bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Molecular Characterization of a Patient with 15q21.2q22.2 Deletion Syndrome
Authors: Velázquez-Wong Ana C. , Ruiz Esparza-Garrido Ruth , Velázquez-Flores Miguel Á. , Huicochea-Montiel Juan C. , Cárdenas-Conejo Alan , Miguez-Muñoz Cristian P. , Araujo-Solís María A. , Salamanca-Gómez Fabio , Arenas-Aranda Diego J.
Published: February 2015

We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.
Cognitive Impairment after Chemotherapy Related to Atypical Network Architecture for Executive Control
Authors: Piccirillo Jay F. , Hardin Frances Mei , Nicklaus Joyce , Kallogjeri Dorina , Wilson Michael , Ma Cynthia X. , Coalson Rebecca S. , Shimony Joshua , Schlaggar Bradley L.
Published: February 2015

Objectives: A common complaint of cancer patients is the experience of cognitive difficulty during and after chemotherapy. We hypothesized that cognitive impairment may result from dysfunction in large-scale brain networks, particularly those involved in attentional control. Methods: Using a case-control design, this study includes women with a history of invasive ductal or lobular triple-negative breast cancer who completed standard adjuvant chemotherapy within 2 years of study entry. Women who reported cognitive impairment by the Global Rating of Cognition question were considered to be cases (n = 15). Women who reported no cognitive impairment were considered to be controls (n = 13). All enrolled participants were eligible for MRI investigation and underwent resting-state functional connectivity MRI. Results: Women who self-reported cognitive impairment were found to have disrupted resting-state functional connectivity, as measured by MRI, when compared to women who did not self-report cognitive impairment. These findings suggest that some women may be more sensitive to the standard treatments for breast cancer and that this increased sensitivity may result in functional connectivity alterations in the brain networks supporting attention and executive function. Conclusions: Neuroimaging analyses confirmed self-reported cognitive deficits in women with breast cancer treated with chemotherapy.
Association between Platelet-to-Lymphocyte Ratio and Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome
Authors: Demircelik Muhammed Bora , Kurtul Alparslan , Ocek Hakan , Cakmak Muzaffer , Ureyen Cagın , Eryonucu Beyhan
Published: February 2015

Objective: Contrast-induced nephropathy (CIN) is associated with significantly increased morbidity and mortality after percutaneous coronary intervention (PCI). Patients with acute coronary syndrome (ACS) are at higher risk of CIN. The platelet-to-lymphocyte ratio (PLR) is closely linked to inflammatory conditions. We hypothesized that PLR levels on admission can predict the development of CIN after PCI for ACS. Subjects and Methods: A total of 426 patients (mean age 63.17 ± 13.01 years, 61.2% males) with ACS undergoing PCI were enrolled in this study. Admission PLR levels were measured before PCI. Serum creatinine values were measured before and within 72 h after the administration of contrast agents. Patients were divided into 2 groups: the CIN group and the no-CIN group. CIN was defined as an increase in serum creatinine level of ≥0.5 mg/dl or 25% above baseline within 72 h after contrast administration. Results: CIN developed in 53 patients (15.9%). Baseline PLR was significantly higher in patients who developed CIN compared to those who did not (160.8 ± 29.7 and 135.1 ± 26.1, respectively; p < 0.001). Multivariate analyses found that PLR [odds ratio (OR) 3.453, 95% confidence interval (CI) 1.453-8.543; p = 0.004] and admission creatinine (OR 6.511, 95% CI 1.759-11.095; p = 0.002) were independent predictors of CIN. Conclusions: The admission PLR level is an independent predictor of the development of CIN after PCI in ACS.
The Effect of Hypothyroidism on Color Contrast Sensitivity: A Prospective Study
Authors: Cakir Mehtap , Turgut Ozturk Banu , Turan Elif , Gonulalan Gulsum , Polat Ilker , Gunduz Kemal
Published: February 2015

Background: Thyroid hormone has been shown to control retinal cone opsin expression, the protein of color vision, in adult rodents. Objectives: The aim of this study was to evaluate the effect of hypothyroidism on color contrast sensitivity in adult overt hypothyroid patients. Methods: Thirty-eight overt hypothyroid (31 females, 7 males) subjects and 20 euthyroid (16 females, 4 males) controls were studied prospectively. Color vision examination was performed by Chromatest, a software program analyzing the tritan (blue-yellow) color contrast threshold (tritan CCT) and protan (red-green) color contrast threshold (protan CCT). Color contrast sensitivity analyses of hypothyroid subjects were performed on admission and after L-thyroxine treatment when biochemical euthyroidism was achieved. Results: After a median period of 90 (90-210) days, 24 (19 females, 5 males) patients were euthyroid and eligible for a second color vision examination. Baseline tritan CCT and protan CCT values were significantly higher in the hypothyroid group compared to euthyroid controls, which clinically translates into impaired color contrast sensitivity (p < 0.001 and p < 0.001, respectively). There was a significant decrease in tritan CCT (p = 0.002) and protan CCT (p < 0.001) values in the hypothyroid group after euthyroidism was achieved, which denotes improvement in color contrast sensitivity. Conclusions: It is a novel finding of the current study that color contrast sensitivity is impaired in hypothyroidism and significantly improves after euthyroidism is achieved.
Ambulatory Assessment in the Research on Aging: Contemporary and Future Applications
Authors: Brose Annette , Ebner-Priemer Ulrich W.
Published: February 2015

