bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers
Authors: Madhra Mayank , Fraser Ian S. , Munro Malcolm G. , Critchley Hilary O. D. 
Published: April 2014

AbstractObjectiveTo highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective.DesignReview and recommendations for local implementation.SettingIn the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM‐COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics).Population and main outcome measuresThis commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation.Results and conclusionsThe PALM‐COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health.
Identification of functional visual field loss by automated static perimetry
Authors: Frisén Lars 
Published: April 2014

AbstractPurposeDiagnosis of functional visual field loss, that is, field loss lacking objective corollaries, has long relied on kinetic visual field examinations using tangent screens or manual perimeters. The modern dominance of automated static perimeters requires the formulation of new diagnostic criteria.MethodsRetrospective review of automated perimetry records from 36 subjects meeting clinical and tangent screen criteria for functional visual field loss. Thirty‐three normal eyes and 57 eyes with true lesions, including optic nerve compression, glaucoma, anterior ischaemic optic neuropathy and vigabatrin toxicity, served as controls.ResultsStandard automated perimetry statistics were unable to reliably discriminate organic versus non‐organic visual field loss. Subjective evaluation of perimetric maps indicated that functional fields generally could be identified by the presence of severe and irregular contractions and depressions that did not conform to the visual system's neuro‐architecture. Further, functional fields generally presented one or more isolated threshold ‘spikes’, that is, isolated locations showing much better than average sensitivity. On repeated examinations, threshold spikes always changed locations. Visual evaluation for spikes proved superior to an objective computational algorithm. Fairly reliable objective discrimination of functional fields could be achieved by point‐wise correlations of repeated examinations: median intertest correlation coefficients equalled 0.47 compared with 0.81 for true lesions.ConclusionFunctional visual loss can be identified by automated static perimetry. Useful criteria include severe and irregular contractions and depressions, the presence of isolated threshold spikes and poor intertest correlations.
Ca2+ signals, NAADP and two‐pore channels: role in cellular differentiation
Authors: Parrington J. , Tunn R. 
Published: April 2014

AbstractCa2+ signals regulate a wide range of physiological processes. Intracellular Ca2+ stores can be mobilized in response to extracellular stimuli via a range of signal transduction mechanisms, often involving recruitment of diffusible second messenger molecules. The Ca2+‐mobilizing messengers InsP3 and cADPR release Ca2+ from the endoplasmic reticulum via the InsP3 and ryanodine receptors, respectively, while a third messenger, NAADP, releases Ca2+ from acidic endosomes and lysosomes. Bidirectional communication between the endoplasmic reticulum (ER) and acidic organelles may have functional relevance for endolysosomal function as well as for the generation of Ca2+ signals. The two‐pore channels (TPCs) are currently strong candidates for being key components of NAADP‐regulated Ca2+ channels. Ca2+ signals have been shown to play important roles in differentiation; however, much remains to be established about the exact signalling mechanisms involved. The investigation of the role of NAADP and TPCs in differentiation is still at an early stage, but recent studies have suggested that they are important mediators of differentiation of neurones, skeletal muscle cells and osteoclasts. NAADP signals and TPCs have also been implicated in autophagy, an important process in differentiation. Further studies will be required to identify the precise mechanism of TPC action and their link with NAADP signalling, as well as relating this to their roles in differentiation and other key processes in the cell and organism.
Real‐world assessment of therapy changes, suboptimal treatment and associated costs in patients with ulcerative colitis or Crohn's disease
Authors: Rubin D. T. , Mody R. , Davis K. L. , Wang C.‐C. 
Published: April 2014

