bluuebunny/crossref_metadata_2025_split huggingface dataset:
The E3 ubiquitin ligase CHIP in normal cell function and in disease conditions
Authors: Wang Tingyu , Wang Wenbo , Wang Qishan , Xie Rong , Landay Alan , Chen Di 
Published: August 2019

AbstractIn eukaryotic cells, ubiquitination and proteasomal degradation is an essential mechanism for regulating protein functions. For example, critical signaling proteins play their roles by controlling different cellular functions. Once a signaling protein has been activated, its activity needs to be quickly downregulated by different mechanisms, including ubiquitination/proteasome regulation. Failure to regulate the activity or expression levels of these proteins may cause human diseases. Protein ubiquitination involves a cascade of biochemical processes and requires three types of ubiquitin enzymes: E1 activating enzyme, E2 conjugating enzyme, and E3 ligase. Among these enzymes, E3 ubiquitin ligases play a specific role in recognizing specific protein substrates. There are several structurally diverse groups of E3 ubiquitin ligases in eukaryotic cells, and one type of these E3 ligases is the U‐box ubiquitin ligases. Carboxyl terminus of HSP70‐interacting protein (CHIP) is a member of a family of U‐box E3 ligases. It plays critical roles in multiple organs and tissues in the body. In this review article, we provide an update on some of the most recent discoveries about CHIP in normal physiological function and in disease.
The triangular nexus causality among economic growth, trade, FDI and Oil Price: time series analyses of Nigeria
Authors: Udemba Edmund N. 
Published: August 2019

AbstractThe central objective of this work was to test and determine the causality between the selected economic indicators such as trade, FDI, Oil Price and GDP in Nigeria and make a recommendation for a timely policy framework for the betterment of the Nigerian economy. Using Nigerian annual data of 1970–2018 with the application of Granger causality test, we found a unidirectional causality that runs from Oil Price to both FDI and trade and from FDI to trade. There was no causal effect transmitting from either trade to Oil Price or trade to FDI. Also, there was no transmission of causality from GDP growth to any of the selected indicators. Our findings expose the heavy influence of oil via price on the economic performance of Nigeria. This could justify the claim that there is a positive relationship between Oil Price and growth. Hence, supporting the findings that FDI is attracted by the availability of oil and the FDI will turn around influenced the rate of trade via trade openness. This will create avenue for a virtuous economic growth circle if policy implication is managed well.
Blood group genotyping of blood donors: validation of a highly accurate routine method
Authors: Krog Grethe Risum , Rieneck Klaus , Clausen Frederik Banch , Steffensen Rudi , Dziegiel Morten Hanefeld 
Published: August 2019

BACKGROUNDIn the past century, blood group determination using serology has been the standard method. Now, molecular methods are gaining traction, which provide additional and easily accessible information. Here we designed and validated a high‐throughput extended genotyping setup.STUDY DESIGN AND METHODSWe developed 35 competitive allele‐specific polymerase chain reaction assays for genotyping of blood donors. Samples from 1034 Danish blood donors were genotyped, and 45,314 red blood cell antigens and 6148 platelet antigens were predicted. Predicted phenotypes were compared with 16,119 serologic phenotypes.RESULTSWe found 62 discrepancies of which 43 were due to serology. After exclusion of the discrepancies caused by serology, the accuracy of genotyping was 99.9%. Of 17 discrepancies caused by the genotype, three were incorrect antigen‐negative predictions and could potentially, as the solitary analysis, have caused an adverse transfusion reaction.CONCLUSIONWe have established a robust and highly accurate blood group genotyping system with a very high capacity for screening blood donors. The system represents a significant improvement over the former serotyping‐only procedure. Almost all new technology in medicine incurs increased costs, but the presented efficient genotyping system is a rare example of a significant qualitative and quantitative technologic progress that is also more cost‐efficient than previous technologies.
"Going the Extra Mile": A descriptive exploratory study of Primary Health Services based on the experiences of Pacific Primary Health Organisation Service managers and providers
Authors: Pack Margaret 
Published: August 2019

