bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso
Authors: Lingani Moussa , Bonkian Léa Nadège , Yerbanga Isidore , Kazienga Adama , Valéa Innocent , Sorgho Hermann , Ouédraogo Jean Bosco , Mens Petronella Francisca , Schallig Henk D. F. H. , Ravinetto Raffaella , d’Alessandro Umberto , Tinto Halidou 
Published: January 2020

Abstract
Background
Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso.

Methods
In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42.

Results
Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05).

Conclusion
These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso.
Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1
Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome
Authors: Wang Guang-chun , Huang Tian-run , Hu Yang-yang , Wang Ke-yi , Shi Heng , Yin Lei , Peng Bo 
Published: January 2020

Abstract
Background
The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Experimental autoimmune prostatitis (EAP) rats.

Methods
EAP was induced in rats by using prostate protein supplemented with immuneadjuvant extraction, and the max-ICP and MAP were measured. IHC and Masson staining were done to assess inflammatory infiltration and collagen deposition in the corpus cavernosum, respectively. Subsequently, normal rat and EAP rat CCSMCs were purified by tissue block implantation and differential adherence method. The oxidative stress, smooth muscle phenotype transformation, cell cycle and intracellular calcium ion transport were also evaluated.

Results
The ratio of max ICP/MAP in EAP rats significantly reduced, and the TNF-α content and collagen deposition in the corpus cavernosum markedly increased as compared to healthy rats. High-purity rat CCSMCs were obtained. Oxidative stress was evident and the cGMP content decreased in the EAP rat CCSMCs. The expression of Cav1.2, IP3R1 and RyR2 increased, but the SERCA2 expression decreased in EAP rat CCSMCs, which was accompanied by increased intracellular calcium. Increased expression of OPN, collagen and KCa3.1, decreased Calponin expression and increased proportion of cells in the S phase were also observed in the EAP rat CCSMCs.

Conclusion
CP causes oxidative stress and imbalance of intracellular calcium in CCSMCs and promotes CCSMCs transformation from contractile to synthetic state, which may be involved in the pathogenesis of ED.
Soybean lecithin stabilizes disulfiram nanosuspensions with a high drug-loading content: remarkably improved antitumor efficacy
Authors: Li Haowen , Liu Biao , Ao Hui , Fu Jingxin , Wang Yian , Feng Yue , Guo Yifei , Wang Xiangtao 
Published: January 2020

AbstractDisulfiram (DSF) has been considered as “Repurposing drug” in cancer therapy in recent years based on its good antitumor efficacy. DSF is traditionally used as an oral drug in the treatment of alcoholism. To overcome its rapid degradation and instability, DSF nanosuspensions (DSF/SPC-NSps) were prepared using soybean lecithin (SPC) as a stabilizer of high drug-loaded content (44.36 ± 1.09%). Comprehensive characterization of the nanosuspensions was performed, and cell cytotoxicity, in vivo antitumor efficacy and biodistribution were studied. DSF/SPC-NSps, having a spherical appearance with particle size of 155 nm, could remain very stable in different physiological media, and sustained release. The in vitro MTT assay indicated that the cytotoxicity of DSF/SPC-NSps was enhanced remarkably compared to free DSF against the 4T1 cell line. The IC50 value decreased by 11-fold (1.23 vs. 13.93 μg/mL, p < 0.01). DSF/SPC-NSps groups administered via intravenous injections exhibited better antitumor efficacy compared to the commercial paclitaxel injection (PTX injection) and had a dose-dependent effect in vivo. Notably, DSF/SPC-NSps exhibited similar antitumor activity following oral administration as PTX administration via injection into a vein. These results suggest that the prepared nanosuspensions can be used as a stable delivery vehicle for disulfiram, which has potential application in breast cancer chemotherapy.
Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study
Authors: Jin Chuyao , Lin Lizi , Han Na , Zhao Zhiling , Liu Zheng , Luo Shusheng , Xu Xiangrong , Liu Jue , Wang Haijun 
Published: January 2020

Abstract
Background
To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM).

Methods
Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM.

Results
The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester.

Conclusions
Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.
Effect of Loureirin B on Crohn’s disease rat model induced by TNBS via IL-6/STAT3/NF-κB signaling pathway
Authors: Sun Xueliang , Wen Ke , Xu Zhizhong , He Zongqi , Wu Bensheng , Yang Xiao , Wang Xiaopeng 
Published: January 2020

Abstract
Background
Crohn’s disease (CD) is a chronic relapsing form of inflammatory bowel disease, seriously threatening human beings health. However, the pathogenesis of CD is still unclear and there is no specific effective drug for treatment of CD. Resina Donis (RD) obtained from Dracaena cochinchinensis (Lour.) S. C. Chen (Liliaceae), has been used for the treatment of CD clinically. Loureirin B (LB) is one of the most important chemical compositions and physiologically active ingredients of resina draconis. It has the molecular structure propan-1-one, 1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl)-1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl) propan-1-one. The aim of this study was to investigate the effect of LB on CD and explore the underlying mechanisms.

