bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the cytotoxic potential of glycoalkaloidic extract in nanoparticles against bladder cancer cells
Authors: Miranda Mariza A , Marcato Priscyla D , Carvalho Ivana P S , Silva Letícia B , Ribeiro Diego L , Amaral Robson , Swiech Kamilla , Bastos Jairo K , Paschoal Jonas A R , dos Reis Rodolfo B , Bentley Maria V L B 
Published: August 2019

Abstract

Objective
This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death.

Methods
NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry.

Key findings
NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI &lt;0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture).

Conclusion
The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.
Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin
Authors: Samkange Tendai , D'Souza Sarah , Obikeze Kenechukwu , Dube Admire 
Published: August 2019

Abstract

Objective
To evaluate the impact of PEG content on poly(lactic-co-glycolic acid) (PLGA) NP physicochemical properties, hydrophobic drug release (rifampicin as a model drug) and human serum protein binding.

Methods
Rifampicin loaded and unloaded nanoparticles with PEG content of 0–17% (w/w) were prepared by an emulsification–evaporation technique. Nanoparticles were characterized for size, zeta potential and morphology. PEGlyation was confirmed using proton nuclear magnetic resonance (1H NMR). Fluorescence spectroscopy and dynamic light scattering were used to determine nanoparticle-protein binding, binding constants and stability of nanoparticles in human serum, respectively. Drug loading and release were determined by UV-VIS spectroscopy and drug release data was mathematically modelled.

Key findings
A NP PEG content of 17% w/w significantly retarded release of rifampicin from PLGA NPs and altered kinetics of drug release. Stern–Volmer (Ksv) protein binding constants decreased upon PEG incorporation. A 2% w/w PEG was sufficient to significantly reduce protein binding extent to PLGA NPs and maintain particle size distributions.

Conclusion
The ability to fine tune drug release and formation of protein corona around nanoparticles is crucial to formulation scientists. This study suggests that PLGA NPs with low PEG content might be suitable for extended circulation and rapid drug release and that higher PEG content retards hydrophobic drug release.
Estimating Excess Sensitivity and Habit Persistence in Consumption Using Greenbook Forecasts
Authors: Bhatt Vipul , Kundan Kishor N. , Marfatia Hardik 
Published: August 2019

AbstractIn this paper, we revisit the issue of excess sensitivity of consumption to income and address the weak instrument problem that is well documented in this literature. Using quarterly data for the US economy, we first highlight the weak instrument problem by showing that the use of conventional instruments tends to overestimate the share of rule‐of‐thumb consumers. To address this weak instrument problem, we propose a new instrument for endogenous disposable income growth in the consumption function, namely, the Greenbook forecast of real disposable income growth. We show that this instrument encompasses the information contained in the conventional set of instruments, and is a superior predictor of income growth. We find that using our proposed instrument ameliorates the weak instrument problem and provides a much smaller estimate for the rule‐of‐thumb consumers. We also extend our empirical framework to allow for habit persistence and provide an estimate for this important parameter of the consumption function. Finally, we use a time‐varying specification of consumption function that allows for endogenous regressors, and document a decline in the share of rule‐of‐thumb consumers and a rise in the habit‐persistence parameter in the US over our sample period.
Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community‐acquired pneumonia
Authors: Villafuerte David , Aliberti Stefano , Soni Nilam J. , Faverio Paola , Marcos Pedro J. , Wunderink Richard G. , Rodriguez Alejandro , Sibila Oriol , Sanz Francisco , Martin‐Loeches Ignacio , Menzella Francesco , Reyes Luis F. , Jankovic Mateja , Spielmanns Marc , Restrepo Marcos I. ,   GLIMP Investigators
Published: August 2019

