bluuebunny/crossref_metadata_2025_split huggingface dataset:
Living and dying with incurable cancer: a qualitative study on older patients’ life values and healthcare professionals’ responsivity
Authors: van Gurp Jelle L. P. , Ebenau Anne , van der Burg Simone , Hasselaar Jeroen 
Published: July 2020

AbstractBackgroundIn ageing Western societies, many older persons live with and die from cancer. Despite that present-day healthcare aims to be patient-centered, scientific literature has little knowledge to offer about how cancer and its treatment impact older persons’ various outlooks on life and underlying life values. Therefore, the aims of this paper are to: 1) describe outlooks on life and life values of older people (≥ 70) living with incurable cancer; 2) elicit how healthcare professionals react and respond to these.MethodsSemi-structured qualitative interviews with 12 older persons with advanced cancer and two group interviews with healthcare professionals were held and followed by an analysis with a grounded theory approach.ResultsSeveral themes and subthemes emerged from the patient interview study: a) handling incurable cancer (the anticipatory outlook on “a reduced life”, hope and, coping with an unpredictable disease) b) being supported by others (“being there”, leaving a legacy, and having reliable healthcare professionals) and; c) making end-of-life choices (anticipatory fears, and place of death). The group interviews explained how healthcare professionals respond to the abovementioned themes in palliative care practice. Some barriers for (open) communication were expressed too by the latter, e.g., lack of continuity of care and advance care planning, and patients’ humble attitudes.ConclusionsOlder adults living with incurable cancer showed particular outlooks on life and life values regarding advanced cancer and the accompanying last phase of life. This paper could support healthcare professionals and patients in jointly exploring and formulating these outlooks and values in the light of treatment plans.
Human placenta induces hair regrowth in chemotherapy-induced alopecia via inhibition of apoptotic factors and proliferation of hair follicles
Authors: Kim Mi Hye , Kim Kyuseok , Lee Haesu , Yang Woong Mo 
Published: July 2020

Abstract
Background
The human placenta (HP) is a complex organ used to alleviate tiredness and promote wound healing. Previous research showed the hair growth-promoting effect of HP. However, no reports have addressed the effects of HP on hair regrowth in chemotherapy-induced alopecia. In this study, we investigated the effects of HP on the apoptosis and proliferation of hair follicles in chemotherapy-induced alopecia.

Methods
Male C57BL/6 mice in telogen were depilated to enter anagen. After 9 days, dystrophic catagen was induced by the intraperitoneal injection of 150 mg/kg cyclophosphamide. During 9 to 16 days, 0.1 and 1 mg/mL HP were topically applied to depilated dorsal skin.

Results
Dystrophic hair follicles by cyclophosphamide were recovered by HP treatment. New hair shafts containing hair fibers appeared to be straight after HP treatment. Immunohistological staining revealed a significant increase of Ki67-positive cells in hair follicles treated with 1 mg/mL HP. Topical HP treatment increased the ratio of Bcl-2/Bax, while it attenuated the expression of pro-apoptotic Bax, p53, and cytochrome c with caspase-9 and -3. In addition, the expression of KGF and the phosphorylation of AKT were upregulated by HP treatment.

Conclusion
These results suggest that HP treatment induced hair growth by inhibiting apoptosis and promoting the proliferation of hair follicles. HP may be useful for treating chemotherapy-induced alopecia.
PACE-IT study protocol: a stepped wedge cluster randomised controlled trial evaluating the implementation of telehealth visual assessment in emergency care for people living in residential aged-care facilities
Authors: Sunner Carla , Giles Michelle Therese , Parker Vicki , Dilworth Sophie , Bantawa Kamana , Kable Ashley , Oldmeadow Chris , Foureur Maralyn 
Published: July 2020

Abstract
Background
Transfer of residential aged-care facility (RACF) residents to Emergency Departments (ED) is common, risky and expensive. RACF residents who present to ED are more likely to have hospital readmissions, longer stays and face major risks related to hospital acquired complications. Aged Care Emergency services (ACE) is a nurse led, protocol- guided, telephone RACF/ED outreach model that has been shown to be effective in reducing hospitalisation and length of hospital stay for RACF residents in the Hunter New England Local Health District, New South Wales (NSW). The Partnerships in Aged-Care Emergency services using Interactive Telehealth (PACE-IT) project enhances ACE by incorporating interactive video assessment and consultation. The PACE-IT project’s primary aim is to assess whether augmentation of ACE services through the addition of protocol-guided interactive Visual Telehealth Consultation (VTC) for clinical decision-making, plus telephone follow-up, reduces RACF resident transfers to ED.

