bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid‐range, and reduced ejection fraction
Authors: Löfman Ida , Szummer Karolina , Dahlström Ulf , Jernberg Tomas , Lund Lars H.
Published: March 2017

Aims

As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid‐range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role.

Methods and results

Patients in the Swedish Heart Failure Registry were divided into three groups based on EF (≥50%, 40–49% and <40%). CKD was defined as an estimated glomerular filtration rate ≤60 mL/min.1.73 m2. Associations between covariates and CKD and between CKD and mortality were assessed with multivariable regressions. Of 40 230 patients, 8875 (22%) had HFpEF, 8374 (21%) had HFmrEF, and 22 981 (57%) had HFrEF, with a CKD prevalence of 56%, 48%, and 45%, respectively. Associations between covariates and CKD were similar in all EF groups. One‐year mortality with vs. without CKD was 23% vs. 13% in HFpEF, 22% vs. 8% in HFmrEF, and 23% vs. 8% in HFrEF (P < 0.001 for all). After adjustment, CKD was more strongly associated with death in HFrEF and HFmrEF than in HFpEF [hazard ratio (HR) and 95% confidence interval (CI); 1.49 (1.42–1.56) and 1.51 (1.40–1.63) vs. 1.32 (1.24–1.42); P for interaction <0.001]. In receiver operating characteristic (ROC) analyses, CKD was also a stronger predictor of death in HFrEF and HFmrEF than in HFpEF [area under the curve (AUC) 0.699 (0.689–0.709) and 0.700 (0.683–0.716) vs. 0.629 (0.613–0.645)].

Conclusion

CKD was associated with similar covariates regardless of EF. Although CKD was more common in HFpEF than in HFmrEF and HFrEF, it may have more of a ‘bystander’ role in HFpEF, being less associated with mortality and with lower prognostic discrimination.
Polyphenic trait promotes liver cancer in a model of epigenetic instability in mice
Authors: Cassano Marco , Offner Sandra , Planet Evarist , Piersigilli Alessandra , Jang Suk Min , Henry Hugues , Geuking Markus B. , Mooser Catherine , McCoy Kathy D. , Macpherson Andrew J. , Trono Didier
Published: March 2017

Hepatocellular carcinoma (HCC) represents the fifth‐most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28hep–/–
mice display sex‐specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and aging precipitate alterations of TRIM28‐dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male‐restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances, and altered responses to gut microbiota in the pathogenesis of Trim28hep–/–
‐associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high‐fat diet challenge. Conclusion: This work underpins how discrete polyphenic traits in epigenetically metastable conditions can contribute to a cancer‐prone state and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota, and cancer. (Hepatology 2017;66:235–251).
Hypoxia mediates mitochondrial biogenesis in hepatocellular carcinoma to promote tumor growth through HMGB1 and TLR9 interaction
Authors: Tohme Samer , Yazdani Hamza O. , Liu Yao , Loughran Patricia , van der Windt Dirk J. , Huang Hai , Simmons Richard L. , Shiva Sruti , Tai Sheng , Tsung Allan
Published: March 2017

The ability of cancer cells to survive and grow under hypoxic conditions has been known for decades, but the mechanisms remain poorly understood. Under certain conditions, cancer cells undergo changes in their bioenergetic profile to favor mitochondrial respiration by activating the peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC‐1α) and up‐regulating mitochondrial biogenesis. In this study, we hypothesized that augmented mitochondrial biogenesis plays a critical role for cancer cells to survive hypoxia. Consistent with this hypothesis, both hypoxic human hepatocellular carcinoma (HCC) tumors and HCC cell lines subjected to hypoxia increase mitochondrial biogenesis. Silencing of PGC‐1α in hypoxic HCC cell lines halts their proliferation. Mechanistic investigations in vitro indicated that intracellular high mobility group box 1 (HMGB1) protein, a nuclear protein overexpressed in HCC, is essential for the process. Silencing of HMGB1 in hypoxic HCC cell lines resulted in a significant decrease in PGC‐1α activation and mitochondrial biogenesis. Without HMGB1, hypoxic HCC cells had significantly reduced adenosine triphosphate production, decreased cellular proliferation, and increased apoptosis. In a diethylnitrosamine‐induced murine model of HCC, genetic blocking of HMGB1 in hypoxic tumors resulted in a significant decrease in tumor growth. Tumors lacking HMGB1 had a significant reduction in mitochondrial biogenesis and a significant increase in mitochondrial dysfunction. Further in vitro mechanistic experiments indicated that during hypoxia HMGB1 translocates from the nucleus to the cytoplasm and binds to cytoplasmic Toll‐like receptor‐9. This binding leads to activation of p38 and subsequent phosphorylation of PGC‐1α, with resultant up‐regulation of mitochondrial biogenesis. Conclusion: Taken together, our findings suggest that during hypoxia HMGB1 up‐regulates mitochondrial biogenesis in HCC cancer cells, promoting tumor survival and proliferation. (Hepatology 2017;66:182–197).
Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study
Authors: Kohara Katsuhiko , Okada Yoko , Ochi Masayuki , Ohara Maya , Nagai Tokihisa , Tabara Yasuharu , Igase Michiya
Published: March 2017

Background

There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross‐sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association.

