bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and long-term outcomes of adult patients with diabetic ketoacidosis admitted to intensive care: A retrospective cohort study
Authors: Ramaesh Aksha 
Published: April 2016

Aims Diabetic ketoacidosis is a life-threatening but avoidable complication of diabetes mellitus often managed in intensive care units. The risk of emergency hospital readmission in patients surviving an intensive care unit episode of diabetic ketoacidosis is unknown. We aimed to report the cumulative incidence of emergency hospital readmission and costs in all patients surviving an intensive care unit episode of diabetic ketoacidosis in Scotland. Methods We used a national six-year cohort of survivors of first diabetic ketoacidosis admissions to Scottish intensive care units (1 January 2005–31 December 2010) identified in the Scottish Intensive Care Society Audit Group registry linked to acute hospital and death records (follow-up censored 31 December 2010). Diabetic ketoacidosis-related emergency readmissions were identified using International Classification of Disease-10 codes. Results During the study period, 386 patients were admitted to intensive care units in Scotland with diabetic ketoacidosis (admission rate 1.5/100,000 Scottish population). Median age was 44 (IQR 29–56); 51% male; 55% required no organ support on admission. Mortality after intensive care unit admission was 8% at 30 days, 18% at one year, and 35% at five years. A total of 349 patients survived their first intensive care unit diabetic ketoacidosis admission [mean (SD) age 42.5 (18.1) years; 50.4% women; 46.1% required ≥1 organ support]. Following hospital discharge, cumulative incidence of 90-day, one-year, and five-year diabetic ketoacidosis readmission (all-cause readmission) was 13.8% (31.8%), 29.7% (58.9%) and 46.4% (82.6%). Discussion Diabetic ketoacidosis in patients requiring intensive care unit admission is associated with high risk of long-term mortality and high hospital costs. An understanding of the precipitating causes of diabetic ketoacidosis in patients admitted to intensive care units may allow patients who are at high risk to be targeted, potentially reducing future morbidity and the substantial burden that diabetic ketoacidosis currently places on the healthcare system.
Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma
Authors: Rodriguez Gregor A. , Shah Ashish H. , Gersey Zachary C. , Shah Sumedh S. , Bregy Amade , Komotar Ricardo J. , Graham Regina M. 
Published: April 2016

Objectives: Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent. Methods: Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups. Conclusions: Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials.
Medical management of gastrinoma in a cat
Authors: Lane Michael , Larson Jeanne , Hecht Silke , Tolbert M Katherine 
Published: April 2016

Case summary A 7-year-old male castrated domestic short-haired cat was evaluated for a 4 week history of intermittent vomiting, ptyalism, lethargy and weight loss. Serum biochemistry revealed mild mixed hepatopathy. Abdominal ultrasonography identified multiple heterogeneous hepatic masses and a linear, hyperechoic focus with associated reverberation artifact in the wall of the stomach consistent with a gastric ulcer. Serum gastrin concentrations were markedly increased. Cytologic interpretation of a fine-needle aspirate of the hepatic masses was consistent with neuroendocrine neoplasia, and a diagnosis of gastrinoma was established. Deterioration of the cat’s condition, despite at-home acid-suppressant therapy, led to hospitalization. The cat was initially stabilized with intravenous crystalloid fluid therapy, maropitant, pantoprazole and octreotide. A continuous radiotelemetric intragastric pH monitoring system was used to monitor the response of intragastric pH to therapy. Long-term therapy was continued with omeprazole (orally q12h), octreotide (subcutaneously q8h) and thrice-weekly toceranib administered orally. Toceranib therapy led to gastrointestinal upset and was discontinued. Gastric ulceration resolved within 8 weeks, and palliation of clinical signs was achieved for approximately 5 months. Relevance and novel information Including this report, only six cases of feline gastrinoma have been reported in the veterinary literature. Little is known regarding non-surgical therapy, and octreotide has not been previously reported for medical management of feline gastrinoma. Results of intragastric pH monitoring and clinical improvement suggest that medical therapy using octreotide and proton pump inhibitors represents a novel therapeutic option for cats with gastrinoma where surgical excision is not feasible.
Digital Imaging Capability for Caries Detection
Authors: Winand C. , Shetty A. , Senior A. , Ganatra S. , De Luca Canto G. , Alsufyani N. , Flores-Mir C. , Pachêco-Pereira C. 
Published: April 2016

