bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Unconventional Role for Gastric Volume in the Response to Bariatric Surgery for Both Weight Loss and Glucose Lowering
Authors: Evers Simon S. , Lewis Alfor G. , Tong Cindy , Shao Yikai , Alvarez Rafael , Ridelman Elika , Grant Bethany , Seeley Randy J. 
Published: March 2019

Objective:
To study the relationship between the amount of surgery-induced gastric volume reduction and long-term weight loss and glucose tolerance.

Background Data:
Vertical sleeve gastrectomy (VSG) has recently surpassed gastric bypass to become the most popular surgical intervention to induce sustained weight loss. Besides inducing significant weight loss, VSG also improves glucose tolerance. Although no clear correlation has been observed between the size of the residual stomach and sustained weight loss, this begs the question whether less aggressive gastric volume reduction may provide sufficient efficacy when weight loss is not the major goal of the surgical intervention.

Methods:
A series of strategies to reduce gastric volume were developed and tested in Long Evans male rats, namely: VSG, Fundal (F)-Resection, Gastric Sleeve Plication (GSP), Fundal-Plication, and Fundal-Constrained.

Results:
All surgical interventions resulted in a reduction of gastric volume relative to sham, but none of the interventions were as effective as the VSG. Gastric volume was linearly correlated to increased gastric emptying rate as well as increased GLP-1 response. Overall, cumulative food intake was the strongest correlate to weight loss and was logarithmically related to gastric volume. Regression modeling revealed a nonlinear inverse relation between body weight reduction and gastric volume, confirming that VSG is the only effective long-term weight loss strategy among the experimental operations tested.

Conclusions:
The data suggest a minimum threshold volume of the residual stomach that is necessary to induce sustained weight loss. Although all gastric volume interventions increased the GLP-1 response, none of the interventions, except VSG, significantly improved glucose tolerance. In conclusion, if weight loss is the primary goal of surgical intervention, significant volume reduction is required, and this most likely requires excising gastric tissue.
Association of Adjuvant Radiotherapy With Survival After Margin-negative Resection of Pancreatic Ductal Adenocarcinoma
Authors: Kamarajah Sivesh K. , Sonnenday Christopher J. , Cho Clifford S. , Frankel Timothy L. , Bednar Filip , Lawrence Theodore S. , Nathan Hari 
Published: March 2019

Introduction:
There is conflicting evidence for the benefit of adjuvant radiotherapy (RT) after resection of pancreatic ductal adenocarcinoma (PDAC), especially for margin-negative (R0) resections. We aimed to evaluate the association of adjuvant RT with survival after R0 resection of PDAC.

Methods:
Using National Cancer Database (NCDB) data from 2004 to 2013, we identified patients with R0 resection of nonmetastatic PDAC. Patients with neoadjuvant radiotherapy and chemotherapy and survival <6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of RT with survival.

Results:
Of 4547 (36%) RT and 7925 (64%) non-RT patients, 3860 RT and 3860 non-RT patients remained in the cohort after matching. Clinicopathologic and demographic variables were well balanced after matching. Lymph node metastases were present in 68% (44% N1, 24% N2). After matching, RT was associated with higher survival (median 25.8 vs 23.9 mo, 5-yr 27% vs 24%, P < 0.001). After multivariable adjustment, RT remained associated with a survival benefit (HR 0.89, 95% CI 0.84–0.94, P < 0.001). Stratified and multivariable interaction analyses showed that this benefit was restricted to patients with node-positive disease: N1 (HR: 0.68, CI95%: 0.62–0.76, P = 0.007) and N2 (HR: 0.59, CI95%: 0.54–0.64, P = 0.04).

Conclusions:
In this large retrospective cohort study, adjuvant RT after R0 PDAC resection was associated with a survival benefit in patients with node-positive disease. Adjuvant RT should be considered after R0 resection of PDAC with node-positive disease.
Concordance Between Registry and Administrative Data in the Determination of Comorbidity
Authors: Etzioni David A. , Lessow Cynthia , Bordeianou Liliana G. , Kunitake Hiroko , Deery Sarah E. , Carchman Evie , Papageorge Christina M. , Fuhrman George , Seiler Rachel L. , Ogilvie James , Habermann Elizabeth B. , Chang Yu-Hui H. , Money Samuel R. 
Published: March 2019

Objective:
To characterize agreement between administrative and registry data in the determination of patient-level comorbidities.