Older adults have surprisingly high levels of well-being, which has been referred to as a paradox in the past. Improved emotion regulation has been suggested to underlie these high levels of well-being. Later life is also a period with enhanced exposure to critical life events, and this comes with risks. During such times, and towards the end of life, emotional well-being may and eventually does decline. We suggest that ambulatory assessment (AA) is ideally suited for the investigation of the above phenomena and for intervention purposes. More precisely, AA can be used to thoroughly examine within-person processes of emotion regulation, including the multiple levels on which emotions occur (physiology, experience, behavior, context, and nonverbal expressions). It thereby provides a basis for understanding competent emotion regulation, the well-being paradox, and emotionally critical periods. Such insights can be utilized to detect person-specific critical periods and for designing immediate person-specific interventions. Although this is still a vision, the benefits of such an approach seem invaluable. The major part of this paper is organized around three general principles that we suggest to further tap the potential of AA in aging research, namely (1) identify within-subject processes and their relations to important life outcomes; (2) capitalize on the full scope of AA technology via multivariate assessments, and (3) combine real-time monitoring with real-time interventions.
Poly r(C) Binding Protein-1 is Central to Maintenance of Cancer Stem Cells in Prostate Cancer Cells
Authors: Chen Qi , Cai Zhi-kang , Chen Yan-bo , Gu Meng , Zheng Da-chao , Zhou Juan , Wang Zhong
Published: February 2015

Aims: To investigate global proteomic changes induced in CD44+CD24- stem cells isolated from the prostate cancer cell lines, LNCaP and DU145, post prolonged TGF-β treatment in order to understand underlying mechanisms that promote stemness in prostate cancer cells. Methods: CD44+CD133+α2β1Integrin+CD24- population was isolated from mock or TGF-β treated (7 days) prostate cancer cell line, LNCaP, through fluorescent activated cell sorting. Cell lysates were obtained from the ±TGF-β cell population and proteomics profiling (MS/MS) was performed by mass spectrometry. Relative enrichment or depletion in the CD44+CD24-population post-TGF-β treatment was determined relative to mock-treated CD44+CD24- cells post normalization to GAPDH expression levels. Results obtained from MS/MS were validated using immunoblotting. Functional validation of one putative regulator was performed using gain-of-function strategy to investigate its role in rendering stemness in LNCaP and DU145 cells in vitro and in promoting tumorigenicity in vivo. Results: TGF-β treatment caused significant enrichment of CD44+CD24- population in LNCaP cells (22.35 ± 0.94% in mock treated vs 95.23 ± 2.34% in TGF-β treated cells; P < 0.01), which were also positive for CD133 and α2β1Integrin. Mass spectrometry analysis of the enriched cell population revealed that sixty-three proteins were either up- or down-regulated greater than five folds, out of which the poly r(C) binding protein (PCBP)-1 was the most down-regulated (9.31 ± 0.05 folds). Ectopic overexpression of PCBP1 in LNCaP and DU145 cells not only attenuated enrichment of CD44+CD133+CD24- population in these cells following TGF-β treatment, but also significantly decreased tumorigenicity of the stem cell subset, as assessed by in vitro soft agar colony formation and in vivo xenograft assays. Conclusion: Our proteomic profiling and subsequent validation indicate that PCBP1 is central to CSCs enrichment and functionality in prostate cancer.
Multiple Myeloma and Atopic Eczema in an Adult
Authors: Hossain Mohammad Amir , Nai Qiang , Zhang Ping , Luo Hongxiu , Hossain Mohammed Amzad , Mahmad Abdul , Yousif Abdalla M. , Sen Shuvendu
Published: February 2015

Multiple myeloma is the fourteenth cause of cancer-related death. The symptoms of myeloma are mostly nonspecific, and there is significant delay between the first symptoms and diagnosis of myeloma. Atopic eczema is a common chronic inflammatory skin disease associated with dysregulation of the immune system. It generally develops in early childhood but can also occur in adults. Eczema is associated with a variety of hematological and solid malignancies, and possibly multiple myeloma. We report a patient with eczema that developed 5 years before the diagnosis of multiple myeloma but was mistaken for psoriasis.
Weddell Sea Export Pathways from Surface Drifters
Authors: Youngs Madeleine K. , Thompson Andrew F. , Flexas M. Mar , Heywood Karen J.
Published: February 2015