Methods

Two sarcopenic indices were measured: thigh muscle cross‐sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel‐type Dementia Assessment Scale, and brachial–ankle pulse wave velocity was measured as an index of arterial stiffness.

Results

Both sarcopenic indices were modestly but significantly associated with brachial–ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel‐type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women.

Conclusions

Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.
Top2b is involved in the formation of outer segment and synapse during late‐stage photoreceptor differentiation by controlling key genes of photoreceptor transcriptional regulatory network
Authors: Li Ying , Hao Hailing , Swerdel Mavis R. , Cho Hyeon‐Yeol , Lee Ki‐Bum , Hart Ronald P. , Lyu Yi Lisa , Cai Li
Published: March 2017

Topoisomerase II beta (Top2b) is an enzyme that alters the topologic states of DNA during transcription. Top2b deletion in early retinal progenitor cells causes severe defects in neural differentiation and affects cell survival in all retinal cell types. However, it is unclear whether the observed severe phenotypes are the result of cell‐autonomous/primary defects or non–cell‐autonomous/secondary defects caused by alterations of other retinal cells. Using photoreceptor cells as a model, we first characterized the phenotypes in Top2b conditional knockout. Top2b deletion leads to malformation of photoreceptor outer segments (OSs) and synapses accompanied by dramatic cell loss at late‐stage photoreceptor differentiation. Then, we performed mosaic analysis with shRNA‐mediated Top2b knockdown in neonatal retina using in vivo electroportation to target rod photoreceptors in neonatal retina. Top2b knockdown causes defective OS without causing a dramatic cell loss, suggesting a Top2b cell‐autonomous function. Furthermore, RNA‐seq analysis reveals that Top2b controls the expression of key genes in the photoreceptor gene–regulatory network (e.g., Crx, Nr2e3, Opn1sw, Vsx2) and retinopathy‐related genes (e.g., Abca4, Bbs7, Pde6b). Together, our data establish a combinatorial cell‐autonomous and non–cell‐autonomous role for Top2b in the late stage of photoreceptor differentiation and maturation. © 2017 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Roles of AEG‐1 in CNS neurons and astrocytes during noncancerous processes
Authors: Yin Xiang , Feng Honglin
Published: March 2017

Since its initial identification, Astrocyte Elevated Gene‐1 (AEG‐1) has been recognized as a “star” gene detected in most of the analyzed cancers; AEG‐1 can interact with signaling transduction molecules, such as PI3K/Akt and MAPK, to affect the function and viability of cells. Furthermore, its multiple other functions are also gradually being recognized. AEG‐1 participates in several biological processes, including embryonic development, glutamate excitotoxicity, inflammation, and endoplasmic reticulum stress. Most of the noncancerous roles of the AEG‐1 were identified in studies of the neurological disorders of the CNS. As an oncogene that promotes aberrant cellular processes within the CNS, AEG‐1 may also represent an important therapeutic target for the treatment of neurological disease. However, the exact role of the AEG‐1 in CNS under normal conditions is still unknown. This review will focus on the literature describing the role of this molecule in CNS neurons and astrocytes during noncancerous processes. © 2017 Wiley Periodicals, Inc.
Evaluating population expansion of black bears using spatial capture‐recapture
Authors: Sun Catherine C. , Fuller Angela K. , Hare Matthew P. , Hurst Jeremy E.
Published: March 2017

