bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporation of drug efflux inhibitor and chemotherapeutic agent into an inorganic/organic platform for the effective treatment of multidrug resistant breast cancer
Authors: Dong Yang , Liao Hongze , Yu Jian , Fu Hao , Zhao De , Gong Ke , Wang Qi , Duan Yourong 
Published: December 2019

Abstract
Background
Multidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR.

Results
This co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration.

Conclusion
The concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.
The relationship between government research funding and the cancer burden in South Korea: implications for prioritising health research
Authors: Jung Ye Lim , Yoo Hyoung Sun , Kim Eun Sun 
Published: December 2019

Abstract
Background
In this study, we aimed to assess health research funding allocation in South Korea by analysing the relationship between government funding and disease burden in South Korea, specifically focusing on cancers.

Methods
The relationship between research funding and the cancer burden, measured in disability-adjusted life-years (DALYs), was analysed using a linear regression method over a 10-year interval. Funding information on 25 types of cancer was obtained from the National Science and Technology Information Service portal in South Korea. Measures of cancer burden were obtained from Global Burden of Disease studies. The funding predictions were derived from regression analysis and compared with actual funding allocations. In addition, we evaluated how the funding distribution reflected long-term changes in the burden and the burden specific to South Korea compared with global values.

Results
Korean funding in four periods, 2005–2007, 2008–2010, 2011–2013 and 2015–2017, were associated with the cancer burden in 2003, 2006, 2009 and 2013, respectively. For DALYs, the correlation coefficients were 0.79 and 0.82 in 2003 and 2013, respectively, which were higher than the values from other countries. However, the changes in DALYs (1990–2006) were not associated with the funding changes (from 2005 to 2007 to 2015–2017). In addition, the value differences between Korean and global DALYs were not associated with Korean government research funding.

Conclusions
Although research funding was associated with the cancer burden in South Korea during the last decade, the distribution of research funds did not appropriately reflect the changes in burden nor the differences between the South Korean and global burden levels. The policy-makers involved in health research budgeting should consider not only the absolute burden values for singular years but also the long-term changes in burden and the country-specific burden when they prioritise public research projects.
Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs
Authors: Hanáková Kateřina , Bernatík Ondřej , Kravec Marek , Micka Miroslav , Kumar Jitender , Harnoš Jakub , Ovesná Petra , Paclíková Petra , Rádsetoulal Matěj , Potěšil David , Tripsianes Konstantinos , Čajánek Lukáš , Zdráhal Zbyněk , Bryja Vítězslav 
Published: December 2019

AbstractBackgroundDishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases.MethodsShotgun proteomics including TiO2enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on immunoprecipitates from HEK293T cells was used to identify and quantify phosphorylation of DVL3 protein induced by 8 kinases. Functional characterization was performed by in-cell analysis of phospho-mimicking/non-phosphorylatable DVL3 mutants and supported by FRET assays and NMR spectroscopy.ResultsWe used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced β-catenin activation. S630–643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization.ConclusionsWe identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome.Graphical abstract
Domestic violence related disclosure among women and girls in Ethiopia: a systematic review and meta-analysis
Authors: Bifftu Berhanu Boru , Dachew Berihun Assefa , Tiruneh Bewket Tadesse , Gezie Lemma Derseh , Guracho Yonas Deressa 
Published: December 2019

Abstract
Background
Domestic violence is common public health problem. Domestic violence related disclosure is an important first step in the process of prevention, control and treatments of domestic violence related adverse effect. Thus, this systematic review and meta-analysis aimed to determine the pooled prevalence of domestic violence related disclosure and synthesize its associated factors.

Methods
We followed the PRISMA Guidelines to report the results of the finding. Databases including PubMed, Cochrane Library and Web of Sciences were searched. The heterogeneity between studies was measured by the index of heterogeneity (I2 statistics) test. Funnel plots and Egger’s test were used to determine publication bias. Moreover, sensitivity analysis was carried out. To calculate the pooled prevalence, a random effects model was utilized.