ABSTRACTBackground and objective
Enterobacteriaceae (EB) spp. family is known to include potentially multidrug‐resistant (MDR) microorganisms, and remains as an important cause of community‐acquired pneumonia (CAP) associated with high mortality. The aim of this study was to determine the prevalence and specific risk factors associated with EB and MDR‐EB in a cohort of hospitalized adults with CAP.MethodsWe performed a multinational, point‐prevalence study of adult patients hospitalized with CAP. MDR‐EB was defined when ≥3 antimicrobial classes were identified as non‐susceptible. Risk factors assessment was also performed for patients with EB and MDR‐EB infection.ResultsOf the 3193 patients enrolled with CAP, 197 (6%) had a positive culture with EB. Fifty‐one percent (n = 100) of EB were resistant to at least one antibiotic and 19% (n = 38) had MDR‐EB. The most commonly EB identified were Klebsiella pneumoniae (n = 111, 56%) and Escherichia coli (n = 56, 28%). The risk factors that were independently associated with EB CAP were male gender, severe CAP, underweight (body mass index (BMI) < 18.5) and prior extended‐spectrum beta‐lactamase (ESBL) infection. Additionally, prior ESBL infection, being underweight, cardiovascular diseases and hospitalization in the last 12 months were independently associated with MDR‐EB CAP.ConclusionThis study of adults hospitalized with CAP found a prevalence of EB of 6% and MDR‐EB of 1.2%, respectively. The presence of specific risk factors, such as prior ESBL infection and being underweight, should raise the clinical suspicion for EB and MDR‐EB in patients hospitalized with CAP.
Depositional controls on a hypertidal barrier‐spit system architecture and evolution, Pointe du Banc spit, north‐western France
Authors: Fruergaard Mikkel , Tessier Bernadette , Poirier Clément , Mouazé Dominique , Weill Pierre , Noël Suzanne 
Published: August 2019

AbstractPhysical stratigraphy, architecture and evolution of barrier systems in hypertidal environments (tidal range above 6 m) are understudied, and depositional controls are poorly understood compared with wave‐dominated barrier systems and barrier spits in microtidal, mesotidal and macrotidal settings. Based on vibracores, ground‐penetrating radar, radiocarbon and optically stimulated luminescence age data, the formation and evolution of the hypertidal barrier system of Pointe du Banc, north‐western France has been reconstructed. The study shows that the barrier spit has a complex composite sedimentary architecture consisting of wave‐dominated and tide‐dominated sedimentary bodies. A morpho‐sedimentary model is presented that demonstrates how barrier‐spit progradation resulting from littoral drift was the main manner of spit elongation, whereas sediment convergence caused by landward migration of swash bars and seaward migration of tidal dunes caused the spit terminus to grow in height and width. These results suggest that long‐term accretion rates varied considerably in response to changes in sediment supply. Variations in storminess together with the large‐scale topography of the coast controlled the sediment supply and thus the evolution of the barrier system during latest Holocene. Despite architectural complexity, hypertidal barrier systems preserve records of past climate changes.
Performance evaluation of iron nanoparticles infused polyethersulphone (Fe‐NPs/PES) membrane during treatment of BTEX‐contaminated wastewater
Authors: Unuigbe Chinwe F. , Fayemiwo Oluwademilade M. , Daramola Michael O. 
Published: August 2019

AbstractIn this study, polyethersulfone (PES) was infused with iron nanoparticles (Fe‐NPs) obtained from the leaf of pomegranate plant to enhance hydrophilicity of the PES membrane. The resulted nanocomposite Fe‐NPs/PES membrane obtained via phase inversion was characterized using a scanning electron microscope (SEM) for the morphology; a texture analyzer for the mechanical strength; an atomic force microscope (AFM) for the surface roughness; and water contact angle measurement for the degree of hydrophilicity. The separation performance of the membrane was evaluated using BTEX‐containing wastewater. SEM images show that Fe‐NPs were distributed uniformly within the membrane with improved mechanical strength. Mechanical strength of PES was enhanced at increasing Fe‐NPs loading from 1.2 MPa for the pure PES to 8.94 MPa for 20 wt.% Fe‐NPs loaded membrane. AFM analysis reveals that membrane roughness increased with increase in Fe‐NPs loading. Also, the contact angle measurement indicates that the hydrophilicity of the composite membrane was enhanced by the addition of Fe‐NPs. The permeation properties reveal that pure water flux of the composite membrane increased with increasing Fe‐NPs loading. In addition, the highest BTEX rejection obtained was 64.55% at 10 wt.% Fe‐NPs loading when compared to the rejection 41.4% obtained from the pure PES membrane evaluated at similar conditions.
The Acute Effects of a “Reduced Sitting Preschool Day” on Executive Function and Musculoskeletal Health in Preschoolers: A Randomized Cross-Over Study
Authors: Ellis Yvonne G. , Cliff Dylan P. , Howard Steven J. , Okely Anthony D. 
Published: August 2019

