bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic and lipidomic analyses of the Arabidopsis atg5 autophagy mutant reveal major changes in endoplasmic reticulum and peroxisome metabolisms and in lipid composition
Authors: Havé Marien , Luo Jie , Tellier Frédérique , Balliau Thierry , Cueff Gwendal , Chardon Fabien , Zivy Michel , Rajjou Loic , Cacas Jean‐Luc , Masclaux‐Daubresse Céline 
Published: May 2019

Summary

Autophagy is a universal mechanism in eukaryotic cells that facilitates the degradation of unwanted cell constituents and is essential for cell homeostasis and nutrient recycling.

The salicylic acid‐independent effects of autophagy defects on leaf metabolism were determined through large‐scale proteomic and lipidomic analyses of atg5 and atg5/sid2 mutants under different nitrogen and sulfur growth conditions.

Results revealed that irrespective of the growth conditions, plants carrying the atg5 mutation presented all the characteristics of endoplasmic reticulum (ER) stress. Increases in peroxisome and ER proteins involved in very long chain fatty acid synthesis and β‐oxidation indicated strong modifications of lipid metabolism. Lipidomic analyses revealed changes in the concentrations of sphingolipids, phospholipids and galactolipids. Significant accumulations of phospholipids and ceramides and changes in GIPCs (glycosyl‐inositol‐phosphoryl‐ceramides) in atg5 mutants indicated large modifications in endomembrane‐lipid and especially plasma membrane‐lipid composition. Decreases in chloroplast proteins and galactolipids in atg5 under low nutrient conditions, indicated that chloroplasts were used as lipid reservoirs for β‐oxidation in atg5 mutants.

In conclusion, this report demonstrates the strong impact of autophagy defect on ER stress and reveals the role of autophagy in the control of plant lipid metabolism and catabolism, influencing both lipid homeostasis and endomembrane composition.
Trends of Opioid Use Disorder Among Hospitalized Patients With Chronic Pain
Authors: Orhurhu Vwaire , Olusunmade Mayowa , Urits Ivan , Viswanath Omar , Peck Jacquelin , Orhurhu Mariam Salisu , Adekoya Peju , Hirji Sameer , Sampson John , Simopoulos Thomas , Jatinder Gill 
Published: May 2019

AbstractBackgroundPatients with chronic pain treated with opioids are at an increased risk for opioid misuse or opioid use disorder (OUD). Recent years have seen a stark increase in abuse, misuse, and diversion of prescription opioid medications. The aim of this study was to investigate trends in changing rates of opioid use disorder among patients with chronic pain.MethodsThe National Inpatient Sample (NIS) database identified chronic pain admissions with OUD from 2011 to 2015. Patients were identified from the NIS database using International Classification of Diseases (9th and 10th revisions) diagnosis codes for chronic pain and OUD. Annual estimates and trends were determined for OUD, patient characteristics, OUD among subgroups of chronic pain conditions, and discharge diagnosis.ResultsWe identified 10.3 million patients with chronic pain. Of these, 680,631 patients were diagnosed with OUD. The number of patients with OUD increased from 109,222 in 2011 to 172,680 in 2015 (P < 0.001). Similarly, there were upward trends of OUD among females (53.2% to 54.5%; P = 0.09), patients 65 to 84 years of age (11.8% to 17%; P < 0.001), Medicare‐insured patients (39.5% to 46.0%; P < 0.01), patients with low annual household incomes (27.8% to 33.3%; P < 0.001), and patients with cannabinoid use disorder (7.2% to 8.3%; P = 0.01). The prevalence of OUD increased from 2011 to 2015 in patients with chronic regional pain syndrome (5.53% to 7.46%; P = 0.01) and spondylosis (1.32% to 1.81%; P < 0.001).ConclusionsThese findings suggest that the prevalence of OUD increased substantially from 2011 to 2015. Disparities of OUD with increasing opioid use among vulnerable populations including women, those with Medicare insurance, tobacco use disorder, and low annual income should be explored further.
Shared preventive factors associated with relapse after a response to electroconvulsive therapy in four major psychiatric disorders
Authors: Omori Wataru , Itagaki Kei , Kajitani Naoto , Abe Hiromi , Okada‐Tsuchioka Mami , Okamoto Yasumasa , Takebayashi Minoru 
Published: May 2019

