bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro anticandidal potency of Syzygium aromaticum (clove) extracts against vaginal candidiasis
Authors: Yassin Mohamed Taha , Mostafa Ashraf Abdel-Fattah , Al-Askar Abdulaziz Abdulrahman 
Published: January 2020

Abstract
Background
Candida vaginitis is a global health hazard that increases morbidity among women of childbearing age. Recent studies have revealed a high incidence of drug-resistant Candida strains. Additionally, treating Candida vulvovaginitis during pregnancy is challenging as antifungal therapy is associated with fetal abnormalities. Hence, it is important to develop novel therapeutic strategies to treat vulvovaginal candidiasis.

Methods
In this study, we used the disc diffusion method to evaluate the anticandidal activity of different Syzygium aromaticum extracts (methanol, ethyl acetate, n-hexane, and diethyl ether) against C. albicans, C. glabrata, and C. tropicalis. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of different S. aromaticum extracts was performed to determine active components exhibiting anticandidal activity. Cytotoxicity of different clove extracts against the HUH7 cell line was evaluated.

Results
The ethyl acetate extract exhibited the highest antifungal activity against C. albicans, C. glabrata, and C. tropicalis with inhibition zone diameters of 20.9, 14.9, and 30.7 mm, respectively. The minimum inhibitory concentration of the S. aromaticum ethyl acetate extract was 250 μg/disc against C. tropicalis, and 500 μg/disc against C. albicans and C. glabrata, while the minimum fungicidal concentration was 0.5 mg/disc against C. tropicalis and 1 mg/disc against the C. albicans and C. glabrata. GC-MS analysis of the ethyl acetate extract revealed the main bioactive compound as eugenol (58.88%), followed by eugenyl acetate (23.86%), trans-caryophyllene (14.44%), and α-humulene (1.88%). The cytotoxicity assay indicated that the diethyl ether extract demonstrated the lowest toxicological effect against the HUH7 cell line, with a relative IC50 of 62.43 μg/ml; the methanolic extract demonstrated a higher toxicity (IC50, 24.17 μg/ml).

Conclusion
As the S. aromaticum extract exhibited high antifungal activity at low concentrations, it can be a potential source of natural antifungal drugs.
Pilot trial of The Living Well Toolkit: qualitative analysis and implications for refinement and future implementation
Authors: Mudge Suzie , Sezier Ann , Payne Deborah , Smith Greta , Kayes Nicola 
Published: January 2020

Abstract
Background
Following a neurological event, people’s long-term health and well-being is hampered by a system that struggles to deliver person-centred communication and coordinated care and fails to harness individual and family capability to live well with the condition. We aimed to implement and evaluate a toolkit package to support these processes for people with long-term neurological conditions.

Methods
This is a multi-phased study drawing on the principles of participatory research. In this pilot phase, the toolkit package was introduced to clinicians, who introduced it to clients in four neurorehabilitation settings (inpatient and community-based). Individual and focus group interviews were carried out with clients (n = 10) and clinicians (n = 9). Data were categorised by the four components of Normalisation Process Theory (NPT), and data within each component was then coded inductively. This analysis was used to inform revisions to the toolkit package and wider implementation processes.

Results
There was widespread support for the principles underpinning the toolkit package from clients and clinicians. However, it was less clear how the client toolkit could support these principles in clinical practice which impacted buy-in. The flexibility of use of the client toolkit, which we encouraged, made it difficult for clinicians and clients to be clear about its purpose and for clinicians to operationalise in practice. Clinicians and clients identified a number of barriers that limited the time, energy and work users were able or prepared to invest, to the extent that uptake of the toolkit package was modest. Use of the toolkit package appeared more likely when clinicians perceived it to augment existing processes (e.g. goal setting) rather than detract from ‘doing’ therapy. This analysis was used to inform revisions to the toolkit package, including simplification of the client toolkit, development of videos with examples of use and a modular and reflective training package for clinical services. The refinements were intended to improve sense-making and minimise the cognitive barriers associated with implementation of a new intervention.

Conclusion
Understanding how supporting the client toolkit could add value to the therapeutic encounter was necessary for clinicians to invest time and perceive the worth of the toolkit package.

