MULTICENTER, PROSPECTIVE TRIAL OF NON-ENDOSCOPIC BIOMARKER-DRIVEN DETECTION OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA.

BACKGROUND: Preliminary data suggest that an encapsulated balloon (EsoCheckTM), coupled with a two methylated DNA biomarker panel (EsoGuardTM), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay required sample freezing upon collection. AIM: Assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by utilizing a CLIA-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD), EAC, junctional adenocarcinoma (JAC), plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at six institutions delivered the encapsulated balloon per orally, with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus, then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1). RESULTS: A total of 243 evaluable patients - 88 cases (median age 68, 78% men, 92% white) and 155 controls (median age 57, 41% men, 88% white) - underwent adequate EsoCheck sampling. Mean procedural time was approximately 3 minutes. Cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) non-dysplastic and dysplastic BE cases were short segment BE (SSBE; < 3 cm). Overall sensitivity was 85% (95% CI= 0.78-0.93), and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n=18). CONCLUSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

A Method of Producing Low-Density, High-Strength Thin Cement Sheets: Pilot Run for a Glass-Free Solar Panel.

This paper presents an innovative method of producing a low-density, high-strength, thin cement sheet. A seaweed powder was mixed with Portland cement, a foaming agent, calcium sulfoaluminate (CSA), and a quantity of water to create an A4-sized thin sheet with a thickness of 7 mm, which can withstand 1.5 kg in weight. This sheet was then covered with ethylene vinyl acetate and a backsheet to create a sandwiched cement sheet. The advantages of this sandwiched cement sheet are two-fold. First, it can support up to 13 kg in a static mechanical loading test, without bending, for over eight hours. Second, it can be quickly recovered at the end of its life cycle. This was a preliminary experiment to produce a large cement sheet that could satisfy the loading requirements for a solar panel. The purpose of the large, thin cement sheet is to replace the glass in a conventional solar panel and create a lightweight solar panel of less than 10 kg, which would mean that the installation of solar panels would become a one-person operation rather than a two-person operation. It would also increase the efficiency of the solar panel installation process.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

NON-ENDOSCOPIC ESOPHAGEAL SAMPLING DEVICE AND BIOMARKER PANEL FOR DETECTION OF BARRETT'S ESOPHAGUS (BE) AND ESOPHAGEAL ADENOCARCINOMA (EAC).

BACKGROUND: We previously reported an encapsulated balloon (EsoCheck TM , EC), which selectively samples the distal esophagus, that coupled with a two methylated DNA biomarker panel (EsoGuard TM , EG), detected Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with a sensitivity and specificity of 90.3% and 91.7%, respectively. This previous study utilized frozen EC samples. AIM: To assess a next generation EC sampling device and EG assay that utilizes a room temperature sample preservative to enable office-based testing. METHODS: Cases with nondysplastic (ND) and dysplastic (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD) BE, EAC, junctional adenocarcinoma (JAC) and controls with no intestinal metaplasia (IM) were included. Nurses or physician assistants at six institutions, who were trained in EC administration, delivered the encapsulated balloon per orally and inflated it in the stomach. The inflated balloon was pulled back to sample 5 cm of the distal esophagus, then deflated and retracted into the EC capsule to prevent sample contamination from proximal esophagus. Nextgen EG sequencing assays performed on bisulfite-treated DNA extracted from EC samples determined levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1) in a CLIA-certified laboratory, blinded to patients' phenotypes. RESULTS: A total of 243 evaluable patients - 88 cases (median age 68 years, 78% men, 92% white) and 155 controls (median age 57 years, 41% men, 88% white) - underwent adequate EC sampling. Mean time for EC sampling was just over 3 minutes. The cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) of the non-dysplastic and dysplastic BE cases were short-segment BE (SSBE; < 3 cm). Overall sensitivity for detecting all cases was 85% (95% CI= 0.78-0.93) and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84% (n=37). The EC/EG test detected 100% of cancers. CONCLUSION: The next-generation EC/EG technology has been both successfully updated to incorporate a room temperature sample collection preservative and successfully implemented in a CLIA certified laboratory. When performed by trained personnel, EC/EG detects non-dysplastic BE, dysplastic BE, and cancer with high sensitivity and specificity, replicating the operating characteristics of the initial pilot study of this technology. Future applications utilizing EC/EG to screen broader populations at risk for developing cancer are proposed. SIGNIFICANCE: This multi-center study demonstrates the successful performance of a commercially available clinically implementable non-endoscopic screening test for BE in the U.S., as recommended in the most recent ACG Guideline and AGA Clinical Update. It transitions and validates a prior academic laboratory-based study of frozen research samples over to a CLIA laboratory, one that also integrates a clinically practical room temperature method for sample acquisition and storage, enabling office-based screening.

Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer.

BACKGROUND: Risk factors contributing to more than 10-fold increase in esophageal cancer in the last 50 years remain underexplored. We aim to examine the associations of sleep behaviors with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). METHODS: We prospectively assessed the associations between sleep behaviors (chronotype, duration, daytime napping, daytime sleepiness, snoring, and insomnia) and EAC and ESCC risk in 393,114 participants in the UK Biobank (2006-2016). Participants with 0, 1, and ≥2 unhealthy behaviors, including sleep <6 or >9 h/d, daytime napping, and usual daytime sleepiness were classified as having a good, intermediate, and poor sleep. For EAC, we also examined interactions with polygenic risk score (PRS). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We documented 294 incident EAC and 95 ESCC. Sleep >9 h/d (HR, 2.05; 95% CI, 1.18-3.57) and sometimes daytime napping (HR, 1.36; 95% CI, 1.06-1.75) were individually associated with increased EAC risk. Compared with individuals with good sleep, those with intermediate sleep had a 47% (HR, 1.47; 95% CI, 1.13-1.91) increased EAC risk, and those with poor sleep showed an 87% (HR, 1.87; 95% CI, 1.24-2.82) higher risk (Ptrend < 0.001). The elevated risks for EAC were similar within strata of PRS (Pinteraction = 0.884). Evening chronotype was associated with elevated risk of ESCC diagnosed after 2 years of enrollment (HR, 2.79; 95% CI, 1.32-5.88). CONCLUSIONS: Unhealthy sleep behaviors were associated with an increased risk of EAC, independent of genetic risk. IMPACT: Sleep behaviors may serve as modifiable factors for the prevention of EAC.

DNA Methylation-Dependent Restriction of Tyrosine Hydroxylase Contributes to Pancreatic ß-Cell Heterogeneity.

The molecular and functional heterogeneity of pancreatic ß-cells is well recognized, but the underlying mechanisms remain unclear. Pancreatic islets harbor a subset of ß-cells that co-express tyrosine hydroxylase (TH), an enzyme involved in synthesis of catecholamines that repress insulin secretion. Restriction of the TH+ ß-cells within islets is essential for appropriate function in mice, such that a higher proportion of these cells corresponds to reduced insulin secretion. Here, we use these cells as a model to dissect the developmental control of ß-cell heterogeneity. We define the specific molecular and metabolic characteristics of TH+ ß-cells and show differences in their developmental restriction in mice and humans. We show that TH expression in ß-cells is restricted by DNA methylation during ß-cell differentiation. Ablation of de novo DNA methyltransferase Dnmt3a in the embryonic progenitors results in a dramatic increase in the proportion of TH+ ß-cells, whereas ß-cell-specific ablation of Dnmt3a does not. We demonstrate that maintenance of Th promoter methylation is essential for its continued restriction in postnatal ß-cells. Loss of Th promoter methylation in response to chronic overnutrition increases the number of TH+ ß-cells, corresponding to impaired ß-cell function. These results reveal a regulatory role of DNA methylation in determining ß-cell heterogeneity.

Patient Factors Affect Ergonomic Strain of Endoscopists During Colonoscopy.

INTRODUCTION: Endoscopic procedures place a great deal of muscular strain on providers, especially over the span of their careers. In this study we quantitatively analyzed the effects of patient factors such as age, body mass index, and sex on the ergonomics of endoscopists performing colonoscopies. METHODS: Surface electromyography (sEMG) was used to measure ergonomic strain of physicians while performing colonoscopies in several key muscle groups. The percent of the maximum voluntary contraction (%MVC) was used as a measure of muscular strain. Data was then analyzed based on the patient characteristics above. RESULTS: Endoscopists performing colonoscopies on female patients (n = 47) experienced significantly higher ergonomic strain in their right trapezius and right posterior forearm muscle groups when compared to colonoscopies performed on males (n = 35) (%MVC R-trapezius: Male: 8.2; Female: 8.9; p = 0.048); (%MVC R-posterior forearm: Male: 10.4; Female: 11.6; p = 0.0006). Operators experienced greater strain in the same muscle groups when performing colonoscopies on patients with BMI ≤ 25 (n = 25) when compared to patients with BMI > 25 (n = 57) (%MVC R-trapezius: BMI < 25: 9.7; BMI ≥ 25: 8.2; p = 0.0002); (%MVC R-posterior forearm: BMI < 25: 11.9; BMI ≥ 25: 10.8; p = 0.0001). CONCLUSION: Physicians experienced greater ergonomic strain when performing colonoscopies on female patients and on patients with a BMI < 25. We believe that these factors potentially impact the tortuosity of the colon and therefore influence the difficulty of navigating the endoscope. These results may aid physicians in gauging the anticipated difficulty of colonoscopies based on patient factors. Increased awareness of their posturing and ergonomics during challenging cases will alleviate musculoskeletal injuries in the long run.