Purpose: To examine the acute effects of a reduced sitting day on executive function (EF) and musculoskeletal health in preschoolers. Methods: A sample of 29 children (54% boys; 4–5 y) participated in a randomized cross-over trial. Each child completed 2 protocols, which simulate a day at childcare in random order for 2.5 hours; a typical preschool day (50% sitting) and a reduced preschool day (25% sitting) where most sitting activities were replaced with standing activities. Sitting, standing, and stepping time were objectively assessed using an activPAL accelerometer. EF was evaluated using tablet-based EF assessments (inhibition, working memory, and task shifting). Musculoskeletal health was assessed using a handheld dynamometer and goniometer. Results: Compared with the typical preschool day, the reduced sitting day showed no significant differences for EF scores. Effect sizes for inhibition (d = 0.04), working memory (d = 0.02), and shifting (d = 0.11) were all small. For musculoskeletal health, no significant differences were reported after the reduced preschool day. The effect sizes for the hip extension force, hamstring flexibility, gastrocnemius length, and balancing on 1 leg were all small (d = 0.21, d = 0.25, d = 0.28, and d = 0.28). Conclusions: This study suggests that reducing sitting time is unlikely to result in acute changes in EF and musculoskeletal health among preschoolers.
Chronic multimorbidity among older adults in rural South Africa
Authors: Chang Angela Y , Gómez-Olivé Francesc Xavier , Payne Collin , Rohr Julia K , Manne-Goehler Jennifer , Wade Alisha N , Wagner Ryan G , Montana Livia , Tollman Stephen , Salomon Joshua A 
Published: August 2019

IntroductionThe rapid ageing of populations around the world is accompanied by increasing prevalence of multimorbidity. This study is one of the first to present the prevalence of multimorbidity that includes HIV in the complex epidemiological setting of South Africa, thus filling a gap in the multimorbidity literature that is dominated by studies in high-income or low-HIV prevalence settings.MethodsOut of the full sample of 5059 people aged 40+, we analysed cross-sectional data on 10 conditions from 3889 people enrolled in the Health and Ageing in Africa: A longitudinal study of an INDEPTH Community in South Africa (HAALSI) Programme. Two definitions of multimorbidity were applied: the presence of more than one condition and the presence of conditions from more than one of the following categories: cardiometabolic conditions, mental disorders, HIV and anaemia. We conducted descriptive and regression analyses to assess the relationship between prevalence of multimorbidity and sociodemographic factors. We examined the frequencies of the most prevalent combinations of conditions and assessed relationships between multimorbidity and physical and psychological functioning.Results69.4 per cent (95% CI 68.0 to 70.9) of the respondents had at least two conditions and 53.9% (52.4–55.5) of the sample had at least two categories of conditions. The most common condition groups and multimorbid profiles were combinations of cardiometabolic conditions, cardiometabolic conditions and depression, HIV and anaemia and combinations of mental disorders. The commonly observed positive relationships between multimorbidity and age and decreasing wealth were not observed in this population, namelydue to different epidemiological profiles in the subgroups, with higher prevalence of HIV and anaemia in the poorer and younger groups, and higher prevalence of cardiometabolic conditions in the richer and older groups. Both physical functioning and well-being negatively associated with multimorbidity.DiscussionMore coordinated, long-term integrated care management across multiple chronic conditions should be provided in rural South Africa.
Time to NIV and mortality in AECOPD hospital admissions: an observational study into real world insights from National COPD Audits
Authors: Jayadev Anita , Stone Robert , Steiner Michael C , McMillan Viktoria , Roberts C Michael 
Published: August 2019