The complex export pathways that connect the surface waters of the Weddell Sea with the Antarctic Circumpolar Current influence water mass modification, nutrient fluxes, and ecosystem dynamics. To study this exchange, 40 surface drifters, equipped with temperature sensors, were released into the northwestern Weddell Sea’s continental shelf and slope frontal system in late January 2012. Comparison of the drifter trajectories with a similar deployment in early February 2007 provides insight into the interannual variability of the surface circulation in this region. Observed differences in the 2007 and 2012 drifter trajectories are related to a variable surface circulation responding to changes in wind stress curl over the Weddell Gyre. Differences between northwestern Weddell Sea properties in 2007 and 2012 include 1) an enhanced cyclonic wind stress forcing over the Weddell Gyre in 2012; 2) an acceleration of the Antarctic Slope Current (ASC) and an offshore shift of the primary drifter export pathway in 2012; and 3) a strengthening of the Coastal Current (CC) over the continental shelf in 2007. The relationship between wind stress forcing and surface circulation is reproduced over a longer time period in virtual drifter deployments advected by a remotely sensed surface velocity product. The mean offshore position and speed of the drifter trajectories are correlated with the wind stress curl over the Weddell Gyre, although with different temporal lags. The drifter observations are consistent with recent modeling studies suggesting that Weddell Sea boundary current variability can significantly impact the rate and source of exported surface waters to the Scotia Sea, a process that determines regional chlorophyll distributions.
Impacts of Increasing Low-Level Shear on Supercells during the Early Evening Transition*
Authors: Coffer Brice E. , Parker Matthew D.
Published: February 2015

The dynamical response of simulated supercells to temporally increasing lower-tropospheric vertical wind shear is investigated using idealized simulations. These simulations are based upon observed soundings from two cases that underwent an early evening transition during the Second Verification of the Origins of Rotation in Tornadoes Experiment (VORTEX2). Mature supercells were simulated in observed afternoon environments with moderate vertical wind shear and then compared to simulated supercells experiencing observed evening increases in lower-tropospheric shear. The primary effect of the increase in low-level shear is to establish larger values of vertical vorticity at lower altitudes in the storm’s updraft. In turn, this leads to a nonlinear increase in the updraft strength due to the enhanced dynamic pressure minimum associated with larger vorticity in the storm’s mesocyclone. This is particularly important at low levels, where it increases the storm's ability to lift cool surface air (including outflow). Trajectories launched in developing vortices show that, despite comparable buoyant accelerations, parcels experience greater vertical velocity and stretching of vertical vorticity due to increased dynamic accelerations when the low-level shear is increased. Thus, even as low-level stability gradually increases in the early evening, the supercells’ low-level updraft intensity and surface vorticity production can increase. These results are consistent with climatological observations of a supercell’s likelihood of tornadogenesis during the early evening hours.
Does Partisanship Shape Attitudes toward Science and Public Policy? The Case for Ideology and Religion
Authors: Blank Joshua M. , Shaw Daron
Published: February 2015

Despite the apparent partisan divide over issues such as global warming and hydraulic fracturing, little is known about what shapes citizens’ willingness to accept scientific recommendations on political issues. We examine the extent to which Democrats, Republicans, and independents are likely to defer to scientific expertise in matters of policy. Our study draws on an October 2013 U.S. national survey of 2,000 respondents. We find that partisan differences exist: our data show that most Americans see science as relevant to policy, but that their willingness to defer to science in policy matters varies considerably across issues. While party, ideology, and religious beliefs clearly influence attitudes toward science, Republicans are not notably skeptical about accepting scientific recommendations. Rather, it seems that Democrats are particularly receptive to the advice and counsel of scientists, when compared to both independents and Republicans.
Why People “Don’t Trust the Evidence”
Authors: Kraft Patrick W. , Lodge Milton , Taber Charles S.
Published: February 2015

In this commentary, we embed the volume’s contributions on public beliefs about science in a broader theoretical discussion of motivated political reasoning. The studies presented in the preceding section of the volume consistently find evidence for hyperskepticism toward scientific evidence among ideologues, no matter the domain or context—and this skepticism seems to be stronger among conservatives than liberals. Here, we show that these patterns can be understood as part of a general tendency among individuals to defend their prior attitudes and actively challenge attitudinally incongruent arguments, a tendency that appears to be evident among liberals and conservatives alike. We integrate the empirical results reported in this volume into a broader theoretical discussion of the John Q. Public model of information processing and motivated reasoning, which posits that both affective and cognitive reactions to events are triggered unconsciously. We find that the work in this volume is largely consistent with our theories of affect-driven motivated reasoning and biased attitude formation.
Questionnaire Design Effects in Climate Change Surveys
Authors: Schuldt Jonathon P. , Roh Sungjong , Schwarz Norbert
Published: February 2015

