bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the multi-step solubilization mechanism of single vesicles by detergents
Authors: Dalgarno Paul A. , Juan-Colás José , Hedley Gordon J. , Piñeiro Lucas , Novo Mercedes , Gonzalez Cibran Perez , Samuel Ifor D. W. , Leake Mark C. , Johnson Steven , Al-Soufi Wajih , Penedo J. Carlos , Quinn Steven D. 
Published: May 2019

AbstractThe solubilization of membranes by detergents is critical for many technological applications and has become widely used in biochemistry research to induce cell rupture, extract cell constituents, and to purify, reconstitute and crystallize membrane proteins. The thermodynamic details of solubilization have been extensively investigated, but the kinetic aspects remain poorly understood. Here we used a combination of single-vesicle Förster resonance energy transfer (svFRET), fluorescence correlation spectroscopy and quartz-crystal microbalance with dissipation monitoring to access the real-time kinetics and elementary solubilization steps of sub-micron sized vesicles, which are inaccessible by conventional diffraction-limited optical methods. Real-time injection of a non-ionic detergent, Triton X, induced biphasic solubilization kinetics of surface-immobilized vesicles labelled with the Dil/DiD FRET pair. The nanoscale sensitivity accessible by svFRET allowed us to unambiguously assign each kinetic step to distortions of the vesicle structure comprising an initial fast vesicle-swelling event followed by slow lipid loss and micellization. We expect the svFRET platform to be applicable beyond the sub-micron sizes studied here and become a unique tool to unravel the complex kinetics of detergent-lipid interactions.
Degree and site of chromosomal instability define its oncogenic potential
Authors: Hoevenaar W.H.M. , Janssen A. , Quirindongo A.I. , Ma H. , Klaasen S. , Teixeira A. , Offerhaus G.J.A. , Medema R.H. , Kops G.J.P.L. , Jelluma N. 
Published: May 2019

ABSTRACTMost human cancers are aneuploid, due to a chromosomal instability (CIN) phenotype. Despite being hallmarks of cancer, however, the roles of CIN and aneuploidy in tumor formation have not unequivocally emerged from animal studies and are thus still unclear. CIN can both promote and suppress tumorigenesis, but variances in mechanisms and timings of CIN induction in different oncogenic backgrounds and associated tissues limit interpretation of the contributions of CIN. Using a novel conditional mouse model for diverse degrees of CIN, we find that a particular range is sufficient to drive very early onset spontaneous adenoma formation in the intestine, showing that CIN can act as a much more potent oncogenic driver than was previously reported. In mice predisposed to intestinal cancer (ApcMin/+), moderate but not low CIN causes a remarkable increase in adenoma burden in the entire intestinal tract, especially in the distal colon, more closely modelling human disease. Strikingly, high levels of CIN promote adenoma formation in the distal colon even more than moderate CIN does, but have no effect in the small intestine. Our results thus show that CIN can be potently oncogenic, but that certain levels of CIN can have contrasting effects in distinct tissues.
ChIP-seq of plasma cell-free nucleosomes identifies cell-of-origin gene expression programs
Authors: Sadeh Ronen , Sharkia Israa , Fialkoff Gavriel , Rahat Ayelet , Gutin Jenia , Chappleboim Alon , Nitzan Mor , Fox-Fisher Ilana , Neiman Daniel , Meler Guy , Kamari Zahala , Yaish Dayana , Peretz Tamar , Hubert Ayala , Cohen Jonatan E , Azzam Salach , Temper Mark , Grinshpun Albert , Maoz Myriam , Abu-Gazala Samir , Ya’acov Ami Ben , Shteyer Eyal , Safadi Rifaat , Kaplan Tommy , Shemer Ruth , Planer David , Galun Eithan , Glaser Benjamin , Zick Aviad , Dor Yuval , Friedman Nir 
Published: May 2019