Background:
Previous research finds poor agreement between these 2 types of data in the determination of outcomes. We hypothesized that concordance between administrative and registry data would also be poor.

Methods:
A cohort of inpatient operations (length of stay 1 day or greater) was obtained from a consortium of 8 hospitals. Within each hospital, National Surgical Quality Improvement Program (NSQIP) data were merged with intra-institutional inpatient administrative data. Twelve different comorbidities (diabetes, hypertension, congestive heart failure, hemodialysis-dependence, cancer diagnosis, chronic obstructive pulmonary disease, ascites, sepsis, smoking, steroid, congestive heart failure, acute renal failure, and dyspnea) were analyzed in terms of agreement between administrative and NSQIP data.

Results:
Forty-one thousand four hundred thirty-two inpatient surgical hospitalizations were analyzed in this study. Concordance (Cohen Kappa value) between the 2 data sources varied from 0.79 (diabetes) to 0.02 (dyspnea). Hospital variation in concordance (intersite variation) was quantified using a test of homogeneity. This test found significant intersite variation at a level of P < 0.001 for each of the comorbidities except for dialysis (P = 0.07) and acute renal failure (P = 0.19). These findings imply significant differences between hospitals in their generation of comorbidity data.

Conclusion:
This study finds significant differences in how administrative versus registry data assess patient-level comorbidity. These differences are of concern to patients, payers, and providers, each of which had a stake in the integrity of these data. Standardized definitions of comorbidity and periodic audits are necessary to ensure data accuracy and minimize bias.
Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases
Authors: Gholami Sepideh , Kemeny Nancy E. , Boucher Taryn M. , Gönen Mithat , Cercek Andrea , Kingham T. Peter , Balachandran Vinod , Allen Peter , DeMatteo Ronald , Drebin Jeffrey , Jarnagin William , D’Angelica Michael 
Published: March 2019

Objective:
To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM).

Background:
Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection.

Methods:
Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders.

Results:
Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors.

Conclusion:
Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.
Nontechnical Skill Assessment of the Collective Surgical Team Using the Non-Technical Skills for Surgeons (NOTSS) System
Authors: Jung James J. , Yule Steven , Boet Sylvain , Szasz Peter , Schulthess Pansy , Grantcharov Teodor 
Published: March 2019

Objective:
To validate the Non-Technical Skills for Surgeons (NOTSS) system for assessment of the collective surgical teams’ nontechnical skills after observing recordings of actual OR environment.

Background:
The NOTSS system is a widely accepted tool to measure nontechnical skills of individual surgeons, and has mostly been used in the simulated setting. Surgical procedures are rarely performed by a single surgeon, but by a surgical team of attending surgeons, surgical assistants, and surgical trainees. Therefore, assessment of nontechnical skills may benefit from holistic assessment of the collective surgical teams.

Methods:
Five trained participants assessed surgical team and attending surgeon using the NOTSS system after watching ten 20-minute long videos obtained from live OR. A set of reference ratings was provided by a multidisciplinary expert committee. We performed analyses to assess system sensitivity; examine inter-rater reliability of ratings; investigate concurrent construct validity; and assess feasibility and acceptability of using the NOTSS system to measure surgical team performance.

Results:
There was adequate system sensitivity when comparing participants’ and reference ratings. Inter-rater reliability among the participants’ ratings was good except for decision-making category. The level of inter-rater reliability was similar when rating teams and attending surgeons. There was strong positive correlation between teams’ and attending surgeons’ NOTSS ratings at category [Pearson coefficient 0.86, 95% confidence interval (CI) 0.82–0.89] and element levels (0.83, 95% CI 0.80–0.85), demonstrating evidence of concurrent construct validity. The participants felt that the use of NOTSS system to measure teams’ nontechnical skills was acceptable and feasible to a fair extent.

Conclusion:
The NOTSS system, although developed for assessment of individual surgeons, is a useful tool for observing and rating surgical teams.
Long-term Survival in Esophageal Cancer After Minimally Invasive Compared to Open Esophagectomy
Authors: Gottlieb-Vedi Eivind , Kauppila Joonas H. , Malietzis George , Nilsson Magnus , Markar Sheraz R. , Lagergren Jesper 
Published: March 2019

Objective:
Evaluate the existing literature comparing long-term survival after minimally invasive esophagectomy (MIE) and open esophagectomy (OE), and conduct a meta-analysis based on relevant studies.