Implementing Educational and Systems-Level Changes to Improve Cancer Screening Rates Among State Employees in Missouri.

As of 2022, only 51% of active eligible state employees in Missouri have been screened for colorectal cancer and 67% for breast cancer, despite having state-sponsored health insurance. In fall 2020, the Missouri Department of Health and Senior Services Comprehensive Cancer Program partnered with the Missouri Cancer Consortium to create a strategy to improve cancer screening rates among state employees. The project was designed to include 3 phases: 1) a colorectal cancer education phase, 2) an expanded education phase that included additional cancers, and 3) a proposed intervention phase that will include screening events. In the first phase, in 2020, colorectal cancer educational materials were sent to all state employees. In the second phase, in 2022, educational resources were expanded to include additional cancers and screening tools. In both initiatives, educational materials and information on current screening recommendations were distributed to approximately 40,000 state employees. A database of screening rates was developed to monitor screening rates and challenge state employees to complete screenings. Evidence-informed interventions were implemented with a focus on health equity. We used a regional approach to identify geographic areas with the greatest need. These efforts will support the next phase of the project, which involves planning breast and colorectal cancer screening events. Policy changes will be encouraged to remove systems-level barriers that discourage employees from being screened for cancer. Recommended tools and strategies can be adopted by similar organizations with complex, multitier employee structures.

The 17-gene stemness score associates with relapse risk and long-term outcomes following allogeneic haematopoietic cell transplantation in acute myeloid leukaemia.

A 17-gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia-free survival (LFS), relapse incidence (RI) and non-relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub-groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft-versus-host-disease was associated with more favourable outcomes in both groups. The 17-gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study.

BACKGROUND: The multifactorial Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) breast cancer risk prediction model has been recently extended to consider all established breast cancer risk factors. We assessed the clinical validity of the model in a large independent prospective cohort. METHODS: We validated BOADICEA (V.6) in the Swedish KARolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort including 66 415 women of European ancestry (median age 54 years, IQR 45-63; 816 incident breast cancers) without previous cancer diagnosis. We calculated 5-year risks on the basis of questionnaire-based risk factors, pedigree-structured first-degree family history, mammographic density (BI-RADS), a validated breast cancer polygenic risk score (PRS) based on 313-SNPs, and pathogenic variant status in 8 breast cancer susceptibility genes: BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D and BARD1. Calibration was assessed by comparing observed and expected risks in deciles of predicted risk and the calibration slope. The discriminatory ability was assessed using the area under the curve (AUC). RESULTS: Among the individual model components, the PRS contributed most to breast cancer risk stratification. BOADICEA was well calibrated in predicting the risks for low-risk and high-risk women when all, or subsets of risk factors are included in the risk prediction. Discrimination was maximised when all risk factors are considered (AUC=0.70, 95% CI: 0.66 to 0.73; expected-to-observed ratio=0.88, 95% CI: 0.75 to 1.04; calibration slope=0.97, 95% CI: 0.95 to 0.99). The full multifactorial model classified 3.6% women as high risk (5-year risk ≥3%) and 11.1% as very low risk (5-year risk <0.33%). CONCLUSION: The multifactorial BOADICEA model provides valid breast cancer risk predictions and a basis for personalised decision-making on disease prevention and screening.

Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia.

PURPOSE: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE). EXPERIMENTAL DESIGN: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples. RESULTS: Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P < 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples. CONCLUSIONS: A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation-based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.

A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia.

The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor and mature cell types. Leukemia hierarchy composition was associated with functional, genomic and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP and Intermediate. Critically, variation in hierarchy composition along the Primitive versus GMP or Primitive versus Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A seven-gene biomarker derived from the Primitive versus Mature axis was associated with response to 105 investigational drugs. Cellular hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.

Age of diagnosis in familial Barrett's associated neoplasia.

The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC. The Familial Barrett's Esophagus Consortium database was used to identify individuals with HGD and EAC. These individuals were subsequently split into three kindred groups: non-familial-a single affected family member, duplex-two affected family members, and multiplex-three or more affected family members. Age of cancer diagnosis and other risk factors were compared between individuals in these groups. The study included 441 non-familial, 46 duplex, and 13 multiplex individuals. There was a statistically significant difference for age of diagnosis for individuals in the multiplex families compared to the non-familial and duplex families (56.0 versus 64.3, 63.5; p = 0.049). There was no significant difference between demographic factors and other cancer risk factors between family types. The results of this study support a genetic basis for familial Barrett's associated neoplasia and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.