Methods
A stepped-wedge cluster randomised controlled trial will be conducted. The intervention will be delivered sequentially to 8 clusters; each cluster comprises one ED and two RACFs in NSW, Australia.
The 16 RACFs in the study will be selected for order of implementation using a computer-generated randomisation sequence. A 2-step randomisation process will be undertaken, randomising the hospital EDs first and then randomising the RACFs aligned with each hospital.
The PACE-IT intervention comprises: an initial phone call by RACFs to the ACE service in the ED; the ACE service in ED responds with a protocol-guided VTC, a management plan agreed between all participants; an automated consultation summary letter to the General Practitioner and the RACF; a post VTC 24 h follow-up phone call to the RACF.

Discussion
If shown to be effective, the intervention has the potential to improve the clinical care and quality of life for residents. Findings will provide high level evidence that will inform sustainable change and broad translation into practice across NSW. It will show how the change has been achieved and highlight success factors for scalability and sustainability. It will inform review of processes, the development of policy and guidelines that will integrate PACE-IT into existing service models in NSW.

Trial registration
The trial is registered with the Australian New Zealand Clinical Trials Registry (Trial ID ACTR N12619001692123) 02/12/2020.)
Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601
Authors: Wang Yuanyuan , Gong Guoliang , Xu Jingyun , Zhang Yuanxin , Wu Shenggui , Wang Shaohong 
Published: July 2020

Abstract
Background
Breast cancer (BC) is a common malignancy worldwide. It has been reported that long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is abnormally expressed in BC. However, the role of HOTAIR in the malignancy of BC is worth further discussion. This study aims to clarify the function and molecular mechanism of HOTAIR in BC.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of HOTAIR, microRNA (miR)-601 and zinc finger E-box binding homeobox 1 (ZEB1). Cell counting kit-8 (CCK-8) and transwell assay were used to detect the proliferation, migration and invasion of cells. Further, the protein levels of AKT, phosphorylated-AKT (p-AKT), ZEB1 and Ki-67 were confirmed by western blot (WB) assay. Moreover, dual-luciferase reporter assay was applied to examine the targeting relationship between HOTAIR and miR-601 or miR-601 and ZEB1. In addition, animal experiments were conducted to verify the effect of HOTAIR on BC tumor growth in vivo.

Results
HOTAIR was upregulated in BC tissues and cells, and its knockdown suppressed the proliferation, migration, invasion and the activity of AKT signaling pathway of BC cells. HOTAIR could serve as a sponge of miR-601. Further experiments revealed that miR-601 inhibitor could reverse the inhibition effect of HOTAIR silencing on the progression of BC. Meanwhile, ZEB1 was a target of miR-601, and its overexpression could invert the suppression effect of miR-601 overexpression on the progression of BC. Additionally, ZEB1 expression was regulated by HOTAIR and miR-601. Furthermore, interference of HOTAIR could attenuate BC tumor growth in vivo.

Conclusion
In short, this study demonstrated that HOTAIR promoted the proliferation, migration, invasion of BC through regulating the miR-601/ZEB1 axis, which provided a theoretical basis for the research on lncRNA-directed therapeutics in BC.
RETRACTED ARTICLE: Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like
Authors: Cheng Shaoqiang , Xia Bingshu , Li Hongbin , Li Yuying , Lv Xinxin , Zhang Yue , Huang Yuanxi 
Published: July 2020

Abstract
Background
Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human cancers. Nevertheless, the effects of lncRNAs and miRNAs on breast cancer (BC) remain to be further investigated. This study was designed to testify the roles of lncRNA antisense transcript of SATB2 protein (SATB2-AS1) and microRNA-155-3p (miR-155-3p) in BC progression.