BackgroundRandomised control trial (RCT)-derived survival figures for acute exacerbation of chronic obstructive pulmonary disease admissions managed with non-invasive ventilation (NIV) have not been replicated in UK clinical audits. Subsequent guidelines have emphasised the need for timely NIV application.MethodsData from the 2008 and 2014 national chronic obstructive pulmonary disease audits was used to analyse the association between time to NIV and mortalityResults1032 patients received NIV in 2008, and 1612 in 2014. Overall mortality rates reduced between the audits from 24.9% in 2008 to 16.8% in 2014 but time to NIV lengthened. In 2014, 20.9% of patients received NIV within 60 min versus 24.9% in 2008 (p=0.001). The proportion of patients receiving NIV between 3 and 24 hours increased from 31.3% in 2008 to 39% in 2014 (p=0.001). Patients admitted with hypercapnic acidotic respiratory failure who received NIV within 3 hours had lower in-patient mortality than those who received NIV between 3 and 24 hours, 15.9% versus 18.4%, but this did not reach statistical significance (p=0.425), but acidotic patients receiving NIV >24 hours after admission had significantly higher mortality (28.9%, p=0.002). A second cohort admitted with hypercapnia but normal range pH, who developed later acidosis, had higher mortality (24.6%), compared with those acidotic on admission (18% p≤0.001) and an extremely high mortality when NIV was given >24 hours after admission (42.6%).ConclusionSurvival rates for those treated with NIV has improved between the two audits but remains lower than reported in RCTs. Patients who developed acidosis after admission and received NIV later in the hospital stay have even higher mortality and deserve further study and clinical attention.
Marital status and age of systemic lupus erythematous diagnosis: the potential for differences related to sex and gender
Authors: Brailovski Eugene , Vinet Evelyne , Pineau Christian A , Lee Jennifer , Lukusa Luck , Kalache Fares , Grenier Louis-Pierre , DaCosta Deborah , Bernatsky Sasha 
Published: August 2019

ObjectivesChronic rheumatic diseases can challenge social and family relationships. We compared marital status in patients with systemic lupus erythematous (SLE) with their general population counterparts, stratified by sex and age of SLE onset.MethodsWe performed a cross-sectional analysis of a cohort of 382 patients with SLE at our centre (349 females, 33 males). We determined how many were married or living common-law at the time of last study visit. Patients were then divided into: SLE diagnosis before 18, between 18 and 30, between 31 and 44 and after 45 years of age. We then compared marital status among male and female patients with SLE, to Quebec age-specific marital statistics.ResultsOf 382 patients with SLE, 202 (52.9%) were married or living common-law, which was 9% lower than general population rates (95% CI 2% to 16%). One-third of women with paediatric-onset SLE were married or living common-law, which was 28% lower than their general population counterparts (95% CI 6% to 46%). Half of women diagnosed between age 18 and 30 were married or living common law, which was 14% less than general population rates (95% CI 4% to 25%). We could not establish significant differences for women diagnosed after age 30, or for males, versus their general population counterparts.ConclusionsWomen diagnosed with SLE before age 30 were less likely to be married/living common-law, versus general population rates. This was not apparent for those diagnosed later in life. We did not clearly establish this effect in males, possibly due to power issues (vs a true effect of sex/gender). Additional studies (eg, focus groups) could elucidate reasons for our findings.
MDM2 Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes
Authors: Casadei Lucia , Calore Federica , Braggio Danielle A. , Zewdu Abeba , Deshmukh Ameya A. , Fadda Paolo , Lopez Gonzalo , Wabitsch Martin , Song Chi , Leight Jennifer L. , Grignol Valerie P. , Lev Dina , Croce Carlo M. , Pollock Raphael E. 
Published: August 2019

Abstract

Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the surrounding microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS.

