bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of health services in the last year of life and cause of death in people with intellectual disability: a retrospective matched cohort study
Authors: Brameld Kate , Spilsbury Katrina , Rosenwax Lorna , Leonard Helen , Semmens James 
Published: February 2018

ObjectiveTo describe the cause of death together with emergency department presentations and hospital admissions in the last year of life of people with intellectual disability.MethodA retrospective matched cohort study using de-identified linked data of people aged 20 years or over, with and without intellectual disability who died during 2009 to 2013 in Western Australia. Emergency department presentations and hospital admissions in the last year of life of people with intellectual disability are described along with cause of death.ResultsOf the 63 508 deaths in Western Australia from 2009 to 2013, there were 591 (0.93%) decedents with a history of intellectual disability. Decedents with intellectual disability tended to be younger, lived in areas of more social disadvantage, did not have a partner and were Australian born compared with all other decedents. A matched comparison cohort of decedents without intellectual disability (n=29 713) was identified from the general population to improve covariate balance.Decedents with intellectual disability attended emergency departments more frequently than the matched cohort (mean visits 3.2 vs 2.5) and on average were admitted to hospital less frequently (mean admissions 4.1 vs 6.1), but once admitted stayed longer (average length of stay 5.2 days vs 4.3 days). People with intellectual disability had increased odds of presentation, admission or death from conditions that have been defined as ambulatory care sensitive and are potentially preventable. These included vaccine-preventable respiratory disease, asthma, cellulitis and convulsions and epilepsy.ConclusionPeople with intellectual disability were more likely to experience potentially preventable conditions at the end of their lives. This indicates a need for further improvements in access, quality and coordination of healthcare to provide optimal health for this group.
Telepresent mechanical ventilation training versus traditional instruction: a simulation-based pilot study
Authors: Ciullo Anna , Yee Jennifer , Frey Jennifer A , Gothard M David , Benner Alma , Hammond Jared , Ballas Derek , Ahmed Rami A 
Published: February 2018

BackgroundMechanical ventilation is a complex topic that requires an in-depth understanding of the cardiopulmonary system, its associated pathophysiology and comprehensive knowledge of equipment capabilities.IntroductionThe use of telepresent faculty to train providers in the use of mechanical ventilation using medical simulation as a teaching methodology is not well established. The aim of this study was to compare the efficacy of telepresent faculty versus traditional in-person instruction to teach mechanical ventilation to medical students.Materials and methodsMedical students for this small cohort pilot study were instructed using either in-person instruction or telementoring. Initiation and management of mechanical ventilation were reviewed. Effectiveness was evaluated by pre- and post-multiple choice tests, confidence surveys and summative simulation scenarios. Students evaluated faculty debriefing using the Debriefing Assessment for Simulation in Healthcare Student Version (DASH-SV).ResultsA 3-day pilot curriculum demonstrated significant improvement in the confidence (in person P<0.001; telementoring P=0.001), knowledge (in person P<0.001; telementoring P=0.022) and performance (in person P<0.001; telementoring P<0.002) of medical students in their ability to manage a critically ill patient on mechanical ventilation. Participants favoured the in-person curriculum over telepresent education, however, resultant mean DASH-SV scores rated both approaches as consistently to extremely effective.DiscussionWhile in-person learners demonstrated larger confidence and knowledge gains than telementored learners, improvement was seen in both cases. Learners rated both methods to be effective. Technological issues may have contributed to students providing a more favourable rating of the in-person curriculum.ConclusionsTelementoring is a viable option to provide medical education to medical students on the fundamentals of ventilator management at institutions that may not have content experts readily available.
Team interaction challenges for medical leadership
Authors: McGuire Stephen John 
Published: February 2018