The population of American black bears (Ursus americanus) in southern New York, USA has been growing and expanding in range since the 1990s. This has motivated a need to anticipate future patterns of range expansion. We conducted a non‐invasive, genetic, spatial capture‐recapture (SCR) study to estimate black bear density and identify spatial patterns of population density that are potentially associated with range expansion. We collected hair samples in a 2,519‐km2 study area in southern New York with barbed‐wire hair snares and identified individuals and measured genetic diversity using 7 microsatellite loci and 1 sex‐linked marker. We estimated a mean density of black bears in the region of 13.7 bears/100 km2, and detected a slight latitudinal gradient in density consistent with the documented range expansion. However, elevation and the amounts of forest, crop, and developed landcover types did not influence density, suggesting that bears are using a diversity of resources in this heterogeneous landscape outside their previously described distribution. These results provide the first robust baseline estimates for population density and distribution associated with different landcover types in the expanded bear range. Further, genetic diversity was comparable to that of non‐expanding black bear populations in the eastern United States, and in combination with the latitudinal density gradient, suggest that the study area is not at the colonizing front of the range expansion. In addition, the diversity of landcover types used by bears in the study area implies a possible lack of constraints for further northern expansion of the black bear range. Our non‐invasive, genetic, spatial capture‐recapture approach has utility for studying populations of other species that may be expanding in range because SCR allows for the testing of explicit, spatial ecological hypotheses. © 2017 The Wildlife Society.
Exercise for chronic musculoskeletal pain: A biopsychosocial approach
Authors: Booth John , Moseley G. Lorimer , Schiltenwolf Marcus , Cashin Aidan , Davies Michael , Hübscher Markus
Published: March 2017

Chronic musculoskeletal pain (CMP) refers to ongoing pain felt in the bones, joints and tissues of the body that persists longer than 3 months. For these conditions, it is widely accepted that secondary pathologies or the consequences of persistent pain, including fear of movement, pain catastrophizing, anxiety and nervous system sensitization appear to be the main contributors to pain and disability. While exercise is a primary treatment modality for CMP, the intent is often to improve physical function with less attention to secondary pathologies. Exercise interventions for CMP which address secondary pathologies align with contemporary pain rehabilitation practices and have greater potential to improve patient outcomes above exercise alone. Biopsychosocial treatment which acknowledges and addresses the biological, psychological and social contributions to pain and disability is currently seen as the most efficacious approach to chronic pain. This clinical update discusses key aspects of a biopsychosocial approach concerning exercise prescription for CMP and considers both patient needs and clinician competencies. There is consensus for individualized, supervised exercise based on patient presentation, goals and preference that is perceived as safe and non‐threatening to avoid fostering unhelpful associations between physical activity and pain. The weight of evidence supporting exercise for CMP has been provided by aerobic and resistance exercise studies, although there is considerable uncertainty on how to best apply the findings to exercise prescription. In this clinical update, we also provide evidence‐based guidance on exercise prescription for CMP through a synthesis of published work within the field of exercise and CMP rehabilitation.
Identification of Potential Plasma microRNA Stratification Biomarkers for Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis
Authors: Mallinson David J. , Dunbar Donald R. , Ridha Susan , Sutton Elizabeth R. , De la Rosa Olga , Dalemans Wilfried , Lombardo Eleuterio
Published: March 2017

The ability to identify and stratify patients that will respond to specific therapies has been transformational in a number of disease areas, particularly oncology. It is anticipated that this will also be the case for cell-based therapies, particularly in complex and heterogeneous diseases such as rheumatoid arthritis (RA). Recently, clinical results with expanded allogenic adipose-derived mesenchymal stem cells (eASCs) have indicated clinical efficacy in highly refractory RA patients. In this study, we set out to determine if circulating microRNAs (miRNAs) could be identified as potential biomarkers associated with response to eASCs in these RA patients. The miRNA expression profiles of pre-treatment plasma samples from responder and nonresponder patients were determined using microarrays. Ten miRNAs were identified that were differentially expressed in the responder group as compared to the nonresponder group. To confirm the differential expression of these 10 miRNA biomarkers, they were further assayed by quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR). From this analysis, three miRNAs, miR-26b-5p, miR-487b-3p and miR-495-3p, were confirmed as being statistically significantly upregulated in the responder group as compared with the nonresponder group. Receiver operating characteristic analysis confirmed their diagnostic potential. These miRNAs could represent novel candidate stratification biomarkers associated with RA patient response to eASCs and are worthy of further clinical validation.
Subcellular‐Scale Drug Transport via Ultrasound‐Degradable Mesoporous Nanosilicon to Bypass Cancer Drug Resistance
Authors: Kang Bin , Zheng Ming‐Bo , Song Pei , Chen Ai‐Ping , Wei Ji‐Wu , Xu Jing‐Juan , Shi Yi , Chen Hong‐Yuan
Published: March 2017