Abstract:Genomic DNA is packed by histone proteins that carry a multitude of post-translational modifications that reflect cellular transcriptional state. Cell-free DNA (cfDNA) is derived from fragmented chromatin in dying cells, and as such it retains the histones markings present in the cells of origin. Here, we pioneer chromatin immunoprecipitation followed by sequencing of cell-free nucleosomes (cfChIP-seq) carrying active chromatin marks. Our results show that cfChIP-seq provides multidimensional epigenetic information that recapitulates the epigenetic and transcriptional landscape in the cells of origin. We applied cfChIP-seq to 268 samples including samples from patients with heart and liver pathologies, and 135 samples from 56 metastatic CRC patients. We show that cfChIP-seq can detect pathology-related transcriptional changes at the site of the disease, beyond the information on tissue of origin. In CRC patients we detect clinically-relevant, and patient-specific information, including transcriptionally active HER2 amplifications. cfChIP-seq provides genome-wide information and requires low sequencing depth. Altogether, we establish cell-free chromatin immunoprecipitation as an exciting modality with potential for diagnosis and interrogation of physiological and pathological processes using a simple blood test.One Sentence SummaryChIP-seq of plasma-circulating nucleosomes (cfChIP-seq) from a simple blood test provides detailed information about gene expression programs in human organs, and cancer.
Genetic screening for single-cell variability modulators driving therapy resistance
Authors: Torre Eduardo A. , Arai Eri , Bayatpour Sareh , Beck Lauren E. , Emert Benjamin L. , Shaffer Sydney M. , Mellis Ian A. , Fane Mitchell , Alicea Gretchen , Budinich Krista A. , Weeraratna Ashani , Shi Junwei , Raj Arjun 
Published: May 2019

AbstractCellular plasticity describes the ability of cells to transition from one set of phenotypes to another. In the context of cancer therapeutics, plasticity refers to transient fluctuations in the molecular state of tumor cells, driving the formation of rare cells primed to survive drug treatment and ultimately reprogram into a stably resistant fate. However, the biological processes governing this cellular plasticity remain unknown. We used CRISPR/Cas9 genetic screens to reveal genes that affect cell fate decisions by altering cellular plasticity across a range of functional categories. We found that cellular plasticity and cell fate decision making can be decoupled in that factors can affect cell fate decisions in both plasticity-dependent and independent manners. We discovered a novel mode of altering resistance based on cellular plasticity that, contrary to known mechanisms, pushes cells towards a more differentiated state. We further confirmed our prediction that manipulating cellular plasticity before the addition of the main therapy would result in changes in therapy resistance more than concurrent administration. Together, our results indicate that identifying pathways modulating cellular plasticity has the potential to alter cell fate decisions and may provide a new avenue for treating drug resistance.
CD38 is a good predictor of anti-PD-1 immunotherapy responsiveness in hepatocellular carcinoma
Authors: Goh Siting , Ng Harry Ho Man , Chew Valerie , Sim Xin Ni , Li Huihua , Lim Sherlly , Lim Jeffrey Chun Tatt , Loh Josh Jie Hua , Sabai Khin , Ong Clara Chong Hui , Loh Tracy , Leow Wei Qiang , Xin Joycelyn Lee Jie , Toh Han Chong , Malavasi Fabio , Tai David Wai Meng , Lee Ser Yee , Chow Pierce , Newell Evan , Choo Su Pin , Yeong Joe , Lim Tony Kiat Hon 
Published: May 2019

AbstractHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality in the world. However, with the associated low five-year survival and high recurrence rates, alternative treatment modalities specifically immunotherapy have been researched. A correlation between CD38+tumour-infiltrating leukocyte (TIL) density and improved prognosis was found in a recent study. However, studies relating to CD38 expression in immune infiltrates within tumours are limited. In the present study, we confirmed the expression of CD38 on macrophages in HCC and determined the relationship between CD38+leukocytes and lymphocytes and patient response to immunotherapy. Using immunohistochemistry, we analysed tissue samples obtained from 20 patients from Singapore with HCC prior to immunotherapy. Tumour infiltrating leukocytes expression within tumour were correlated to the responsiveness of patients to immunotherapy.Expression of CD38 was found within the tumour cells and surrounding immune infiltrates including lymphocytes and macrophages. We then ask whether CD38 expression by the distinct cell populations may acquire theranostic relevance. Patients with higher level of CD38+immune infiltrate subsets had significantly better response to anti-PD-1 immunotherapy, and this is also true for CD38+lymphocytes within the tumour microenvironment. In particular, a cut-off of 13.0% positive out of total leukocytes and 12.4% positive out of total lymphocytes is found to be of strong predictive value of responsiveness to immunotherapy treatment, thus a strong theranostic impact is seen by using CD38 as a biomarker for anti-PD-1 therapy.The establishment of an association between CD38 expression and the response to anti-PD-1 immunotherapy in HCC, could be applied to a larger cohort outside Singapore. These may eventually change the routine testing in clinical practice to identify HCC patients suitable for immunotherapy.
Prediction of risk scores for colorectal cancer patients from the concentration of proteins involved in mitochondrial apoptotic pathway
Authors: Lathwal Anjali , Arora Chakit , Raghava Gajendra P. S. 
Published: May 2019

AbstractOne of the major challenges in managing the treatment of colorectal cancer (CRC) patients is to predict risk scores or level of risk for CRC patients. In past, several biomarkers, based on concentration of proteins involved in type-2/intrinsic/mitochondrial apoptotic pathway, have been identified for prognosis of colorectal cancer patients. Recently, a prognostic tool DR MOMP has been developed that can discriminate high and low risk CRC patients with reasonably high accuracy (Hazard Ratio, HR = 5.24 and p-value = 0.0031). This prognostic tool showed an accuracy of 59.7% when used to predict favorable/unfavorable survival outcomes. In this study, we developed knowledge based models for predicting risk scores of CRC patients. Models were trained and evaluated on 134 stage III CRC patients. Firstly, we developed multiple linear regression based models using different techniques and achieved a maximum HR value of 6.34 with p-value = 0.0032 for a model developed using LassoLars technique. Secondly, models were developed using a parameter optimization technique and achieved a maximum HR value of 38.13 with p-value 0.0006. We also predicted favorable/unfavorable survival outcomes and achieved maximum prediction accuracy value of 71.64%. The performance of our models were evaluated using five-fold cross-validation technique. For providing service to the community we also developed a web server ‘CRCRpred’, to predict risk scores of CRC patients, which is freely available at https://webs.iiitd.edu.in/raghava/crcrpred.
Nociception testing during fixed-wing ambulance flights. An interventional pilot study on the effects of flight-related environmental changes on the nociception of healthy volunteers
Authors: Prottengeier Johannes , Elsner Stefan , Wehrfritz Andreas , Moritz Andreas , Schmidt Joachim , Meyer Michael 
Published: May 2019

AbstractBackgroundThe effects of environmental changes on the somato-sensory system during long-distance air ambulance flights need to be further investigated. Changes in nociceptive capacity are conceivable in light of previous studies performed under related environmental settings. We used standardized somato-sensory testing to investigate nociception in healthy volunteers during air-ambulance flights.MethodsTwenty-five healthy individuals were submitted to a test compilation analogous to the quantitative sensory testing battery – performed during actual air-ambulance flights. Measurements were paired around the major changes of external factors during take-off/climb and descent/landing. Bland-Altman-Plots were calculated to identify possible systemic effects.ResultsBland-Altman-analyses suggest that the thresholds of stimulus detection and pain as well as above-threshold pain along critical waypoints of travel are not subject to systemic effects but instead demonstrate random variations.ConclusionsWe provide a novel description of a real-life experimental setup and demonstrate the general feasibility of performing somato-sensory testing during ambulance flights. No systematic effects on the nociception of healthy individuals were apparent from our data. Our findings open up the possibility of future investigations into potential effects of ambulance flights on patients suffering acute or chronic pain.
Examining the impact of goal attainment and training goal on overall training satisfaction among vocational education and training completers
Authors: Skues Jason , Alexander Sarah-Louise , Wise Lisa 
Published: May 2019

Purpose
The purpose of this paper was to examine whether there is a relationship between goal attainment and overall training satisfaction among vocational education and training (VET) completers, and in turn whether this relationship varies across the different goals for undertaking training in a VET course.