AimThe efficacy of electroconvulsive therapy (ECT) has been established in psychiatric disorders but the high rate of relapse is a critical problem. The current study sought preventative factors associated with relapse after a response to ECT in a continuum of four major psychiatric disorders.MethodsThe records of 255 patients with four psychiatric disorders (83 unipolar depression, 60 bipolar depression, 91 schizophrenia, 21 schizoaffective disorder) were retrospectively reviewed.ResultsThe relapse‐free rate of all patients at 1 year was 56.3% in the four psychiatric disorders without a difference. As a result of univariate analysis, three items could be considered as preventative factors associated with relapse: a small number of psychiatric symptom episodes before an acute course of ECT, the use of mood stabilizers, and the use of maintenance ECT. Multivariate analysis was performed, keeping age, sex, and diagnosis constant in addition to the three items, and small number of psychiatric symptom episodes before an acute course of ECT (P = 0.003), the use of lithium (P = 0.025), the use of valproate (P = 0.027), and the use of maintenance ECT (P = 0.001) were found to be significant preventative measures against relapse.ConclusionThe use of mood stabilizers, such as lithium and valproate, and maintenance ECT could be shared preventive factors associated with relapse after a response to ECT in four major psychiatric disorders.
Does Negative Group Information Moderate Ideological Identity? An Experimental Test
Authors: Amira Karyn 
Published: May 2019

ObjectiveThis study tests whether Americans moderate their ideological identity when exposed to news reports that present ideological activists negatively. I hypothesize that certain people will be more likely to do this: high self‐monitors and those with “issue constraint” (consistency in issue positions).MethodTwo survey experiments are conducted to test these hypotheses: one with a nationally representative sample and one with an online sample.ResultsDespite evidence that people moderate or opt out of other political identities in similar scenarios, I find no evidence this happens for ideological identification. This was the case even when the dependent variable was altered in the second experiment, making it easier for subjects to opt out of the identity.ConclusionThese null findings provide evidence that dislodging people from ideological labels is difficult at this point in time. Ideology scholars should continue to test how resilient these identities are with different designs and manipulations.
In‐hospital postoperative infection after heart transplantation: Risk factors and development of a novel predictive score
Authors: Fernández‐Ugidos Paula , Barge‐Caballero Eduardo , Gómez‐López Rocío , Paniagua‐Martin María J. , Barge‐Caballero Gonzalo , Couto‐Mallón David , Solla‐Buceta Miguel , Iglesias‐Gil Carmen , Aller‐Fernández Vanesa , González‐Barbeito Miguel , Vázquez‐ Rodríguez Jose Manuel , Crespo‐Leiro María G. 
Published: May 2019

AbstractIntroductionInfection is one of the most significant complications following heart transplantation (HT). The aim of this study was to identify specific risk factors for early postoperative infections in HT recipients, and to develop a multivariable predictive model to identify HT recipients at high risk.MethodsA single‐center, observational, and retrospective study was conducted. The dependent variable was in‐hospital postoperative infection. We examined demographic and epidemiological data from donors and recipients, surgical features, and adverse postoperative events as independent variables. Backwards, stepwise multivariable logistic regression with a P‐value < 0.05 was used to identify clinical factors independently associated with the risk of in‐hospital postoperative infections following HT.ResultsSix hundred seventy‐seven patients were included in this study. During the in‐hospital postoperative period, 348 episodes of infection were diagnosed in 239 (35.9%) patients. Seven variables were identified as independent clinical predictors of early postoperative infection after HT: history of diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and use of itraconazole. Based on the results of multivariable models, we constructed a 7‐variable (8‐point) score to predict the risk of in‐hospital postoperative infection in HT recipients, which showed a reasonable ability to predict the risk of in‐hospital postoperative infection in this population. Prospective external validation of this new score is warranted to confirm its clinical applicability.ConclusionsIn‐hospital postoperative infection is a common complication after HT, affecting 35% of patients who underwent this procedure at our institution. Diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and itraconazole were all independent clinical predictors of early postoperative infection after HT.
Outcomes of outborn extremely preterm neonates admitted to a NICU with respiratory distress
Authors: Fang Jennifer L , Mara Kristin C , Weaver Amy L , Clark Reese H , Carey William A 
Published: May 2019