Delivering and releasing anticancer agents directly to their subcellular targets of action in a controlled manner are almost the ultimate goal of pharmacology, but it is challenging. In recent decades, plenty of efforts have been made to send drugs to tumor tissue or even specifically to cancer cells; however, at the subcellular scale, cancer cells have multiple cunning ways to hinder drugs from reaching their final action targets. Here, we demonstrate a strategy to bypass the last defense of cancer drug resistance by contolling the drug transportation and release at subcellular scale. We developed a platform based on ultrasound‐degradable mesoporous nanosilicon, which allows drug delivery towards, ultrasound controlled drug release into the cell nucleus. This strategy altered the drug distribution within cells and remarkably enhanced the drug accumulation ratio at the action target, i.e. nucleus. In vitro and in vivo studies proved that this strategy reduced the drug dosage by an order of magnitude, prolonged drug retention and amplified therapeutic efficacy in tumor‐bearing mice. These results offer new insights into bypassing cancer drug resistance through transport and release drugs directly to their action targets in a controlled manner.
An Experimental Study on Strain Rate Sensitivity of Strain‐induced Martensitic Transformation in SUS304 by Real‐time Measurement of Relative Magnetic Permeability
Authors: Cao Bo , Iwamoto Takeshi
Published: March 2017

With excellent mechanical properties because of strain‐induced martensitic transformation (SIMT), applications of austenitic stainless steels can be extended to a further broad range of engineering fields. In order to discover applications from a clarification of their mechanical properties, especially at higher deformation rate, it is important to evaluate an amount of martensite, which can control such excellent performances of the steels during deformation. However, until now, it is quite hard to find experimental studies for the evaluation during deformation at various strain rates. In the past, volume resistivity and impedance have been measured during deformation. However, these studies have not been successful to evaluate it with a higher precision. Instead of those, it is useful to measure directly relative magnetic permeability, which has a correlation with the amount of martensite, because of focusing on a ferromagnetic characteristic of martensite. In this study, at first, SUS304, which is a kind of austenitic stainless steels, is deformed plastically under tension at various strain rates. Then, it is attempted to evaluate the amount of martensite during deformation by measuring the relative magnetic permeability expressing ferromagnetism directly. Finally, the strain and strain rate sensitivity of SIMT in the steel is discussed by obtained results.
Party Reputations and Policy Priorities: How Issue Ownership Shapes Executive and Legislative Agendas
Authors: Green Jane , Jennings Will
Published: March 2017

Election-oriented elites are expected to emphasize issues on which their party possesses ‘issue ownership’ during campaigns. This article extends those theories to the content of executive and legislative agendas. Arguing that executives have incentives to pursue their party’s owned issues in the legislature, it theorizes three conditions under which these incentives are constrained: when governments are responsive to issues prioritized by the public, when a party has a stronger electoral mandate and under divided government. The theory is tested using time-series analyses of policy agendas of US congressional statutes and State of the Union addresses (1947–2012) and UK acts of Parliament and the Queen’s Speech (1950–2010). The results offer support for the theory, and are particularly strong for the US State of the Union address, providing insights into institutional differences. The implications provide reassurance concerning the conditions under which governments focus attention only on their partisan issue priorities.
Tillering dynamics of Mulato grass subjected to strategies of rotational grazing management
Authors: DA SILVA S. C. , CHIAVEGATO M. B. , PENA K. S. , SILVEIRA M. C. T. , BARBERO L. M. , JUNIOR S. J. S. , RODRIGUES C. S. , LIMÃO V. A. , PEREIRA L. E. T.
Published: March 2017

Plants’ ability to rebuild their tiller population is affected by weather changes and management strategies. The hypothesis of the present study was that frequency and severity of defoliation alter Mulato grass (Brachiaria ruziziensis × Brachiaria brizantha cv. Marandu) sward development, and the proportion of aerial and basal tillers, interfering with sward stability. The objective was to evaluate aerial, basal and total tiller population density and changes in tillering dynamics. Treatments corresponded to strategies of rotational grazing characterized by combinations between two pre-grazing (95% and maximum canopy light interception during regrowth; LI95% and LIMax) and two post-grazing conditions (15 and 20 cm stubble height). The experimental period comprised four seasons of the year: summer 2008 (February–March 2008); autumn–early spring (April to mid-November 2008); late spring (mid-November–December 2008); and summer 2009 (January–March 2009). Density of aerial tillers decreased from summer 2008 to late spring. Tiller death decreased from summer 2008 to autumn–early spring. Aerial and total tiller death increased from late spring to summer 2009, mainly for the LI95% treatment. No differences were observed in the tiller population stability index of aerial tillers for LI treatments or post-grazing heights. The balance between tiller appearance and death for basal tillers remained relatively stable from summer 2008 to late spring. For aerial tillers the balance decreased to negative values from summer 2008 to autumn–early spring for both LI treatments. For total tiller population, the balance decreased to negative values from summer 2008 to autumn–early spring. Results indicated a strong seasonal effect on Mulato grass tillering and growth. Tillering dynamics were affected primarily by grazing frequency, which changed the relative importance of basal and aerial tillers. The results suggested that basal tillering was the predominant perennation pathway.
Food-based dietary guidelines: a comparative analysis between the Dietary Guidelines for the Brazilian Population 2006 and 2014
Authors: Oliveira Mayara Sanay da Silva , Silva-Amparo Ligia
Published: March 2017