The objective of this study was to identify the diagnostic capability of photostimulable phosphor plates (PSPs) and direct digital sensors (DDSs) in the detection of interproximal caries. Studies were identified that evaluated the diagnostic capability of PSPs and DDSs in detecting interproximal caries in human teeth, in both dentin and enamel. Histologic sections were the gold standard. This systematic review searched several electronic databases. In addition, Google Scholar and reference lists of the finally included studies were screened. QUADAS-2 was applied to evaluate the risk of bias among included studies. Six studies were finally included; 4 of which were considered homogeneous enough to conduct a meta-analysis. The meta-analysis evaluated 668 interproximal human tooth surfaces. All studies used extracted human teeth ranging from no caries present to caries into dentin. Each tooth was radiographed by both PSP and DDS technologies and then submitted for histologic analysis as the gold standard. Meta-analysis showed that intraoral digital imaging is of high specificity but low sensitivity in the detection of interproximal caries. The sensitivity and specificity for different studies with PSPs varied substantially from 15% to 54% and from 84% to 100%, respectively. Direct sensor analysis sensitivity and specificity ranged from 16% to 56% and from 90% to 100%, respectively. Newer PSP and DDS technologies had statistically significant higher sensitivities, yet the differences in diagnostic capabilities between the older and newer technologies were clinically insignificant. Both digital systems were excellent in identifying surfaces without caries (specificity) but were not sensitive enough to reliably identify interproximal surfaces with caries. Clinicians must therefore remain vigilant in performing a careful clinical examination and other diagnostic tests rather than relying solely on radiographic imaging to diagnose interproximal caries. Knowledge Transfer Statement: This study will help clinicians make an evidence-based decision when deciding which digital radiography system to use when evaluating interproximal caries. Time, patient radiation safety, cost, and image quality are factors to be considered. The performance of the different available digital imaging systems was compared with the current gold standard—a histologic analysis—via meta-analysis.
A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells
Authors: Wang Xiaoli , Haylock David , Hu Cing Siang , Kowalczyk Wioleta , Jiang Tianbo , Qiu Jiajing , Mosoyan Goar , He Wu , Marshall Netonia , Mascarenhas John , Tarasova Anna , Brody Joshua , Winkler David , Hoffman Ronald 
Published: April 2016

Key Points
Treatment of MF CD34+ cells with a TPO receptor antagonist selectively depletes MF HSCs and HPCs. Agents that target the TPO receptor represent potentially new approaches for the treatment of MF patients.
Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype
Authors: Toubiana Julie , Okada Satoshi , Hiller Julia , Oleastro Matias , Lagos Gomez Macarena , Aldave Becerra Juan Carlos , Ouachée-Chardin Marie , Fouyssac Fanny , Girisha Katta Mohan , Etzioni Amos , Van Montfrans Joris , Camcioglu Yildiz , Kerns Leigh Ann , Belohradsky Bernd , Blanche Stéphane , Bousfiha Aziz , Rodriguez-Gallego Carlos , Meyts Isabelle , Kisand Kai , Reichenbach Janine , Renner Ellen D. , Rosenzweig Sergio , Grimbacher Bodo , van de Veerdonk Frank L. , Traidl-Hoffmann Claudia , Picard Capucine , Marodi Laszlo , Morio Tomohiro , Kobayashi Masao , Lilic Desa , Milner Joshua D. , Holland Steven , Casanova Jean-Laurent , Puel Anne 
Published: April 2016

Key Points
AD STAT1 GOF is the most common genetic cause of inherited CMC and is not restricted to a specific age or ethnic group. STAT1 GOF underlies a variety of infectious and autoimmune features, as well as carcinomas and aneurysms associated with a poor outcome.
Matriptase activation connects tissue factor–dependent coagulation initiation to epithelial proteolysis and signaling
Authors: Le Gall Sylvain M. , Szabo Roman , Lee Melody , Kirchhofer Daniel , Craik Charles S. , Bugge Thomas H. , Camerer Eric 
Published: April 2016

Abstract
The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.
How I treat patients with a history of heparin-induced thrombocytopenia
Authors: Warkentin Theodore E. , Anderson Julia A. M. 
Published: April 2016

