bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local/Regional Recurrence Rates After Breast-Conserving Therapy in Patients Enrolled in Legacy Trials of the Alliance for Clinical Trials in Oncology (AFT-01)
Authors: Schumacher Jessica R. , Wiener Alyssa A. , Greenberg Caprice C. , Hanlon Bret , Edge Stephen B. , Ruddy Kathryn J. , Partridge Ann H. , Le-Rademacher Jennifer G. , Yu Menggang , Vanness David J. , Yang Dou-Yan , Havlena Jeffrey , Strand Carrie , Neuman Heather B. 
Published: December 2022

Objective:
We sought to evaluate local/regional recurrence rates after breast-conserving surgery in a cohort of patients enrolled in legacy trials of the Alliance for Clinical Trials in Oncology and to evaluate variation in recurrence rates by receptor subtype.

Background:
Multiple randomized controlled trials have demonstrated equivalent survival between breast conservation and mastectomy, albeit with higher local/regional recurrence rates after breast conservation. However, absolute rates of local/regional recurrence have been declining with multi-modality treatment.

Methods:
Data from 5 Alliance for Clinical Trials in Oncology legacy trials that enrolled women diagnosed with breast cancer between 1997 and 2010 were included. Women who underwent breast-conserving surgery and standard systemic therapies (n=4,404) were included. Five-year rates of local/regional recurrence were estimated from Kaplan-Meier curves. Patients were censored at the time of distant recurrence (if recorded as the first recurrence), death, or last follow-up. Multivariable Cox proportional hazards models were used to identify factors associated with time to local/regional recurrence, including patient age, tumor size, lymph node status, and receptor subtype.

Results:
Overall 5-year recurrence was 4.6% (95% CI=4.0-5.4%). Five-year recurrence rates were lowest in those with ER+ or PR+ tumors (Her2+ 3.4% [95% CI 2.0-5.7%], Her2- 4.0% [95% CI 3.2-4.9%]) and highest in the triple-negative subtype (7.1% [95% CI 5.4-9.3%]). On multivariable analysis, increasing nodal involvement and triple-negative subtype were positively associated with recurrence (P<0.0001).

Conclusions:
Rates of local/regional recurrence after breast conservation in women with breast cancer enrolled in legacy trials of the Alliance for Clinical Trials in Oncology are significantly lower than historic estimates. This data can better inform patient discussions and surgical decision-making.
Trends in Surgeon Burnout in the US and Canada: Systematic Review and Meta-Regression Analysis
Authors: Etheridge James C , Evans Devon , Zhao Lily , Ibrahim Nourah , Wick Elizabeth C , Freischlag Julie A , Brownstein Michelle R 
Published: December 2022

BACKGROUND:
Burnout among surgeons is increasingly recognized as a crisis. However, little is known about changes in burnout prevalence over time. We evaluated temporal trends in burnout among surgeons and surgical trainees of all specialties in the US and Canada.

STUDY DESIGN:
We systematically reviewed MEDLINE, Embase, and PsycINFO for studies assessing surgeon burnout from January 1981 through September 2021. Changes in dichotomized Maslach Burnout Inventory scores and mean subscale scores over time were assessed using multivariable random-effects meta-regression.

RESULTS:
Of 3,575 studies screened, 103 studies representing 63,587 individuals met inclusion criteria. Publication dates ranged from 1996 through 2021. Overall, 41% of surgeons met criteria for burnout. Trainees were more affected than attending surgeons (46% vs 36%, p = 0.012). Prevalence remained stable over the study period (−4.8% per decade, 95% CI −13.2% to 3.5%). Mean scores for emotional exhaustion declined and depersonalization declined over time (−4.1 per decade, 95% CI −7.4 to −0.8 and −1.4 per decade, 95% CI −3.0 to −0.2). Personal accomplishment scores remained unchanged. A high degree of heterogeneity was noted in all analyses despite adjustment for training status, specialty, practice setting, and study quality.

