bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Acute Pain After Surgery
Authors: Baca Quentin , Marti Florian , Poblete Beate , Gaudilliere Brice , Aghaeepour Nima , Angst Martin S. 
Published: June 2019

Objectives:
To identify perioperative practice patterns that predictably impact postoperative pain.

Background:
Despite significant advances in perioperative medicine, a significant portion of patients still experience severe pain after major surgery. Postoperative pain is associated with serious adverse outcomes that are costly to patients and society.

Methods:
The presented analysis took advantage of a unique observational data set providing unprecedented detailed pharmacological information. The data were collected by PAIN OUT, a multinational registry project established by the European Commission to improve postoperative pain outcomes. A multivariate approach was used to derive and validate a model predictive of pain on postoperative day 1 (POD1) in 1008 patients undergoing back surgery.

Results:
The predictive and validated model was highly significant (P = 8.9E-15) and identified modifiable practice patterns. Importantly, the number of nonopioid analgesic drug classes administered during surgery predicted decreased pain on POD1. At least 2 different nonopioid analgesic drug classes (cyclooxygenase inhibitors, acetaminophen, nefopam, or metamizol) were required to provide meaningful pain relief (>30%). However, only a quarter of patients received at least 2 nonanalgesic drug classes during surgery. In addition, the use of very short-acting opioids predicted increased pain on POD1, suggesting room for improvement in the perioperative management of these patients. Although the model was highly significant, it only accounted for a relatively small fraction of the observed variance.

Conclusion:
The presented analysis offers detailed insight into current practice patterns and reveals modifications that can be implemented in today's clinical practice. Our results also suggest that parameters other than those currently studied are relevant for postoperative pain including biological and psychological variables.
Five-year Longitudinal Cohort Study of Reinterventions After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass
Authors: Li Robert A. , Liu Liyan , Arterburn David , Coleman Karen J. , Courcoulas Anita P. , Fisher David , Haneuse Sebastien , Johnson Eric , Theis Mary Kay , Yoon Tae K. , Fisher Heidi , Fraser James R. , Herrinton Lisa J. 
Published: June 2019

Objective:
To compare the long-term risks of reintervention following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in a large surgical cohort.

Background:
The use of SG has increased dramatically relative to RYGB for the treatment of obesity. However, long-term risks following SG compared with RYGB have not been adequately defined in a large population-based study.

Methods:
A retrospective longitudinal cohort study of all adult health-plan members undergoing SG or RYGB for obesity in a multistate integrated health care system from January 2005 through September 2015. The risks of nutritional, endoscopic, radiologic, and surgical reintervention as well as the overall risk of any reinterventions at 1, 3, and 5 years were identified using diagnosis and procedure codes from comprehensive electronic medical records.

Results:
The study included 15,319 patients who underwent SG and 19,954 patients who underwent RYGB with a follow-up of 79.2%. The overall risk of any reintervention at 5 years was 21.3% for SG and 28.3% for RYGB (P < 0.0001). After adjustment, SG was associated with fewer reinterventions through 5 years than RYGB (hazard ratio, 0.78; 95% confidence interval, 0.74–0.84). When comparing subcategories, SG also had a lower risk of nutritional, endoscopic, radiologic, and surgical reinterventions when examined versus RYGB. The findings for risks of reinterventions were consistent across clinical subgroups.

Conclusion:
SG has significantly lower risk of reintervention in all categories studied when compared with RYGB at 5-year follow-up. The long-term safety profile of LSG compared with RYGB should be an essential part of the discussion in patient-centered decision making when choosing between bariatric procedure options.
Frailty in Older Patients Undergoing Emergency Laparotomy
Authors: Parmar Kat L. , Law Jennifer , Carter Ben , Hewitt Jonathan , Boyle Jemma M. , Casey Patrick , Maitra Ishaan , Farrell Ian S. , Pearce Lyndsay , Moug Susan J. 
Published: June 2019

Objective:
This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality.

Summary Background Data:
The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions.

Methods:
An observational multicenter (n=49) UK study was performed (March–June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5–7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay.

Results:
A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24–8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26–16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay.

