bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge of childhood burn risks and burn first aid: Cool Runnings
Authors: Burgess Jacqueline D , Watt Kerrianne A , Kimble Roy M , Cameron Cate M 
Published: February 2018

AimThe high incidence of hot beverage scalds among young children has not changed in the past 15 years, but preventive campaigns have been scarce. A novel approach was used to engage mothers of young children in an app-based hot beverage scald prevention campaign ‘Cool Runnings’. This paper provides baseline data for this randomised controlled trial (RCT).MethodQueensland-based mothers aged 18+ years with at least one child aged 5–12 months were recruited via social media to Cool Runnings, which is a two-group, parallel, single-blinded RCT.ResultsIn total, 498 participants from across Queensland completed the baseline questionnaire. The most common source of burn first aid information was the internet (79%). One-third (33%) correctly identified hot beverage scalds as the leading cause of childhood burns, 43% knew the age group most at risk. While 94% reported they would cool a burn with water, only 10% reported the recommended 20min duration. After adjusting for all relevant variables, there were two independent predictors of adequate burn first aid knowledge: first aid training in the past year (OR=3.32; 95% CI 1.8 to 6.1) and smoking status (OR=0.17; 95% CI 0.04 to 0.7).ConclusionIn this study, mothers of young children were largely unaware how frequently hot beverage scalds occur and the age group most susceptible to them. Inadequate burn first aid knowledge is prevalent across mothers of young children; there is an urgent and compelling need to improve burn first aid knowledge in this group. Given the high incidence of hot beverages scalds in children aged 6–24 months, it is important to target future burn prevention/first aid campaigns at parents of young children.Trial registration numberACTRN12616000019404; Pre-results.
Regimes of mini black hole abandoned to accretion
Authors: Paik Biplab 
Published: February 2018

Being inspired by the Eddington’s idea, along with other auxiliary arguments, it is unveiled that there exist regimes of a black hole that would prohibit accretion of ordinary energy. In explicit words, there exists a lower bound to black hole mass below which matter accretion process does not run for black holes. Not merely the baryonic matter, but, in regimes, also the massless photons could get prohibited from rushing into a black hole. However, unlike the baryon accretion abandoned black hole regime, the mass-regime of a black hole prohibiting accretion of radiation could vary along with its ambient temperature. For example, we discuss that earlier to [Formula: see text] s after the big-bang, as the cosmological temperature of the Universe grew above [Formula: see text] K, the mass range of black hole designating the radiation accretion abandoned regime, had to be in varying state being connected with the instantaneous age of the evolving Universe by an “one half” power law. It happens to be a fact that a black hole holding regimes prohibiting accretion of energy is gigantic by its size in comparison to the Planck length-scale. Hence the emergence of these regimes demands mini black holes for not being viable as profound suckers of energy. Consideration of accretion abandoned regimes could be crucial for constraining or judging the evolution of primordial black holes over the age of the Universe.
Transcription factor GATA6: a novel marker and putative inducer of ductal metaplasia in biliary atresia
Authors: Soini Tea , Pihlajoki Marjut , Andersson Noora , Lohi Jouko , Huppert Kari A. , Rudnick David A. , Huppert Stacey S. , Wilson David B. , Pakarinen Mikko P. , Heikinheimo Markku 
Published: February 2018

Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive liver fibrosis. To gain insights into the pathophysiology of BA, we focused attention on GATA6, a transcription factor implicated in biliary development. Early in fetal development GATA6 expression is evident in cholangiocytes and hepatocytes, but by late gestation it is extinguished in hepatocytes. Utilizing a unique set of BA liver samples collected before and after successful portoenterostomy (PE), we found that GATA6 expression is markedly upregulated in hepatocytes of patients with BA compared with healthy and cholestatic disease controls. This upregulation is recapitulated in two murine models simulating bile duct obstruction and intrahepatic bile ductule expansion. GATA6 expression in BA livers correlates with two established negative prognostic indicators (age at PE, degree of intrahepatic bile ductule expansion) and decreases after normalization of serum bilirubin by PE. GATA6 expression in BA livers correlates with expression of known regulators of cholangiocyte differentiation ( JAGGED1, HNF1β, and HNF6). These same genes are upregulated after enforced expression of GATA6 in human hepatocyte cell models. In conclusion, GATA6 is a novel marker and a putative driver of hepatocyte-cholangiocyte metaplasia in BA, and its expression in hepatocytes is downregulated after successful PE.NEW & NOTEWORTHY A pathological hallmark in the liver of patients with biliary atresia is ductular reaction, an expansion of new bile ductules that are thought to arise from conversion of mature hepatocytes. Here, we show that transcription factor GATA6 is a marker and potential driver of hepatocyte ductal metaplasia in biliary atresia. Hepatocyte GATA6 expression is elevated in biliary atresia, correlates with bile duct expansion, and decreases after successful portoenterostomy.
Effect of dietary arachidonic acid supplementation on acute muscle adaptive responses to resistance exercise in trained men: a randomized controlled trial
Authors: Mitchell Cameron J. , D'Souza Randall F. , Figueiredo Vandre C. , Chan Alex , Aasen Kirsten , Durainayagam Brenan , Mitchell Sarah , Sinclair Andrew J. , Egner Ingrid M. , Raastad Truls , Cameron-Smith David , Markworth James F. 
Published: February 2018

Arachidonic acid (ARA), a polyunsaturated ω-6 fatty acid, acts as precursor to a number of prostaglandins with potential roles in muscle anabolism. It was hypothesized that ARA supplementation might enhance the early anabolic response to resistance exercise (RE) by increasing muscle protein synthesis (MPS) via mammalian target of rapamycin (mTOR) pathway activation and/or the late anabolic response by modulating ribosome biogenesis and satellite cell expansion. Nineteen men with ≥1 yr of resistance-training experience were randomized to consume either 1.5 g daily ARA or a corn-soy-oil placebo in a double-blind manner for 4 wk. Participants then undertook fasted RE (8 sets each of leg press and extension at 80% 1-repetition maximum), with vastus lateralis biopsies obtained before exercise, immediately postexercise, and at 2, 4, and 48 h of recovery. MPS (measured via stable isotope infusion) was not different between groups ( P = 0.212) over the 4-h recovery period. mTOR pathway members p70 S6 kinase and S6 ribosomal protein were phosphorylated postexercise ( P < 0.05), with no difference between groups. 45S preribosomal RNA increased 48 h after exercise only in ARA ( P = 0.012). Neural cell adhesion molecule-positive satellite cells per fiber increased 48 h after exercise ( P = 0.013), with no difference between groups ( P = 0.331). Prior ARA supplementation did not alter the acute anabolic response to RE in previously resistance-trained men; however, at 48 h of recovery, ribosome biogenesis was stimulated only in the ARA group. The findings do not support a mechanistic link between ARA and short-term anabolism, but ARA supplementation in conjunction with resistance training may stimulate increases in translational capacity.NEW & NOTEWORTHY Four weeks of daily arachidonic acid supplementation in trained men did not alter their acute muscle protein synthetic or anabolic signaling response to resistance exercise. However, 48 h after exercise, men supplemented with arachidonic acid showed greater ribosome biogenesis and a trend toward greater change in satellite cell content. Chronic arachidonic acid supplementation does not appear to regulate the acute anabolic response to resistance exercise but may augment muscle adaptation in the following days of recovery.
Overcoming Resistance to DNA-Targeted Agents by Epigenetic Activation of Schlafen 11 (SLFN11) Expression with Class I Histone Deacetylase Inhibitors
Authors: Tang Sai-Wen , Thomas Anish , Murai Junko , Trepel Jane B. , Bates Susan E. , Rajapakse Vinodh N. , Pommier Yves 
Published: February 2018