Background:
It is unknown whether the choice between MIE and OE influences the long-term survival in esophageal cancer.

Methods:
A systematic electronic search for articles was performed in Medline, Embase, Web of Science, and Cochrane Library for studies comparing long-term survival after MIE and OE. Additionally, an extensive hand-search was conducted. The I
2 test and χ2 test were used to test for statistical heterogeneity. Publication bias and small-study effects were assessed using Egger test. A random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year mortality outcomes with adjustment for the covariates age, physical status, tumor stage, and neoadjuvant or adjuvant therapy. The results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results:
The review identified 55 relevant studies. Among all 14,592 patients, 7358 (50.4%) underwent MIE and 7234 (49.6%) underwent OE. The statistical heterogeneity was limited [I
2 = 12%, 95% confidence interval (CI) 0%–41%, and χ2 = 0.26] and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Pooled analysis revealed 18% lower 5-year all-cause mortality after MIE compared with OE (HR 0.82, 95% CI 0.76–0.88). The meta-regression indicated no confounding.

Conclusions:
The long-term survival after MIE compares well with OE and may even be better. Thus, MIE can be recommended as a standard surgical approach for esophageal cancer.
The Impact of Preoperative Immune Modulating Nutrition on Outcomes in Patients Undergoing Surgery for Gastrointestinal Cancer
Authors: Adiamah Alfred , Skořepa Pavel , Weimann Arved , Lobo Dileep N. 
Published: March 2019

Objective:
To define the influence of preoperative immune modulating nutrition (IMN) on postoperative outcomes in patients undergoing surgery for gastrointestinal cancer.

Background:
Although studies have shown that perioperative IMN may reduce postoperative infectious complications, many of these have included patients with benign and malignant disease, and the optimal timing of such an intervention is not clear.

Methods:
The Embase, Medline, and Cochrane databases were searched from 2000 to 2018, for prospective randomized controlled trials evaluating preoperative oral or enteral IMN in patients undergoing surgery for gastrointestinal cancer. The primary endpoint was the development of postoperative infectious complications. Secondary endpoints included postoperative noninfectious complications, length of stay, and up to 30-day mortality. The analysis was performed using RevMan v5.3 software.

Results:
Sixteen studies reporting on 1387 patients (715 IMN group, 672 control group) were included. Six of the included studies reported on a mixed population of patients undergoing all gastrointestinal cancer surgery. Of the remaining, 4 investigated IMN in colorectal cancer surgery, 2 in pancreatic surgery, and another 2 in patients undergoing surgery for gastric cancer. There was 1 study each on liver and esophageal cancer. The formulation of nutrition used in all studies in the treated patients was Impact (Novartis/Nestlé), which contains ω-3 fatty acids, arginine, and nucleotides. Preoperative IMN in patients undergoing surgery for gastrointestinal cancer reduced infectious complications [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.38–0.71, P < 0.0001, I
2 = 16%, n = 1387] and length of hospital stay (weighted mean difference −1.57 days, 95% CI −2.48 to −0.66, P = 0.0007, I
2 = 34%, n = 995) when compared with control (isocaloric isonitrogeneous feed or normal diet). It, however, did not affect noninfectious complications (OR 0.98, 95% CI 0.73–1.33, P = 0.91, I
2 = 0%, n = 1303) or mortality (OR 0.55, 95% CI 0.18–1.68, P = 0.29, I
2 = 0%, n = 955).

Conclusion:
Given the significant impact on infectious complications and a tendency to shorten length of stay, preoperative IMN should be encouraged in routine practice in patients undergoing surgery for gastrointestinal cancer.
Clinical Significance of Alloantibodies in Hand Transplantation: A Multicenter Study
Authors: Berglund Erik , Andersen Ljungdahl Mette , Bogdanović Darko , Berglund David , Wadström Jonas , Kowalski Jan , Brandacher Gerald , Kamińska Dorota , Kaufman Christina L. , Talbot Simon G. , Azari Kodi , Landin Luis , Höhnke Christoph , Dwyer Karen M. , Cavadas Pedro C. , Thione Alessandro , Clarke Brendan , Kay Simon , Wilks Dan , Iyer Subramania , Iglesias Martin , Özkan Ömer , Özkan Özlenen , Krapf Johanna , Weissenbacher Annemarie , Petruzzo Palmina , Schneeberger Stefan 
Published: March 2019

Background.
Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact.

Methods.
We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome.