Despite strong agreement among scientists, public opinion surveys reveal wide partisan disagreement on climate issues in the United States. We suggest that this divide may be exaggerated by questionnaire design variables. Following a brief literature review, we report on a national survey experiment involving U.S. Democrats and Republicans ( n = 2,041) (fielded August 25–September 5, 2012) that examined the effects of question wording and order on the belief that climate change exists, perceptions of scientific consensus, and support for limiting greenhouse gas emissions. Wording a questionnaire in terms of “global warming” (versus “climate change”) reduced Republicans’ (but not Democrats’) existence beliefs and weakened perceptions of the scientific consensus for both groups. Moreover, “global warming” reduced Republicans’ support for limiting greenhouse gases when this question immediately followed personal existence beliefs but not when the scientific consensus question intervened. We highlight the importance of attending to questionnaire design in the analysis of partisan differences.
Technology Optimism or Pessimism about Genomic Science
Authors: Hochschild Jennifer , Sen Maya
Published: February 2015

Like lay people, experts vary in their technology optimism or pessimism about scientific endeavors, for reasons that are poorly understood. We explore experts’ technology optimism through a focus on genomics; its novelty, life-and-death implications, complex technology, and broad but as yet unknown societal implications make it an excellent subject for studying views about new knowledge. We use interviews with scientific and medical elites to show a wide range of views about genomics, and we analyze about 750 articles by prominent social scientists, law professors, and biologists to explore how values and norms reinforce or supersede experts’ shared scientific knowledge. We find that experts in some fields give genomics more attention than experts in others; that they differ in the aspects of genomics on which they focus; and that within a discipline or field, scholars differ in the extent to which they find genomics attractive or aversive. Overall, however, experts in more liberal or humanities-oriented disciplines tend to be less optimistic about genomics than scholars in relatively more conservative or scientifically oriented disciplines. We speculate on why genomics is an exception to the usual finding that liberals support science more than conservatives do.
Attributing minds to vampires in Richard Matheson’s I Am Legend
Authors: Nuttall Louise
Published: February 2015

For Palmer (2004, 2010), and other proponents of a cognitive narratology, research into real-world minds in the cognitive sciences provides insights into readers’ experiences of fictional minds. In this article, I explore the application of such research to the minds constructed for the vampire characters in Richard Matheson’s 1954 science fiction/horror novel I Am Legend. I draw upon empirical research into ‘mind attribution’ in social psychology, and apply Cognitive Grammar (Langacker, 2008), and its notion of ‘construal’, as a framework for the application of such findings to narrative. In my analysis, I suggest that readers’ attribution of mental-states to the vampires in Matheson’s novel is strategically limited through a number of choices in their linguistic construal. Drawing on online reader responses to the novel, I argue that readers’ understanding of these other minds plays an important role in their empathetic experience and ethical judgement of the novel’s main character and focaliser, Robert Neville. Finally, I suggest that the limited mind attribution for the vampires invited through their construal contributes to the presentation of a ‘mind style’ (Fowler, 1977) for this character.
Person deixis and impersonation in Iain Banks’s Complicity
Authors: Sorlin Sandrine
Published: February 2015

The article focuses on the specific use of the second-person pronoun in Iain Banks’s Complicity and the complex relationship it entertains with its first-person counterpart as the novel alternates between first- and second-person narratives. The personal pronouns construct two completely opposed mindstyles: the highly personal narrative of the first-person protagonist contrasts with the depersonalized style of the ‘you’ protagonist-narrator. Not only is the second-person pronoun a grammatical ‘imposter’ (Collins and Postal, 2012) – it actually hides an ‘I’ – but it is a psychological one as the narrator seems to hide his real self behind a convenient ‘you persona’. In addition, the article brings to light the pragmatic paradox that ‘self-address you’ embodies in the peculiar position it assigns to the readers. If it tends to ‘encroach upon’ their territory, forcing them into complicity, it is also guilty of manipulating their emotions. Lastly, the linguistic and stylistic analysis of Banks’s novel will here be coupled with cognitive and psycholinguistic approaches in order to understand how the reader switches from one ‘frame’ of mind to the other. Particularly helpful is the ‘Rhetorical Processing Framework’ discussed by Sanford and Emmott (2012) in order to grasp how readers construct mental representations to process the writer’s sometimes misleading style.
The Year in Review
Authors: Ing Richard J. , Twite Mark D.
Published: February 2015

Congenital cardiac anesthesiology is a rapidly expanding field at both ends of the life spectrum. The care of the unborn child with congenital heart disease is becoming highly specialized in regional centers that offer advanced imaging techniques, coordinated specialist care, and potentially fetal interventions. As more children with congenital heart disease survive to adulthood, patients and their health care providers are facing new challenges. The growing volume of publications reflects this expanding field of congenital cardiac anesthesiology. This year in review article highlights some developing trends in the literature.
Laparoscopic resection of a rare gastrointestinal stromal tumor in children
Authors: Lima Mario , Gargano Tommaso , Ruggeri Giovanni , Pession Andrea , Mariotto Arianna , Maffi Michela
Published: February 2015

Introduction

Gastrointestinal stromal tumors (GIST) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract, accounting for 0.1% to 3% of all GI malignancies. Paediatric GIST have an annual incidence of 0.02 per million children, have a female predisposition, are usually located in the stomach (50–60%) and in up to 85% of cases CD117-cKit or PDGFRA mutation is absent, resulting in a decreased efficacy of the target therapy.