Abstract
Purpose: Schlafen 11 (SLFN11), a putative DNA/RNA helicase is a dominant genomic determinant of response to DNA-damaging agents and is frequently not expressed in cancer cells. Whether histone deacetylase (HDAC) inhibitors can be used to release SLFN11 and sensitize SLFN11-inactivated cancers to DNA-targeted agents is tested here.
Experimental Design: SLFN11 expression was examined in The Cancer Genome Atlas (TCGA), in cancer cell line databases and in patients treated with romidepsin. Isogenic cells overexpressing or genetically inactivated for SLFN11 were used to investigate the effect of HDAC inhibitors on SLFN11 expression and sensitivity to DNA-damaging agents.
Results: SLFN11 expression is suppressed in a broad fraction of common cancers and cancer cell lines. In cancer cells not expressing SLFN11, transfection of SLFN11 sensitized the cells to camptothecin, topotecan, hydroxyurea, and cisplatin but not to paclitaxel. SLFN11 mRNA and protein levels were strongly induced by class I (romidepsin, entinostat), but not class II (roclinostat) HDAC inhibitors in a broad panel of cancer cells. SLFN11 expression was also enhanced in peripheral blood mononuclear cells of patients with circulating cutaneous T-cell lymphoma treated with romidepsin. Consistent with the epigenetic regulation of SLFN11, camptothecin and class I HDAC inhibitors were synergistic in many of the cell lines tested.
Conclusions: This study reports the prevalent epigenetic regulation of SLFN11 and the dominant stimulatory effect of HDAC inhibitors on SLFN11 expression. Our results provide a rationale for combining class I HDAC inhibitors and DNA-damaging agents to overcome epigenetic inactivation of SLFN11-mediated resistance to DNA-targeted agents. Clin Cancer Res; 24(8); 1944–53. ©2018 AACR.
HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target
Authors: Fok Jacqueline H.L. , Hedayat Somaieh , Zhang Lei , Aronson Lauren I. , Mirabella Fabio , Pawlyn Charlotte , Bright Michael D. , Wardell Christopher P. , Keats Jonathan J. , De Billy Emmanuel , Rye Carl S. , Chessum Nicola E.A. , Jones Keith , Morgan Gareth J. , Eccles Suzanne A. , Workman Paul , Davies Faith E. 
Published: February 2018

AbstractPurpose: Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) was an attractive therapeutic target for myeloma due to its direct regulation of transcriptional programs implicated in both protein homeostasis and the oncogenic phenotype. Here, we interrogate HSF1 as a therapeutic target in myeloma using bioinformatic, genetic, and pharmacologic means.Experimental Design: To assess the clinical relevance of HSF1, we analyzed publicly available patient myeloma gene expression datasets. Validation of this novel target was conducted in in vitro experiments using shRNA or inhibitors of the HSF1 pathway in human myeloma cell lines and primary cells as well as in in vivo human myeloma xenograft models.Results: Expression of HSF1 and its target genes were associated with poorer myeloma patient survival. ShRNA-mediated knockdown or pharmacologic inhibition of the HSF1 pathway with a novel chemical probe, CCT251236, or with KRIBB11, led to caspase-mediated cell death that was associated with an increase in EIF2α phosphorylation, CHOP expression and a decrease in overall protein synthesis. Importantly, both CCT251236 and KRIBB11 induced cytotoxicity in human myeloma cell lines and patient-derived primary myeloma cells with a therapeutic window over normal cells. Pharmacologic inhibition induced tumor growth inhibition and was well-tolerated in a human myeloma xenograft murine model with evidence of pharmacodynamic biomarker modulation.Conclusions: Taken together, our studies demonstrate the dependence of myeloma cells on HSF1 for survival and support the clinical evaluation of pharmacologic inhibitors of the HSF1 pathway in myeloma. Clin Cancer Res; 24(10); 2395–407. ©2018 AACR.See related commentary by Parekh, p. 2237
NK Cell–Specific CDK8 Deletion Enhances Antitumor Responses
Authors: Witalisz-Siepracka Agnieszka , Gotthardt Dagmar , Prchal-Murphy Michaela , Didara Zrinka , Menzl Ingeborg , Prinz Daniela , Edlinger Leo , Putz Eva Maria , Sexl Veronika 
Published: February 2018

