to transmitM. hyopneumoniaein herds (11.1%) was calculated. In addition, there was a significant difference in detection rates among farms depending on herd size, gilt replacement rate, acclimation method, and antibiotic usage, suggesting various parameters that influence sow stability.

Conclusions

The results demonstrated that laryngeal swabs from suckling pigs have provided useful information regarding vertical transmission from sows in South Korean farm conditions. This result demonstrated that farms with larger herd sizes, higher gilt replacement rates, and a practice of naturally exposing gilts for acclimation had higher detection rates in weaning piglets, indicating an unstable sow infection state.
Effect of sterilization on the canine vaginal microbiota: a pilot study
Authors: Rota Ada , Corrò Michela , Patuzzi Ilaria , Milani Chiara , Masia Stefania , Mastrorilli Eleonora , Petrin Sara , Longo Alessandra , Del Carro Angela , Losasso Carmen
Published: November 2020

Background

Surgical sterilization is the most effective method of contraception for dogs. It also prevents pyometra and reduces the risk of mammary tumour development. However, this procedure also has negative effects, such as urinary incontinence. Steroid hormone deprivation following gonadectomy could also affect canine vaginal mucosa conditions and the microbial community colonizing the vaginal tract. This hypothesis was tested by comparing the vaginal cytology and microbial community of two groups of bitches, including 11 in anoestrus and 10 sterilized bitches (post-pubertal sterilization in the last 4 years). Bacteria were identified through metataxonomic analysis, amplifying the V3-V4 regions of16S rRNAgene, and culturing methods.

Results

Vaginal mucosa cytology was suggestive of dystrophic conditions in sterilized bitches, whereas a typical anoestrus pattern with parabasal and intermediate cells was appreciable in anoestrous animals. Metataxonomic analysis revealed large inter-individual variability.Salmonella,MycoplasmaandStaphylococcuswere present in moderate quantities in almost all the samples in both groups. Mollicutes (class level) and Tenericutes (phylum level) were commonly present in moderate quantities in anoestrus samples, whereas these microbes were present at high levels in a single sample from the sterilized group.

Based on culturing, a higher number of different species were isolated from the anoestrous bitches, andMycoplasma caniswas exclusively identified in an anoestrous bitch.Staphylococcusspp.was the most frequently isolated genus in both groups, followed byStreptococcusspp., and, among gram-negative bacteria,Escherichiaspp.andHaemophilusspp.A comparison of the numbers of the most frequently isolated genera of bacteria from vaginal cultures of bitches revealed thatPasteurellaandProteuswere the most frequently identified in sterilized animals based on metataxonomic analysis (p-value = 0.0497 and 0.0382, respectively), whereasStreptococcuswas significantly and most frequently isolated from anoestrous bitches using culture methods (pvalue = 0.0436).

Conclusions

In this preliminary investigation, no global patterns of the vaginal bacteria community were noted that characterized the condition of the bitches; however, cytology suggested local modifications. Sterilization after puberty caused minimal alterations in the vaginal microbial community of bitches within 4 years after surgery.
Isolation, heterologous expression, and purification of a novel antifungal protein from Bacillus subtilis strain Z-14
Authors: Zhang Xuechao , Guo Xiaojun , Wu Cuihong , Li Chengcui , Zhang Dongdong , Zhu Baocheng
Published: November 2020

Background

Wheat sheath blight, a soil borne fungal disease caused byRhizoctonia cerealis, is considered as one of the most serious threats to wheat worldwide.Bacillus subtilisZ-14 was isolated from soil sampled from a wheat rhizosphere and was confirmed to have strong antifungal activity againstR. cerealis.