Trial registration
ANZCTR: ACTRN12614000537651. Registered 21 May, 2014.
Patients with positive malaria tests not given artemisinin-based combination therapies: a research synthesis describing under-prescription of antimalarial medicines in Africa
Authors: O’Boyle Shennae , Bruxvoort Katia J. , Ansah Evelyn K. , Burchett Helen E. D. , Chandler Clare I. R. , Clarke Siân E. , Goodman Catherine , Mbacham Wilfred , Mbonye Anthony K. , Onwujekwe Obinna E. , Staedke Sarah G. , Wiseman Virginia L. , Whitty Christopher J. M. , Hopkins Heidi 
Published: January 2020

AbstractBackgroundThere has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given.MethodsAnalysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones.ResultsOf 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of < 5-year-olds not prescribed ACT ranged up to 41.8% across sites. The odds of not being prescribed an ACT were 2–32 times higher for patients in settings with lower-transmission intensity (using test positivity as a proxy) compared to areas of higher transmission. mRDT-positive children in low-transmission settings were especially likely not to be prescribed ACT, with proportions untreated up to 70%. Of the 7426 mRDT-positive patients not prescribed an ACT, 4121 (55.5%) were prescribed other, non-recommended non-ACT antimalarial medications, and the remainder (44.5%) were prescribed no antimalarial.ConclusionsIn eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children < 5 years and those in low-transmission settings, were most likely to not be prescribed antimalarials, and young children in low-transmission settings were least likely to be treated for malaria. This major public health risk must be addressed in training and practice.Trial registrationReported in individual primary studies.
Blood signatures for second stage human African trypanosomiasis: a transcriptomic approach
Authors: Mulindwa Julius , Matovu Enock , Enyaru John , Clayton Christine 
Published: January 2020

Abstract
Background
Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient’s immune response in the early and late stages of the disease.

Methods
RNASeq was carried out on blood and cerebral spinal fluid (CSF) samples obtained from T. b. rhodesiense infected patients. The control samples used were from healthy individuals in the same foci. The Illumina sequenced reads were analysed using the Tuxedo suite pipeline (Tophat, Cufflinks, Cuffmerge, Cuffdiff) and differential expression analysis carried out using the R package DESeq2. The gene enrichment and function annotation analysis were done using the ToppCluster, DAVID and InnateDB algorithms.

Results
We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n = 3) and late stage CSF (n = 3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n = 3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3–10) that were up-regulated (log2 FC > 2.5) in both the blood and CSF.

Conclusion
The data yields insights into the host’s response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.
Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study
Authors: Fratta Pasini A. M. , Stranieri C. , Ferrari M. , Garbin U. , Cazzoletti L. , Mozzini C. , Spelta F. , Peserico D. , Cominacini L. 
Published: January 2020

Abstract
Background
A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.

Methods
33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.

Results
In COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced. Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD. The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001). Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03). No correlation was found between ΔFEV1, ΔCRP and ΔWBCs. By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.

Conclusions
Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.
Influence of house characteristics on mosquito distribution and malaria transmission in the city of Yaoundé, Cameroon
Authors: Ngadjeu Carmene S. , Doumbe-Belisse Patricia , Talipouo Abdou , Djamouko-Djonkam Landre , Awono-Ambene Parfait , Kekeunou Sevilor , Toussile Wilson , Wondji Charles S. , Antonio-Nkondjio Christophe 
Published: January 2020

Abstract
Background
Improving house structure is known to limit contact between humans and mosquitoes and reduce malaria transmission risk. In the present study, the influence of house characteristics on mosquito distribution and malaria transmission risk was assessed in the city of Yaoundé.

Methods
The study was conducted from March 2017 to June 2018 in 32 districts of the city of Yaoundé. Mosquito collections were performed indoor in 10 to 15 houses per district using CDC light traps. A total of 467 houses, selected randomly were used. A pretested questionnaire was submitted to participants of the study to collect information on the household: the number of people per house, education level, type of walls, presence of ceilings and eaves, number of windows, usage of long-lasting insecticidal nets (LLINs), number of bedroom and number of window. Mosquitoes collected were identified morphologically. Anophelines were tested by ELISA to detect infection by Plasmodium parasites. General Estimating Equations adjusting for repeated measures in the same house fitting negative binomial analysis were used to assess the influence of house characteristics on mosquito distribution.

Results
A total of 168,039 mosquitoes were collected; Culex spp emerged as the predominant species (96.48%), followed by Anopheles gambiae sensu lato (s.l.) (2.49%). Out of the 1033 An. gambiae s.l. identified by PCR, 90.03% were Anopheles coluzzii and the remaining were An. gambiae sensu stricto (s.s.) (9.97%). The high number of people per household, the presence of screens on window and the possession of LLINs were all associated with fewer mosquitoes collected indoors, whilst opened eaves, the high number of windows, the presence of holes in walls and living close to breeding sites were associated with high densities of mosquitoes indoor. Out of 3557 Anophelines tested using ELISA CSP, 80 were found infected by Plasmodium falciparum parasites. The proportion of mosquitoes infected did not vary significantly according to house characteristics.

