tbuckley/cabot-search huggingface dataset:
Abstract PS3-25: Quantitation of serum thioredoxin 1 could mitigate difficulty to detect breast cancer from dense breasts by mammography
Authors: Kyoung Hoon Suh, Bo Bae Choi, Youn Ju Lee, Je Ryoong Kim, Jin Sun Lee, Young Kim
Journal: Cancer Research (2021)

Abstract Background: Even though almost half of women have dense breasts (DB), the density of breasts has been an obstacle to detect breast cancer (BC) correctly by the gold standard of screening, mammography. It is strongly recommended to take consideration of breast density in analyzing mammogram. We have reported the possibility of serum level of thioredoxin 1 (Trx1) as a novel means to assess the risk of BC regardless of various conditions of breasts. In present study, we have evaluated how serum level of Trx1 can mitigate the difficulty to detect BC from dense breast by mammography. Methods: We have generated monoclonal antibodies against Trx1 and developed an ELISA kit that quantitates Trx1 in serum. The level of Trx1 was determined in each serum from BC patients (n=106) who had been confirmed as BC by various examinations including mammography as well as surgery. Each Trx1 level was analyzed with corresponding patient’s mammography results such as patterns, asymmetry, shapes, margin, and density. The analyzed results were compared with those from other biomarker tests including CA15-5 and CEA to evaluate the clinical validity of Trx1 in this study. Each test was duplicated two times, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests.Results: Most of BC patients (82.6%, n=86) was classified as mammography pattern 3 and 4, and BI-RADS score higher than 4 (74.0%, n=77). More than half of patients’ breast density was in high density group (54.8%, n=57), whereas 5.8% of iso density (n=6) and 39.4% of not determined (n=41). The blood Trx1 levels of patients were higher than the cut-off value of 14 U/ml indicating BC regardless of characteristics of breasts. Although other breast cancer biomarker tests such as CA15-3 and CEA could not identify BC, Trx1 level could correctly detect BC even in the cases that mammography could not show the mass clearly. The sensitivity/specificity of mammography and Trx1 test were 75.2%/74.0% and 96.2%/99.0%, respectively. When mammography and Trx1 test were combined, the whole sensitivity/specificity was 99.3%/100.0%. Conclusion: Even though it is obvious that larger size of further study necessary, the serum Trx1 level showed that it could identify BC in dense breasts easily. These results indicated that serum Trx1 level could efficiently mitigate the difficulty to detect BC from dense breasts by mammography. Keywords: Thioredoxin 1, Breast cancer, Dense breast, Diagnostics, Sensitivity, Specificity, Blood Citation Format: Kyoung Hoon Suh, Bo Bae Choi, Youn Ju Lee, Je Ryoong Kim, Jin Sun Lee, Young Kim. Quantitation of serum thioredoxin 1 could mitigate difficulty to detect breast cancer from dense breasts by mammography [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-25.
Myofibroblast‐Specific Msi2 Knockout Inhibits HCC Progression in a Mouse Model
Authors: Chen Qu, Lu He, Nan Yao, Jinying Li, Yuchuan Jiang, Binkui Li, Shuang Peng, Kunpeng Hu, Dong Chen, Guo Chen, Wei Huang, Mingrong Cao, Jun Fan, Yunfei Yuan, Wencai Ye, Jian Hong
Journal: Hepatology (2021)