INTRODUCTION: This exploratory study is part of a larger evaluation of the primary health care strategy (PHCS) in Aotearoa New Zealand, using a mixed methods research approach. The aims of this qualitative arm of the research were to explore the extent of use and satisfaction with the PHCS through the operation of Pacific-led Primary Health Organisations (PHOs) in relation to service provision and delivery from the service providers’ and managers’ perspectives.METHOD: The exploratory study was conducted using a case study design and in-depth interviews with service managers and health providers at six Pacific-led PHOs. A review of the literature on primary healthcare was conducted prior to undertaking the research. In this literature review, several themes were noted from the review of policy documents providing background to the development of primary healthcare in New Zealand. CONCLUSION: The themes from interviews suggest a core tension between the business model, Ministry reporting requirements, and more altruistic values of both managers and service providers in their delivery of services. Overall, there was a positive response to the lowered cost of healthcare from the providers and managers interviewed in the Pacific-led primary health services, mirroring the findings of the larger evaluation report of PHOs (Cumming et al., 2005). The availability of wrap-around, holistically based, accessible services delivered by culturally responsive health providers who were considered to “go the extra mile” for their clients was the predominant theme accounting for an increased uptake and use of the services. The implications for health social work are discussed.
Noqu Vale: Community organisation professionals’ views on what works and what needs to change for Pasifika housing
Authors: Camaira Joanna , Mafile’o Tracie 
Published: August 2019

INTRODUCTION: The shortage of suitable and affordable housing within Aotearoa New Zealand is creating vulnerability in communities and is a barrier encountered by community organisation professionals (COPs) working in the housing field. Pasifika peoples are particularly disadvantaged, experiencing higher levels of household overcrowding, being less likely to own their own home, and being more likely to be tenants of social housing than other ethnicities. Increasing numbers of Pasifika peoples affected by housing issues require immediate (emergency, crisis) or long-term community social housing support, in an already constrained housing system. While there continues to be significant literature exploring facets of Pasifika housing in AotearoaNew Zealand, there is a lack of research on COPs’ perspectives regarding Pasifika housing focused on the Wellington region. METHOD: This research takes an exploratory, qualitative approach using semi-structured interviews with three COPs based in the Wellington region. Interview transcripts were thematically analysed. FINDINGS: Findings address “what’s working” and include: wrap-around services, collaboration, advocacy, and empowering families. COP perspectives on “what needs to change” include: quality and quantity of housing, affordability, and racism and discrimination. IMPLICATIONS: The implications are that a holistic and collaborative practice approach taken between community and government organisations, needs to be harnessed if outcomes for Pasifika housing are to improve.
Reviewing the benefits and challenges of overseas practice: Reflections upon coming home
Authors: Beddoe Liz , Bartley Allen 
Published: August 2019

INTRODUCTION: Given the diversity of practice and understanding of social work across the globe and its distinctive shape in specific national settings, practitioners working in a new country encounter different community, professional and workplace cultures which may pose challenges. This current study contributes to a larger programme of work undertaken to address the transnational nature of the social work profession in Aotearoa New Zealand and elsewhere. METHOD: The study aim was to explore the experiences of Aotearoa New Zealand qualified social workers who have practised in another country and have returned home. Participants in an online survey were recruited via an invitation to all members of the Aotearoa New Zealand Association of Social Workers. The questionnaire was designed to obtain broad data about the experiences of social workers in their overseas employment and perceptions on their return home. FINDINGS: Many participants had layers of transnational experience having practised as social workers in multiple countries. Participants reported overall satisfaction with overseas experiences which had provided professional opportunities for learning and development, and better pay and conditions. Coming home presented new challenges and interesting perceptions of social work in Aotearoa. IMPLICATIONS: Adjustment to new practice locations and, as shown in this small exploratory study, returning “home” can be disruptive to professional perspectives. While overseas practice is enriching, it carries with it both relocation benefits and costs, confirming earlier research. Better employer recognition of the challenges of returning social workers, and the enhanced skills they bring home may offset any dislocation experienced.
Pregnancy duration and endometrial cancer risk: nationwide cohort study
Authors: Husby Anders , Wohlfahrt Jan , Melbye Mads 
Published: August 2019

AbstractObjectiveTo explore the association between pregnancy duration and risk of endometrial cancer.DesignNationwide register based cohort study.SettingDenmark.ParticipantsAll Danish women born from 1935 to 2002.Main outcome measuresRelative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression.ResultsAmong 2 311 332 Danish women with 3 947 650 pregnancies, 6743 women developed endometrial cancer during 57 347 622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results.ConclusionsThe risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.
Structural, elastic and electronic properties of new superhard orthorhombic C28
Authors: Zhang Rui , Wei Qun , Wei Bing , Yang Ruike , Cheng Ke , Zhang Meiguang , Yan Haiyan , Chen Qinghua , Xue Minhua 
Published: August 2019