Objective

In 2014, the Brazilian Ministry of Health launched the second edition of the Dietary Guidelines for the Brazilian Population (DGBP), which deploys the new food classification NOVA. It esteems that the second DGBP overcomes the limitations in the previous food guide, reformulating the diet concepts, food pattern, culture and system. The present paper analyses the advances and limits established in the second edition, contrasting with its first edition.

Design

The study employs a discourse analysis. The corpus was established through four stages: (i) floating reading of the empirical materials; (ii) deepening readings; (iii) selected discursive sequences; and (iv) organization of the discursive sequences into a matrix for analysis. The data analysis used three steps: (i) identification of similar texts in external materials; (ii) elucidation of linguistic effect through deepening readings of the external materials; and (iii) systematic analysis to identify sequences that expressed equivalence or disparities.

Setting

Brazil.

Subjects

DGBP 2006 and 2014.

Results

Adoption of the NOVA food classification, based on food processing level, enabled the development of dietary guidelines that consider the limitations of the nutritional discourse and may incorporate the sociocultural and social-environmental discourses, evoking pleasure in food, diversity of feeding habits and stimulating culinary practices as promoters of healthy eating practices.

Conclusions

The second DGBP enables a new way of thinking about meals and foods, on the strengthening of socio-cultural dimensions of feeding, and on addressing food and nutritional guidelines on culinary practices, eating and edibility.
Dyadic psychological intervention for patients with cancer and caregivers in home-based specialized palliative care: The Domus model
Authors: von Heymann-Horan Annika B. , Puggaard Louise B. , Nissen Kathrine G. , Benthien Kirstine Skov , Bidstrup Pernille , Coyne James , Johansen Christoffer , Kjellberg Jakob , Nordly Mie , Sjøgren Per , Timm Helle , von der Maase Hans , Guldin Mai-Britt
Published: March 2017

Objective:

Patients with incurable cancer and their informal caregivers have numerous psychological and psychosocial needs. Many of these patients wish to receive their care and die at home. Few home-based specialized palliative care (SPC) interventions systematically integrate psychological support. We present a psychological intervention for patient–caregiver dyads developed for an ongoing randomized controlled trial (RCT) of home-based SPC, known as Domus, as well as the results of an assessment of its acceptability and feasibility.

Method:

The Domus model of SPC for patients with incurable cancer and their caregivers offered systematic psychological assessment and dyadic intervention as part of interdisciplinary care. Through accelerated transition to SPC, the aim of the model was to enhance patients' chances of receiving care and dying at home. Integration of psychological support sought to facilitate this goal by alleviating distress in patients and caregivers. Psychologists provided needs-based sessions based on existential-phenomenological therapy. Feasibility and acceptability were investigated by examining enrollment, nonparticipation, and completion of psychological sessions.

Results:

Enrollment in the RCT and uptake of the psychological intervention indicated that it was feasible and acceptable to patients and caregivers. The strengths of the intervention included its focus on dyads, psychological distress, and existential concerns, as well as interdisciplinary collaboration and psychological interventions offered according to need. Its main limitation was a lack of an intervention for other family members.

Significance of Results:

Our results show that psychological intervention can be systematically integrated into SPC and that it appears feasible to provide dyadic needs-based sessions with an existential therapeutic approach. The Domus RCT will provide evidence of the efficacy of a novel model of multidisciplinary SPC.
Perceptions of the care received from Australian palliative care services: A caregiver perspective
Authors: Pidgeon Tanya M. , Johnson Claire E. , Lester Leanne , Currow David , Yates Patsy , Allingham Samuel F. , Bird Sonia , Eagar Kathy
Published: March 2017

Background:

Caregiver satisfaction and experience surveys help health professionals to understand, measure, and improve the quality of care provided for patients and their families.

Objective:

Our aim was to explore caregiver perceptions of the care received from Australian specialist palliative care services.

Method:

Caregivers of patients receiving palliative care in services registered with Australia's Palliative Care Outcomes Collaboration were invited to participate in a caregiver survey. The survey included the FAMCARE–2 and four items from the Ongoing Needs Identification: Caregiver Profile questionnaire.