ObjectiveTo compare the risk of mortality and morbidity between outborn and propensity score-matched inborn extremely preterm neonates.SettingMultiple neonatal intensive care units (NICU) across the USA.PatientsSingleton neonates born at 22–29 weeks’ gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth.MethodsThe association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity.ResultsThere were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24).ConclusionAdditional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.
Does soft tissue balancing using intraoperative pressure sensors improve clinical outcomes in total knee arthroplasty? A protocol of a multicentre randomised controlled trial
Authors: MacDessi Samuel J , Bhimani Aziz , Burns Alexander W R , Chen Darren B , Leong Anthony K L , Molnar Robert B , Mulford Jonathan S , Walker Richard M , Harris Ian A , Diwan Ashish , Wood Jil A 
Published: May 2019

IntroductionSoft tissue imbalance is considered to be a major surgical cause of dissatisfaction following total knee arthroplasty (TKA). Surgeon-determined manual assessment of ligament tension has been shown to be a poor determinant of the true knee balance state. The recent introduction of intraoperative sensors, however, allows surgeons to precisely quantify knee compartment pressures and tibiofemoral kinematics, thereby optimising coronal and sagittal plane soft tissue balance. The primary hypothesis of this study is that achieving knee balance with use of sensors in TKA will improve patient-reported outcomes when compared with manual balancing.Methods and analysisA multicentred, randomised controlled trial will compare patient-reported outcomes in 222 patients undergoing TKA using sensor-guided balancing versus manual balancing. The sensor will be used in both arms for purposes of data collection; however, surgeons will be blinded to the pressure data in patients randomised to manual balancing. The primary outcome will be the change from baseline to 1 year postoperatively in the mean of the four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) that are most specific to TKA recovery: pain, symptoms, function and knee-related quality of life. Secondary outcomes will include the surgeon’s capacity to determine knee balance, radiographic and functional measures and additional patient-reported outcomes. Normality of data will be assessed, and a Student’s t-test and equivalent non-parametric tests will be used to compare differences in means among the two groups.Ethics and disseminationEthics approval was obtained from South Eastern Sydney Local Health District, Approval (HREC/18/POWH/320). Results of the trial will be presented at orthopaedic surgical meetings and submitted for publication in a peer-reviewed journal.Trial registration numberACTRN#12618000817246
Faecal immunochemical testing (FIT) in symptomatic patients: what are we missing?
Authors: Farrugia Alexia , Widlak Monika , Evans Charles , Smith Stephen Charles , Arasaradnam Ramesh 
Published: May 2019