Design/methodology/approach
A request was made to the National Centre for Vocational Education Research in Australia for access to the unit record data from the 2016 Student Outcomes Survey. Approval was obtained. The final sample comprised 149,632 students who completed a VET course in 2016, where 55 per cent of the sample were women and the average age was 36.55 years (SD=13.17).

Findings
Students who achieved or did not yet know whether they had achieved their training goal were more satisfied with their overall training compared with those who partly achieved their goal, who in turn were more satisfied than those who did not attain their goal across the various training goals. However, participants who were training for personal reasons or reasons other than for employment or pursuing further study, and either partly achieved, did not achieve or did not know yet whether they had achieved their training goal reported the lowest levels of training satisfaction, although these participants were still satisfied overall with their training.

Originality/value
These results highlight the importance of understanding the impact of goals on achievement-related activities and should be used to inform learning and teaching approaches as well as the provision of support services in the VET sector.
Community housing: functional outcome of severe mental illness is associated with the personality traits of the case manager
Authors: Lodder Mandy , Schrijvers A.J.P. , Leeuw J.R.J. de , Brouwer R.M. , Cahn W. 
Published: May 2019

PurposeThe purpose of this paper is to examine whether there is an association between case managers’ personality traits and functional outcome of people with severe mental illness (SMI) living in community housing programs (CHP).Design/methodology/approachFunctional outcome is measured by the extent of self-reliance. Self-reliance of people with SMI was measured with the Dutch Self-Sufficiency Matrix. The personality of the case manager was measured with the NEO Five Factor Inventory.FindingsConscientiousness of case managers was associated with an increased self-reliance over a period of two years, in those with SMI living in CHP (OR.2.800ρ= 0.04).Practical implicationsWhen these findings are replicated, they could be used in the case managers selection process and/or training programs.Social implicationsConscientiousness of case managers was associated with functional outcome of persons with SMI living in supported housing and that female subjects benefitted the most. This study suggests that conscientious care planning is essential in the recovery process.Originality/valueNo previous studies have been performed examining the specific relationship between the case manager’s personality traits and functional outcome of people with SMI.
Building connection against the odds: project workers relationships with people experiencing homelessness
Authors: Watson Clare , Nolte Lizette , Brown Rachel 
Published: May 2019

Purpose
Trusting and empathic relationships between project workers and people experiencing homelessness (PEH) form the cornerstone for their needs to be met. However, under the UK austerity agenda project workers practice in a context of increasing pressure and limited resources; with relationships often characterised by conditionality and disconnection. The purpose of this paper is to report on a study investigating project workers’ experiences of building relationships with PEH living in supported housing projects.

Design/methodology/approach
A qualitative design was employed in which focus groups were carried out in six projects, using an opportunity sample of 22 project workers. Data were analysed using thematic analysis, within a social constructionist epistemology.

Findings
Three main themes were identified: “Working hard to build connection”, “Supporting each other within an unsupportive context” and “Draining but sustaining”. Project workers acted out of strong value systems in building relationships with residents against a backdrop of systemic disconnection.

Originality/value
Clear clinical implications are put forward with in a Psychologically Informed Environment framework. Services supporting PEH need to be psychologically informed and organisations need to embed reflection within their policies and every day practice. In developing services for PEH interdependence not in/dependence needs to be the aim. Finally, the responsibility for improving the lives of PEH should be placed back on society to provide a context in which PEH can thrive.
Supporting the development of skills for extended practice in biomedical science
Authors: Smith Sara , Karnik Uttara , Kendall Karen , Pugh Abigail , Robson Kelvin , Salmons Nabeel , Khechara Martin 
Published: May 2019

Purpose
Continual professional development is essential to foster and enhance professionals’ abilities. A wide variety of methods have been adopted to support professional learning for healthcare professions but many still focus upon a need to update knowledge and the learning of isolated competencies for practice. The purpose of this paper is to report upon a collaborative partnership that enabled the reframing of a professional development course away from this objectivist epistemology to foster pedagogically appropriate approaches nurturing the development of the knowledge and skills required for extended practice in specimen dissection.