Methods and results
In this study, the result demonstrated that LB prolonged the survival time of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rats and alleviated colonic damage in a dose dependent manner. Besides, LB remarkably ameliorated TNBS-induced inflammatory response via regulation of cytokines in the colonic tissues. Moreover, LB could reverse the established fibrosis and impede the accumulation infiltration, and improve the apoptosis induced by TNBS in a dose dependent manner. Further, LB dramatically suppressed TNBS-induced the activation of IL-6/STAT3/NF-κB signaling pathway.

Conclusions
These findings suggested that LB could be beneficial regarding ameliorating TNBS-induced CD, which may represent a novel approach to treat CD and provide an alternative choice for disorders associated with CD.
The small GTPase ARF6 regulates GABAergic synapse development
Authors: Kim Hyeonho , Jung Hyeji , Jung Hyunsu , Kwon Seok-Kyu , Ko Jaewon , Um Ji Won 
Published: January 2020

AbstractADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1–6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at glutamatergic synapses, but their roles at GABAergic synapses have not been investigated. Here, we show that a subset of ARF6 protein is localized at GABAergic synapses in cultured hippocampal neurons. In addition, we found that knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure susceptibility in an induced epilepsy model. Viewed together, our results suggest that modulating ARF6 and its regulators could be a therapeutic strategy against brain pathologies involving hippocampal network dysfunction, such as epilepsy.
A reflection on the role of genetics in the concept of “epileptic encephalopathy”, as emerged from the most recent ILEA classification of epilepsy
Authors: Russo Angelo , Gobbi Giuseppe 
Published: January 2020

AbstractThe International League Against Epilepsy (ILAE) has been working to standardize the epilepsy classifications for over a hundred years.The latest epilepsy classification has been recently carried out with a careful overview on several topics including the “epileptic encephalopathies” concept and several constructive discussions on this topic have taken place in the international community of epileptologists.Here we wish to share our reflection on a statement of the ILAE commission on the “epileptic encephalopathy” concept, which in our opinion pays less attention to the “electroclinical syndromes” concept in favor of the new and very rapid genetic advances, thus generating confusion.Our aim is both to preserve the role of electroclinical syndromes, while allowing for the association of the phenotype with specific gene mutations, and to underline the importance of bringing electroclinical syndromes back to the forefront of epileptology.We believe the “match” is still open and for this reason we would like to share our considerations and to open a constructive debate on the “epileptic encephalopathy” concept.
High Quality Targeted Temperature Management (TTM) After Cardiac Arrest
Authors: Taccone Fabio Silvio , Picetti Edoardo , Vincent Jean-Louis 
Published: January 2020

AbstractTargeted temperature management (TTM) is a complex intervention used with the aim of minimizing post-anoxic injury and improving neurological outcome after cardiac arrest. There is large variability in the devices used to achieve cooling and in protocols (e.g., for induction, target temperature, maintenance, rewarming, sedation, management of post-TTM fever). This variability can explain the limited benefits of TTM that have sometimes been reported. We therefore propose the concept of “high-quality TTM” as a way to increase the effectiveness of TTM and standardize its use in future interventional studies.
Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial
Authors: Shi Haoyue , Yang Deshuang , Qiao Jiajun , Sun Rui , Li Ruihan , Zhu Chunlin , Jing Ruiqing , Liu Liping , Huang Li , Li Lin 
Published: January 2020

Abstract
Background
Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown.

Methods/design
In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle–brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators.

Discussion
This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension.