Conclusions:
A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies.
Molecular Profiles of Matched Primary and Metastatic Tumor Samples Support a Linear Evolutionary Model of Breast Cancer
Authors: Chen Runpu , Goodison Steve , Sun Yijun 
Published: June 2019

AbstractThe interpretation of accumulating genomic data with respect to tumor evolution and cancer progression requires integrated models. We developed a computational approach that enables the construction of disease progression models using static sample data. Application to breast cancer data revealed a linear, branching evolutionary model with two distinct trajectories for malignant progression. Here, we used the progression model as a foundation to investigate the relationships between matched primary and metastasis breast tumor samples. Mapping paired data onto the model confirmed that molecular breast cancer subtypes can shift during progression, and supported directional tumor evolution through luminal subtypes to increasingly malignant states. Cancer progression modeling through the analysis of available static samples represents a promising breakthrough. Further refinement of a roadmap of breast cancer progression will facilitate the development of improved cancer diagnostics, prognostics and targeted therapeutics.
Engineering the yeastSaccharomyces cerevisiaefor the production of L-(+)-ergothioneine
Authors: van der Hoek Steven A. , Darbani Behrooz , Zugaj Karolina E. , Prabhala Bala Krishna , Biron Mathias Bernfried , Randelovic Milica , Medina Jacqueline B. , Kell Douglas B. , Borodina Irina 
Published: June 2019

AbstractL-(+)-Ergothioneine is an unusual, naturally occurring antioxidant nutraceutical that has been shown to help reduce cellular oxidative damage. Humans do not biosynthesise it, so can acquire it only from their diet; it exploits a specific transporter (SLC22A4) for its uptake. ERG is considered to be a nutraceutical and possible vitamin that is involved in the maintenance of health, and seems to be at too low a concentration in several diseasesin vivo. Ergothioneine is thus a potentially useful dietary supplement. Present methods of commercial production rely on extraction from natural sources or on chemical synthesis. Here we describe the engineering of the baker’s yeastSaccharomyces cerevisiaeto produce ergothioneine by fermentation in defined media. After integrating combinations of ERG biosynthetic pathways from different organisms, we screened yeast strains for their production of ERG. The highest-producing strain was also engineered with known ergothioneine transporters. The effect of amino acid supplementation of the medium was investigated and the nitrogen metabolism ofS. cerevisiaewas altered by knock-out ofTOR1 orYIH1. We also optimized the media composition using fractional factorial methods. Our optimal strategy led to a titer of 598 ± 18 mg/L ergothioneine in fed-batch culture in bioreactors. BecauseS. cerevisiaeis a GRAS (‘generally recognised as safe’) organism that is widely used for nutraceutical production, this work provides a promising process for the biosynthetic production of ERG.
The ciliary membrane of polarized epithelial cells stems from a midbody remnant-associated membrane patch with condensed nanodomains
Authors: Bernabé-Rubio Miguel , Bosch-Fortea Minerva , García Esther , de la Serna Jorge Bernardino , Alonso Miguel A. 
Published: June 2019

AbstractThe primary cilium is a specialized plasma membrane protrusion that harbors receptors involved in important signaling pathways. Despite its central role in regulating cellular behavior, the biogenesis of the primary cilium is not fully understood. In fact, the source of the ciliary membrane remains a mystery in cell types that assemble their primary cilium entirely at the cell surface, such as polarized renal epithelial cells. After cytokinesis, the remnant of the midbody of these cells moves to the center of the apical surface, where it licenses the centrosome for ciliogenesis through an unidentified mechanism. Here, to investigate the origin of the ciliary membrane and the role of the midbody remnant, we analyzed membrane compaction and lipid dynamics at the microscale and nanoscale in living renal epithelial MDCK cells. We found that a specialized patch made of condensed membranes with restricted lipid lateral mobility surrounds the midbody remnant. This patch accompanies the remnant on its journey towards the centrosome and, once the two structures have met, the remnant delivers part of membranes of the patch to build the ciliary membrane. In this way, we have determined the origin of the ciliary membrane and the contribution of the midbody remnant to primary cilium formation in cells whose primary cilium is assembled at the plasma membrane.
Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1,ETV1, andETV4on whole mount radical prostatectomy tissue
Authors: Lu Zhichun , Williamson Sean R. , Carskadon Shannon , Arachchige Pavithra D. , Dhamdhere Gaury , Schultz Daniel S. , Stricker Hans , Peabody James O. , Jeong Wooju , Chitale Dhananjay , Bismar Tarek , Rogers Craig G. , Menon Mani , Gupta Nilesh S. , Palanisamy Nallasivam 
Published: June 2019