Results

An antifungal protein, termed F2, was isolated from the culture supernatant of Z-14 strain using precipitation with ammonium sulfate, anion exchange chromatography, and reverse phase chromatography. Purified F2 had a molecular mass of approximately 8 kDa, as assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Edman degradation was used to determine the amino acid sequence of theN-terminus, which was NH2ASGGTVGIYGANMRS. This sequence is identical to a hypothetical protein RBAM_004680 (YP_001420098.1) synthesized byB. amyloliquefaciensFZB42. The recombinant F2 protein (rF2) was heterologously expressed in the yeast hostPichia pastoris, purified using a Niaffinity column, and demonstrated significant antifungal activity againstR. cerealis. The purified rF2 demonstrated broad spectrum antifungal activity against different varieties of fungi such asFusarium oxysporum,Verticillium dahliae,Bipolaris papendorfii, andFusarium proliferatum. rF2 was thermostable, retaining 91.5% of its activity when incubated for 30 min at 100 °C. Meanwhile, rF2 maintained its activity under treatment by proteinase K and trypsin and over a wide pH range from 5 to 10.

Conclusions

A novel antifungal protein, F2, was purified from biocontrolBacillus subtilisZ-14 strain fermentation supernatant and heterologously expressed inPichia pastoristo verify its antifungal activity againstR. cerealisand the validity of the gene encoding F2. Considering its significant antifungal activity and stable characteristics, protein F2 presents an alternative compound to resist fungal infections caused byR. cerealis.
Epigenetic signature predicts overall survival clear cell renal cell carcinoma
Authors: Wang Yejinpeng , Chen Liang , Ju Lingao , Qian Kaiyu , Wang Xinghuan , Xiao Yu , Wang Gang
Published: November 2020

Background

Recently, increasing study have found that DNA methylation plays an important role in tumor, including clear cell renal cell carcinoma (ccRCC).

Methods

We used the DNA methylation dataset of The Cancer Genome Atlas (TCGA) database to construct a 31-CpG-based signature which could accurately predict the overall survival of ccRCC. Meanwhile, we constructed a nomogram to predict the prognosis of patients with ccRCC.

Result

Through LASSO Cox regression analysis, we obtained the 31-CpG-based epigenetic signature which were significantly related to the prognosis of ccRCC. According to the epigenetic signature, patients were divided into two groups with high and low risk, and the predictive value of the epigenetic signature was verified by other two sets. In the training set, hazard ratio (HR) = 13.0, 95% confidence interval (CI) 8.0–21.2,P < 0.0001; testing set: HR = 4.1, CI 2.2–7.7,P < 0.0001; entire set: HR = 7.2, CI 4.9–10.6,P < 0.0001, Moreover, combined with clinical indicators, the prediction of 5-year survival of ccRCC reached an AUC of 0.871.

Conclusions

Our study constructed a 31-CpG-based epigenetic signature that could accurately predicted overall survival of ccRCC and staging progression of ccRCC. At the same time, we constructed a nomogram, which may facilitate the prediction of prognosis for patients with ccRCC.
FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer
Authors: Xie Qin , Xiao Ying-sheng , Jia Shi-cheng , Zheng Jie-xuan , Du Zhen-chao , Chen Yi-chun , Chen Mu-tong , Liang Yuan-ke , Lin Hao-yu , Zeng De
Published: November 2020

Background

Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients.

Methods

Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism.

Results

Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy.

Conclusion

FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.
Building momentum for malaria vaccine research and development: key considerations
Authors: Chitnis Chetan E. , Schellenberg David , Vekemans Johan , Asturias Edwin J. , Bejon Philip , Collins Katharine A. , Crabb Brendan S. , Herrera Socrates , Laufer Miriam , Rabinovich N. Regina , Roestenberg Meta , Shearley Adelaide , Tinto Halidou , Wentworth Marian , O’Brien Kate , Alonso Pedro
Published: November 2020

To maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1) promote the development and short to medium term deployment of first generation vaccine candidates and (2) support innovation and discovery to identify and develop highly effective, long-lasting and affordable next generation malaria vaccines.
Identification of main malaria vectors and their insecticide resistance profile in internally displaced and indigenous communities in Eastern Democratic Republic of the Congo (DRC)
Authors: Loonen Jeanine A. C. M. , Dery Dominic B. , Musaka Bertin Z. , Bandibabone Janvier B. , Bousema Teun , van Lenthe Marit , Pop-Stefanija Biserka , Fesselet Jean-François , Koenraadt Constantianus J. M.
Published: November 2020

Background

Malaria remains a major public health concern in the Democratic Republic of the Congo (DRC) and its control is affected by recurrent conflicts. Médecins Sans Frontières (MSF) initiated several studies to better understand the unprecedented incidence of malaria to effectively target and implement interventions in emergency settings. The current study evaluated the main vector species involved in malaria transmission and their resistance to insecticides, with the aim to propose the most effective tools and strategies for control of local malaria vectors.