SummaryBackgroundTreatments for Crohn's disease (CD) and ulcerative colitis (UC) are not uniformly effective, thus necessitating dose changes, switching, and augmentation and carry adverse event risk, often requiring discontinuation, which reduces treatment benefits.AimTo assess continuity of and changes to initial CD and UC treatments, as well as costs associated with specific parameters defining suboptimal therapy.MethodsCommercial US insurance claims (2006–2010) were retrospectively analysed. CD and UC patients receiving monotherapy with 5‐aminosalicylates (5‐ASAs), corticosteroids (CS), immunomodulators (IM) or biologics were included. Continuity of and changes to initial (index) therapy and associated costs (2011 US$) were assessed over 12 months following therapy initiation. Suboptimal therapy included discontinuation or switch (except for CS), dose escalation, augmentation, inadequate loading (biologics only), prolonged CS use (>3 months), surgery or hospitalisation.ResultsThe study included 13 005 CD and 19 878 UC patients. Augmentation was a common index therapy change (~20% of 5‐ASA initiators, ~40% of CS initiators, ≥40% of IM initiators and 26–55% of biologic initiators) in both CD and UC patients. Approximately 50% of CD and UC 5‐ASA initiators discontinued/interrupted treatment. Approximately 80% of CD and UC patients had ≥1 suboptimal therapy marker. Mean all‐cause total costs per CD patient were significantly higher in those with vs. without suboptimal therapy ($18 736 vs. $10 878; P < 0.001); in UC, the disparity was smaller ($12 679 vs. $9653; P < 0.001).ConclusionsFrequent dose and treatment changes were observed in all classes of initial UC and CD treatments. The economic impact of suboptimal therapy among UC and CD patients is substantial.
Moving Toward Patient‐Centered Care: Women's Decisions, Perceptions, and Experiences of the Induction of Labor Process
Authors: Moore Jennifer E. , Low Lisa Kane , Titler Marita G. , Dalton Vanessa K. , Sampselle Carolyn M. 
Published: April 2014

AbstractBackgroundPatient preferences and clinician practices are possible causative factors to explain the increase in induction of labor, but scientific studies that demonstrate this link are limited. The purpose of this study is to identify factors that influence inductions from the perspective of women.MethodsA qualitative investigation using grounded theory methodology was conducted. Women were interviewed preinduction and postinduction. Analysis of the interviews was conducted using constant comparison to identify codes, categories, and themes. Through this process the complex intersection between women, their clinician, and the application of evidence‐based care in clinical practice was explored.ResultsFive major themes from the preinduction interview were identified; safety of baby, women's trust in their clinician, relief of discomfort and/or anxiety, diminish potential or actual risk, and lack of informed decision making. Five major themes were identified from the postinduction interview; lack of informed decision making, induction as part of a checklist, women's trust in their clinician, happy with induction, and opportunities to improve the experience.ConclusionsLack of informed decision making was cited as a barrier to optimal care. This study has important implications for patient‐centered research and clinical care, requiring the inclusion of women and the salient concepts of care that they identify.
Does a Large Infant Head or a Short Perineal Body Increase the Risk of Obstetrical Perineal Trauma?
Authors: Komorowski Leanne K. , Leeman Lawrence M. , Fullilove Anne M. , Bedrick Edward J. , Migliaccio Laura D. , Rogers Rebecca G. 
Published: April 2014

AbstractBackgroundPerineal trauma after vaginal delivery can have significant long‐term consequences. It is unknown if a larger infant head circumference or smaller maternal perineal anatomy are risk factors for perineal trauma after vaginal delivery.MethodsWe conducted a prospective cohort study of low‐risk nulliparous women. Data collected included maternal characteristics, antepartum Pelvic Organ Prolapse Quantification measurements of the perineal body and genital hiatus, labor characteristics, perineal trauma, and infant head circumference. Perineal trauma was defined as trauma that extended into the muscles of the perineum (second‐degree or deeper). Univariate and multivariate logistic models were created to calculate odds ratios (OR) and 95 percent confidence intervals (CI).ResultsWe observed 448 vaginal births. Multivariate analysis demonstrated a significant association between infant head circumference at birth and perineal trauma: OR 1.22 for each increase of 1 cm in head circumference (95% CI 1.05–1.43). There was no association between perineal body or genital hiatus length and perineal trauma.ConclusionsIn nulliparous low‐risk women a larger infant head circumference at birth increases the likelihood of perineal trauma, although the effect is modest. Antenatal perineal body and genital hiatus measurements do not predict perineal trauma. These results do not support alteration in mode of delivery or other obstetric practices.
Parent and child distress after war exposure
Authors: Lai Betty S. , Hadi Fawzyiah , Llabre Maria M. 
Published: April 2014