Results
Twenty one eligible studies were included in this systematic review and meta-analysis. The pooled prevalence of domestic violence related non-disclosure was found to be 36.2% (95% CI, 31.8–40.5%). Considering violence as normal or not serious, shame, embarrassment and fear of disclosure related consequences were the common barriers for non-disclosure.

Conclusion
More than one third of women and girls were not disclosed their experience of domestic violence. The finding of this study suggests the need of evaluation and strengthening of the collaborative work among different sectors such as: policy-makers, service providers, administrative personnel and community leaders including the engagement of men partner. This study also suggests the needs of women empowerments against the traditional belief, attitude, and practice.
Robotic body weight support enables safe stair negotiation in compliance with basic locomotor principles
Authors: Bannwart M. , Rohland E. , Easthope C. A. , Rauter G. , Bolliger M. 
Published: December 2019

AbstractBackgroundAfter a neurological injury, mobility focused rehabilitation programs intensively train walking on treadmills or overground. However, after discharge, quite a few patients are not able to independently negotiate stairs, a real-world task with high physical and psychological demands and a high injury risk. To decrease fall risk and improve patients’ capacity to navigate typical environments, early stair negotiation training can help restore competence and confidence in safe stair negotiation. One way to enable early training in a safe and permissive environment is to unload the patient with a body weight support system. We here investigated if unloaded stair negotiation complies with basic locomotor principles, in terms of enabling performance of a physiological movement pattern with minimal compensation.MethodsSeventeen able-bodied participants were unloaded with 0–50% bodyweight during self-paced ascent and descent of a 4-tread staircase. Spatio-temporal parameters, joint ranges of motion, ground reaction forces and myoelectric activity in the main lower limb muscles of participants were compared between unloading levels. Likelihood ratio tests of separated linear mixed models of the investigated outcomes assessed if unloading affects the parameters in general. Subsequent post-hoc testing revealed which levels of unloading differed from unsupported stair negotiation.ResultsUnloading affected walking velocity, joint ranges of motion, vertical ground reaction force parameters and myoelectric activity in all investigated muscles for stair ascent and descent while step width and single support duration were only affected during ascent. A reduction with increasing levels of body weight support was seen in walking velocity (0.07–0.12 m/s), ranges of motion of the knee and hip (2–10°), vertical ground reaction force peaks (10–70%) and myoelectric activity (17–70%). An increase with unloading was only seen during ascent for ankle range of motion and tibialis anterior activity at substantial unloading.ConclusionsBody weight support facilitates stair negotiation by providing safety and support against gravity. Although unloading effects are present in most parameters, up to 30% body weight support these changes are small, and no dysfunctional patterns are introduced. Body weight support therefore fulfills all the necessary requirements for early stair negotiation training.
People who inject drugs (PWID) and HIV/aids cases in Mexico City: 1987–2015
Authors: Romero Mendoza Martha , Meza-Mercado Denize , Martínez-Martínez Rosario , Magis-Rodríguez Carlos , Ortiz Castro Arturo , Medina-Mora Maria Elena 
Published: December 2019

Abstract
Background
The purpose of this study is to describe the characteristics of individuals who inject drugs, to explore use trends in the past 25 years, and to review the profile of users of various drugs, both legal and illegal, that have been used intravenously without medical prescription in Mexico City.

Methods
Information was drawn from the Drug Information Reporting System (SRID, 1987–2015) and data from the National Center for the Prevention and Control of HIV/aids (CENSIDA, 1983–2018). SRID is based on two 30-day cross-sectional evaluations carried out during June and November. It has served as an uninterrupted epidemiological surveillance system for 32 years, operating both in health and justice institutions in Mexico City and the metropolitan area. The timely identification of changes in use patterns is regarded as the most consistent tool to track the trajectory of the phenomenon. CENSIDA cases were analyzed based on the number of HIV and aids positive injectable drug users during the same period of time in Mexico City.