Methods

This study was performed in 52 households in Shamwana (Katanga, 2014), 168 households in Baraka (South Kivu, 2015) and 269 households in Kashuga (North Kivu, 2017).Anophelesvectors were collected and subjected to standardized Word Health Organization (WHO) and Center for Disease Control (CDC) insecticide susceptibility bioassays. Mosquito species determination was done using PCR andPlasmodium falciparuminfection in mosquitoes was assessed by ELISA targeting circumsporozoite protein.

Results

Of 3517Anophelesspp. mosquitoes collected,Anopheles gambiaesensu lato (s.l.) (29.6%) andAnopheles funestus(69.1%) were the main malaria vectors. Plasmodium falciparuminfection rates forAn. gambiaes.l. were 1.0, 2.1 and 13.9% for Shamwana, Baraka and Kashuga, respectively.Anopheles funestusshowed positivity rates of 1.6% in Shamwana and 4.4% in Baraka. NoAn. funestuswere collected in Kashuga. Insecticide susceptibility tests showed resistance development towards pyrethroids in all locations. Exposure to bendiocarb, malathion and pirimiphos-methyl still resulted in high mosquito mortality.

Conclusions

This is one of only few studies from these conflict areas in DRC to report insecticide resistance in local malaria vectors. The data suggest that current malaria prevention methods in these populations are only partially effective, and require additional tools and strategies. Importantly, the results triggered MSF to consider the selection of a new insecticide for indoor residual spraying (IRS) and a new long-lasting insecticide-treated net (LLIN). The reinforcement of correct usage of LLINs and the introduction of targeted larviciding were also included as additional vector control tools as a result of the studies.
Definition of constitutive and stage-enriched promoters in the rodent malaria parasite, Plasmodium yoelii
Authors: Bowman Laura M. , Finger Logan E. , Hart Kevin J. , Lindner Scott E.
Published: November 2020

Background

Well-defined promoters are essential elements for genetic studies in all organisms, and enable controlled expression of endogenous genes, transgene expression, and gene editing. Despite this, there is a paucity of defined promoters for the rodent-infectious malaria parasites. This is especially true for Plasmodium yoelii, which is often used to study the mosquito and liver stages of malarial infection, as well as host immune responses to infection.

Methods

Here six promoters were selected from across the parasite’s life cycle (clag-a, dynein heavy chain delta, lap4, trap, uis4, lisp2) that have been invoked in the literature as controlling their genes in a stage-specific manner. A minimal promoter length for the constitutive pybip promoter that confers strong expression levels was also determined, which is useful for expression of reporters and gene editing enzymes.

Results

Instead, it was observed that these promoters confer stage-enriched gene control, as some parasites also effectively use these promoters in other stages. Thus, when used alone, these promoters could complicate the interpretation of results obtained from promoter swaps, stage-targeted recombination, or gene editing experiments.

Conclusions

Together these data indicate that achieving stage-specific effects, such as gene editing, is likely best done using a two-component system with independent promoter activities overlapping only in the intended life cycle stage.
Effect of bed net colour and shape preferences on bed net usage: a secondary data analysis of the 2017 Malawi Malaria Indicator Survey
Authors: Mategula Donnie , Ndeketa Latif , Gichuki Judy , Zimba Boston , Ching’ani Wilson , Chipeta Michael Give
Published: November 2020

Background

Malaria remains a significant cause of morbidity and mortality in the paediatric population in Malawi. Insecticide-treated bed nets are a key vector malaria control intervention, however, advancement towards universal access is progressing slowly. Malawi Malaria indicator surveys (MMIS) show diverse user preferences of bed net shape and colour. The objective of this work was to understand if bed net shape and colour preferences affect usage.