Case description

We report the case of an incidentally diagnosed gastric GIST in a 14-year-old boy with multiple malformations. Genetic tests and Kariotype resulted negative.

Recently, an abdominal US visualized an hypoechoic heterogeneous abdominal mass. The common tumor markers resulted negative and the abdominal CT-scan confirmed the presence of a solid round lesion (42×36mm) in contact with the stomach and the pancreas. Laparoscopy allowed the recognition and the removal of the nodular mass at the posterior margin of the stomach. The histopathologic and the molecular biology findings were consistent with a kit-wilde type GIST. Surgical margins were microscopically free of tumor cells.

These results justify the decision not to add other surgical or medical therapy. However, for high risk of recurrence and metastasis, a close follow-up was started.

Discussion and evaluation

GIST are asymptomatic in 10% to 30% of patients or present nonspecific symptoms and signs. These tumors present usually irregular, lobulated and ulcerated. CT-scan of the abdomen and pelvis or magnetic resonance imaging (MRI) are mandatory in the diagnostic work-up. The final diagnosis is based on histology and immunohistochemistry. Surgery is the first-line treatment in patients with localized disease.

Conclusion

Guidelines for the management of pediatric GIST are not presently available for the paucity of reports and data. However it is widely accepted that surgery is the first-line treatment and gross resection with negative microscopic margins can be considered therapeutic and lead to full remission of the pathology. Laparoscopy is a safe surgical approach for the exploration of the abdominal cavity, the evaluation of the disease and the complete removal of the tumor.
Practical remediation of the PCB-contaminated soils
Authors: Ido Akiko , Niikawa Miki , Ishihara Shinji , Sawama Yoshinari , Nakanishi Tsuyoshi , Monguchi Yasunari , Sajiki Hironao , Nagase Hisamitsu
Published: February 2015

A practical method for the elimination of PCBs from PCB-contaminated soil has been developed by the combination of Soxhlet extraction using a newly-developed modified Soxhlet extractor possessing an outlet valve on the extraction chamber with the chemical degradation. Various types of PCBs contaminated in soils could be completely extracted in refluxing hexane, and the subsequent hydrodechlorination could also be completed within 1 h in a hexane–MeOH (1 : 5) solution in the presence of Pd/C and Et3N under ordinary hydrogen pressure and temperature without the transfer of the extracted PCBs to other reaction container (a complete one-pot procedure). The present system is quite useful as a simple, safe, mild and reliable remediation method of PCB-contaminated soil.
Fabrication of a wafer-scale uniform array of single-crystal organic nanowire complementary inverters by nanotransfer printing
Authors: Park Kyung Sun , Baek Jangmi , Koo Lee Yong-Eun , Sung Myung Mo
Published: February 2015

We report the fabrication and electrical characterization of a wafer-scale array of organic complementary inverters using single-crystal 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-PEN) and fullerene (C60) nanowires asp- andn-channels, respectively. Two arrays of single-crystal organic nanowires were generated consecutively on desired locations of a common substrate with a desired mutual alignment by a direct printing method (liquid-bridge-mediated nanotransfer molding). Another direct printing of silver micron scale structures, as source and drain electrodes, on the substrate with the two printed nanowire arrays produced an array of complementary inverters with a bottom gate, top contact configuration. Field-effect mobilities of single-crystal TIPS-PEN and C60nanowire field-effect transistors (FETs) in the arrays were uniform with 1.01 ± 0.14 and 0.10 ± 0.01 cm2V−1 s−1, respectively. A wafer-scale array of complementary inverters produced all by the direct printing method showed good performance with an average gain of 25 and with low variations among the inverters.
Randomized Controlled Trial of the Prophylactic Effect of Urea-Based Cream on Sorafenib-Associated Hand-Foot Skin Reactions in Patients With Advanced Hepatocellular Carcinoma
Authors: Ren ZhengGang , Zhu KangShun , Kang HaiYan , Lu MinQiang , Qu ZengQiang , Lu LiGong , Song TianQiang , Zhou WeiPing , Wang Hui , Yang WeiZhu , Wang Xuan , Yang YongPing , Shi LeHua , Bai YuXian , Guo XiaoFeng , Ye Sheng-Long
Published: February 2015

Purpose

To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC).

Patients and Methods

In this randomized, open-label trial, 871 patients with advanced HCC throughout China were treated with 10% UBC three times per day plus best supportive care (BSC; n = 439) or BSC alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks. HFSR was assessed every 2 weeks and at 14 weeks for patients completing the study. Once HFSR occurred, patients were allowed any cream, including a UBC.