BackgroundTeam interaction in medical practice directly affects patients, organisations and individual doctors. This study aimed to gather a set of quantitative data to identify (1) the aspects of team performance where doctors are comfortable and (2) where to focus development activities.MethodsDoctors were invited to undertake a 1-hour online course exploring concepts related to team formation, performance and dysfunction. This included completing the Healthy Team Member Self-Assessment questionnaire, designed specifically to collect the desired quantitative data. Questionnaire responses were then collated as a survey and analysed in line with the study’s aims.Results202 participants completed the questionnaire including 45 consultants, 85 doctors in training, 24 locums, 3 medical directors, 6 general practitioners and 35 other doctors. Five practice or hospital managers and five other healthcare professionals also submitted results. Collective analysis of the participants’ self-assessment reveals a number of behaviours where doctors indicate improvements are required, including: 45% are not challenging or giving feedback to their colleagues, 42% not proactively seeking honest feedback, 40% not discussing progress towards goals and 39% not discussing support they require to fulfil their role. In addition, unhelpful disparities of perception within teams are suggested. A Wilcoxon-Mann-Whitney test confirmed a statistically significant difference between the 33% of consultants who state their team is in the unproductive ‘Storming’ stage of development and just 12% of all other participants stating the same (P=0.0008). Feelings of ‘I am committed but others are not’ and ‘I am willing to help others but they are not willing to help me’ are also suggested.ConclusionsThe author relates these issues to the duty of candour, proposing that both individual doctors and medical leadership have responsibilities to ensure improvements. In particular, individual doctors should ensure ongoing development in team interaction skills, and medical leadership must foster the appropriate culture for individuals to function within real teams.
Variability of cardiovascular magnetic resonance (CMR) T1 mapping parameters in healthy volunteers during long-term follow-up
Authors: aus dem Siepen Fabian , Baumgärtner Christian , Müller-Henessen Matthias , André Florian , Messroghli Daniel , Ochs Marco , Riffel Johannes , Giannitsis Evangelos , Katus Hugo A , Friedrich Matthias G , Buss Sebastian J 
Published: February 2018

BackgroundMyocardial T1 and extracellular volume (ECV) derived from cardiovascular MRIs are more and more widely accepted as important markers for diagnosis, risk prediction and monitoring of cardiac disease. Yet data regarding long-term stability of myocardial T1 mapping are lacking. The aim of this study was to investigate the long-term stability of native and postcontrast T1 mapping values in healthy volunteers.Methods18 strictly selected healthy volunteers (52±10 years, 12 men) were studied on a Philips Achieva 1.5 Tesla scanner. T1 relaxation times were measured before and 15 min after a bolus contrast injection of gadolinium diethylenetriamine penta-acetic acid (DTPA) (0.2 mmol/kg) using a single-breath-hold modified Look-Locker inversion recovery 3(3)3(3)5 sequence. ECV was calculated using native and postcontrast T1 times of myocardium and blood correcting for blood haematocrit. Exams were repeated 3.6±0.5 years later under the same conditions and using the same scan protocols.ResultsCardiac biomarkers (high-sensitivity troponin T and N terminal pro-brain natriuretic peptide) remained unchanged, as well as left ventricular mass, and global and longitudinal function. No significant change occurred regarding native T1 times (1017±24 ms vs 1015±21 ms; P=0.6), postcontrast T1 times (426±38 ms vs 413±20 ms; P=0.13) or ECV (22%±2% vs 23%±2%; P=0.3). Native T1 time and ECV appeared to be better reproducible than postcontrast T1, resulting in lower coefficients of variation (ECV: 3.5%, native T1: 1.3%, postcontrast T1: 6.4%) and smaller limits of agreement (ECV: 2%/−2%, native T1: 39 ms/−35 ms, postcontrast T1: 85 ms/−59 ms).ConclusionsDuring long-term follow-up, native T1 and ECV values are very robust markers, whereas postcontrast T1 results appear less stable.
Prevalence of axial spondyloarthritis in patients with acute anterior uveitis: a cross-sectional study utilising MRI
Authors: Sykes Mark P , Hamilton Louise , Jones Colin , Gaffney Karl 
Published: February 2018