Methods
Levels of SATB2-AS1, miR-155-3p and breast cancer metastasis suppressor 1-like (BRMS1L) in BC were determined. The prognostic role of SATB2-AS1 in BC patients was assessed. The screened cells were respectively introduced with altered SATB2-AS1 or miR-155-3p to figure out their roles in malignant phenotypes of BC cells. The effect of varied SATB2-AS1 and miR-155-3p on BC cells in vivo was observed. Dual luciferase reporter gene assay and RNA-pull down assay were implemented to detect the targeting relationship of SATB2-AS1, miR-155-3p, and BRMS1L.

Results
SATB2-AS1 and BRMS1L were decreased while miR-155-3p was increased in BC cells and tissues. Patients with lower SATB2-AS1 expression had poor prognosis. Elevated SATB2-AS1 and inhibited miR-155-3p were able to restrain malignant behaviors of BC cells in vitro, as well as decelerate tumor growth in vivo. Oppositely, inhibited SATB2-AS1 and amplified miR-155-3p had converse effects on BC cell growth. MiR-155-3p mimic abrogated the impact of overexpressed SATB2-AS1. SATB2-AS1 could sponge miR-155-3p, and BRMS1L was the target gene of miR-155-3p.

Conclusion
Elevated SATB2-AS1 and inhibited miR-155-3p could suppress the malignant phenotypes of BC cells, thereby restricting the development of BC.
Evolution of insecticide resistance and its mechanisms in Anopheles stephensi in the WHO Eastern Mediterranean Region
Authors: Enayati Ahmadali , Hanafi-Bojd Ahmad Ali , Sedaghat Mohammad Mehdi , Zaim Morteza , Hemingway Janet 
Published: July 2020

Abstract
Background
While Iran is on the path to eliminating malaria, the disease with 4.9 million estimated cases and 9300 estimated deaths in 2018 remains a serious health problem in the World Health Organization (WHO) Eastern Mediterranean Region. Anopheles stephensi is the main malaria vector in Iran and its range extends from Iraq to western China. Recently, the vector invaded new territories in Sri Lanka and countries in the Horn of Africa. Insecticide resistance in An. stephensi is a potential issue in controlling the spread of this vector.

Methods
Data were collated from national and international databases, including PubMed, Google Scholar, Scopus, ScienceDirect, SID, and IranMedex using appropriate search terms.

Results
Indoor residual spaying (IRS) with DDT was piloted in Iran in 1945 and subsequently used in the malaria eradication programme. Resistance to DDT in An. stephensi was detected in Iran, Iraq, Pakistan, and Saudi Arabia in the late 1960s. Malathion was used for malaria control in Iran in 1967, then propoxur in 1978, followed by pirimiphos-methyl from 1992 to 1994. The pyrethroid insecticide lambda-cyhalothrin was used from 1994 to 2003 followed by deltamethrin IRS and long-lasting insecticidal nets (LLINs). Some of these insecticides with the same sequence were used in other malaria-endemic countries of the region. Pyrethroid resistance was detected in An. stephensi in Afghanistan in 2010, in 2011 in India and in 2012 in Iran. The newly invaded population of An. stephensi in Ethiopia was resistant to insecticides of all four major insecticide classes. Different mechanisms of insecticide resistance, including metabolic and insecticide target site insensitivity, have been developed in An. stephensi. Resistance to DDT was initially glutathione S-transferase based. Target site knockdown resistance was later selected by pyrethroids. Esterases and altered acetylcholinesterase are the underlying cause of organophosphate resistance and cytochrome p450s were involved in pyrethroid metabolic resistance.

Conclusions
Anopheles stephensi is a major malaria vector in Iran and many countries in the region and beyond. The species is leading in terms of development of insecticide resistance as well as developing a variety of resistance mechanisms. Knowledge of the evolution of insecticide resistance and their underlying mechanisms, in particular, are important to Iran, considering the final steps the country is taking towards malaria elimination, but also to other countries in the region for their battle against malaria. This systematic review may also be of value to countries and territories newly invaded by this species, especially in the Horn of Africa, where the malaria situation is already dire.
Slc6a3-dependent expression of a CAPS-associated Nlrp3 allele results in progressive behavioral abnormalities and neuroinflammation in aging mice
Authors: von Herrmann Katharine M. , Anderson Faith L. , Martinez Eileen M. , Young Alison L. , Havrda Matthew C. 
Published: July 2020