BACKGROUND AND AIMS Myofibroblasts play a pivotal role in the development and progression of HCC. Here, we aimed to explore the role and mechanism of myofibroblast Musashi RNA binding protein 2 (MSI2) in HCC progression. APPROACH AND RESULTS Myofibroblast infiltration and collagen deposition were detected and assessed in the tissues from 117 patients with HCC. Transgenic mice ( Msi2ΔCol1a1 ) with floxed Msi2 allele and collagen type I alpha 1 chain ( Col1a1 )–ligand inducible Cre recombinases ( CreER ) were constructed to generate a myofibroblast‐specific Msi2 knockout model. Mouse HCC cells were orthotopically transplanted into the Msi2ΔCol1a1 or the control mice ( Msi2F/F ). We found that the deposition of collagen fibers, the main product of myofibroblasts, predicted a poor prognosis for HCC; meanwhile, we detected high MSI2 expression in the peritumoral infiltrated myofibroblasts. Conditional deletion of Msi2 in myofibroblasts significantly inhibited the growth of orthotopically implanted HCC, reduced both intrahepatic and lung metastasis, and prolonged the overall survival of tumor‐bearing mice ( P = 0.002). In vitro analysis demonstrated that myofibroblasts promoted cell proliferation, invasion, and epithelial–mesenchymal transformation of HCC cells, whereas Msi2 deletion in myofibroblasts reversed these effects. Mechanically, Msi2 knockout decreased myofibroblast‐derived IL‐6 and IL‐11 secretion by inhibiting the extracellular signal–regulated kinase 1/2 pathway, and thus attenuated the cancer stem cell–promoting effect of myofibroblasts. Interestingly, we found that the simultaneous knockout of Msi2 in myofibroblasts and knockdown of Msi2 in HCC cells could not further attenuate the implanted HCC progression. CONCLUSIONS Myofibroblast‐specific Msi2 knockout abrogated the tumor‐promoting function of myofibroblasts and inhibited HCC progression in mouse models. Targeting myofibroblast MSI2 expression may therefore prove to be a therapeutic strategy for HCC treatment in the future.
mRNA vaccine: a potential therapeutic strategy
Authors: Yang Wang, Ziqi Zhang, Jingwen Luo, Xuejiao Han, Yuquan Wei, Xiawei Wei
Journal: Molecular Cancer (2021)

Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.
Urology surgeon faces GMC charges of inappropriate treatments for financial gain
Authors: Clare Dyer
Journal: BMJ (2021)

A consultant surgeon faces accusations by the General Medical Council (GMC) of administering inappropriate cancer treatments for financial gain, at a tribunal hearing scheduled to last until June.

Paul Miller, 62, was dismissed as a consultant by Sussex and Surrey Healthcare NHS Trust in 2014 after an investigation by the Royal College of Surgeons found that 27 patients had been harmed in his care.

A 2019 inquest into the deaths of 10 of his patients heard that he had been the subject of complaints from colleagues as long ago as 2008 …
Abstract 14716: Differences in Pharmacological Potency Influence Blood Pressure Response to Celecoxib and Naproxen
Authors: Katherine N Theken, Soumita Ghosh, Carsten Skarke, Susanne Fries, Nicholas F Lahens, Dimitra Sarantopoulou, Gregory R Grant, Garret A FitzGerald, Tilo Grosser
Journal: Circulation (2019)

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of adverse cardiovascular events via suppression of cyclooxygenase (COX)-2-derived prostacyclin (PGI2) formation in he...
Therapeutic Potential of Ketone Bodies for Patients With Cardiovascular Disease
Authors: Salva R. Yurista, Cher-Rin Chong, Juan J. Badimon, Daniel P. Kelly, Rudolf A. de Boer, B. Daan Westenbrink
Journal: Journal of the American College of Cardiology (2021)

Metabolic perturbations underlie a variety of cardiovascular disease states; yet, metabolic interventions to prevent or treat these disorders are sparse. Ketones carry a negative clinical stigma as they are involved in diabetic ketoacidosis. However, evidence from both experimental and clinical research has uncovered a protective role for ketones in cardiovascular disease. Although ketones may provide supplemental fuel for the energy-starved heart, their cardiovascular effects appear to extend far beyond cardiac energetics. Indeed, ketone bodies have been shown to influence a variety of cellular processes including gene transcription, inflammation and oxidative stress, endothelial function, cardiac remodeling, and cardiovascular risk factors. This paper reviews the bioenergetic and pleiotropic effects of ketone bodies that could potentially contribute to its cardiovascular benefits based on evidence from animal and human studies.
Association of Bone Metastatic Burden With Survival Benefit From Prostate Radiotherapy in Patients With Newly Diagnosed Metastatic Prostate Cancer
Authors: Adnan Ali, Alex Hoyle, Áine M. Haran, Christopher D. Brawley, Adrian Cook, Claire Amos, Joanna Calvert, Hassan Douis, Malcolm D. Mason, David Dearnaley, Gerhardt Attard, Silke Gillessen, Mahesh K. B. Parmar, Christopher C. Parker, Matthew R. Sydes, Nicholas D. James, Noel W. Clarke
Journal: JAMA Oncology (2021)