ObjectiveAcute anterior uveitis (AAU) is the most common extra-articular manifestation of axial spondyloarthritis (axSpA). In this study, patients presenting with AAU were evaluated clinically and with MRI in order to estimate the prevalence of axSpA.MethodsConsecutive patients presenting to a university teaching hospital between February 2014 and March 2015 with AAU were invited to participate. Those with a history of chronic back pain (CBP) beginning <45 years were evaluated clinically and with MRI of thoracolumbar spine and sacroiliac joints.ResultsOf 366 patients with AAU, 57 had a pre-existing diagnosis of axSpA; 77 others fulfilled the study eligibility criteria and 73 (95%) completed the study. Seventeen patients (23.3%) were diagnosed with axSpA by an experienced rheumatologist; of these, eight were human leucocyte antigen-B27 negative. Including those with a previous diagnosis, this equates to a minimum axSpA prevalence of 20.2%; one-quarter of patients were previously undiagnosed.ConclusionThis is the first study to actively search for the presence of axSpA in unselected patients presenting with AAU utilising MRI as an essential part of the assessment. There is a significant burden of undiagnosed axSpA in patients with AAU, but there does not appear to be a simple mechanism for screening. We recommend that ophthalmologists refer all patients with AAU with CBP, onset <45 years, to rheumatology for further evaluation.
Transplantation of Human Amniotic Membrane over the Liver Surface Reduces Hepatic Fibrosis in a Cholestatic Model in Young Rats
Authors: Garrido M. , Escobar C. , Zamora C. , Rejas C. , Varas J. , Córdova C. , Papuzinski C. , Párraga M. , San Martín S. , Montedonico S. 
Published: February 2018

Purpose. Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods. Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks. Biochemical and histopathological analyses of liver tissue were performed. Collagen was expressed as a percentage of total liver tissue area. qPCR was performed to analyse gene expression levels of transforming growth factor-β1 (Tgfb1) and apelin (Apln). Statistical analysis performed considered p<0.05 was significant. Results. Groups undergoing BDL developed cholestasis. Biochemical markers from BDL + AM group improved compared to BDL group. Ductular reaction, portal fibrosis, and bile plugs were markedly reduced in the BDL + AM group compared to BDL group. Collagen area in BDL + AM group was statistically decreased compared to BDL group. Finally, expression levels of both Apln and Tgfb1 mRNA were statistically downregulated in BDL + AM group versus BDL group. Conclusion. AM significantly reduces liver fibrosis in a surgical animal model of cholestasis. Our results suggest that AM may be useful as a therapeutic tool in liver cirrhosis.
Targeting the SUMO Pathway Primes All-trans Retinoic Acid–Induced Differentiation of Nonpromyelocytic Acute Myeloid Leukemias
Authors: Baik Hayeon , Boulanger Mathias , Hosseini Mohsen , Kowalczyk Julie , Zaghdoudi Sonia , Salem Tamara , Sarry Jean-Emmanuel , Hicheri Yosr , Cartron Guillaume , Piechaczyk Marc , Bossis Guillaume 
Published: February 2018

Abstract
Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a posttranslational modification related to ubiquitination, restores the prodifferentiation and antiproliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with the pharmacologic inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells. This activated ATRA-induced terminal myeloid differentiation and reduced cell proliferation and viability, including in AML cells resistant to chemotherapeutic drugs. Conversely, enhancement of SUMOylation via overexpression of the SUMO-conjugating enzyme Ubc9 dampened expression of ATRA-responsive genes and prevented differentiation. Thus, inhibition of the SUMO pathway is a promising strategy to sensitize patients with non-APL AML to retinoids and improve the treatment of this poor-prognosis cancer.
Significance: SUMOylation silences key ATRA-responsive genes in nonpromyelocytic acute myeloid leukemias. Cancer Res; 78(10); 2601–13. ©2018 AACR.
EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors
Authors: Chen Kenneth S. , Fustino Nicholas J. , Shukla Abhay A. , Stroup Emily K. , Budhipramono Albert , Ateek Christina , Stuart Sarai H. , Yamaguchi Kiyoshi , Kapur Payal , Frazier A. Lindsay , Lum Lawrence , Looijenga Leendert H.J. , Laetsch Theodore W. , Rakheja Dinesh , Amatruda James F. 
Published: February 2018