CONCLUSIONS:
Contrary to popular perceptions, we found no evidence of rising surgeon burnout in published literature. Rather, emotional exhaustion and depersonalization may be decreasing. Nonetheless, burnout levels remain unacceptably high, indicating a need for meaningful interventions across training levels and specialties. Future research should be deliberately designed to support longitudinal integration through prospective meta-regression to facilitate monitoring of trends in surgeon burnout.
Effect of Present at Time of Surgery on Unadjusted and Risk-Adjusted Postoperative Complication Rate
Authors: Bronsert Michael R , Henderson William G , Colborn Kathryn L , Dyas Adam R , Madsen Helen J , Zhuang Yaxu , Lambert-Kerzner Anne , Meguid Robert A 
Published: December 2022

BACKGROUND:
Present at the time of surgery (PATOS) is an important measure to collect in postoperative complication surveillance systems because it may affect a patient’s risk of a subsequent complication and the estimation of postoperative complication rates attributed to the healthcare system. The American College of Surgeons (ACS) NSQIP started collecting PATOS data for 8 postoperative complications in 2011, but no one has used these data to quantify how this may affect unadjusted and risk-adjusted postoperative complication rates.

STUDY DESIGN:
This study was a retrospective observational study of the ACS NSQIP database from 2012 to 2018. PATOS data were analyzed for the 8 postoperative complications of superficial, deep, and organ space surgical site infection; pneumonia; urinary tract infection; ventilator dependence; sepsis; and septic shock. Unadjusted postoperative complication rates were compared ignoring PATOS vs taking PATOS into account. Observed to expected ratios over time were also compared by calculating expected values using multiple logistic regression analyses with complication as the dependent variable and the 28 nonlaboratory preoperative variables in the ACS NSQIP database as the independent variables.

RESULTS:
In 5,777,108 patients, observed event rates for each outcome were reduced by between 6.1% (superficial surgical site infection) and 52.5% (sepsis) when PATOS was taken into account. The observed to expected ratios were similar each year for all outcomes, except for sepsis and septic shock in the early years.

CONCLUSIONS:
Taking PATOS into account is important for reporting unadjusted event rates. The effect varied by type of complication—lowest for superficial surgical site infection and highest for sepsis and septic shock. Taking PATOS into account was less important for risk-adjusted outcomes (observed to expected ratios), except for sepsis and septic shock.
Immunological and Clinico-Molecular Features of Tumor Border Configuration in Colorectal Cancer
Authors: Sonal Swati , Deshpande Vikram , Ting David T , Neyaz Azfar , Pankaj Amaya , Taylor Martin S , Dinaux Anne M , Leijssen Lieve GJ , Boudreau Chloe , Berger David L 
Published: December 2022

INTRODUCTION:
Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA).

STUDY DESIGN:
Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded.

RESULTS:
There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001).

CONCLUSIONS:
Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined.
Ligation of Intersphincteric Fistulous Tract vs Endorectal Advancement Flap for High-Type Fistula in Ano: A Randomized Controlled Trial
Authors: Kumar Pankaj , Sarthak Siddhant , Singh Pradeep K , Mishra Tushar S , Sasmal Prakash K 
Published: December 2022

BACKGROUND:
This study aimed to compare the postoperative outcomes and success rate of the endorectal advancement flap and ligation of intersphincteric fistulous tract (LIFT) in high-type fistula in ano.

STUDY DESIGN:
This randomized control trial included patients with high-type fistula in ano of cryptoglandular origin. The primary endpoint was complete fistula healing at the end of 6 months. However, the patients were followed up for 2 years. Other parameters studied were perioperative complications, duration of surgery, postoperative pain, hospital stay in hours, continence, and quality of life at 6 months.

RESULTS:
A total of 84 patients were recruited (42 in each group). The healing rate in the LIFT arm was better than that in the endorectal advancement flap arm (76.2.% vs 54.7%, p = 0.039). Four patients in the endorectal advancement flap group and two in the LIFT group had flatus incontinence at the end of 6 months, but all were continent at 2 years. At the end of the first week, the Visual Analog Scale score and quality of life at 6 months were better in the LIFT arm (3.7 ± 1.16 vs 4.7 ± 0.81 and 0.7 vs 0.6, p < 0.05). The mean duration of surgery was significantly less in the LIFT group (46.43 ± 9.32 vs 89.29 ± 10.90 minutes). None had any postoperative complications, and >80% were discharged within 24 hours.

CONCLUSIONS:
The shorter operative duration, better quality of life at 6 months, and higher healing rate make LIFT a superior treatment option for high fistula in ano. However, studies with a large sample size will be needed to verify these results.
Using Right-Sided Roll to Improve Reliability of Focused Assessment with Sonography in Trauma: An Eastern Association for the Surgery of Trauma Multicenter Prospective Study
Authors: Cibulas Shumway Megan , Granet Jason , Solomon Rachele J , Parreco Joshua P , Lee Seong K , Pigneri Danielle A ,   for the FASTeR Study Group
Published: December 2022

BACKGROUND:
The Focused Assessment Sonography in Trauma (FAST) examination is the standard of care for detecting hemoperitoneum in hypotensive blunt trauma patients. A pilot study demonstrated earlier identification of intra-abdominal fluid via FAST after right-sided roll (FASTeR) when compared with the standard FAST. The purpose of this study was to evaluate this phenomenon prospectively in hypotensive blunt trauma patients.