ObjectiveFaecal immunochemical test (FIT) shows promise as a non-invasive triage test for colorectal cancer (CRC) in the symptomatic population. The aim of this study was to assess the use of FIT within the recent NG12 and DG30 National Institute for Health and Care Excellence (NICE) guidelines.DesignA single-centre prospective study of patients referred to University Hospitals Coventry and Warwickshire NHS Trust via the 2-week wait (TWW) pathway between January 2015 and March 2016 was conducted. 612 patients were reviewed, of which 519 were found to meet the NG12 criteria and 79 met the DG30 criteria. Data included age, sex, symptoms, colonoscopy or CT colonography, histology and FIT results.Main outcome measuresFIT was performed in all patients and sensitivity, specificity, positive predictive value and negative predictive value, with 95% CI, for cancers and adenomas within each pathway (TWW, NG12 and DG30) was calculated.ResultsCRC sensitivity in TWW pathway patients, NG12 and DG30 group was 86.84% (95% CI 71.91% to 95.59%), 84.85% (95% CI 68.1% to 94.89%) and 100% (95% CI 47.82% to 100%), respectively. Specificity was 82.23% (95% CI 78.85% to 85.27%), 81.28% (95% CI 77.52% to 84.65%) and 91.89% (95% CI 83.18% to 96.97%), respectively. Adenoma sensitivity in the groups was 30.69% (95% CI 29.9% to 40.66%), 30.77% (95% CI 21.51% to 41.32%) and 25% (95% CI 3.19% to 65.09%), respectively.ConclusionUse of FIT within the remit of the NG12 NICE guidelines shows a high sensitivity and specificity and may be an effective triage tool when considering whether to perform investigations. However, there is still a miss rate. FIT within DG30 has excellent sensitivity and improved specificity; however, DG30 targets lower risk groups and accounts for only 13% of the entire referrals for suspected cancer. Therefore, managing the larger, higher risk NG12 group may require the addition of another test or marker to ensure that CRC is not missed.
Gyrification abnormalities in presymptomatic c9orf72 expansion carriers
Authors: Caverzasi Eduardo , Battistella Giovanni , Chu Stephanie A , Rosen Howie , Zanto Theodore P , Karydas Anna , Shwe Wendy , Coppola Giovanni , Geschwind Daniel H , Rademakers Rosa , Miller Bruce L , Gorno-Tempini Maria Luisa , Lee Suzee E 
Published: May 2019

ObjectiveTo investigate in-vivo cortical gyrification patterns measured by the local gyrification index (lGI) in presymptomatic c9orf72 expansion carriers compared with healthy controls, and investigate relationships between lGI and cortical thickness, an established morphometric measure of neurodegeneration.MethodsWe assessed cortical gyrification and thickness patterns in a cohort of 15 presymptomatic c9orf72 expansion carriers (age 43.7 ± 10.2 years, 9 females) compared with 67 (age 42.4 ± 12.4 years, 36 females) age and sex matched healthy controls using the dedicated Freesurfer pipeline.ResultsCompared with controls, presymptomatic carriers showed significantly lower lGI in left frontal and right parieto-occipital regions. Interestingly, those areas with abnormal gyrification in presymptomatic carriers showed no concomitant cortical thickness abnormality. Overall, for both presymptomatic carriers and healthy controls, gyrification and cortical thickness measures were not correlated, suggesting that gyrification captures a feature distinct from cortical thickness.ConclusionsPresymptomatic c9orf72 expansion carriers show regions of abnormally low gyrification as early as their 30s, decades before expected symptom onset. Cortical gyrification represents a novel grey matter metric distinctive from grey matter thickness or volume and detects differences in presymptomatic carriers at an early age.
Abstract DD01-04: NVP-BKM120: A selective inhibitor of type I PI3 kinases
Authors: Sellers William R. 
Published: May 2019