ABSTRACTExpression profiles of ETS related genes and SPINK1 in early onset prostate cancer have not been thoroughly explored. We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55yrs) and characterized the expression of ERG, SPINK1,ETV1andETV4by dual immunohistochemistry and dual RNAin-situhybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence and pathological variables using whole mount radical prostatectomy tissue were collected. 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans. Positive family history of prostate cancer was observed in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/ml (mean 7.04). Follow-up period ranged from 1 to 123.7 months (Mean 30.3). Biochemical recurrence was encountered in 8/151 (5%). ERG overexpression was observed in 85/151 (56%) cases, followed by SPINK1 in 61/151 (40%),ETV1in 9/149 (6%), andETV4in 4/141 (3%). There were 25/151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤ 45 years old) (76% vs. 49%,p= 0.002213), Caucasian men (71% vs. 41%p= 0.000707), organ-confined tumors (64% vs. 33%,p= 0.00079), and tumors of Grade Groups 1 and 2 (62% vs. 26%,p= 0.008794). SPINK1 overexpression was more in African American men (68% vs. 26%,p= 0.00008), in tumors with high tumor volume (> 20%) and with anterior located tumors.ETV1andETV4demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.
Dual RNase and β-lactamase activity of a single enzyme encoded in most Archaea
Authors: Diene Seydina M. , Pinault Lucile , Armstrong Nicholas , Azza Said , Keshri Vivek , Khelaifia Saber , Chabrière Eric , Caetano-Anolles Gustavo , Rolain Jean-Marc , Pontarotti Pierre , Raoult Didier 
Published: June 2019

Abstractβ-lactams targeting the bacterial cell wall are not active on archaea. Here, we figure out that annotation of genes as β-lactamase in Archeae on the basis of homologous genes, initially annotated β-lactamases, is a remnant of the identification of the original activities of this group of enzymes, which in fact, have multiple functions including nuclease, ribonuclease, β-lactamase, or glyoxalase; which may specialized over time. We expressed a class B β-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while a weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The β-lactamase activity was inhibited by a β-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to has been transferred to the Flavobacteriaceae group including Elizabethkingia genus in which the expressed gene shows a more specialized activity toward resistance to tienanmicin but no glyoxalase activity. The expressed class C-like β-lactamase gene, also from Methanosarcina sp., shows also hydrolysis activity and was more closely related to DD-peptidase enzymes than known bacterial class C β-lactamases. Our findings highlight the requalification needness of annotated enzymes as β-lactamases and the specification overtime of multipotent enzymes in different ways in Archaea and bacteria.
Decoupling the effects of nutrition, age and behavioral caste on honey bee physiology and immunity
Authors: Corona Miguel , Branchiccela Belen , Madella Shayne , Chen Yanping , Evans Jay 
Published: June 2019

AbstractNutritional stress, and especially a dearth of pollen, is considered an important factor associated with honey bee colony losses. We used pollen-restricted colonies as a model to study the nutritional stress conditions experienced in colonies within intensively cultivated agricultural areas. This model was complemented by the establishment of an experimental design, which allowed us to uncouple the effect of nutrition, behavior and age in colonies of similar size and demography. We used this system to determine the effect of pollen restriction on workers’ behavioral development. Then, we analyzed the effect of nutritional stress, behavior and age on the expression of key physiological genes involved in the regulation of division of labor. Finally, we analyzed the effects of these variables on the expression of immune genes and the titers of honey bee viruses. Our results show that pollen restriction led to an increased number of precocious foragers and this behavioral transition was associated with important changes in the expression of nutritionally regulated physiological genes, immunity and viral titers.Vitellogenin (vg)andmajor royal jelly protein1 (mrjp1)were the most predictive markers of nutrition and behavior. The expression of immune genes was primarily affected by behavior, with higher levels in foragers. Deformed wing virus (DWV) titers were significantly affected by behavior and nutritional status, with higher titer in foragers and increased levels associated with pollen ingestion. Correlation analyses support the predominant effect of behavior on immunity and susceptibility to viral infection, revealing that both immune genes and DWV exhibited strong negative correlations with genes associated with nursing, but positive correlations with genes associated with foraging. Our results provide valuable insights into the physiological mechanisms by which nutritional stress induce precocious foraging and increased susceptibility to viral infections.
Night watch during REM sleep for the first-night effect
Authors: Tamaki Masako , Sasaki Yuka 
Published: June 2019