Methods

This is a secondary analysis of data from households that participated in the 2016–2017 MMIS. The main outcome variable was net usage defined, at net level, whether someone slept under a particular net on the night before the survey. The main exposure variables were preference attributes, whether a particular net is of a preferred colour or shape as defined by the household respondent. Both bivariate and multivariate logistic regression analyses were done to determine the association between the exposure and outcome variables.

Results

A total of 3729 households with 16,755 individuals were included in this analysis. There were a total 7710 bed nets in households that participated in the survey of which 5435 (70.5%) of these nets had someone sleep under them the previous night before the survey. Bed nets that are of a preferred shape have 3.55 times higher odds of being used than those not preferred [AOR 3.55 (95% CI 2.98, 4.23; p value < 0.001)]. Bed nets that are of a preferred colour have 1.61 times higher odds of being used than those that are not of a preferred colour [AOR 1.61 (95% CI 1.41, 1.84; p value < 0.001].

Conclusions

The results indicate that if a bed net is of a preferred colour or shape, it is more likely to be used. Bed net purchase by malaria stakeholders need to balance more factors on top of preferences such as price and efficacy.
Prevalence of sickle cell disorders and malaria infection in children aged 1–12 years in the Volta Region, Ghana: a community-based study
Authors: Oppong Mavis , Lamptey Helena , Kyei-Baafour Eric , Aculley Belinda , Ofori Ebenezer Addo , Tornyigah Bernard , Kweku Margaret , Ofori Michael F.
Published: November 2020

Background

Alterations in the structure of haemoglobin (Hb) are usually brought about by point mutations affecting one or, in some cases, two codons encoding amino acids of the globin chains. One in three Ghanaians are said to have sickle cell disorders, whereas malaria continues to be one of the leading causes of mortality among children. This study determined the prevalence of sickle cell disorders and malaria infection among children aged 1–12 years in the Volta Region.

Methods

This was a community-based cross-sectional survey that involved 938 children aged 1–12 years selected from three districts, one each from the 3 geographical zones of the Volta Region using a multistage sampling method. Demographic information was collected using a standard questionnaire and anthropometric indices were measured. Isoelectric focusing (IEF) electrophoresis was used to determine the Hb genotypes and sub-microscopic parasites were determined by PCR.

Results

The prevalence of sickling screening positive was 16.0% with an overall prevalence of sickle cell disorders being 2.0%. Among the individual genotypes making up the sickle cell disorders, genotype HbSF was the highest (0.9% as compared to 0.2%; HbSS, 0.6%; HbSC and 0.3%; HbSCF). MicroscopicPlasmodium falciparumparasitaemia was detected among 5.5% of the children and 14.2% sub-microscopic prevalence by PCR. Children with sickle cell disorders were more likely to have sub-microscopic parasitaemia (AOR = 5.51 95%CI (2.15, 14.10),p < 0.001) as well as anaemia (AOR = 3.03 95% CI (1.04, 8.82),p = 0.042), compared to those with normal genotypes. There was no significant difference observed between sickle cell disorders and growth and development of the children screened.

Conclusions

Sickle cell disorders were significantly associated with sub-microscopic parasitaemia as well as anaemia in this study. Establishment of sickle cell clinics in the district and regional hospitals will help in the management of children with the disorder and also generate a national database on sickle cell disorders. National neonatal screening policies must also be put in place to help in early detection and management of these disorders.
Performance evaluation of machine learning-based infectious screening flags on the HORIBA Medical Yumizen H550 Haematology Analyzer for vivax malaria and dengue fever
Authors: Dharap Parag , Raimbault Sebastien
Published: November 2020

Background

Automated detection of malaria and dengue infection has been actively researched for more than two decades. Although many improvements have been achieved, these solutions remain too expensive for most laboratories and clinics in developing countries. The low range HORIBA Medical Haematology Analyzer, Yumizen H550, now provides dedicated flags ‘vivax malaria’ and ‘dengue fever’ in routine blood testing, developed through machine learning methods, to be used as a screening tool for malaria and dengue fever in endemic areas. This study sought to evaluate the effectiveness of these flags under real clinical conditions.