Results
Cocaine users represented the highest number of cases, with a total of N = 293. Back in 2000, the use of this substance showed a significant increase of up to 50%. In turn, heroine and opiates user trends by sex increased from being almost non-existent in 1987 to 13% in 1994. Results provide evidence of the changes in the number of users over the years, with the largest increases being recorded in 1996 (16.5%), 1999 (17%), and 2010 (13%).

Conclusions
The increase observed in the results coincides with domestic and world political situations that have caused an upturn in the use of some substances over the years. It is not far-fetched to think that in the coming years there will be an increase in the number of individuals who inject drugs due to the high production and availability of heroin in Mexico and the emergence of fentanyl use as indicated by ethnographic research in Mexico City and the deaths linked to its consumption. The latest reports, published in 2018, documented at least five cases of fentanyl users.
Evaluation of the efficacy of simplified nutritional instructions from physicians on dietary salt restriction for patients with type 2 diabetes mellitus consuming excessive salt: protocol for a randomized controlled trial
Authors: Ushigome Emi , Oyabu Chikako , Shiraishi Makoto , Kitagawa Nobuko , Kitae Aya , Iwai Keiko , Ushigome Hidetaka , Yokota Isao , Hamaguchi Masahide , Yamazaki Masahiro , Fukui Michiaki 
Published: December 2019

Abstract
Background
Hypertension is present in more than 50% of patients with type 2 diabetes mellitus. Dietary salt restriction is recommended for the management of high blood pressure. Instructions on dietary salt restriction, provided by a dietitian, have been shown to help patients reduce their salt intake. However, appointments for the dietitians in hospitals are often already fully booked, making it difficult for patients to receive instructions on the same day as the outpatient clinic visit.

Aim
The aim of this trial is to test a new intervention to assess whether guidance on dietary salt restriction provided by physicians during outpatient visits is effective in reducing salt intake in patients with type 2 diabetes mellitus who have an excessive salt intake.

Methods
In this unblinded randomized controlled trial (RCT), a total of 200 patients, male or female, aged between 20 and 90 years, who have type 2 diabetes mellitus and consume excessive salt will be randomly assigned to two groups: an intervention group and a control group. In addition to being given routine treatment, participants in the intervention group will be given individual guidance on restricting their dietary salt intake by a physician upon enrollment. The control group will only be given routine treatment. Participants will be followed up for 24 weeks. The primary outcome will be dietary salt intake, which will be assessed at baseline and at 8, 16, and 24 weeks. The secondary outcomes, including body weight, body mass index, hemoglobin A1c level, blood pressure, blood glucose level, serum lipid profile, and urinary albumin excretion level, will be assessed at baseline and at 8, 16, and 24 weeks.

Discussion
The results of this RCT have the potential to provide a simple and novel clinical approach to reduce salt intake among patients with type 2 diabetes, making regular visits to their physician, in outpatient facilities. This protocol will contribute to the literature because it describes a practical intervention that has not been tested previously, and it may serve as guidance to other researchers interested in testing similar interventions.

Trial registration
University Hospital Medical Information Network (UMIN), UMIN000028809. Registered retrospectively on 24 August 2017. http://www.umin.ac.jp.
In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection
Authors: Guegan Hélène , Ory Kevin , Belaz Sorya , Jan Aurélien , Dion Sarah , Legentil Laurent , Manuel Christelle , Lemiègre Loïc , Vives Thomas , Ferrières Vincent , Gangneux Jean-Pierre , Robert-Gangneux Florence 
Published: December 2019

Abstract
Background
The chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses.

Methods
Here, immunostimulating and leishmanicidal properties of octyl-β-d-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations.

Results
Both treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1β and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1β, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment.