ABSTRACTWe experience disturbed sleep in a new place, and this effect is known as the first-night effect (FNE) in sleep research. We previously demonstrated that the FNE was associated with a protective night-watch system during NREM sleep in one hemisphere, which is shown as interhemispheric asymmetry in sleep depth in the default-mode network (DMN), and interhemispheric asymmetry in increased vigilance to monitor external stimuli. The present study investigated whether rapid eye movement (REM) sleep exhibited a form similar to a night-watch system during NREM sleep. First, we tested whether theta activity, which is an index of the depth of REM sleep, showed interhemispheric asymmetry in association with the FNE, by source-localizing to the DMN. However, interhemispheric asymmetry in theta activity during REM sleep was not found in association with the FNE. Next, we tested whether vigilance, as measured by evoked brain responses to deviant sounds, was increased in one hemisphere and showed interhemispheric asymmetry in association with the FNE during REM sleep. Because vigilance is different between the phasic period where rapid eye movements occur and the tonic period where rapid eye movements do not occur during REM sleep, REM sleep was split into phasic and tonic periods for measurements of evoked brain responses. While the evoked brain responses are generally small during the phasic period without the FNE, we found that the evoked brain response was significantly augmented by the FNE during the phasic period. In contrast, the evoked brain response during the tonic period did not differ by the presence of the FNE. Interhemispheric asymmetry in brain responses was not found during the phasic or tonic periods. These results suggest that a night-watch system for the FNE appears as interhemispheric asymmetry in sleep depth and vigilance during NREM sleep, but it appears as increased vigilance in both hemispheres during the phasic period, when vigilance to external stimuli is generally reduced without the FNE, during REM sleep. Therefore, a night-watch system associated with the FNE may be subserved by different neural mechanisms during NREM and REM sleep.
Variance heterogeneity genome-wide mapping for cadmium in bread wheat reveals novel genomic loci and epistatic interactions
Authors: Hussain Waseem , Campbell Malachy , Jarquin Diego , Walia Harkamal , Morota Gota 
Published: June 2019

AbstractGenome-wide association mapping identifies quantitative trait loci (QTL) that influence the mean differences between the marker genotypes for a given trait. While most loci influence the mean value of a trait, certain loci, known as variance heterogeneity QTL (vQTL) determine the variability of the trait instead of the mean trait value (mQTL). In the present study, we performed a variance heterogeneity genome-wide association study (vGWAS) for grain cadmium (Cd) concentration in bread wheat. We used double generalized linear model and hierarchical generalized linear model to identify vQTL associated with grain Cd. We identified novel vQTL regions on chromosomes 2A and 2B that contribute to the Cd variation and loci that affect both mean and variance heterogeneity (mvQTL) on chromosome 5A. In addition, our results demonstrated the presence of epistatic interactions between vQTL and mvQTL, which could explain variance heterogeneity. Overall, we provide novel insights into the genetic architecture of grain Cd concentration and report the first application of vGWAS in wheat. Moreover, our findings indicated that epistasis is an important mechanism underlying natural variation for grain Cd concentration.
Temporal quantitative proteomics of protein translation and phosphorylation in synaptic plasticity
Authors: van Gelder Charlotte AGH , Penning Renske , Catsburg Lisa , Hoogenraad Casper C , MacGillavry Harold D , Altelaar Maarten 
Published: June 2019

AbstractAt neuronal synapses, activation of metabotropic glutamate receptors (mGluR1/5) triggers a form of long-term depression (mGluR-LTD) that relies on new protein synthesis and the internalization of AMPA-type glutamate receptors. Dysregulation of these processes has been implicated in the development of mental disorders such as autism spectrum disorders and therefore merit a better understanding on a molecular level. Here, to study mGluR-LTD, we integrated quantitative high-resolution phosphoproteomics with the analyses of newly synthesized proteins via bio-orthogonal amino acids (azidohomoalanine) in a pulsed labeling strategy combined with tandem mass tag label-based quantification in cultured hippocampal neurons stimulated with DHPG. We identified several kinases with important roles in DHPG-mGluR-LTD, which we confirmed using small molecule kinase inhibitors. Furthermore, changes in the AMPA receptor endocytosis pathway in both protein synthesis and protein phosphorylation upon LTD were identified, whereby Intersectin-1 was validated as a vital player in this pathway. This study revealed several novel insights into the molecular mechanisms underlying mGluR-LTD and provides a broad view on its molecular basis, which serves as a rich resource for further analyses.