Abstract
Germ cell tumors (GCT) are malignant tumors that arise from pluripotent embryonic germ cells and occur in children and young adults. GCTs are treated with cisplatin-based regimens which, while overall effective, fail to cure all patients and cause significant adverse late effects. The seminoma and nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, and response to treatment; however, the molecular mechanisms of GCT differentiation are not fully understood. We tested whether the activity of the mTORC1 and MAPK pathways were differentially active in the two classes of GCT. Here we show that nonseminomatous germ cell tumors (NSGCT, including embryonal carcinoma, yolk sac tumor, and choriocarcinoma) from both children and adults display activation of the mTORC1 pathway, while seminomas do not. In seminomas, high levels of REDD1 may negatively regulate mTORC1 activity. In NSGCTs, on the other hand, EGF and FGF2 ligands can stimulate mTORC1 and MAPK signaling, and members of the EGF and FGF receptor families are more highly expressed. Finally, proliferation of NSGCT cells in vitro and in vivo is significantly inhibited by combined treatment with the clinically available agents erlotinib and rapamycin, which target EGFR and mTORC1 signaling, respectively. These results provide an understanding of the signaling network that drives GCT growth and a rationale for therapeutic targeting of GCTs with agents that antagonize the EGFR and mTORC1 pathways. Mol Cancer Ther; 17(5); 1079–89. ©2018 AACR.
Analysis of Tissue and Circulating Tumor DNA by Next-Generation Sequencing of Hepatocellular Carcinoma: Implications for Targeted Therapeutics
Authors: Ikeda Sadakatsu , Lim Jordan S. , Kurzrock Razelle 
Published: February 2018

Abstract
Hepatocellular carcinoma (HCC) has limited treatment options. Molecular analysis of its mutational landscape may enable the identification of novel therapies. However, biopsy is not routinely performed in HCC. The utility of analyzing cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is not established. We performed 32 ctDNA NGS analyses on 26 patients; 10 of these patients had tissue NGS (236 to 626 genes). ctDNA was evaluated using an assay that detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion alterations in 54 to 70 genes. The ctDNA demonstrated that 23 of 26 patients (88.5%) had ≥1 characterized alteration, and all these individuals had ≥1 potentially actionable alteration. The most frequently mutated gene was TP53 (16 of 26 patients, 61.5%). There were 47 unique characterized molecular alterations among 18 total gene alterations [variants of unknown significance (VUS) excluded)]. ctDNA and tissue NGS frequently showed different profiles, perhaps due to length of time between tissue and blood samples [median = 370 days (range, 29 to 876 days)]. Serial ctDNA evaluation in an illustrative patient treated with capecitabine demonstrated emergence of a new TP53 alteration after progression. In conclusion, ctDNA profiling is feasible in advanced HCC, and serial assessment using ctDNA NGS can reveal genomic changes with time. NGS of ctDNA provides a minimally invasive alternative for identifying potentially actionable gene alterations and potential molecular targeted therapies. Dynamic changes in molecular portfolio associated with therapeutic pressure in difficult-to-biopsy patients can be observed. Mol Cancer Ther; 17(5); 1114–22. ©2018 AACR.
Targeting PRPK Function Blocks Colon Cancer Metastasis
Authors: Zykova Tatyana , Zhu Feng , Wang Lei , Li Haitao , Lim Do Young , Yao Ke , Roh Eunmiri , Yoon Sang-Pil , Kim Hong-Gyum , Bae Ki Beom , Wen Weihong , Shin Seung Ho , Nadas Janos , Li Yan , Ma Weiya , Bode Ann M. , Dong Zigang 
Published: February 2018

Abstract
The biological functions of the p53-related protein kinase (PRPK) remain unclear. We have previously demonstrated that PRPK is phosphorylated by the T-LAK cell-originated protein kinase (TOPK) and that phosphorylated PRPK (p-PRPK) promotes colon cancer metastasis. Here, we analyzed colon adenocarcinomas from 87 patients and found that higher expression levels of p-PRPK were associated with later stages of metastatic dissemination (stage III and IV) as compared with earlier stages (stages I and II). Indeed, levels of p-PRPK were higher in metastatic versus malignant human colon adenocarcinomas. Knocking down PRPK expression attenuated colorectal liver and lung metastasis of colon cancer cells in vivo. An in vitro kinase assay indicated that active PRPK does not phosphorylate p53 directly. We found that PRPK phosphorylates survivin, a regulator of colon cancer metastasis. PRPK phosphorylates survivin at Thr34, which is important for survivin stability. Taken together, our data strongly suggest that the PRPK signaling pathway promotes colon cancer metastasis by modulating survivin stability, and that PRPK could be a new prognostic marker for the survival of colon cancer patients. In addition, we identified an FDA-approved bacteriostatic antibiotic, fusidic acid sodium salt (fusidic acid or FA) as an inhibitor of PRPK, and show that FA combined with 5-fluorouracil (5-FU) inhibited PRPK activity and colon cancer metastasis to the lung in mice. We contend that the combination of FA with 5-FU could be an alternative therapeutic strategy to traditional chemotherapy for colon cancer patients with poor prognosis. Mol Cancer Ther; 17(5); 1101–13. ©2018 AACR.
Genome‐Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β‐Blockers
Authors: Shahin Mohamed H. , Conrado Daniela J. , Gonzalez Daniel , Gong Yan , Lobmeyer Maximilian T. , Beitelshees Amber L. , Boerwinkle Eric , Gums John G. , Chapman Arlene , Turner Stephen T. , Cooper‐DeHoff Rhonda M. , Johnson Julie A. 
Published: February 2018