Conclusions
Overall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.
Herpes simplex virus and Cytomegalovirus reactivation among severe ARDS patients under veno-venous ECMO
Authors: Hraiech Sami , Bonnardel Eline , Guervilly Christophe , Fabre Cyprien , Loundou Anderson , Forel Jean-Marie , Adda Mélanie , Parzy Gabriel , Cavaille Guilhem , Coiffard Benjamin , Roch Antoine , Papazian Laurent 
Published: December 2019

Abstract
Background
Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS). However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO). We tried to determine the frequency of Herpesviridae reactivation and its impact on patients’ prognosis during ECMO for severe ARDS.

Results
During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a veno-venous ECMO were included. Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone). HSV reactivation occurred earlier than CMV after the beginning of MV [(6–15) vs. 19 (13–29) days; p < 0.01] and after ECMO implementation [(2–8) vs. 14 (10–20) days; p < 0.01]. In univariate analysis, HSV/CMV reactivation was associated with a longer duration of mechanical ventilation [(22–52.5) vs. 17.5 (9–28) days; p < 0.01], a longer duration of ECMO [15 (10–22.5) vs. 9 (5–14) days; p < 0.01], and a prolonged ICU [29 (19.5–47.5) vs. 16 (9–30) days; p < 0.01] and hospital stay [44 (29–63.5) vs. 24 (11–43) days; p < 0.01] as compared to non-reactivated patients. However, in multivariate analysis, viral reactivation remained associated with prolonged MV only. When considered separately, both HSV and CMV reactivation were associated with a longer duration of MV as compared to non-reactivation patients [29 (19.5–41) and 28 (20.5–37), respectively, vs. 17.5 (9–28) days; p < 0.05]. Co-reactivation patients had a longer duration of MV [58.5 (38–72.3); p < 0.05] and ICU stay [51.5 (32.5–69) vs. 27.5 (17.75–35.5) and 29 (20–30.5), respectively] as compared to patients with HSV or CMV reactivation alone. In multivariate analysis, HSV reactivation remained independently associated with a longer duration of MV and hospital length of stay.

Conclusions
Herpesviridae reactivation is frequent among patients with severe ARDS under veno-venous ECMO and is associated with a longer duration of mechanical ventilation. The direct causative link between HSV and CMV reactivation and respiratory function worsening under ECMO remains to be confirmed.
Towards a sustainable distributed energy system in China: decision-making for strategies and policy implications
Authors: Lin Ruojue , Liu Yue , Man Yi , Ren Jingzheng 
Published: December 2019

Abstract
Background
The conflict between the Chinese fossil fuel-based economy and worsening environmental conditions requires further research to be carried out. Due to their clean, highly-efficient and flexible properties, distributed energy systems (DESs) have become a global research focus in the field of energy conservation. China, as the largest coal-fired energy user and highest power consumer in the world, has to conduct further research and apply the DESs to resolve the conflict. This study aims to provide a comprehensive review of DES development in China as well as improvement suggestions for the development of DESs by use of scientific analysis.

Methods
The analysis of strengths-weaknesses-opportunities threats (SWOT) was adapted for the analysis of improvement strategies. The directions for how to improve the application of these strategies were selected by the prioritization method of analytic hierarchy processes (AHP) and evaluated by the best-worst method (BWM). The suggestions were provided according to the ranks figured out by AHP and BWM. Five enablers were selected from the respective economic, environmental, technological and social aspects for participating in this analysis.

Results
Resulting from the SWOT analysis, capital investment, technology development and regulation completeness are three aspects of strategies summarized as SO strategies, ST strategies, WO strategies and WT strategies. The research perspectives of DESs that are suggested for investment, technology development and regulation completeness are illustrated by AHP and BWM. The results show that the reduction of solid particle emissions, the improvement of generation reliability, the improvement of the production rate, the reduction of production costs, the improvement of on-site safety, the fulfilment of electricity demand, the reduction of noxious gas emissions as well as the improvement of energy efficiency need to be carried out for the sake of environmental protection and quality of DES generation in China.

Conclusions
There are high potentials for China to further develop and apply DES approaches. The direction of current development might be set to solve three problematic aspects, which are capital investment, technology development and regulation completeness.