The structural, mechanical and electronic properties of recently reported superhard material C[Formula: see text] are studied by first-principles calculations. The unit cell of C[Formula: see text] is composed of 28 carbon atoms and all sp3 hybridized bonds. From 0 GPa to 100 GPa, C[Formula: see text] satisfies the mechanical stability criteria and the phonon spectrum of C[Formula: see text] has no imaginary frequency, which means that C[Formula: see text] is mechanically and dynamically stable. The results of hardness calculated show that C[Formula: see text] is a potential superhard material with the Vickers hardness of 84.0 GPa. By analyzing the elastic anisotropy, we found that elastic anisotropy of C[Formula: see text] increases with pressure. The calculations of band structure demonstrates that C[Formula: see text] is an indirect bandgap semiconductor with the gap of 4.406 eV. These analyses demonstrate C[Formula: see text] is a superhard semiconductor material.
Gneisses (
Serizzo
and
Beola
) of the Verbano–Cusio–Ossola District (Piedmont, northern Italy): possible candidates for designation as Global Heritage Stone Resources
Authors: Cavallo Alessandro , Dino Giovanna Antonella , Primavori Piero 
Published: August 2019

Abstract

The Verbano–Cusio–Ossola quarrying district (Piedmont, northern Italy) produces many different ornamental stones (granites, gneisses, marbles); two important categories are represented by
Serizzo
and
Beola
gneisses. The
Serizzo
, a group of foliated orthogneisses, is the most important and extensively exploited ornamental stone, largely used to produce columns since the end of fifteenth century and used for many parts of the Duomo di Milano.
Beola
is the name of a group of heterogeneous orthogneisses with mylonitic foliation and strong mineralogical lineation, easy to split into thin slabs with hammer and chisel, occurring in the middle Ossola Valley. The quarries of
Beola
are probably the oldest of the Ossola Valley (since the Roman period), and the
Beola
trade probably started at the end of the thirteenth century. In general,
Beola and Serizzo
gneisses have been used for ornamental purposes and for the construction of churches, palaces and monuments, widely documented in many towns and villages of the Ossola Valley and in northern Italy. This contribution reviews the history and distinctiveness of these materials, their importance in local and national culture, and their present international diffusion. Both stones are recommended as Global Heritage Stone Resources within a Global Heritage Stone Province.
Periodicity, time constants of drainage, and the mechanical determinants of peak cardiac output during exercise
Authors: Magder Sheldon , Famulari Gabriel , Gariepy Brian 
Published: August 2019

To analyze mechanical adaptations that must occur in the cardiovascular system to reach the high cardiac outputs known to occur at peak aerobic performance, we adapted a computational model of the circulation by adding a second parallel venous compartment as proposed by August Krogh in 1912. One venous compartment has a large compliance and slow time constant of emptying; it is representative of the splanchnic circulation. The other has a low compliance and fast time constant of emptying and is representative of muscle beds. Fractional distribution between the two compartments is an important determinant of cardiac output. Parameters in the model were based on values from animal and human studies normalized to a 70 kg male. The baseline cardiac output was set at 5 L/min, and we aimed for 25 L/min at peak exercise with a fractional flow to the peripheral-muscle region of 90%. Finally, we added the equivalent of a muscle pump. Adjustments in circuit and cardiac parameters alone increased cardiac output to only 15.6 L/min because volume accumulated in the muscle compartment and limited a higher cardiac output. Addition of muscle contractions decompressed the muscle region and allowed cardiac output to increase to 23.4 L/min. The pulsatility of blood flow imposes important constraints on the adaptations of cardiac and circulatory functions because it fixes the times for filling and emptying. Flow is further limited by the limits of cardiac filling on each beat. Muscle contractions play a key role by decompressing volume that would otherwise accumulate in the muscle vasculature and by decreasing the time for stroke return to the right ventricle.NEW & NOTEWORTHY We used a computational model of the circulation and previous human and animal data to model mechanical changes in the heart and circulation that are needed to reach the known high cardiac output at peak aerobic exercise. Key points are that time constants of drainage of circulatory compartments put limits on peak flow in a pulsatile system. Muscle contractions increase the rate of return to the heart and by doing so prevent accumulation of volume in the muscle compartment and greatly increase circulatory capacity.
ERBB3 and IGF1R Signaling Are Required for Nrf2-Dependent Growth in KEAP1-Mutant Lung Cancer
Authors: Vartanian Steffan , Lee James , Klijn Christiaan , Gnad Florian , Bagniewska Maria , Schaefer Gabriele , Zhang Donglu , Tan Jenille , Watson Sara A. , Liu Liling , Chen Honglin , Liang Yuxin , Watanabe Colin , Cuellar Trinna , Kan David , Hartmaier Ryan J. , Lau Ted , Costa Michael R. , Martin Scott E. , Merchant Mark , Haley Benjamin , Stokoe David 
Published: August 2019