Results:

Surveys were completed by 1,592 caregivers from 49 services. Most respondents reported high satisfaction and positive experiences. Caregivers receiving care from community-based palliative care teams were less satisfied with the management of physical symptoms and comfort (odds ratio [OR] = 0.29; 95% confidence interval [CI95%] = 0.14, 0.59), with patient psychological care (OR = 0.56; CI95% = 0.32, 0.98), and with family support (OR = 0.52; CI95% = 0.35, 0.77) than caregivers of patients in an inpatient setting. If aged over 60 years, caregivers were less likely to have their information needs met regarding available support services (OR = 0.98; CI95% = 0.97, 0.98) and carer payments (OR = 0.99; CI95% = 0.98, 1.00). Also, caregivers were less likely to receive adequate information about carer payments if located in an outer regional area (OR = 0.41; CI95% = 0.25, 0.64). With practical training, caregivers receiving care from community services reported inadequate information provision to support them in caring for patients (OR = 0.60; CI95% = 0.45, 0.81).

Significance of Results:

While our study identified caregivers as having positive and satisfactory experiences across all domains of care, there is room for improvement in the delivery of palliative care across symptom management, as well as patient and caregiver support, especially in community settings. Caregiver surveys can facilitate the identification and evaluation of both patients' and caregivers' experiences, satisfaction, distress, and unmet needs.
Versorgungslücken bei Hepatitis-C-infizierten Drogenkonsumierenden
Authors: Bruggmann Philip
Published: March 2017

Zusammenfassung. Drogenkonsumierende sind mit einer Prävalenz von 56 % die grösste Hepatitis-C-Risikogruppe in der Schweiz. Ihre ungenügende Versorgungssituation stellt ein ernsthaftes Problem für die öffentliche Gesundheit dar, einerseits durch die Weiterverbreitung des Virus und anderseits durch die Folgeerkrankungen der Infektion mit den entsprechenden Kosten. Es sind neue Ansätze gefragt in der Hepatitis-C-Versorgung bei Drogenkonsumierenden. Eine Suchterkrankung und auch Hepatitis C sind chronische Leiden, die häufig von weiteren chronischen Krankheiten begleitet werden. Sie bedürfen einer integrierten multidisziplinären Versorgung. Mit einer Einbindung der Hepatitis-C-Versorgung in das medizinische Grundversorgungssetting können bislang unerreichte Patientengruppen behandelt werden. Die aktuelle Entwicklung in der HCV-Therapie, weg von anspruchsvollen interferonbasierten Behandlungsschemata und hin zu einfachen Kombinationstherapien, unterstützt die Versorgung dieser Risikogruppe.
Confucian Conceptions of Human Intelligence
Authors: Pang Weiguo , Esping Amber , Plucker Jonathan A.
Published: March 2017

The work of Confucius has been—and continues to be—part of the foundation of Chinese culture. Understanding his work provides insights into many aspects of Chinese societies, ranging from politics to the arts, from economies to education systems. The present article summarizes Confucius’ view of human intelligence, comparing and contrasting it with Western theory and research on related constructs. Confucius’ formulation encompassed qualities such as (a) the ability to identify areas of intelligence in others, (b) self-knowledge, (c) problem-solving skills, (d) verbal fluency, (e) the ability to think actively and flexibly, and (f) the capacity to make healthy personal decisions. Confucius and his followers also developed classification systems for categorizing individuals based on their intelligence. For average people, Confucius held an incremental view of intelligence that relied heavily on extensive study, inquiry, reflection, and transfer. For people with very high or very low intelligence, however, he saw intelligence as being determined by heaven or their inborn nature. A thorough understanding of Confucian conceptions of intelligence provides insight into the present-day study of intelligence within China.
Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells
Authors: Basit Farhan , van Oppen Lisanne MPE , Schöckel Laura , Bossenbroek Hasse M , van Emst-de Vries Sjenet E , Hermeling Johannes CW , Grefte Sander , Kopitz Charlotte , Heroult Melanie , HGM Willems Peter , Koopman Werner JH
Published: March 2017