AbstractCyclin-dependent kinase 8 (CDK8) is a member of the transcription-regulating CDK family. CDK8 activates or represses transcription by associating with the mediator complex or by regulating transcription factors. Oncogenic activity of CDK8 has been demonstrated in several cancer types. Targeting CDK8 represents a potential therapeutic strategy. Because knockdown of CDK8 in a natural killer (NK) cell line enhances cytotoxicity and NK cells provide the first line of immune defense against transformed cells, we asked whether inhibiting CDK8 would improve NK-cell antitumor responses. In this study, we investigated the role of CDK8 in NK-cell function in vivo using mice with conditional ablation of CDK8 in NKp46+ cells (Cdk8fl/flNcr1Cre). Regardless of CDK8 expression, NK cells develop and mature normally in bone marrow and spleen. However, CDK8 deletion increased expression of the lytic molecule perforin, which correlated with enhanced NK-cell cytotoxicity in vitro. This translates into improved NK cell–mediated tumor surveillance in vivo in three independent models: B16F10 melanoma, v-abl+ lymphoma, and a slowly developing oncogene-driven leukemia. Our results thereby define a suppressive effect of CDK8 on NK-cell activity. Therapies that target CDK8 in cancer patients may enhance NK-cell responses against tumor cells. Cancer Immunol Res; 6(4); 458–66. ©2018 AACR.
Correlation of Fecal Markers with Magnifying Endoscopic Stratification in Patients with Ulcerative Colitis Who Are in Clinical Remission
Authors: Mine Shoichiro , Takeshima Fuminao , Akazawa Yuko , Matsushima Kayoko , Minami Hitomi , Yamaguchi Naoyuki , Ohnita Ken , Isomoto Hajime , Nakao Kazuhiko 
Published: February 2018

Background: Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored. Summary: This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman’s correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission.
Restless Legs Syndrome: An Unresolved Uremic Disorder after Renal Transplantation
Authors: Calviño Jesús , Cigarrán Secundino , Gonzalez-Tabares Lourdes , Guijarro Monica , Millán Beatriz , Cobelo Carmen , Cillero Sonia , Sobrido María-Jesús 
Published: February 2018

<b><i>Background:</i></b> Restless legs syndrome (RLS) is a common complication of uremia that may improve after transplantation. Its frequency might not be as low as expected, as some uremic disturbances may continue even after a successful graft. Our aim was to investigate the prevalence and related conditions for RLS in renal transplant patients. <b><i>Methods:</i></b> We carried out a cross-sectional, observational study. A self-administered questionnaire following the International Restless Legs Syndrome Study Group diagnostic criteria was administered to 129 patients (82 men and 47 women) aged 57 ± 12.8 years followed up for at least 1 year, with stable renal function (Cr 1.5 ± 0.54 mg/dL). Patients with probable RLS according to the screening questionnaire underwent comprehensive neurological examination to exclude RLS mimics. <b><i>Results:</i></b> The frequency of RLS according to questionnaires was 29.5% (18 men/20 women). After neurological exam, RLS was confirmed in 19 patients providing an overall frequency of 14.8% (higher than the prevalence in the general population). A definitive diagnosis of RLS was established for 6 men (7.3%) and 13 women (27.7%), indicating a positive predictive value for the screening questionnaire of 65% for women and 33% for men. There were fewer patients under renin-angiotensin aldosterone system (RAAS) blocking treatment in the RLS group (21.1 vs. 47.3%). Women with RLS had poorer renal function (52 ± 17.5 vs. 42 ± 13.9 mL/min) and phosphate-reabsorption rate (75 ± 10.5 vs. 65 ± 9.2). There was no difference in age, comorbidities, anticalcineurin therapy, renal function, anemia and time since transplantation between transplant patients with and without RLS. <b><i>Conclusion:</i></b> The prevalence of RLS after transplantation remains high (14.8%). This condition is twice more prevalent for females. Contribution of RAAS, graft function and phosphate overload requires further investigation.
РОЛЬ МЕДИЧНОЇ СЕСТРИ У НАВЧАННІ ХВОРИХ ПО ДОГЛЯДУ ЗА ДІАБЕТИЧНИМИ СТОПАМИ
Authors: Berkela I. O. , Naumova L. V. 
Published: February 2018