Abstract
Background
An association between neuroinflammation and age-related neurologic disorders has been established but the molecular mechanisms and cell types involved have not been thoroughly characterized. Activity of the proinflammatory NLRP3 inflammasome is implicated in Alzheimer’s and Parkinson’s disease and our recent studies in patients suggest that dopaminergic neurons within the degenerating mesencephalon express NLRP3 throughout the progression of PD. Here, we directly test the impact of enhanced inflammasome activity in mesencephalic neurons by characterizing motor function, tissue integrity, and neuroinflammation in aging mice harboring hyperactivating mutations within the endogenous murine Nlrp3 locus, enabled only in cells expressing the dopaminergic neuron-specific Slc6a3 promoter.

Methods
We compared mice harboring inducible alleles encoding the cryopyrin-associated periodic syndrome activating mutations Nlrp3A350V and Nlrp3L351P inserted into the endogenous mouse Nlrp3 locus. Tissue specific expression was driven by breeding these animals with mice expressing Cre recombinase under the control of the dopaminergic neuron-specific Slc6a3 promoter. The experimental mice, designed to express hyperactive NLRP3 only when the endogenous mouse Nlrp3 promotor is active in dopaminergic neurons, were analyzed throughout 18 months of aging using longitudinal motor function assessments. Biochemical and histologic analyses of mesencephalic tissues were conducted in 1- and 18-month-old animals.

Results
We observed progressive and significant deficits in motor function in animals expressing Nlrp3L351P, compared with animals expressing Nlrp3WT and Nlrp3A350V. Age-dependent neuroinflammatory changes in the mesencephalon were noted in all animals. Analysis of GFAP-immunoreactive astrocytes in the substantia nigra revealed a significant increase in astrocyte number in animals expressing Nlrp3L351P compared with Nlrp3WT and Nlrp3A350V. Further analysis of Nlrp3L351P striatal tissues indicated genotype specific gliosis, elevated Il1b expression, and both morphologic and gene expression indicators of proinflammatory A1 astrocytes.

Conclusions
Dopaminergic neurons have the potential to accumulate NLRP3 inflammasome activators with age, including reactive oxygen species, dopamine metabolites, and misfolded proteins. Results indicate the Nlrp3 locus is active in dopaminergic neurons in aging mice, and that the hyperactive Nlrp3L351P allele can drive neuroinflammatory changes in association with progressive behavioral deficits. Findings suggest neuronal NLRP3 inflammasome activity may contribute to neuroinflammation observed during normal aging and the progression of neurologic disorders.
Cytokine profile and nitric oxide levels in peritoneal macrophages of BALB/c mice exposed to the fucose-mannose ligand of Leishmania infantum combined with glycyrrhizin
Authors: Namdar Ahmadabad Hasan , Shafiei Reza , Hatam Gholam Reza , Zolfaghari Emameh Reza , Aspatwar Ashok 
Published: July 2020

AbstractBackgroundThe fucose-mannose ligand (FML) ofLeishmania infantumis a complex glycoprotein which does not elicit adequate immunogenicity in humans. In recent years, adjuvant compounds derived from plants have been used for improving the immunogenicity of vaccines. Glycyrrhizin (GL) is a natural triterpenoid saponin that has known immunomodulatory activities. In the present study, we investigated the effects of co-treatment with FML and GL on the production of cytokines and nitric oxide(NO) by macrophages,in vitro.MethodsLipopolysaccharide (LPS) stimulated murine peritoneal macrophages were treated with FML (5 μg/ml) ofL. infantumand various concentrations of GL (1 μg/ml, 10 μg/ml and 20 μg/ml). After 48 h of treatment, cell culture supernatants were recovered and the levels of TNF-α, IL-10, IL-12p70 and IP-10 were measured by sandwich ELISA and NO concentration by Griess reaction.ResultsOur results indicate that the treatment of activated macrophages with FML plus GL leads to enhanced production of NO, TNF-α and IL-12p70, and reduction of IL-10 levels in comparison with FML treatment alone.ConclusionsTherefore, we concluded that GL can improve the immunostimulatory effect of FML on macrophages and leads to their polarization towards an M1-like phenotype.
Diabetes prediction model based on an enhanced deep neural network
Authors: Zhou Huaping , Myrzashova Raushan , Zheng Rui 
Published: July 2020