Results

The 12-week incidence of any grade HFSR was significantly lower in the UBC group versus the BSC-alone group (56.0% v 73.6%, respectively; odds ratio [OR], 0.457; 95% CI, 0.344 to 0.608; P < .001), as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004). Median time to first occurrence of HFSR was significantly longer in the UBC group than the BSC-alone group (84 v 34 days, respectively; hazard ratio, 0.658; 95% CI, 0.541 to 0.799; P < .001). Elevated AST was associated with increased risk of HFSR but did not alter the treatment effect of UBC. UBC plus BSC, compared with BSC alone, did not affect the sorafenib dose reduction or interruption rate (9.1% v 11.8%, respectively; P = .1937), response rate (11.1% v 10.1%, respectively; P = .6674), or disease control rate (98.8% v 98.2%, respectively; P = .5350) at week 12.

Conclusion

UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared with BSC. Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HFSR are warranted.
Safety and Efficacy of Oral Octreotide in Acromegaly: Results of a Multicenter Phase III Trial
Authors: Melmed Shlomo , Popovic Vera , Bidlingmaier Martin , Mercado Moises , van der Lely Aart Jan , Biermasz Nienke , Bolanowski Marek , Coculescu Mihail , Schopohl Jochen , Racz Karoly , Glaser Benjamin , Goth Miklos , Greenman Yona , Trainer Peter , Mezosi Emese , Shimon Ilan , Giustina Andrea , Korbonits Márta , Bronstein Marcello D. , Kleinberg David , Teichman Sam , Gliko-Kabir Irit , Mamluk Roni , Haviv Asi , Strasburger Christian
Published: February 2015

Background:

A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly.

Methods:

We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension.

Results:

Of 151 evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1 <1.3 × ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85 % of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1 ≥1.3 × ULN) terminated early, and 23 withdrew for adverse events, consistent with those known for octreotide or disease related.

Conclusions:

OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.
PGRN Induces Impaired Insulin Sensitivity and Defective Autophagy in Hepatic Insulin Resistance
Authors: Liu Jiali , Li Huixia , Zhou Bo , Xu Lin , Kang Xiaomin , Yang Wei , Wu Shufang , Sun Hongzhi
Published: February 2015

Progranulin (PGRN) has recently emerged as an important regulator for glucose metabolism and insulin sensitivity. However, the underlying mechanisms of PGRN in the regulation of insulin sensitivity and autophagy remain elusive. In this study, we aimed to address the direct effects of PGRN in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. We found that mice treated with PGRN for 21 days exhibited the impaired glucose tolerance and insulin tolerance and hepatic autophagy imbalance as well as defective insulin signaling. Furthermore, treatment of mice with TNF receptor (TNFR)-1 blocking peptide-Fc, a TNFR1 blocking peptide-Fc fusion protein to competitively block the interaction of PGRN and TNFR1, resulted in the restoration of systemic insulin sensitivity and the recovery of autophagy and insulin signaling in liver. Consistent with these findings in vivo, we also observed that PGRN treatment induced defective autophagy and impaired insulin signaling in hepatocytes, with such effects being drastically nullified by the addition of TNFR1 blocking peptide -Fc or TNFR1-small interference RNA via the TNFR1-nuclear factor-κB-dependent manner, indicating the causative role of PGRN in hepatic insulin resistance. In conclusion, our findings supported the notion that PGRN is a key regulator of hepatic insulin resistance and that PGRN may mediate its effects, at least in part, by inducing defective autophagy via TNFR1/nuclear factor-κB.
Formation of Acyl and Dioxycarbene Ruthenium Complexes via Double C–S Bond Cleavage and CO Insertion
Authors: Santo Kiyokazu , Hirotsu Masakazu , Kawamoto Keisuke , Nishioka Takanori , Kinoshita Isamu
Published: February 2015

Ruthenium complexes containing an N,N,C,S-metalloligand or an N,N,C,O-organoligand with a sulfido carbonyl Ru cluster were obtained by the reaction of 6-(4′′-dibenzothienyl)-2,2′-bipyridine with [Ru3(CO)12]. The dibenzothienyl group undergoes double carbon–sulfur bond cleavage and CO insertion reactions to give a bridging acyl group and a metallacyclic dioxycarbene donor.
Surface Modification and Aggregation Control of Gold Nanoparticles via Multifunctional Stabilizer Based on Polyhedral Oligomeric Silsesquioxane
Authors: Imoto Hiroaki , Suzuki Shigeyoshi , Naka Kensuke
Published: February 2015