ObjectivesThe purpose of this study was to examine multiple distress symptoms (i.e., post‐traumatic stress [PTS], anxiety, depression) among parents and children exposed to the Gulf Crisis in 1990–1991. Profiles of parent distress were identified, and the relationship between parent distress and specific child distress symptoms was examined.DesignParents and children were assessed at one time point.MethodsParticipants included 151 children (Mage = 10.62 years; 51% female) and 140 parents (Mage = 40 years; 81% female).ResultsUtilizing latent profile analysis, three parallel profiles of parent distress were identified: low distress, moderate distress, and high distress. Parent distress was a risk factor for child depression, but it was not a risk factor for child PTS or anxiety.ConclusionsFindings support the importance of broadening the scope of research conducted after exposure to traumatic events to include the assessment of anxiety and depression, as well as PTS, among both parents and children. Additional implications for research and clinical work are discussed.Practitioner points

Findings support the importance of screening for multiple distress symptoms among both children and parents after war exposure.

Based on our findings, clinicians may want to consider including parents in therapy for children reporting psychological distress, especially depression symptoms, after exposure to traumatic events.

This study was cross‐sectional. Thus, we are not able to infer direction or causality.

The generalizability of our study should be interpreted with caution, as findings will need to be replicated across other populations and other cultures.
Technological utopia, dystopia and ambivalence: Teaching with social media at aSouthAfrican university
Authors: Rambe Patient , Nel Liezel 
Published: April 2014

AbstractThe discourse of social media adoption in higher education has often been funnelled through utopian and dystopian perspectives, which are polarised but determinist theorisations of human engagement with educational technologies. Consequently, these determinist approaches have obscured a broadened grasp of the situated, socially constructed nature of human interaction with educational technologies and failed to explain ambivalent positions of technology adoption. To contest the innate determinism embodied in the aforementioned technological views, this paper draws on technological ambivalence to unravel the complex, multiple possibilities in pragmatic use of technology—including the double‐bound relationship between human agency and educational technology. A phenomenological approach that draws on self‐narratives of the use of social media byComputerScience andInformatics educators at aSouthAfrican university is employed to unravel how their perceptions of social media shaped and informed their pragmatic instructional uses of these technologies. Findings suggest that the sharp contrasting experiences of collaborative engagement, enactment of decentralised power and democratic expression in social media coexist recursively with the disempowering, dependence‐ridden and distractive effects of these technologies. This technological divergence is further compounded by ambivalent views that neither celebrate the unrealistic hopes of social media nor grossly protest against the debilitating effects of these technologies. This view foregrounds the social embeddedness of technology and its potentially multiple, contradictory effects. The implications of these findings include the need for educators to consider social conditions of technology use, the alignment of such conditions with innovative social media‐enhanced pedagogical models and the use of proven models to demonstrate the educational potential of social media technologies.
Lymphoma diagnosis at an academic centre: rate of revision and impact on patient care
Authors: Bowen Joslin M. , Perry Anamarija M. , Laurini Javier A. , Smith Lynette M. , Klinetobe Kimberly , Bast Martin , Vose Julie M. , Aoun Patricia , Fu Kai , Greiner Timothy C. , Chan Wing C. , Armitage James O. , Weisenburger Dennis D. 
Published: April 2014