У статті наведено дані щодо необхідності проведення навчання хворих із діабетичною стопою з метою кращої компенсації цукрового діабету. Доведено, що правильний догляд за стопами дозволяє сповільнити прогресування мікросудинних уражень при цукровому діабеті та скоротити час перебування пацієнта в стаціонарі.
Distinct Pathogenesis of Pancreatic Cancer Microvesicle–Associated Venous Thrombosis Identifies New Antithrombotic Targets In Vivo
Authors: Stark Konstantin , Schubert Irene , Joshi Urjita , Kilani Badr , Hoseinpour Parandis , Thakur Manovriti , Grünauer Petra , Pfeiler Susanne , Schmidergall Tobias , Stockhausen Sven , Bäumer Markus , Chandraratne Sue , von Brühl Marie-Luise , Lorenz Michael , Coletti Raffaele , Reese Sven , Laitinen Iina , Wörmann Sonja Maria , Algül Hana , Bruns Christiane J. , Ware Jerry , Mackman Nigel , Engelmann Bernd , Massberg Steffen 
Published: February 2018

Objective—
Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT.

Approach and Results—
Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT. We show that microvesicles released by pancreatic adenocarcinoma cells (pancreatic tumor–derived microvesicles [pcMV]) boost thrombus formation in a model of flow restriction of the mouse vena cava. This depends on the synergistic activation of coagulation by pcMV and host tissue factor. Unlike nonmalignant DVT, which is initiated and propagated by innate immune cells, thrombosis triggered by pcMV was largely independent of myeloid leukocytes or platelets. Instead, we identified externalization of the phospholipid phosphatidylethanolamine as a major mechanism controlling the prothrombotic activity of pcMV. Disrupting phosphatidylethanolamine-dependent activation of factor X suppressed pcMV-induced DVT without causing changes in hemostasis.

Conclusions—
Together, we show here that the pathophysiology of pcMV-associated experimental DVT differs markedly from innate immune cell–promoted nonmalignant DVT and is therefore amenable to distinct antithrombotic strategies. Targeting phosphatidylethanolamine on tumor microvesicles could be a new strategy for prevention of cancer-associated DVT without causing bleeding complications.
Anticoagulant Protein S Targets the Factor IXa Heparin-Binding Exosite to Prevent Thrombosis
Authors: Plautz William E. , Sekhar Pilli Vijaya Satish , Cooley Brian C. , Chattopadhyay Rima , Westmark Pamela R. , Getz Todd , Paul David , Bergmeier Wolfgang , Sheehan John P. , Majumder Rinku 
Published: February 2018

Objective—
PS (protein S) is a plasma protein that directly inhibits the coagulation FIXa (factor IXa) in vitro. Because elevated FIXa is associated with increased risk of venous thromboembolism, it is important to establish how PS inhibits FIXa function in vivo. The goal of this study is to confirm direct binding of PS with FIXa in vivo, identify FIXa amino acid residues required for binding PS in vivo, and use an enzymatically active FIXa mutant that is unable to bind PS to measure the significance of PS–FIXa interaction in hemostasis.

Approach and Results—
We demonstrate that PS inhibits FIXa in vivo by associating with the FIXa heparin-binding exosite. We used fluorescence tagging, immunohistochemistry, and protein–protein crosslinking to show in vivo interaction between FIXa and PS. Importantly, platelet colocalization required a direct interaction between the 2 proteins. FIXa and PS also coimmunoprecipitated from plasma, substantiating their interaction in a physiological milieu. PS binding to FIXa and PS inhibition of the intrinsic Xase complex required residues K132, K126, and R170 in the FIXa heparin-binding exosite. A double mutant, K132A/R170A, retained full activity but could not bind to PS. Crucially, Hemophilia B mice infused with FIXa K132A/R170A displayed an accelerated rate of fibrin clot formation compared with wild-type FIXa.

Conclusions—
Our findings establish PS as an important in vivo inhibitor of FIXa. Disruption of the interaction between PS and FIXa causes an increased rate of thrombus formation in mice. This newly discovered function of PS implies an unexploited target for antithrombotic therapeutics.