Conclusion
The study indicated that several house characteristics such as, the presence of holes on walls, opened eaves, unscreened window and living close to breeding sites, favored mosquito presence in houses. Promoting frequent use of LLINs and house improvement measures, such as the use of screen on windows, closing eaves, cleaning the nearby environment, should be integrated in strategies to improve malaria control in the city of Yaoundé.
Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment?
Authors: Cetintas Vildan B. , Batada Nizar N. 
Published: January 2020

AbstractThe PTEN tumor suppressor is the second most commonly inactivated gene across cancer types. While it’s role in PI3K/AKT and DNA damage pathways are clear, increasing evidences suggest that PTEN may also promote anti-tumor immunity. PTEN-deficient tumors are characterized by (i) reduced levels of cytotoxic T cells, helper T cells and NK cells, (ii) elevated pro-oncogenic inflammatory cytokines like CCL2 and (iii) increased levels of immunosuppressive cells such as MDSCs and Tregs. An intriguing possibility is that link between PTEN and anti-tumor immunity is mediated by the interferon signaling pathway. In this review, we summarize the evidences for the mechanistic link between PTEN deficiency and immunosuppressive tumor microenvironment and the interferon signaling pathway. We further discuss how the link between these pathways can be exploited for development of personalized immunotherapy for patients with PTEN deficient tumors.
Bioresorbable scaffold implantation in STEMI patients: 5 years imaging subanalysis of PRAGUE-19 study
Authors: Kočka Viktor , Toušek Petr , Kozel Martin , Buono Andrea , Hajšl Martin , Lisa Libor , Buděšínský Tomáš , Malý Martin , Widimský Petr 
Published: January 2020

Abstract
Background
Bioresorbable scaffold (BRS) Absorb™ clinical use has been stopped due to higher rate of device thrombosis. Scaffold struts persist longer than 2 years in the vessel wall. Second generation devices are being developed. This study evaluates long-term invasive imaging in STEMI patients.

Methods
PRAGUE-19 study is an academic study enrolling consecutive STEMI patients with intention to implant Absorb™ BRS. A total of 83 STEMI patients between December 2012 and March 2014 fulfilled entry criteria. Coronary angiography and optical coherence tomography at 5 year follow-up was performed in 25 patients.

Results
Primary combined clinical endpoint (death, myocardial infarction or target vessel revascularization) occurred in 12.6% during the five-year follow-up with overall mortality 6.3%. Definite scaffold thrombosis occurred in 2 patients in the early phase after BRS implantation. Quantitative coronary angiography after 5 years demonstrated low late lumen loss of 0.11 ± 0.35 mm with binary restenosis rate of 0%. Optical coherence tomography demonstrated complete resorption of scaffold struts and mean lumen diameter of 3.25 ± 0.30 and 3.22 ± 0.49 (P = 0.73) at baseline and after 5 years, respectively. Three patients developed small coronary artery aneurysm in the treated segment.

Conclusion
Invasive imaging results 5 years after BRS implantation in STEMI showed complete resorption of scaffold struts and stable lumen vessel diameter.
Trial registration ISRCTN43696201 (retrospectivelly registred, June 7th, 2019). https://www.isrctn.com/ISRCTN43696201.
Improve the dosimetric outcome in bilateral head and neck cancer (HNC) treatment using spot-scanning proton arc (SPArc) therapy: a feasibility study
Authors: Liu Gang , Li Xiaoqiang , Qin An , Zheng Weili , Yan Di , Zhang Sheng , Stevens Craig , Kabolizadeh Peyman , Ding Xuanfeng 
Published: January 2020

Abstract
Background
To explore the dosimetric improvement, delivery efficiency, and plan robustness for bilateral head and neck cancer (HNC) treatment utilizing a novel proton therapy technique – the spot-scanning proton arc (SPArc) therapy.

Methods
We evaluated fourteen bilateral HNC patients retrospectively. Both SPArc and 3-field Intensity Modulated Proton Therapy (IMPT) plans were generated for each patient using the same robust optimization parameters. The prescription doses were 70Gy (relative biological effectiveness (RBE) for CTV_high and 60Gy[RBE] for CTV_low. Clinically significant dosimetric parameters were extracted and compared. Root-mean-square deviation dose (RMSDs) Volume Histogram(RVH) was used to evaluate the plan robustness. Total treatment delivery time was estimated based on the machine parameters.