Abstract

Mutations in KEAP1 and NFE2L2 (encoding the protein Nrf2) are prevalent in both adeno and squamous subtypes of non–small cell lung cancer, as well as additional tumor indications. The consequence of these mutations is stabilized Nrf2 and chronic induction of a battery of Nrf2 target genes. We show that knockdown of Nrf2 caused modest growth inhibition of cells growing in two-dimension, which was more pronounced in cell lines expressing mutant KEAP1. In contrast, Nrf2 knockdown caused almost complete regression of established KEAP1-mutant tumors in mice, with little effect on wild-type (WT) KEAP1 tumors. The strong dependency on Nrf2 could be recapitulated in certain anchorage-independent growth environments and was not prevented by excess extracellular glutathione. A CRISPR screen was used to investigate the mechanism(s) underlying this dependence. We identified alternative pathways critical for Nrf2-dependent growth in KEAP1-mutant cell lines, including the redox proteins thioredoxin and peroxiredoxin, as well as the growth factor receptors IGF1R and ERBB3. IGF1R inhibition was effective in KEAP1-mutant cells compared with WT, especially under conditions of anchorage-independent growth. These results point to addiction of KEAP1-mutant tumor cells to Nrf2 and suggest that inhibition of Nrf2 or discrete druggable Nrf2 target genes such as IGF1R could be an effective therapeutic strategy for disabling these tumors.

Significance:
This study identifies pathways activated by Nrf2 that are important for the proliferation and tumorigenicity of KEAP1-mutant non–small cell lung cancer.
Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial
Authors: Landi Lorenza , Chiari Rita , Tiseo Marcello , D'Incà Federica , Dazzi Claudio , Chella Antonio , Delmonte Angelo , Bonanno Laura , Giannarelli Diana , Cortinovis Diego Luigi , de Marinis Filippo , Borra Gloria , Morabito Alessandro , Gridelli Cesare , Galetta Domenico , Barbieri Fausto , Grossi Francesco , Capelletto Enrica , Minuti Gabriele , Mazzoni Francesca , Verusio Claudio , Bria Emilio , Alì Greta , Bruno Rossella , Proietti Agnese , Fontanini Gabriella , Crinò Lucio , Cappuzzo Federico 
Published: August 2019

AbstractPurpose:MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations.Patients and Methods:Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 &gt;2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts.Results:From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2–30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0–5.8), and overall survival was 5.4 months (95% CI, 4.2–6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14–mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts.Conclusions:Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.
RETRACTED: CDX1 Expression Induced by CagA-Expressing Helicobacter pylori Promotes Gastric Tumorigenesis
Authors: Choi Sang Il , Yoon Changhwan , Park Mi Ree , Lee DaHyung , Kook Myeong-Cherl , Lin Jian-Xian , Kang Jun Hyuk , Ashktorab Hassan , Smoot Duane T. , Yoon Sam S. , Cho Soo-Jeong 
Published: August 2019

Abstract

Intestinal-type gastric cancer often results from Helicobacter pylori infection through intestinal metaplasia, a transdifferentiated premalignant phenotype. Because H. pylori virulence factor CagA has been associated with aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with H. pylori infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines. Infection of HFE 145 cells with CagA+ H. pylori increased expression of CDX1, as well as the epithelial-to-mesenchymal transition (EMT) markers Snail and Slug, increased invasion and migration, but those effects were not found in HFE 145 cells infected with CagA-deficient H. pylori. CDX1 overexpression increased expression of the intestinal markers Villin, sucrose isomaltase (SI), and MUC2, induced spheroid formation, and enhanced expression of the stem cell markers CD44, SOX2, Oct4, and Nanog, while CDX1 knockdown inhibited proliferation and intestinal stemness. Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation. In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone. Patients with more advanced intestinal metaplasia staging exhibited higher CDX1 expression than those with earlier intestinal metaplasia staging (P = 0.039), and those with H. pylori tended to have more CDX1 expression than noninfected patients (P = 0.061). Finally, human tissue samples with higher CDX1 levels showed prominent CD44/SOX2 expression. Our findings indicate CagA+ H. pylori–induced CDX1 expression may enhance gastric cancer tumorigenesis and progression, and support therapeutic targeting of CDX1 in gastric cancer.

Implications:
This study shows that CDX1 contributes to the tumorigenesis and progression of gastric cancer and suggests the potential of targeting CDX1 to treat this malignancy.