Design/methodology/approach
An action research approach informed this study which drew upon aspects of simulated learning, “creative play” and “hands-on” practice to nurture development of the knowledge and mastery of essential skills required for extended practice in dissection. A questionnaire allowed the gathering of quantitative and qualitative data from delegates. Open coding of delegate free-text responses enabled thematic analysis of the data.

Findings
Delegates reported upon a positive learning and teaching experience providing them with a unique opportunity to develop the essential skills and knowledge required to enhance their extended practice. Four key themes were identified from delegate feedback: legitimacy of learning experience; safe-space for learning; confidence as a practitioner; and professional and social interactions.

Originality/value
Research into skill development in this field is currently lacking. Findings highlight the value of a creative approach to professional development which enables individuals to master the skills required for practice. It also underlines the importance and value of collaborative partnerships. As allied health professionals advance and extend their roles professional development must move away from the didactic delivery of isolated topics and ensure that it offers legitimate learning experiences allowing skill development and technique mastery alongside knowledge enhancement.
Content and instructional design of MOOCs on information literacy
Authors: Dreisiebner Stefan 
Published: May 2019

PurposeThis paper aims to uncover the current status of information literacy (IL) instruction through massive open online courses (MOOCs), comparing the content and instructional design of existing offers and showing avenues for future MOOCs.Design/methodology/approachAn extensive search for existing MOOCs on IL revealed 11 offers that are available for analysis. A content analysis is conducted to compare their content and instructional design. The category system is based on the IL standards and performance indicators of the Association of College and Research Libraries (2000), which has been supplemented with additional categories and an evaluation grid for MOOCs.FindingsThe results suggest first, that the topics covered by IL MOOCs differ widely. While some of the MOOCs mainly reflect the performance indicators suggested by the ACRL standards on IL from 2000, some other MOOCs focus on completely different topics such as fake news or internet security. Second, they show that MOOCs on IL tend not to emphasize subject-specific and country- or culture-specific contexts. Third, it shows that input-based teaching approaches dominate, while collaborative and interactive activities are only rarely used. Fourth, they allow drawing a possible connection between student engagement and design of the learning contents.Research limitations/implicationsThis work reflects the current status of IL facilitation through MOOCs. Further research is needed.Practical implicationsThe results confirm that MOOCs are a promising approach for developing IL skills and provide avenues for future MOOC projects, especially on IL.Originality/valueThis paper is one of few works to discuss IL facilitation through MOOCs.
An evaluation of community-managed libraries in Liverpool
Authors: Smith Charlie 
Published: May 2019

Purpose
Community libraries now constitute a significant proportion of library provision in the UK; however, there is relatively little research on how the transfer to this model has affected those libraries and the wider balance of provision. The purpose of this paper is to broaden the discourse and understanding about the impact of changing libraries to community models.

Design/methodology/approach
The paper provides a qualitative evaluation of all the libraries transferred to community-managed models within a large city council region in the UK. Structured research visits were made to appraise each library. These are discussed in the context of published literature and data, both specific to the study area and nationally.

Findings
Transferring the management of libraries to community organisations is often reactive and perceived with negative associations. This study uncovers increases in use and diversification of services following transfer; however, support from the local authority and the previous experience of managing organisations are significant factors. The paper also reveals how the successful transfer of a library to a community organisation led to more being moved out of local authority control, but that the support they receive from the local authority can be inconsistent between them.

Originality/value
The paper provides a study of community-managed libraries across a large city council area, affording an in-depth understanding of their impact on overall provision over one region. It will be of value to those involved in library management and service provision at both local and strategic levels, including local authorities and community groups considering library transfer.