Inhibition of complex I (CI) of the mitochondrial respiratory chain by BAY 87-2243 (‘BAY’) triggers death of BRAFV600E melanoma cell lines and inhibits in vivo tumor growth. Here we studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential (Δψ), increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. These effects were paralleled by increased opening of the mitochondrial permeability transition pore (mPTP) and stimulation of autophagosome formation and mitophagy. BAY-induced cell death was not due to glucose shortage and inhibited by the antioxidant α-tocopherol and the mPTP inhibitor cyclosporin A. Tumor necrosis factor receptor-associated protein 1 (TRAP1) overexpression in BAY-treated cells lowered ROS levels and inhibited mPTP opening and cell death, whereas the latter was potentiated by TRAP1 knockdown. Knockdown of autophagy-related 5 (ATG5) inhibited the BAY-stimulated autophagosome formation, cellular ROS increase and cell death. Knockdown of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) inhibited the BAY-induced Δψ depolarization, mitophagy stimulation, ROS increase and cell death. Dynamin-related protein 1 (Drp1) knockdown induced mitochondrial filamentation and inhibited BAY-induced cell death. The latter was insensitive to the pancaspase inhibitor z-VAD-FMK, but reduced by necroptosis inhibitors (necrostatin-1, necrostatin-1s)) and knockdown of key necroptosis proteins (receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and mixed lineage kinase domain-like (MLKL)). BAY-induced cell death was also reduced by the ferroptosis inhibitor ferrostatin-1 and overexpression of the ferroptosis-inhibiting protein glutathione peroxidase 4 (GPX4). This overexpression also inhibited the BAY-induced ROS increase and lipid peroxidation. Conversely, GPX4 knockdown potentiated BAY-induced cell death. We propose a chain of events in which: (i) CI inhibition induces mPTP opening and Δψ depolarization, that (ii) stimulate autophagosome formation, mitophagy and an associated ROS increase, leading to (iii) activation of combined necroptotic/ferroptotic cell death.
Synergistic targeting of breast cancer stem‐like cells by human γδ T cells and CD8+ T cells
Authors: Chen Hung‐Chang , Joalland Noémie , Bridgeman John S , Alchami Fouad S , Jarry Ulrich , Khan Mohd Wajid A , Piggott Luke , Shanneik Yasmin , Li Jianqiang , Herold Marco J , Herrmann Thomas , Price David A , Gallimore Awen M , Clarkson Richard W , Scotet Emmanuel , Moser Bernhard , Eberl Matthias
Published: March 2017

The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non‐CSCs was set up to study their interaction with non‐MHC‐restricted γδ T cells and antigen‐specific CD8+ T cells. Stable lines with characteristics of breast CSC‐like cells were generated from ras‐transformed human mammary epithelial (HMLER) cells as confirmed by their CD44hi CD24lo GD2+ phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non‐adherent conditions, as well as their potent tumorigenicity, self‐renewal and differentiation in xenografted mice. The resistance of CSC‐like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS‐targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM‐1 on CSC‐like cells and thereby increased the susceptibility to antigen‐specific killing by CD8+ T cells. Alternatively, γδ T‐cell responses could be specifically directed against CSC‐like cells using the humanised anti‐GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC‐restricted and non‐MHC‐restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two‐pronged approach combining γδ T‐cell and CD8+ T‐cell targeting strategies that triggers effective innate‐like and tumour‐specific adaptive responses.
FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Authors: Errichelli Lorenzo , Dini Modigliani Stefano , Laneve Pietro , Colantoni Alessio , Legnini Ivano , Capauto Davide , Rosa Alessandro , De Santis Riccardo , Scarfò Rebecca , Peruzzi Giovanna , Lu Lei , Caffarelli Elisa , Shneider Neil A. , Morlando Mariangela , Bozzoni Irene
Published: March 2017

The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS.
Epithelial tension in the second heart field promotes mouse heart tube elongation
Authors: Francou Alexandre , De Bono Christopher , Kelly Robert G.
Published: March 2017

Extension of the vertebrate heart tube is driven by progressive addition of second heart field (SHF) progenitor cells to the poles of the heart. Defects in this process cause a spectrum of congenital anomalies. SHF cells form an epithelial layer in splanchnic mesoderm in the dorsal wall of the pericardial cavity. Here we report oriented cell elongation, polarized actomyosin distribution and nuclear YAP/TAZ in a proliferative centre in the posterior dorsal pericardial wall during heart tube extension. These parameters are indicative of mechanical stress, further supported by analysis of cell shape changes in wound assays. Time course and mutant analysis identifies SHF deployment as a source of epithelial tension. Moreover, cell division and oriented growth in the dorsal pericardial wall align with the axis of cell elongation, suggesting that epithelial tension in turn contributes to heart tube extension. Our results implicate tissue-level forces in the regulation of heart tube extension.
Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
Authors: Afshari Natalie A. , Igo Robert P. , Morris Nathan J. , Stambolian Dwight , Sharma Shiwani , Pulagam V. Lakshmi , Dunn Steven , Stamler John F. , Truitt Barbara J. , Rimmler Jacqueline , Kuot Abraham , Croasdale Christopher R. , Qin Xuejun , Burdon Kathryn P. , Riazuddin S. Amer , Mills Richard , Klebe Sonja , Minear Mollie A. , Zhao Jiagang , Balajonda Elmer , Rosenwasser George O. , Baratz Keith H , Mootha V. Vinod , Patel Sanjay V. , Gregory Simon G. , Bailey-Wilson Joan E. , Price Marianne O. , Price Francis W. , Craig Jamie E. , Fingert John H. , Gottsch John D. , Aldave Anthony J. , Klintworth Gordon K. , Lass Jonathan H. , Li Yi-Ju , Iyengar Sudha K.
Published: March 2017