Significance:
Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.
DAXX Suppresses Tumor-Initiating Cells in Estrogen Receptor–Positive Breast Cancer Following Endocrine Therapy
Authors: Peiffer Daniel S. , Wyatt Debra , Zlobin Andrei , Piracha Ali , Ng Jeffrey , Dingwall Andrew K. , Albain Kathy S. , Osipo Clodia 
Published: August 2019

Abstract

Estrogen receptor (ER)-positive breast cancer recurrence is thought to be driven by tumor-initiating cells (TIC). TICs are enriched by endocrine therapy through NOTCH signaling. Side effects have limited clinical trial testing of NOTCH-targeted therapies. Death-associated factor 6 (DAXX) is a newly identified marker whose RNA expression inversely correlates with NOTCH in human ER+ breast tumor samples. In this study, knockdown and overexpression approaches were used to investigate the role of DAXX on stem/pluripotent gene expression, TIC survival in vitro, and TIC frequency in vivo, and the mechanism by which DAXX suppresses TICs in ER+ breast cancer. 17β-Estradiol (E2)-mediated ER activation stabilized the DAXX protein, which was required for repressing stem/pluripotent genes (NOTCH4, SOX2, OCT4, NANOG, and ALDH1A1), and TICs in vitro and in vivo. Conversely, endocrine therapy promoted rapid protein depletion due to increased proteasome activity. DAXX was enriched at promoters of stem/pluripotent genes, which was lost with endocrine therapy. Ectopic expression of DAXX decreased stem/pluripotent gene transcripts to levels similar to E2 treatment. DAXX-mediated repression of stem/pluripotent genes and suppression of TICs was dependent on DNMT1. DAXX or DNMT1 was necessary to inhibit methylation of CpGs within the SOX2 promoter and moderately within the gene body of NOTCH4, NOTCH activation, and TIC survival. E2-mediated stabilization of DAXX was necessary and sufficient to repress stem/pluripotent genes by recruiting DNMT1 to methylate some promoters and suppress TICs. These findings suggest that a combination of endocrine therapy and DAXX-stabilizing agents may inhibit ER+ tumor recurrence.

Significance:
Estradiol-mediated stabilization of DAXX is necessary and sufficient to repress genes associated with stemness, suggesting that the combination of endocrine therapy and DAXX-stabilizing agents may inhibit tumor recurrence in ER+ breast cancer.
Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma
Authors: Baro Marta , Lopez Sambrooks Cecilia , Burtness Barbara A. , Lemmon Mark A. , Contessa Joseph N. 
Published: August 2019

Abstract
EGFR signaling confers resistance to radiotherapy and is a validated target in head and neck squamous cell carcinoma (HNSCC). The inhibition of EGFR in combination with radiotherapy improves local control and overall survival in these patients; however, therapeutic resistance limits the efficacy of this approach. We therefore sought to identify cellular mechanisms that cause resistance to EGFR inhibition and radiotherapy in HNSCC. Though clonal isolation of carcinoma cells exposed to increasing concentrations of cetuximab, we found that resistant cells upregulate prosurvival ErbB3 and AKT signaling. Using EFM-19 cells and confirmatory analysis of protein levels, we demonstrate that cetuximab resistance is characterized by enhanced neuregulin expression identifying a novel adaptive mechanism of therapeutic resistance. Inhibition of this autocrine loop with CDX-3379 (an ErbB3 specific antibody) was sufficient to block ErbB3/AKT signaling in cetuximab resistant cells. The combination of CDX-3379 and cetuximab reduced proliferation and survival after radiotherapy in several HNSCC cell lines. These in vitro findings were confirmed in xenograft tumor growth experiments including an approach using growth factor–supplemented Matrigel. In vivo, the delivery of EGFR and ErbB3 antibodies significantly reduced tumor growth in cetuximab-resistant FaDu and CAL27 xenografts. In summary, this work demonstrates that autocrine NRG ligand secretion is a mechanism for therapeutic resistance to cetuximab and radiotherapy. This cross-resistance to both therapeutic modalities identifies NRG as an actionable therapeutic target for improving treatment regimens in HNSCC.