Methods

A total of 1420 samples were tested using the Yumizen H550 Haematology Analyzer, including 1339 samples from febrile patients among whom 202 were infected with malaria parasites (Plasmodium vivax only: 182, Plasmodium falciparum only: 18, both: 2), 210 were from febrile dengue infected patients, 3 were from afebrile dengue infected patients and 78 were samples from healthy controls, in an outpatient laboratory clinic in Mumbai, India. Microscopic examination was carried out as the confirmatory reference method for detection of malarial parasite, species identification and assessing parasitaemia based on different stages of parasite life cycle. Rapid diagnostic malarial antigen tests were used for additional confirmation. For dengue infection, NS1 antigen detection by ELISA was used as a diagnostic marker.

Results

For the automated vivax malaria flag, the original manufacturer’s cut off yielded a sensitivity and specificity of 65.2% and 98.9% respectively with the ROC AUC of 0.9. After optimization of cut-off value, flag performance improved to 72% for sensitivity and 97.9% specificity. Additionally it demonstrated a positive correlation with increasing levels of parasitaemia. For the automated dengue fever flag it yielded a ROC AUC of 0.82 with 79.3% sensitivity and 71.5% specificity.

Conclusions

The results demonstrate a possibility of the effective use of automated infectious flags for screening vivax malaria and dengue infection in a clinical setting.
Prevalence, characteristics and risk factors of imported and local malaria cases in North-Western Province, Zambia: a cross-sectional study
Authors: Chipoya Maureen N. , Shimaponda-Mataa Nzooma M.
Published: November 2020

Background

Imported malaria is a major challenge for countries that are in malaria elimination stage such as Zambia. Legitimate cross-border activities add to the risk of transmission, necessitating determination of prevalence, characteristics and risk factors of imported and local malaria.

Methods

This cross-sectional study was conducted in 103 consented child and adult patients with clinical malaria symptoms, from selected health facilities in north-western Zambia. Patient demographic data and blood samples for malaria microscopy and full blood count were obtained. Chi-square and penalized logistic regression were performed to describe the characteristics and assess the risk factors of imported and local malaria in North-Western Province.

Results

Overall, malaria prevalence was 78.6% with 93.8% Plasmodium falciparum and 6.2% other species. The local cases were 72 (88.9%) while the imported were 9 (11.1%) out of the 81 positive participants. About 98.6% of the local cases were P. falciparum compared to 55.6% (χ2 = 52.4; p < 0.01) P. falciparum among the imported cases. Among the imported cases, 44% were species other than P. falciparum (χ2 = 48; p < 0.01) while among the local cases only 1.4% were. Gametocytes were present in 44% of the imported malaria cases and only in 2.8% of the local cases (χ2 = 48; p < 0.01). About 48.6% of local participants had severe anaemia compared to 33.3% of participants from the two neighbouring countries who had (χ2 = 4.9; p = 0.03). In the final model, only country of residence related positively to presence of species other than P. falciparum (OR = 39.0, CI [5.9, 445.9]; p < 0.01) and presence of gametocytes (OR = 23.1, CI [4.2, 161.6]; p < 0.01).

Conclusion

Malaria prevalence in North-Western Province is high, with P. falciparum as the predominant species although importation of Plasmodium ovale and Plasmodium malariae is happening as well. Country of residence of patients is a major risk factor for malaria species and gametocyte presence. The need for enhanced malaria control with specific focus on border controls to detect and treat, for specific diagnosis and treatment according to species obtaining, for further research in the role of species and gametocytaemia in imported malaria, cannot be overemphasized.
Correction to: Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study
Authors: Windhagen Henning , Radtke Kerstin , Weizbauer Andreas , Diekmann Julia , Noll Yvonne , Kreimeyer Ulrike , Schavan Robert , Stukenborg-Colsman Christina , Waizy Hazibullah
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.