Abstract
Heparin-induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse drug reaction of unusual pathogenesis that features platelet-activating immunoglobulin G antibodies. The HIT immune response is remarkably transient, with heparin-dependent antibodies no longer detectable 40 to 100 days (median) after an episode of HIT, depending on the assay performed. Moreover, the minimum interval from an immunizing heparin exposure to the development of HIT is 5 days irrespective of the patient’s previous heparin exposure status or history of HIT. This means that short-term heparin reexposure can be safely performed if platelet-activating antibodies are no longer detectable at reexposure baseline and is recommended when heparin is the clear anticoagulant of choice, such as for cardiac or vascular surgery. The risk of recurrent HIT 1 to 2 weeks after heparin reexposure is ∼2% to 5% and is attributable to formation of delayed-onset (or autoimmune-like) HIT antibodies that activate platelets even in the absence of pharmacologic heparin. Some studies suggest that longer-term heparin reexposure (eg, for chronic hemodialysis) may also be reasonable. However, for other antithrombotic indications that involve patients with a history of HIT (eg, treatment of venous thromboembolism or acute coronary syndrome), preference should be given to non-heparin agents such as fondaparinux, danaparoid, argatroban, bivalirudin, or one of the new direct-acting oral anticoagulants as appropriate.
Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study
Authors: de Rooij Jasmijn D. E. , Masetti Riccardo , van den Heuvel-Eibrink Marry M. , Cayuela Jean-Michel , Trka Jan , Reinhardt Dirk , Rasche Mareike , Sonneveld Edwin , Alonzo Todd A. , Fornerod Maarten , Zimmermann Martin , Pigazzi Martina , Pieters Rob , Meshinchi Soheil , Zwaan C. Michel , Locatelli Franco 
Published: April 2016

Key Points
NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearrangements, and monosomy 7 are associated with poor outcome; RBM15/MKL1 and others fare better. Screening for NUP98/KDM5A, RBM15/MKL1, CBFA2T3/GLIS2, and KMT2A rearrangements combined with conventional karyotyping is advisable.
Sequence-based prediction of protein-protein interactions using weighted sparse representation model combined with global encoding
Authors: Huang Yu-An , You Zhu-Hong , Chen Xing , Chan Keith , Luo Xin 
Published: April 2016

Abstract
Background
Proteins are the important molecules which participate in virtually every aspect of cellular function within an organism in pairs. Although high-throughput technologies have generated considerable protein-protein interactions (PPIs) data for various species, the processes of experimental methods are both time-consuming and expensive. In addition, they are usually associated with high rates of both false positive and false negative results. Accordingly, a number of computational approaches have been developed to effectively and accurately predict protein interactions. However, most of these methods typically perform worse when other biological data sources (e.g., protein structure information, protein domains, or gene neighborhoods information) are not available. Therefore, it is very urgent to develop effective computational methods for prediction of PPIs solely using protein sequence information.

Results
In this study, we present a novel computational model combining weighted sparse representation based classifier (WSRC) and global encoding (GE) of amino acid sequence. Two kinds of protein descriptors, composition and transition, are extracted for representing each protein sequence. On the basis of such a feature representation, novel weighted sparse representation based classifier is introduced to predict protein interaction class. When the proposed method was evaluated with the PPIs data of S. cerevisiae, Human and H. pylori, it achieved high prediction accuracies of 96.82, 97.66 and 92.83 % respectively. Extensive experiments were performed for cross-species PPIs prediction and the prediction accuracies were also very promising.

Conclusions
To further evaluate the performance of the proposed method, we then compared its performance with the method based on support vector machine (SVM). The results show that the proposed method achieved a significant improvement. Thus, the proposed method is a very efficient method to predict PPIs and may be a useful supplementary tool for future proteomics studies.
Comparative effectiveness of β-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia
Authors: Wong Davie , Wong Titus , Romney Marc , Leung Victor 
Published: April 2016

Abstract
Background
Vancomycin may be inferior to β-lactams for the empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We compared empiric β-lactams to vancomycin to assess clinical outcomes in patients with MSSA bacteremia.

Methods
We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric β-lactam with or without vancomycin or vancomycin monotherapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, duration of bacteremia, and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression.

Results
Of 669 patients identified, 255 met inclusion criteria (β-lactam = 131, vancomycin = 124). Overall 28-day mortality was 7.06 % (n = 18). There were more cases of infective endocarditis in the β-lactam than in the vancomycin group [24 (18.3 %) vs 12 (9.7 %), p = 0.05]. Adjusted mortality at 28 days was similar between the two groups (OR 0.85; 95 % CI 0.27–2.67). The duration of bacteremia was longer in the vancomycin group (97.1 vs 70.7 h, p = 0.007). Transition to cloxacillin or cefazolin occurred within a median of 68.3 h in the vancomycin group.