Does quantification of [11C]meta-hydroxyephedrine and [13N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.

BACKGROUND: In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. METHODS: This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling. RESULTS: During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67). CONCLUSION: Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

A clinical laboratory-developed LSC17 stemness score assay for rapid risk assessment of patients with acute myeloid leukemia.

Leukemia stem cells (LSCs) are linked to relapse in acute myeloid leukemia (AML). The LSC17 gene expression score robustly captures LSC stemness properties in AML and can be used to predict survival outcomes and response to therapy, enabling risk-adapted, upfront treatment approaches. The LSC17 score was developed and validated in a research setting. To enable widespread use of the LSC17 score in clinical decision making, we established a laboratory-developed test (LDT) for the LSC17 score that can be deployed broadly in clinical molecular diagnostic laboratories. We extensively validated the LSC17 LDT in a College of American Pathologists/Clinical Laboratory Improvements Act (CAP/CLIA)-certified laboratory, determining specimen requirements, a synthetic control, and performance parameters for the assay. Importantly, we correlated values from the LSC17 LDT to clinical outcome in a reference cohort of patients with AML, establishing a median assay value that can be used for clinical risk stratification of individual patients with newly diagnosed AML. The assay was established in a second independent CAP/CLIA-certified laboratory, and its technical performance was validated using an independent cohort of patient samples, demonstrating that the LSC17 LDT can be readily implemented in other settings. This study enables the clinical use of the LSC17 score for upfront risk-adapted management of patients with AML.

Smaller hands and less experience are associated with greater ergonomic strain during endoscopic procedures.

INTRODUCTION: Up to 89% of physicians who routinely perform endoscopy experience some type of musculoskeletal pain. In this study, we sought to quantitatively analyze provider factors that influence ergonomic strain during live endoscopic procedures. METHODS: Surface electromyography (sEMG) was used to measure ergonomic strain on physicians while performing upper and lower endoscopies. EMG data were normalized to a maximal voluntary contraction (MVC) recording for each muscle group, yielding a %MVC value. Subgroup analyses were performed based on glove size, physician training level, specialty, and handedness. RESULTS: A total of 165 upper (n = 68) and lower (n = 97) endoscopies were recorded. Endoscopists with small hand sizes had significantly higher ergonomic strain in the left anterior and posterior forearm muscle compartments as compared to endoscopists with medium or large hands (%MVC L-anterior: small: 9.1 ± 1.1; medium: 6.4 ± 1.2; large: 5.9 ± 1.6; p < 0.001); (%MVC L-posterior: small: 12.0 ± 0.8; medium: 9.4 ± 1.3; large: 8.8 ± 1.4; p < 0.001). Additionally, upper body muscle groups had significantly higher ergonomic strain in endoscopists with less lifetime endoscopic experience (%MVC R-trapezius: expert: 8.4 ± 1.2; novice: 9.3 ± 1.2; p < 0.05); (%MVC R-deltoid: expert: 6.1 ± 1.4; novice: 8.5 ± 1.3; p < 0.001). There were no significant ergonomic differences between surgeons or gastroenterologists and no differences between right- and left-handed dominant individuals. CONCLUSIONS: Endoscopists with small hands experienced great ergonomic strain in their left forearm. Our data support the widely held belief that "one size does not fit all" and will hopefully spark change in the design of future endoscopes by device manufacturers. Our data also support that the experience level of the endoscopist contributed significantly to ergonomic performance, likely due to postural differences leading to decreased upper body strain. Therefore, it remains critically important to educate young proceduralists on strategies for ergonomic relief early in his or her endoscopic training program that can ameliorate ergonomic strain that accrues over the lifetime of a physician's career.

SUMO wrestling cancer stem cells.

Sumoylation is a reversible post-translational modification implicated in cancer. In this issue of Cell Chemical Biology, Benoit et al. describe an inhibitor of sumoylation that results in anti-proliferative effects in cancer stem cell models via the sumoylation enzyme SAE2.

Colonoscopy polyp detection and classification: Dataset creation and comparative evaluations.

Colorectal cancer (CRC) is one of the most common types of cancer with a high mortality rate. Colonoscopy is the preferred procedure for CRC screening and has proven to be effective in reducing CRC mortality. Thus, a reliable computer-aided polyp detection and classification system can significantly increase the effectiveness of colonoscopy. In this paper, we create an endoscopic dataset collected from various sources and annotate the ground truth of polyp location and classification results with the help of experienced gastroenterologists. The dataset can serve as a benchmark platform to train and evaluate the machine learning models for polyp classification. We have also compared the performance of eight state-of-the-art deep learning-based object detection models. The results demonstrate that deep CNN models are promising in CRC screening. This work can serve as a baseline for future research in polyp detection and classification.