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10−8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.
An Improved Racetrack Structure for Transporting a Skyrmion
Authors: Lai P. , Zhao G. P. , Tang H. , Ran N. , Wu S. Q. , Xia J. , Zhang X. , Zhou Y.
Published: March 2017

Magnetic skyrmions are promising building blocks for next generation data storage due to their stability, small size and extremely low currents to drive them, which can be used instead of traditional magnetic domain walls to store information as data bits in metalic racetrack memories. However, skyrmions can drift from the direction of electron flow due to the Magnus force and thus may annihilate at the racetrack edges, resulting in the loss of information. Here we propose a new skyrmion-based racetrack structure by adding high-K materials (materials with high magnetic crystalline anisotropy) at the edges, which confines the skyrmions in the center region of the metalic racetrack efficiently. This design can overcome both the clogging and annihilation of skyrmions according to our micromagnetic simulation, which occur normally for skyrmions moving on a racetrack under small and large driving currents, respectively. Phase diagrams for skyrmion motion on the proposed racetrack with various values of current density and racetrack edge width have been calculated and given, showing that skyrmions can be driven at a high speed (about 300 m/s) in the racetrack under relatively smaller driving currents. This design offers the possiblity of building an ultrafast and energy-efficient skyrmion transport device.
STITCHER 2.0: primer design for overlapping PCR applications
Authors: O’Halloran Damien M. , Uriagereka-Herburger Isabel , Bode Katrin
Published: March 2017

Overlapping polymerase chain reaction (PCR) is a common technique used by researchers in very diverse fields that enables the user to ‘stitch’ individual pieces of DNA together. Previously, we have reported a web based tool called STITCHER that provides a platform for researchers to automate the design of primers for overlapping PCR applications. Here we present STITCHER 2.0, which represents a substantial update to STITCHER. STITCHER 2.0 is a newly designed web tool that automates the design of primers for overlapping PCR. Unlike STITCHER, STITCHER 2.0 considers diverse algorithmic parameters, and returns multiple result files that include a facility for the user to draw their own primers as well as comprehensive visual guides to the user’s input, output, and designed primers. These result files provide greater control and insight during experimental design and troubleshooting. STITCHER 2.0 is freely available to all users without signup or login requirements and can be accessed at the following webpage: www.ohalloranlab.net/STITCHER2.html.
SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation
Authors: Dattilo Vincenzo , D’Antona Lucia , Talarico Cristina , Capula Mjriam , Catalogna Giada , Iuliano Rodolfo , Schenone Silvia , Roperto Sante , Bianco Cataldo , Perrotti Nicola , Amato Rosario
Published: March 2017

The serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction. RANBP1 expression is the limiting step in the regulation of SGK1-SP1 dependent nuclear export. These results were validated in unrelated tumor models and primary human fibroblasts and corroborated in tumor-engrafted nude mice. The levels of pri-miRNAs, DROSHA, DICER and the compartmental distribution of XPO5 were documented. Experiments using RANGTP conformational antibodies confirmed that SGK1, through RANBP1, decreases the level of the GTP-bound state of RAN. This novel mechanism may play a role in the epigenomic regulation of cell physiology and fate.
Work Function Tuning in Two-Dimensional MoS2 Field-Effect-Transistors with Graphene and Titanium Source-Drain Contacts
Authors: Baik Seung Su , Im Seongil , Choi Hyoung Joon
Published: March 2017

Based on the first principles calculation, we investigate the electronic band structures of graphene-MoS2and Ti-MoS2heterojunctions under gate-voltages. By simultaneous control of external electric fields and carrier charging concentrations, we show that the graphene’s Dirac point position inside the MoS2bandgap is easily modulated with respect to the co-varying Fermi level, while keeping the graphene’s linear band structure around the Dirac point. The easy modulation of graphene bands is not confined to the special cases where the conduction-band-minimum point of MoS2and the Dirac point of graphene are matched up in reciprocal space, but is generalized to their dislocated cases. This flexibility caused by the strong decoupling between graphene and MoS2bands enhances the gate-controlled switching performance in MoS2-graphene hybrid stacking-device.