Conclusions
Empiric β-lactams was associated with earlier clearance of bacteremia by a median of 1 day compared to vancomycin. Future prospective studies are needed to confirm our findings.
Foot health education provision for people with rheumatoid arthritis–an online survey of UK podiatrists' perceptions
Authors: Graham Andrea S , Williams Anita E 
Published: April 2016

AbstractBackgroundPatient education supports general disease self‐management and in relation to foot problems, it is recommended as a key intervention for people with rheumatoid arthritis (RA). Further, it is known what the foot health educational (FHE) needs are in relation to their experiences of foot problems. Podiatrists are the key health professionals who provide the management of RA‐related foot pathology and this includes the delivery of FHE. However, we do not know what is currently provided and what podiatrists' perceptions are of this intervention. It is possible that there is a difference between what is provided and what patients need in order to maximise their foot health benefits and hence this may contribute to the persistence of foot problems and symptoms. This study primarily aims to define what UK podiatrists' perceptions of FHE are in relation to; what is delivered, how it is delivered, and the timing of its delivery, in the context of its' accessibility. The secondary aim is to identify any influence of the participants' gender, age and duration of professional qualification on their responses.MethodAn online survey of UK HCPC registered podiatrists was used to capture quantitative data in relation to the perceived; aims, content, methods and effectiveness, timing and barriers to FHE provision to people with RA. Data was analysed to assess significant associations between the participant responses and their gender, age and duration of professional qualification. Free text comments were analysed using thematic analysis.Results43 podiatrists across the UK completed the survey. The majority of participants stated that, they provided FHE and agreed with its overall aims. The most common methods of delivery that were perceived to be most effective were: verbal, written and website based information. The best times at which to deliver FHE were thought to be at the point of diagnosis of RA and at any available opportunity of health care delivery. The majority of participants thought they had enough knowledge and access to information resources to effectively deliver FHE, but half of the participants felt that consultation duration limited their ability to do so. Gender and duration of professional qualification influenced participants' perceptions of FHE.ConclusionThe importance and content of FHE for people with RA has been defined, but time limitations are seen to restrict its delivery. The development of an education needs analysis tool to facilitate efficient identification of patients FHE needs could enable timely and tailored delivery of FHE to people with RA.
The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ
Authors: Kubosch Eva Johanna , Heidt Emanuel , Bernstein Anke , Böttiger Katharina , Schmal Hagen 
Published: April 2016

Abstract
Background
Synovial mesenchymal stem cells (SMSC) possess a high chondrogenic differentiation potential, which possibly supports natural and surgically induced healing of cartilage lesions. We hypothesized enhanced chondrogenesis of SMSC caused by the vicinity of chondrocytes (CHDR).

Methods
Human SMSC and CHDR interactions were investigated in an in-vitro trans-well monolayer coculture over a time period of up to 21 days. Protein expression was analyzed using histology, immunostaining, or enzyme-linked immunosorbent assay. Additionally, mRNA expression was assessed by quantitative PCR.

Results
After 7 days, phase-contrast microscopy revealed cell aggregation of SMSC in coculture with CHDR. Afterwards, cells formed spheres and lost adherence. However, this phenomenon was not observed when culturing SMSC alone. Fluorescence labeling showed concurrent collagen type II expression. Addition of transforming growth factor beta (TGFβ) to the cocultures induced SMSC aggregation in less time and with higher intensity. Additionally, alcian blue staining demonstrated enhanced glycosaminoglycan expression around SMSC aggregates after 1 and 2 weeks. Although TGFβ mRNA was expressed in all SMSC, the protein was measured with constantly increasing levels over 21 days only in supernatants of the cocultures. Considering the enhanced mRNA levels following supplementation with TGFβ, a positive feedback mechanism can be supposed. In line with the development of a chondrogenic phenotype, aggrecan mRNA expression increased after 7 and 14 days in the cocultures with and without TGFβ. Coculture conditions also amplified collagen type II mRNA expression after 2 weeks without and already after 1 week with TGFβ. There was no difference in collagen type I and type X expression between SMSC alone and the coculture with CHDR. Expression of both collagens increased following addition of TGFβ. mRNA data correlated with the intensity of immunofluorescence staining.

Conclusions
Paracrine effects of CHDR induce a chondrogenic phenotype in SMSC possibly mimicking joint homeostasis. Coculture approaches may lead to a better understanding of cellular interactions with potential implications for cartilage repair procedures.