AbstractToday, diabetes is one of the most common, chronic, and, due to some complications, deadliest diseases in the world. The early detection of diabetes is very important for its timely treatment since it can stop the progression of the disease. The proposed method can help not only to predict the occurrence of diabetes in the future but also to determine the type of the disease that a person experiences. Considering that type 1 diabetes and type 2 diabetes have many differences in their treatment methods, this method will help to provide the right treatment for the patient. By transforming the task into a classification problem, our model is mainly built using the hidden layers of a deep neural network and uses dropout regularization to prevent overfitting. We tuned a number of parameters and used the binary cross-entropy loss function, which obtained a deep neural network prediction model with high accuracy. The experimental results show the effectiveness and adequacy of the proposed DLPD (Deep Learning for Predicting Diabetes) model. The best training accuracy of the diabetes type data set is 94.02174%, and the training accuracy of the Pima Indians diabetes data set is 99.4112%. Extensive experiments have been conducted on the Pima Indians diabetes and diabetic type datasets. The experimental results show the improvements of our proposed model over the state-of-the-art methods.
Hybrid method for equilibrium problems and variational inclusions
Authors: Rezapour Shahram , Zakeri Seyyed Hasan 
Published: July 2020

AbstractBy providing a new iterative method our aim is finding a common element of the set of fixed points of two nonexpansive mappings, the set of solutions to a variational inclusion and the set of solutions of a generalized equilibrium problem in a real Hilbert space. We review the strong convergence of the new iterative method in the framework of Hilbert spaces. Finally, we show that our main result is a generalization for some known theorems in this field.
Novel Genetic and Biochemical Findings of DLK1 in Children with Central Precocious Puberty: A Brazilian–Spanish Study
Authors: Montenegro Luciana , Labarta José I , Piovesan Maira , Canton Ana P M , Corripio Raquel , Soriano-Guillén Leandro , Travieso-Suárez Lourdes , Martín-Rivada Álvaro , Barrios Vicente , Seraphim Carlos E , Brito Vinicius N , Latronico Ana Claudia , Argente Jesús 
Published: July 2020

Abstract

Background
Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood.

Objective
Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations.

Patients
A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed.

Results
Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401_404 + 8del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (&lt;0.4 ng/mL), indicating that the deletion led to complete lack of DLK1 production. Three others rare allelic variants of DLK1 were also identified (p.Asn134=; g.-222 C&gt;A and g.-223 G&gt;A) in 2 girls with CPP. However, both had normal DLK1 serum levels.

Conclusion
Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing.
The Neighborhood Deprivation Index and Provider Geocoding Identify Critical Catchment Areas for Diabetes Outreach
Authors: Walker Ashby F , Hu Hui , Cuttriss Nicolas , Anez-Zabala Claudia , Yabut Katarina , Haller Michael J , Maahs David M 
Published: July 2020

AbstractPurposeIn designing a Project ECHO™ type 1 diabetes (T1D) program in Florida and California, the Neighborhood Deprivation Index (NDI) was used in conjunction with geocoding of primary care providers (PCPs) and endocrinologists in each state to concurrently identify areas with low endocrinology provider density and high health risk/poverty areas. The NDI measures many aspects of poverty proven to be critical indicators of health outcomes.MethodsThe data from the 2013-2017 American Community Survey (ACS) 5-year estimates were used to create NDI maps for California and Florida. In addition, geocoding and 30-minute drive-time buffers were performed using publicly available provider directories for PCPs and endocrinologists in both states by Google Geocoding API and the TravelTime Search Application Programming Interface (API).ResultsBased on these findings, we defined high-need catchment areas as areas with (1) more than a 30-minute drive to the nearest endocrinologist but within a 30-minute drive to the nearest PCP; (2) an NDI in the highest quartile; and (3) a population above the median (5199 for census tracts, and 1394 for census block groups). Out of the 12 181 census tracts and 34 490 census block groups in California and Florida, we identified 57 tracts and 215 block groups meeting these criteria as high-need catchment areas.ConclusionGeospatial analysis provides an important initial methodologic step to effectively focus outreach efforts in diabetes program development. The integration of the NDI with geocoded provider directories enables more cost-effective and targeted interventions to reach the most vulnerable populations living with T1D.