Trial registration
Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.
Tailored, psychological intervention for anxiety or depression in people with chronic obstructive pulmonary disease (COPD), TANDEM (Tailored intervention for ANxiety and DEpression Management in COPD): protocol for a randomised controlled trial
Authors:   On behalf of the TANDEM Investigators, Sohanpal Ratna , Pinnock Hilary , Steed Liz , Heslop Marshall Karen , Chan Claire , Kelly Moira , Priebe Stefan , Roberts C. Michael , Singh Sally , Smuk Melanie , Saqi-Waseem Sarah , Healey Andy , Underwood Martin , White Patrick , Warburton Chris , Taylor Stephanie J. C. 
Published: January 2020

Abstract
Background
People with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and anxiety, which greatly reduces their quality of life and is associated with worse outcomes; but these psychological co-morbidities are under-recognised and undertreated in COPD patients. Pulmonary rehabilitation (PR) improves mood for up to 6 months but health practitioners under-refer, and patients commonly fail to attend/complete PR. Research suggests that complex non-pharmacological interventions, including both psychological and exercise components, may reduce anxiety and depression in COPD.
We have developed a tailored, cognitive behavioural approach (CBA) intervention for patients with COPD and co-morbid anxiety and/or depression (‘TANDEM’), which precedes and optimises the benefits of currently offered PR. We hypothesise that such a psychological intervention, delivered by supervised, trained respiratory healthcare professionals, will improve mood in patients with mild to moderate anxiety and/or depression and encourage uptake and completion of PR.

Methods
We will conduct a multi-centre, pragmatic, randomised controlled trial of the TANDEM intervention compared to usual care across the Midlands, London, the South East and Bristol, UK.
We will train healthcare professionals familiar with COPD to deliver the manualised, tailored, face-to-face, one-to-one intervention weekly for 6–8 weeks.
We will recruit 430 participants from primary, community and secondary care with confirmed COPD and moderate to very severe airflow limitation, who are eligible for assessment for PR, and who screen positive for symptoms of mild/moderate depression and/or anxiety using the Hospital Anxiety and Depression scale (HADS). Participants will be randomised 1.25:1 (intervention: usual care).
The co-primary outcomes are the HADS anxiety and depression subscale scores at 6 months; participants will be followed up to 12 months. Secondary outcomes include uptake and completion of PR and healthcare resource use. There will be a parallel process evaluation and a health economic evaluation.

Discussion
The TANDEM intervention has the potential to optimise the unrealised synergy between a psychological intervention and PR. The CBA sessions will precede PR and target individuals’ cognitions, behaviours and symptoms associated with anxiety and depression to decrease psychological morbidity and increase effective self-management amongst patients with COPD.

Trial registration
ISRCTN, ID: ISRCTN59537391. Registered on 20 March 2017. Protocol version 6.0, 22 April 2018.
Comparing how patients value and respond to information on risk given in three different forms during dental check-ups: the PREFER randomised controlled trial
Authors: Harris R. , Lowers V. , Laverty L. , Vernazza C. , Burnside G. , Brown S. , Ternent L. 
Published: January 2020

Abstract
Background
This study aims to compare patient preference for, and subsequent change in, oral health behaviour for three forms of risk information given at dental check-ups (verbal advice compared to verbal advice accompanied by a traffic light (TL) risk card; or compared to verbal advice with a quantitative light fluorescence (QLF) photograph of the patient’s mouth).

Methods
A multi-centre, parallel-group, patient-randomised clinical trial was undertaken between August 2015 and September 2016. Computer-generated random numbers using block stratification allocated patients to three arms. The setting was four English NHS dental practices. Participants were 412 dentate adults at medium/high risk of poor oral health. Patients rated preference and willingness to pay (WTP) for the three types of information. The primary outcome was WTP. After receiving their check-up, patients received the type of information according to their group allocation. Follow-up was by telephone/e-mail at 6 and 12 months. Mean and median WTP for the three arms were compared using Wilcoxon signed-rank tests. Tobit regression models were used to investigate factors affecting WTP and preference for information type. Secondary outcomes included self-rated oral health and change in oral health behaviours (tooth-brushing, sugar consumption and smoking) and were investigated using multivariate generalised linear mixed models.

Results
A total of 412 patients were randomised (138 to verbal, 134 to TL and 140 to QLF); 391 revisited their WTP scores after the check-up (23 withdrew). Follow-up data were obtained for 185 (46%) participants at 6 months and 153 (38%) participants at 12 months. Verbal advice was the first preference for 51% (209 participants), QLF for 35% (145 participants) and TL for 14% (58 participants). TL information was valued lower than either verbal or QLF information (p < 0.0001). Practice attended was predictive of verbal as first preference, and being older. Practice attended, preferring TL the most and having fewer than 20 teeth were associated with increased WTP; and living in a relatively deprived area or having low literacy decreased WTP. There were no significant differences in behaviour change on follow-up.

Conclusions
Although a new NHS dental contract based on TL risk stratification is being tested, patients prefer the usual verbal advice. There was also a practice effect which will needs to be considered for successful implementation of this government policy.

Trial registration
ISRCTN, ISRCTN71242343. Retrospectively registered on 27 March 2018.