Results
The SPArc plan was able to provide equivalent or better robust target coverage while showed significant dosimetric improvements over IMPT in most of the organs at risk (OARs). More specifically, it reduced the mean dose of the ipsilateral parotid, contralateral parotid, and oral cavity by 25.8%(p = 0.001), 20.8%(p = 0.001) and 20.3%(p = 0.001) respectively compared to IMPT. This technique reduced D1 (the maximum dose covering 1% volume of a structure) of cord and brain stem by 20.8% (p = 0.009) and 10.7% (p = 0.048), respectively. SPArc also reduced the average integral dose by 17.2%(p = 0.001) and external V3Gy (the volume received 3Gy[RBE]) by 8.3%(p = 0.008) as well. RVH analysis showed that the SPArc plans reduced the dose uncertainties in most OARs compared to IMPT, such as cord: 1.1 ± 0.4Gy[RBE] vs 0.7 ± 0.3Gy[RBE](p = 0.001), brain stem: 0.9 ± 0.7Gy[RBE] vs 0.7 ± 0.7Gy[RBE](p = 0.019), contralateral parotid: 2.5 ± 0.5Gy[RBE] vs 2.2 ± 0.6Gy[RBE](p = 0.022) and ipsilateral parotid: 3.1 ± 0.7Gy[RBE] vs 2.8 ± 0.6Gy[RBE](p = 0.004) respectively. The average total estimated treatment delivery time were 283.4 ± 56.2 s, 469.2 ± 62.0 s and 1294.9 ± 106.7 s based on energy-layer-switching-time (ELST) of 0.1 s, 1 s, and 5 s respectively for SPArc plans, compared to the respective values of 328.0 ± 47.6 s(p = 0.002), 434.1 ± 52.0 s(p = 0.002), and 901.7 ± 74.8 s(p = 0.001) for 3-field IMPT plans. The potential clinical benefit of utilizing SPArc will lead to a decrease in the mean probability of salivary flow dysfunction by 31.3%(p = 0.001) compared with IMPT.

Conclusions
SPArc could significantly spare OARs while providing a similar or better robust target coverage compared with IMPT in the treatment of bilateral HNC. In the modern proton system with ELST less than 0.5 s, SPArc could potentially be implemented in the routine clinic with a practical, achievable treatment delivery efficiency.
A new improvement: subperiosteal cocktail application to effectively reduce pain and blood loss after total knee arthroplasty
Authors: Wang Yanxin , Zhou Aiguo 
Published: January 2020

AbstractBackgroundPain and blood loss after total knee arthroplasty (TKA) are unsolved clinical problems. Some studies reported that periarticular cocktail injection can effectively reduce pain and blood loss. However, there was no gold standard about the cocktail ingredient and injection location. More osteotomy and less soft tissue release in TKA with mild deformity; besides, plenty of nerves and blood vessels are contained in the periosteums and bone marrow. In this study, we aimed to detect the clinical results of subperiosteal cocktail application in TKA.MethodsTwo groups were included according to the different injection location in our study. In group 1, cocktails were injected into the muscles, tendons, suprapatellar bursa, and subpatellar bursa surrounding knee joint. In group 2, cocktail injection was performed under the periosteum of the distal femur and proximal tibia. Our primary outcomes were visual analogue scale (VAS) and hemoglobin (Hb), and the secondary outcomes were wound healing, infection, deep vein thrombosis (DVT), operation time, and hospitalization.ResultsAt the first operative day, the mean (standard deviation) VAS score in a state of static was lower in group 2 compared with group 1 (0.98 ± 0.27 in group 1 and 0.86 ± 0.60 in group 2,p < 0.05). In the state of flexion and extension, the mean (standard deviation) VAS was 1.61 ± 0.66 in group 1 and 1.10 ± 0.57 in group 2 (p < 0.05). The mean (standard deviation) blood loss was higher in group 1 than in group 2 at the first postoperative day (440.19 (167.68) ml in group 1 and 333.67 (205.99) ml in group 2,p < 0.05). At the third day after surgery, the mean (standard deviation) blood loss was 686.44 (140.29) ml in group 1 and 609.19 (260.30) ml in group 2, and there was significant difference between these two groups (p < 0.05).ConclusionsWe concluded that subperiosteal cocktail injection can significantly reduce pain and blood loss compared with periarticular cocktail injection after TKA.