Results.
Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge.

Conclusions.
While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
Chordoid Glioma Infiltrating Optic Structures
Authors: Sanda Nicolae , Mircea Claudiu-Nicolae , Bernier Michèle , Safran Avinoam B. , Aldea Sorin 
Published: March 2019

Abstract:
Chordoid glioma of the third ventricle (CGTV) is a rare, slow-growing, World Health Organization Grade II glial tumor, with stereotyped localization in the anterior third ventricle. Despite being considered a noninvasive tumor, CGTV is usually associated with a poor clinical outcome due to its close proximity to important cerebral structures, such as the hypothalamus and visual pathways. Our patient with CGTV experienced visual involvement, but after subtotal surgical resection showed no evidence of progression at 5-year follow-up.
Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: Insights from accelerated molecular dynamics simulations
Authors: Bueren-Calabuig Juan A. , Bage Marcus , Cowling Victoria H. , Pisliakov Andrei V. 
Published: March 2019

ABSTRACTThe RNA guanine-7 methyltransferase (RNMT) in complex with RNMT-Activating Miniprotein (RAM) catalyses the formation of a N7-methylated guanosine cap structure on the 5’ end of nascent RNA polymerase II transcripts. The mRNA cap protects the transcript from exonucleases and recruits cap-binding complexes that mediate RNA processing, export and translation. By using microsecond standard and accelerated molecular dynamics simulations, we provide for the first time a detailed molecular mechanism of allosteric regulation of RNMT by RAM. We show that RAM selects the RNMT active site conformations that are optimal for binding of substrates (AdoMet and the cap), thus enhancing their affinity. Furthermore, our results strongly suggest the likely scenario in which the cap binding promotes the subsequent AdoMet binding, consistent with the previously suggested cooperative binding model. By employing the dynamic network and community analyses, we revealed the underlying long-range allosteric networks and paths that are crucial for allosteric regulation by RAM. Our findings complement and explain previous experimental data on RNMT activity. Moreover, this study provides the most complete description of the cap and AdoMet binding poses and interactions within the enzyme’s active site. This information is critical for the drug discovery efforts that consider RNMT as a promising anti-cancer target.
Network resonance during slow-wave sleep facilitates memory consolidation through phase-coding
Authors: Skilling Quinton M. , Clawson Brittany C. , Eniwaye Bolaji , Shaver James , Ognjanovski Nicolette , Aton Sara J. , Zochowski Michal 
Published: March 2019

AbstractSleep plays a critical role in memory consolidation, however, the exact role that sleep and its effects on neural network dynamics play in this process is still unclear. Here, we combine computational and experimental approaches to study the dynamical, network-wide underpinnings of hippocampal memory consolidation during sleep. We provide data to support a novel hypothesis on the role of cellular resonance with sleep-associated theta band (4-12 Hz) hippocampal oscillations in this process. We show that increases in the stability of hippocampal memory representations after learning (which predicts successful memory consolidation) are mediated through emergent network-wide resonance and locking of neuronal activity to network oscillations. These changes arise in the network as a function of changes to network structure during learning, and mirror experimental findings in the hippocampus. Finally, we show that input-dependent pattern formation (e.g. “replay”) in the hippocampus during sleep states, together with spike timing dependent plasticity (STDP)-based memory consolidation, leads to universal network activity reorganization. This reorganization generates heterogeneous changes in neuronal spiking frequency, similar to what has been observed in a variety of brain circuits across periods of sleep. Our results support the hypothesis that sleep plays an active role in memory consolidation by switching the hippocampal network from rate-based to phase-based information representation. The mechanisms through which this occurs supports the integration of heterogeneous cell populations into memory traces.Significance StatementIn this study, we provide a mechanistic explanation of how sleep selectively facilitates memory consolidation, through recruitment of heterogeneous neuronal populations and structural reorganization of the network into an engram. Specifically, we show that emergent theta band oscillations during sleep facilitate stabilization of memory representations via spike timing dependent reinforcement. This stabilization, together with STDP, allows for systematic reorganization of synaptic connections within these populations, universally redistributing firing rates of participating neurons. Simultaneously, network oscillations facilitate a switch from rate-to phase-coding of information among neuronal populations with highly heterogenous firing frequencies, incorporating more neurons into the engram. Our results reconcile discrepant findings on network reorganization during sleep, and demonstrate a clear mechanism for both strengthening and weakening of synaptic efficacy during sleep.