SummaryFew studies have examined the value of a mandatory second review of outside pathology material for haematological malignancies. Therefore, we compared diagnoses on biopsies referred to an academic medical centre to determine the rate and therapeutic impact of revised diagnoses resulting from a second review. We reviewed 1010 cases referred for lymphoma during 2009–2010. For each case, referral diagnosis and second review diagnosis were compared. Revised diagnoses were grouped into major and minor discrepancies and all major discrepancies were reviewed by a haematologist to determine the effect the diagnostic change would have on therapy. There was no change in diagnosis in 861 (85·2%) cases. In 149 (14·8%) cases, second review resulted in major diagnostic change, of which 131 (12·9%) would have resulted in a therapeutic change. The highest rates of revision were for follicular, high‐grade B‐cell, and T‐cell lymphomas. We found higher rates of major discrepancy in diagnoses from non‐academic centres (15·8%) compared to academic centres (8·5%; P = 0·022), and in excisional biopsies (17·9%) compared to smaller biopsies (9·6%; P = 0·0003). Mandatory review of outside pathology material prior to treatment of patients for lymphoma will identify a significant number of misclassified cases with a major change in therapy.
Disturbed CXCR4/CXCL12 axis in paediatric precursor B‐cell acute lymphoblastic leukaemia
Authors: van den Berk Lieke C. J. , van der Veer Arian , Willemse Marieke E. , Theeuwes Myrte J. G. A. , Luijendijk Mirjam W. , Tong Wing H. , van der Sluis Inge M. , Pieters Rob , den Boer Monique L. 
Published: April 2014

SummaryMalignant cells infiltrating the bone marrow (BM) interfere with normal cellular behaviour of supporting cells, thereby creating a malignant niche. We found that CXCR4‐receptor expression was increased in paediatric precursor B‐cell acute lymphoblastic leukaemia (BCP‐ALL) cells compared with normal mononuclear haematopoietic cells (P < 0·0001). Furthermore, high CXCR4‐expression correlated with an unfavourable outcome in BCP‐ALL (5‐year cumulative incidence of relapse ± standard error: 38·4% ± 6·9% in CXCR4‐high versus 12% ± 4·6% in CXCR4‐low expressing cases, P < 0·0001). Interestingly, BM levels of the CXCR4‐ligand (CXCL12) were 2·7‐fold lower (P = 0·005) in diagnostic BCP‐ALL samples compared with non‐leukaemic controls. Induction chemotherapy restored CXCL12 levels to normal. Blocking the CXCR4‐receptor with Plerixafor showed that the lower CXCL12 serum levels at diagnosis could not be explained by consumption by the leukaemic cells, nor did we observe an altered CXCL12‐production capacity of BM‐mesenchymal stromal cells (BM‐MSC) at this time‐point. We rather observed that a very high density of leukaemic cells negatively affected CXCL12‐production by the BM‐MSC while stimulating the secretion levels of granulocyte colony‐stimulating factor (G‐CSF). These results suggest that highly proliferative leukaemic cells are able to down‐regulate secretion of cytokines involved in homing (CXCL12), while simultaneously up‐regulating those involved in haematopoietic mobilization (G‐CSF). Therefore, interference with the CXCR4/CXCL12 axis may be an effective way to mobilize BCP‐ALL cells.
YC‐1 inhibits proliferation of breast cancer cells by down‐regulating EZH2 expression via activation of c‐Cbl and ERK
Authors: Chang Ling‐Chu , Lin Hui‐Yi , Tsai Meng‐Tung , Chou Ruey‐Hwang , Lee Fang‐Yu , Teng Che‐Ming , Hsieh Min‐Tsang , Hung Hsin‐Yi , Huang Li‐Jiau , Yu Yung‐Luen , Kuo Sheng‐Chu 
Published: April 2014

Background and PurposeYC‐1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC‐1 in an MDA‐MB‐468 xenograft model and elucidated the mechanism of down‐regulation of enhancer of zeste homology 2 (EZH2) by YC‐1 in breast cancer cells.Experimental ApproachIn YC–1‐treated breast cancer cells and tumour specimens from YC–1‐treated MDA‐MB‐468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA‐mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down‐regulation by YC‐1.Key ResultsYC‐1 reduced the viability of breast cancer cells and tumour growth in MDA‐MB‐468 xenografts. In breast cancer cells, YC‐1 down‐regulated EZH2 expression in a concentration‐ and time‐dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC–1‐induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC–1‐treated MDA‐MB‐468 xenograft mice. YC‐1 enhanced both the degradation rate and ubiquitination of EZH2. The down‐regulation of EZH2 by YC‐1 was associated with activation of PKA and Src–Raf–ERK‐mediated signalling pathways. Furthermore, depletion of Casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase, abolished YC–1‐induced apoptosis and suppression of EZH2. YC‐1 rapidly activated c‐Cbl to induce signalling associated with ERK and EZH2.Conclusion and ImplicationsWe discovered that YC‐1 induces apoptosis and inhibits tumour growth of breast cancer cells via down‐regulation of EZH2 by activating c‐Cbl and ERK. These data suggest that YC‐1 is a potential anticancer drug candidate for triple‐negative breast cancer.
Subsurface evidence for late Mesozoic extension in western Mongolia: tectonic and petroleum systems implications
Authors: Johnson C. L. , Constenius K. C. , Graham S. A. , Mackey G. , Menotti T. , Payton A. , Tully J. 
Published: April 2014