Background

For many indications, the negative chronotropic effect of β‐blockers is important to their efficacy, yet the heart rate (
HR
) response to β‐blockers varies. Herein, we sought to use a genome‐wide association approach to identify novel single nucleotide polymorphisms (
SNP
s) associated with
HR
response to β‐blockers.

Methods and Results

We first performed 4 genome‐wide association analyses for
HR
response to atenolol (a β1‐adrenergic receptor blocker) as: (1) monotherapy or (2) add‐on therapy, in 426 whites and 273 blacks separately from the
PEAR
(Pharmacogenomic Evaluation of Antihypertensive Responses) study. A meta‐analysis was then performed between the genome‐wide association analysis performed in
PEAR
atenolol monotherapy and add‐on therapy, in each race separately, using the inverse variance method assuming fixed effects. From this analysis,
SNP
s associated with
HR
response to atenolol at a
P
<1E‐05 were tested for replication in whites (n=200) and blacks (n=168) treated with metoprolol (a β1‐adrenergic receptor blocker). From the genome‐wide association meta‐analyses,
SNP
rs17117817 near olfactory receptor family10 subfamily‐p‐member1 (

OR
10P1

), and
SNP
rs2364349 in sorting nexin‐9 (

SNX
9

) replicated in blacks. The combined studies meta‐analysis
P
values for the rs17117817 and rs2364349 reached genome‐wide significance (rs17117817G‐allele; Meta‐β=5.53 beats per minute, Meta‐
P
=2E‐09 and rs2364349 A‐allele; Meta‐β=3.5 beats per minute, Meta‐
P
=1E‐08). Additionally,
SNP
s in the

OR
10P1

and

SNX
9

gene regions were also associated with
HR
response in whites.

Conclusions

This study highlights

OR
10P1

and

SNX
9

as novel genes associated with changes in
HR
in response to β‐blockers.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00246519.
High‐Sensitivity Troponin T and C‐Reactive Protein Have Different Prognostic Values in Hemo‐ and Peritoneal Dialysis Populations: A Cohort Study
Authors: Chen Titi , Hassan Hicham C. , Qian Pierre , Vu Monica , Makris Angela 
Published: February 2018

Background

Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high‐sensitivity cardiac troponin T (hs‐
cTnT
) and CRP (C‐reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (
PD
) patients. Variability in hs‐
cTnT
was also examined.

Methods and Results

A retrospective cohort study included 574 dialysis patients (hemodialysis 347,
PD
227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow‐up of 3.5 years. hs‐
cTnT
was an independent predictor of both outcomes in hemodialysis and
PD
patients. Increased risk only became significant when hs‐
cTnT
reached quintile 3 (>49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs‐
cTnT
to clinical parameters significantly improved its prognostic performance for mortality in
PD
patients (
P
=0.002). CRP was an independent predictor of both outcomes in
PD
patients only. Only CRP in the highest quintile (>16.8 mg/L) was associated with increased risk. hs‐
cTnT
remained relatively stable for the whole follow‐up period for hemodialysis patients, whereas for
PD
patients, hs‐
cTnT
increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline (
P
<0.001).

Conclusions

hs‐
cTnT
and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and
PD
patients. Given that hs‐
cTnT
levels increase over time in
PD
patients, interval monitoring may be valuable for risk assessment. In contrast, hs‐
cTnT
in hemodialysis patients has little interval change and progress monitoring is not indicated.