STUDY DESIGN:
An Eastern Association for the Surgery of Trauma–approved multicenter prospective trial was performed June 2016 to October 2020 at 8 designated trauma centers. Hypotensive adult blunt trauma patients were included. A traditional FAST examination was performed. After this, the secondary survey logroll for back examination was standardized to the patient’s right side. A repeat supine right upper quadrant ultrasound view was obtained. The presence or absence of hemoperitoneum was confirmed by CT scan or intraoperative findings. FAST and FASTeR were compared using receiver operating characteristics. The area under the curve was calculated.

RESULTS:
A total of 182 patients met inclusion criteria. A total of 65 patients (35.7%) had hemoperitoneum on CT scan or intraoperative findings. The sensitivity of FASTeR was 47.7%, and of FAST was 40.0% (p = 0.019). The receiver operating characteristics area under the curve of the FASTeR examination was 0.717 vs 0.687 for the FAST examination (p = 0.091).

CONCLUSIONS:
Addition of a right upper quadrant view after right-sided roll does improve the sensitivity of the FAST examination while maintaining the standard positive predictive value. We demonstrate a trend that does not reach statistical significance about the overall accuracy. This multicenter prospective trial was underpowered to reveal a statistically significant difference in the overall accuracy as measured by the receiver operating characteristics area under the curve.
Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer
Authors: Rebernick Ryan J , Bell Hannah N , Bauer Tyler M , McEwen Dyke , Werkman Douglas F , Chang Andrew C , Lin Jules , Reddy Rishindra M , Kresty Laura , Lagisetty Kiran 
Published: December 2022

BACKGROUND:
Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study’s objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients.

STUDY DESIGN:
A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma).

RESULTS:
Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040).

CONCLUSIONS:
These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.
Mass Dynamics 2.0: An improved modular web-based platform for accelerated proteomics insight generation and decision making
Authors: Quaglieri Anna , Bloom Joseph , Triantafyllidis Aaron , Green Bradley , Condina Mark R. , Ngov Paula Burton , Infusini Giuseppe , Webb Andrew I. 
Published: December 2022

ABSTRACTData processing is essential to reliably generate knowledge from proteomics studies. The complexity of the proteomics data, as well as the ability of research teams to adopt complex analysis pipelines, have proven to be an obstacle to effective collaboration and more efficient biological insight generation.Here, we introduce MD 2.0, a cloud- and web-based platform for quantitative proteomics data, which implements a novel analysis workspace where statistical analyses, visualizations, and external knowledge generation are integrated into a modular framework. This modularity enables researchers the flexibility to test different hypotheses, and customize and template complex proteomics analyses, thereby expediting insight generation for complex datasets. The extensible MD 2.0 environment has been built with a scalable architecture to allow rapid development of future analysis modules and enhanced tools for remote collaboration, like experiment sharing and a live chat capability.The new drag-and-drop modules allow researchers to easily and quickly assess different aspects of an experiment, including quality control, differential expression and enrichment analysis. The modularity of MD 2.0 lays the foundation to support broader community-based analytical template generation and optimized sharing and collaboration between proteomics experts and biologists, thereby accelerating research teams’ abilities to extract knowledge from complex proteomics datasets.
Application of Aligned-UMAP to longitudinal biomedical studies
Authors: Dadu Anant , Satone Vipul K. , Kaur Rachneet , Koretsky Mathew J. , Iwaki Hirotaka , Qi Yue A. , Ramos Daniel M. , Avants Brian , Hesterman Jacob , Gunn Roger , Cookson Mark R. , Ward Michael E. , Singleton Andrew B , Campbell Roy H , Nalls Mike A , Faghri Faraz 
Published: December 2022