Octa(3-aminopropyl) polyhedral oligomeric silsesquioxane (POSS-NH2), adopting a rigid cubic structure, have been employed as a stabilizer for gold nanoparticles (AuNPs). The AuNPs possessing POSS-NH2 were stable enough to tolerate evaporation by incubating for 24 h after the preparation. Changing molar ratio of POSS-NH2 controlled the size of particle aggregates. In addition, the affinity of the AuNPs to organic solvents was changed via Michael addition with methyl acrylate to the amino groups on POSS-NH2. Redispersibility, aggregation control, and surface modification were successfully achieved with POSS-NH2 as a multifunctional single molecule.
Small molecules with antiviral activity against the Ebola virus
Authors: Litterman Nadia , Lipinski Christopher , Ekins Sean
Published: February 2015

The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.
The role of point of care testing in diabetes management
Authors: Meetoo Danny D , Wong Louise
Published: February 2015

Diabetes is a multi-system life-long metabolic disorder requiring complex management provided by health care professionals (HCPs) who are part of a multidisciplinary team. Comprehensive care of people with diabetes requires periodic testing of HbA1c. One approach of achieving this is through point-of-care-testing (POCT) or near patient testing, which is conducted outside of a centralised laboratory by clinical staff. POCT has the advantage of enabling clinical decisions during clinical encounters, optimising care, increasing satisfaction level and improving adherence to diabetes self-care activities. Educating the clinical staff and maintaining their competency levels, required for reliable test results, remain the cornerstones of a safe and efficient use of POCT. This article provides a brief overview of POCT and its role in the management of diabetes.
The barriers of stigma for service users: A critical realist viewpoint
Authors: Chidanyika Joe , McSherry Robert
Published: February 2015

Mental illness stigma presents significant barriers for service users to engage in meaningful civic participation, or to obtain or maintain work, subjecting them to systematic disadvantages in most facets of their lives. Evidence suggests that public attitudes towards mental health service users have not significantly improved over the past decades in spite of recent greater understanding about the causes of stigma. This article explores from a critical realist perspective, the central role of service users in challenging stigmatic attitudes to instigate a societal shift and bring parity of esteem between mental and physical health. The article articulates a salient recognition that service user experiences harnessed through the promotion of social contact with the wider community can help tackle stigma. A consideration of investing in the notions of co-production and the promotion of social capital is discussed in relation to the high cost of mental illnesses which not only are enumerated financially but also have higher personal and societal impact. The article concludes with a discussion regarding both the ethical and pragmatic importance of why service user involvement should not be tokenistic but rather service users have to be at the epicentre of any such a movement.
Addressing benzodiazepine dependence in substance misuse
Authors: Fernandez Jeff
Published: February 2015

Benzodiazepines dependency is a particular problem for GPs in primary care in the UK. Since the prevalence of prescribing drugs such as temezepam and diazepam was high in the 1970s and 1980s, this prescribing has led some people to become dependent on these medications. Since the establishment of drug services across the UK, there has been a focus to try and address this problem. However, in drug services most specialist centres are reluctant to try and treat this cohort of patient's—mainly because there is no clear funding for this provision. In Islington, London, the local primary care service has attempted to address this, and developed workable guidelines for drug services and primary care from national and local resources. This article explains the rationale and procedure to treat benzodiazepine dependence and the need for auditing this guideline to update and make it relevant for today's services in Islington. It is hoped this article shows the need to develop guidelines for treatment in this area, and the need to audit and update guidelines to make them applicable, therefore illustrating the fact it has a wider relevance then a localised study and should be viewed by a wider audience.
Mental illness and employment: Progress at last?
Authors: Gournay Kevin
Published: February 2015

BJMHN consultant editor Kevin Gournay discusses the findings of a new report highlighting health inequalities of employment outcomes
How to plan safe and enjoyable residential visits
Authors: Gibbons Ted
Published: February 2015

Ted Gibbons, a retired head teacher from Happisburgh, Norfolk, explains why residential visits should be part of a primary school year.
Who in their right mind would become a head?
Authors: Andrews Crispin
Published: February 2015

Crispin Andrews, a freelance education writer from Aylesbury, Bucks, reports on the head teacher recruitment crisis.
I was electrified by my first teaching experience
Authors: Ashworth Sherry
Published: February 2015

Sherry Ashworth speaks exclusively to Five to Eleven's editor, Catherine Lewis, about why teachers should be free to teach the English curriculum in the way they want to — a creative approach for children and their teachers.
Science facts and Venndiagrams
Authors: Dabell John
Published: February 2015

Sort gorilla facts mathematically. By John Dabell, maths co-ordinator at Derby High Junior School, Derby.
Just imagine your life as a gorilla
Authors: Redmond Ian
Published: February 2015

Use role-play based on facts to get under the skin of an endangered species. By Ian Redmond, an internationally renown naturalist and conservationist, based in Bristol.
New approach to key stage 1 SATs on trial
Authors: Bawden Jackie
Published: February 2015

Jackie Bawden, Director of Testing at the QCA, explains how the trials for a more flexible approach to testing at key stage 1 are working. If the evaluation this autumn is successful, then the system could be implemented nationally next year.
Teaching literacy: Where are we five years on?
Authors: Rhodes Liz
Published: February 2015