Abstract
AACR 2010 - poster I
Biological characterization of NVP-BKM120, a novel inhibitor of phosphoinosotide 3-kinase in Phase I/II clinical trials
The PI3K/Akt/mTor signaling pathway plays an important role in controlling cell growth, proliferation and survival. Through various mechanisms, the pathway is frequently dysregulated in human cancers, suggesting the use of pathway modulators as novel targeted anticancer therapeutic agents. To this end, substantial drug discovery efforts have been devoted both in pharmaceutical companies and in academia to identify and develop therapeutic agents able to specifically down regulate this pathway in tumors cells. Following the discovery of NVP-BEZ235, our first dual pan-PI3K/mTOR clinical compound, we sought to identify additional PI3K inhibitors from different chemical classes with more stringent selectivity profiles. The key to achieve these objectives was to pursue a structure-based design approach coupled with intensive pharmacological evaluation of selected compounds during the medicinal chemistry optimization process. Here we report on the biological characterization of the pan-PI3K pyrimidine-derived inhibitor NVP-BKM120. This compound inhibits all four Class I PI3K isoforms (IC50 values in the 35 to 248 nM range) with at least 50-fold selectivity (compared to p110[[Unsupported Character - Symbol Font ]]) towards protein kinases. The compound is also active against the most common somatic PI3K[[Unsupported Character - Symbol Font ]] mutations (H1047R, E542K and E545K). NVP-BKM120 does not significantly inhibit the related Class III (Vps34) and Class IV (mTOR, DNA-PK) PI3K kinases. Consistent with its mechanism of action, NVP-BKM120 decreases the cellular levels of p-Akt in mechanistic and relevant tumor cell lines (e.g., IC50 for S473P-Akt in Rat1-p110[[Unsupported Character - Symbol Font ]] cells of 93 nM). This biological activity correlates with inhibition of various Akt downstream signaling pathway components, and with its anti-proliferative activity. Thus, the compound demonstrates significant, concentration dependent cell growth inhibition and induction of apoptosis in a variety of tumor cancer cells, particularly for those harboring p110[[Unsupported Character - Symbol Font ]] mutants and/or over-expressing erbB2. In addition, NVP-BKM120 demonstrates significant, dose dependent in vivo pharmacodynamic activity as measured by inhibition of p-Akt in relevant xenograft models. The pharmacological, biological and preclinical
safety profile of NVP-BKM120 supports its clinical development and the compound is currently undergoing Phase 1/II clinical trials in cancer patients.
Citation Format: William R. Sellers. NVP-BKM120: A selective inhibitor of type I PI3 kinases [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr DD01-04
Abstract SS02-04: How much can we afford to pay for new drugs, and how do we make those decisions?
Authors: Smith Thomas J. 
Published: May 2019

Abstract
Cancer and overall medical care costs are rising at an unsustainable rate. At the same time there are a plethora of new cancer drugs with some activity, all coming to market with a cost of $3000-10,000/month, independent of their absolute benefit. And the cost of drugs does not fall when there are competitors. How should patients, payers, physicians and society choose, in the real world of limited resources? We will explore several alternatives including US and Canadian models and the UK NICE (National Institute for Health and Clinical Excellence) model.
Citation Format: Thomas J. Smith. How much can we afford to pay for new drugs, and how do we make those decisions? [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SS02-04
Abstract SY02-03: Studying tumor evolution in mouse models of cancer
Authors: Jacks Tyler 
Published: May 2019

Abstract
Like other solid tumors, lung adenocarcinoma progresses through multiple stages including tumor initiation, expansion in the lung, and metastasis of the primary tumor to distant organs. Dissection of this process requires quantitative and tractable models that recapitulate the human disease at the genetic and histological level. We have employed autochthonous mouse models of lung adenocarcinoma that recapitulate tumor initiation, progression and metastasis in the human disease both genetically, and pathologically. We have established oncogenic Kras as the initiating event in lung adenoma and amplification of the oncogenic signaling is associated with progression to adenocarcinoma. The p53 tumor suppressor limits tumor progression in this model. Restoration of the Trp53 locus has pinpointed the adenoma-adenocarcinoma transition as the stage in which p53 function is critical for tumor suppression. Expression of oncogenic Kras in the absence of p53 leads to the development of distant metastases after long latency. Identification of the lentiviral integration site in each tumor allows the clonal relationship between metastases and the primary tumors to be unequivocally established. Gene expression and DNA copy number analyses of metastasis-derived cell lines and primary lung tumors have uncovered a metastasis associated gene expression signature and recurrent genomic alterations. Integration of these datasets, other genome-wide analyses and human tumor data are providing insights into the molecular mechanism and biology of lung cancer progression and metastasis.
Citation Format: Tyler Jacks. Studying tumor evolution in mouse models of cancer [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY02-03