AbstractNew seismic reflection profiles from the Tugrug basin in the Gobi‐Altai region of western Mongolia demonstrate the existence of preserved Mesozoic extensional basins by imaging listric normal faults, extensional growth strata, and partially inverted grabens. A core hole from this region recovered ca. 1600 continuous meters of Upper Jurassic – Lower Cretaceous (Kimmeridgian–Berriasian) strata overlying Late Triassic volcanic basement. The cored succession is dominated by lacustrine and marginal lacustrine deposits ranging from stratified lacustrine, to subaqueous fan and delta, to subaerial alluvial‐fluvial environments. Multiple unconformities are encountered, and these represent distinct phases in basin evolution including syn‐extensional deposition and basin inversion. Prospective petroleum source and reservoir intervals occur, and both fluid inclusions and oil staining in the core provide evidence of hydrocarbon migration. Ties to correlative outcrop sections underscore that, in general, this basin appears to share a similar tectono‐stratigraphic evolution with petroliferous rift basins in eastern Mongolia and China. Nevertheless, some interesting contrasts to these other basins are noted, including distinct sandstone provenance, less overburden, and younger (Neogene) inversion structures. The Tugrug basin occupies an important but perplexing paleogeographic position between late Mesozoic contractile and extensional provinces. Its formation may record a rapid temporal shift from orogenic crustal thickening to extensional collapse in the Late Jurassic, and/or an accommodation zone with a Mesozoic strike‐slip component.
Molecular pathways linking non‐shivering thermogenesis and obesity: focusing on brown adipose tissue development
Authors: Valente Angelica , Jamurtas Athanasios Z. , Koutedakis Yiannis , Flouris Andreas D. 
Published: April 2014

ABSTRACTAn increase in energy intake and/or a decrease in energy expenditure lead to fat storage, causing overweight and obesity phenotypes. The objective of this review was to analyse, for the first time using a systematic approach, all published evidence from the past 8 years regarding the molecular pathways linking non‐shivering thermogenesis and obesity in mammals, focusing on mechanisms involved in brown adipose tissue development. Two major databases were scanned from 2006 to 2013 using ‘brown adipose tissue’ AND ‘uncoupling protein‐1’ AND ‘mammalian thermoregulation’ AND ‘obesity’ as key words. A total of 61 articles were retrieved using the search criteria. The available research used knockout methodologies, various substances, molecules and agonist treatments, or different temperature and diet conditions, to assess the molecular pathways linking non‐shivering thermogenesis and obesity. By integrating the results of the evaluated animal and human studies, our analysis identified specific molecules that enhance non‐shivering thermogenesis and metabolism by: (i) stimulating ‘brite’ (brown‐like) cell development in white adipose tissue; (ii) increasing uncoupling protein‐1 expression in brite adipocytes; and (iii) augmenting brown and/or brite adipose tissue mass. The latter can be also increased through low temperature, hibernation and/or molecules involved in brown adipocyte differentiation. Cold stimuli and/or certain molecules activate uncoupling protein‐1 in the existing brown adipocytes, thus increasing total energy expenditure by a magnitude proportional to the number of available brown adipocytes. Future research should address the interplay between body mass, brown adipose tissue mass, as well as the main molecules involved in brite cell development.