AbstractLongitudinal multi-dimensional biological datasets are ubiquitous and highly abundant. These datasets are essential to understanding disease progression, identifying subtypes, and drug discovery. Discovering meaningful patterns or disease pathophysiologies in these datasets is challenging due to their high dimensionality, making it difficult to visualize hidden patterns. Several methods have been developed for dimensionality reduction, but they are limited to cross-sectional datasets. Recently proposed Aligned-UMAP, an extension of the UMAP algorithm, can visualize high-dimensional longitudinal datasets. In this work, we applied Aligned-UMAP on a broad spectrum of clinical, imaging, proteomics, and single-cell datasets. Aligned-UMAP reveals time-dependent hidden patterns when color-coded with the metadata. We found that the algorithm parameters also play a crucial role and must be tuned carefully to utilize the algorithm’s potential fully.Altogether, based on its ease of use and our evaluation of its performance on different modalities, we anticipate that Aligned-UMAP will be a valuable tool for the biomedical community. We also believe our benchmarking study becomes more important as more and more high-dimensional longitudinal data in biomedical research becomes available.Highlights-explored the utility of Aligned-UMAP in longitudinal biomedical datasets-offer insights on optimal uses for the technique-provide recommendations for best practicesIn BriefHigh-dimensional longitudinal data is prevalent yet understudied in biological literature. High-dimensional data analysis starts with projecting the data to low dimensions to visualize and understand the underlying data structure. Though few methods are available for visualizing high dimensional longitudinal data, they are not studied extensively in real-world biological datasets. A recently developed nonlinear dimensionality reduction technique, Aligned-UMAP, analyzes sequential data. Here, we give an overview of applications of Aligned-UMAP on various biomedical datasets. We further provide recommendations for best practices and offer insights on optimal uses for the technique.
Generalizing the isothermal efficiency by using Gaussian distributions
Authors: Schneider Thomas D. 
Published: December 2022

AbstractUnlike the Carnot heat engine efficiency published in 1824, an isothermal efficiency derived from thermodynamics and information theory can be applied to biological systems. The original approach by Pierce and Cutler in 1959 to derive the isothermal efficiency equation came from Shannon’s channel capacity of 1949 and from Felker’s 1952 determination of the minimum energy dissipation needed to gain a bit. In 1991 and 2010 Schneider showed how the isothermal efficiency equation can be applied to molecular machines and that this can be used to explain why several molecular machines are 70% efficient. Surprisingly, some macroscopic biological systems, such as whole ecosystems, are also 70% efficient but it is hard to see how this could be explained by a thermodynamic and molecular theory. The thesis of this paper is that the isothermal efficiency can be derived without using thermodynamics by starting from a set of independent Gaussian distributions. This novel derivation generalizes the isothermal efficiency equation for use at all levels of biology, from molecules to ecosystems.
The role of Absorbing Markov Chains in childhood cancer
Authors: Margarit David H. , Reale Marcela V. , Scagliotti Ariel F. , Romanelli Lilia M. 
Published: December 2022

AbstractAbsorbing Markov Chains are an important mathematical tool used for different applications in science. On the other hand, cancer and its metastases in children have a significant impact on health due to their degree of lethality. Therefore, the aim of this work is to model the metastatic pathways of the main childhood cancers worldwide. The probabilities of generating metastases, from a primary site to secondary and tertiary sites, were characterized by constructing a directed graph and the associated transition matrix. In addition, the time of absorption and the probabilities of absorption by each absorbing state were calculated.
Deciphering the determinants of recombinant protein yield across the human secretome
Authors: Masson Helen O. , Kuo Chih-Chung , Malm Magdalena , Lundqvist Magnus , Sievertsson Åsa , Berling Anna , Tegel Hanna , Hober Sophia , Uhlén Mathias , Grassi Luigi , Hatton Diane , Rockberg Johan , Lewis Nathan E. 
Published: December 2022

AbstractMammalian cells are critical hosts for the production of most therapeutic proteins and many proteins for biomedical research. While cell line engineering and bioprocess optimization have yielded high protein titers of some recombinant proteins, many proteins remain difficult to express. Here, we decipher the factors influencing yields in Chinese hamster ovary (CHO) cells as they produce 2165 different proteins from the human secretome. We demonstrate that variation within our panel of proteins cannot be explained by transgene mRNA abundance. Analyzing the expression of the 2165 human proteins with machine learning, we find that protein features account for only 15% of the variability in recombinant protein yield. Meanwhile, transcriptomic signatures account for 75% of the variability across 95 representative samples. In particular, we observe divergent signatures regarding ER stress and metabolism among the panel of cultures expressing different recombinant proteins. Thus, our study unravels the factors underlying the variation on recombinant protein production in CHO and highlights transcriptomics signatures that could guide the rational design of CHO cell systems tailored to specific proteins.