Has the National Literacy Strategy worked? Liz Rhodes assesses the evidence after five years and asks what has been gained.
History from the Norse Sagas
Authors: Eades Jenny
Published: February 2015

The Orkneyinga Saga follows the journeys of two Viking brothers in search of their sister, claiming new kingdoms as they travel over land and sea
Dance of the Planets
Authors: Brett Lindy , Noble Roger
Published: February 2015

Introduce the Solar System by getting children to act out ten years in the life of the Sun and planets, with each planet represented by a child positioned at the correct relative distance from the Sun. By Dr Lindy Brett and Roger Noble.
The aliens are coming to attack!
Authors: Andrews Crispin
Published: February 2015

Children will be witnesses to an alien invasion, writing reports and working together to analyse information as Crispin Andrews explores the science fiction genre.
Learning about democracy
Authors: Andrews Crispin
Published: February 2015

In preparing to play an active role as citizens, children will need to learn about democratic institutions and how decisions are taken and laws are made. Crispin Andrews explores some of the issues.
Educating The Whole Dyslexic
Authors: Rowlandson Julia
Published: February 2015

Dyslexia isn't just a case of struggling to read. A holistic approach to the condition reveals many ways of providing classroom support. By Julia Rowlandson, Education Director of Barrington Stoke Publishing, and formerly Deputy Head of More House School, Frensham
Discover the value of writing as therapy
Authors: Bolton Gillie
Published: February 2015

With time and space, writing allows children to explore thoughts and feelings in a safe environment. By Gillie Bolton, a senior research fellow in medicine and the arts, King's College London University
School is no place for collective worship
Authors: Rhodes Liz
Published: February 2015

Liz Rhodes claims that prescribed religion is outdated in the 21st century
Action rhymes for whole-brain learning
Authors: Freer Fiona
Published: February 2015

A lively literacy hour packed with rhyming sounds and seafaring adventure was the result when Devon-based teacher Fiona Freer used a book of clapping games with her class
Two weeks teaching in Kenya changed my life
Authors: Hart Vanessa
Published: February 2015

Vanessa Hart, a teacher at Hazeldown Primary School, Devon, describes some of the pleasures and problems of teaching in a developing country.
Statements for autism: An Ongoing Battle
Authors: Eades Jenny
Published: February 2015

The first of a series of three articles on autism considers the complex issue of statements for children with autistic spectrum disorders. By Jenny Eades, a special needs consultant and education writer and adviser.
Labels carry a price: Naming The Outsiders
Authors: Thornton Stephanie
Published: February 2015

Diagnosing children with special educational requirements and giving their condition a name can seem a good idea and can even be a relief to children and parents. But, Dr Thornton says, there are always consequences for the child.
Amazing African animal data
Authors: Dabell John
Published: February 2015

Use these superb African animal data cards designed for Five to Eleven by John Dabell, maths co-ordinator at Derby High Junior School, Derby.
Teaching assistants are proving to be invaluable
Authors: Eldridge Fiona
Published: February 2015

Fiona Eldridge, chairman of Teaching Personnel, Hertfordshire, looks at changes in the role of teaching assistants a year after the workload agreement.
Ten myths of autism A PARENT INVESTIGATES
Authors: Brett Lindy
Published: February 2015

The second of our series of three articles on autism considers 10 common myths associated with the disorder. By Dr Lindy Brett, Macclesfield, Cheshire.
Mediating policy-relevant evidence at speed: are systematic reviews of systematic reviews a useful approach?
Authors: Caird Jenny , Sutcliffe Katy , Kwan Irene , Dickson Kelly , Thomas James
Published: February 2015

When swift, accurate appraisal of evidence is required to inform policy concerning broad research questions, and budgetary constraints limit the employment of large research teams, researchers face a significant challenge which is sometimes met by reviewing existing systematic reviews. In this paper we highlight the challenges inherent in the reviews of reviews (RoR) method in order to advance understanding of this important tool for policy makers. Drawing on our experiences, we present, where possible, potential solutions to these challenges to demonstrate that RoRs, despite their limitations, can be useful for mediating policy-relevant evidence at speed.
The usefulness of different types of health research: perspectives from a low-income country
Authors: Burchett Helen ED , Mayhew Susannah H , Lavis John N , Dobrow Mark J
Published: February 2015

This article explores the perceived value of public health research and the types of research considered useful in Ghana. Sixty-nine decision makers, researchers and stakeholders were interviewed. A broad range of research was highly valued. Two traits were important: an applied, relevant topic and quickly produced findings. Interviewees valued research which explored implementation issues or identified and increased understanding of health problems. Effectiveness research often lacked these traits and was not generally considered as important because it was implicitly assumed that as long as interventions (that were based on a good understanding of the situation) were implemented well, they would be effective.