Prostate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site.
Cardiac Transthyretin Amyloidosis
Authors: Ana Roteta Unceta Barrenechea, Miguel Angel Aibar Arregui, Daniel Nogueira Souto, Jorge Melero Polo, Inmaculada Moreno Gázquez, Leticia Tardin Cardoso, Yasmina Saker Diffalah, Alejandro Andrés Gracia
Journal: Clinical Nuclear Medicine (2021)

Amyloidosis is a heterogeneous group of diseases caused by abnormal extracellular deposition of insoluble proteins and can involve myocardium. One of the causes of myocardial involvement is TTR amyloidosis. Our objective has been to evaluate the situation of cardiac amyloidosis (CA) in our center and the role of nuclear medicine, and to review the state of the art of nuclear medicine in this entity.We have evaluated retrospectively 186 patients with clinical suspicion of CA and analyzed the clinical characteristics, free light chains and immunofixation in serum and/or urine, and the most relevant biomarkers associated with transthyretin CA (C-ATTR) of these patients and compared them with the results of the 99mTc-DPD scintigraphy.We have verified the growing bibliographic evidence concerning C-ATTR. A total of 51 scintigraphies (27.4%) were positive, 2 (1.1%) indeterminate and 133 (71.5%) negative according to the Perugini score. ATTR was diagnosed in 22 (11.8%; 77.3% males; mean age, 79.4 years). Of these, 12 (75% men; 82.3 years) were ATTRwt (wild-type or age-associated) patients, 2 (50% men; 52 years) experienced ATTRv (variant or hereditary), and 8 (87.5% men; 82.3 years) were not classified because of the absence genetic test. The origin of amyloidosis could not be determined in 31 (16.7%; 80.7% males; 84.5 years). In 29 of them (93.6%), it was because there was no study of free light chains or immunofixation.Nuclear medicine is playing an increasing role in the diagnosis and classification of CA. However, the monitoring of these is still patchy.
Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity
Authors: Thomas A. Wadden, Timothy S. Bailey, Liana K. Billings, Melanie Davies, Juan P. Frias, Anna Koroleva, Ildiko Lingvay, Patrick M. O’Neil, Domenica M. Rubino, Dorthe Skovgaard, Signe O. R. Wallenstein, W. Timothy Garvey
Journal: JAMA (2021)

<h3>Importance</h3> Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. <h3>Objective</h3> To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. <h3>Design, Setting, and Participants</h3> Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). <h3>Interventions</h3> Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. <h3>Main Outcomes and Measures</h3> The co–primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. <h3>Results</h3> Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo (difference, −10.3 percentage points [95% CI, −12.0 to −8.6];<i>P</i> &lt; .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively;<i>P</i> &lt; .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively;<i>P</i> &lt; .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. <h3>Conclusions and Relevance</h3> Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03611582
Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters
Authors: Frederik Trinkmann, Máté Maros, Katharina Roth, Arne Hermanns, Julia Schäfer, Joshua Gawlitza, Joachim Saur, Ibrahim Akin, Martin Borggrefe, Felix J F Herth, Thomas Ganslandt
Journal: Thorax (2021)

Background Multiple breath washout (MBW) using sulfur hexafluoride (SF 6 ) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF 6 -MBW reference values in pulmonary healthy adults. Methods We evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20–88 years). Lung clearance index (LCI), acinar (S acin ) and conductive (S cond ) ventilation heterogeneity were derived from triplicate SF 6 -MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI 2.5 ) and 5% (LCI 5 ) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile. Results Age was the only meaningful parameter influencing SF 6 -MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in S acin and 10% (CI 2% to 22%) in S cond . Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in S acin and 3% (CI 0% to 13%) in S cond . Conclusion SF 6 -MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF 6 -MBW outcome parameters over the whole age range. Trial registration number NCT04099225 .
RET Fluorescence In Situ Hybridization Analysis Is a Sensitive but Highly Unspecific Screening Method for RET Fusions in Lung Cancer
Authors: Teodora Radonic, W.R.R. Geurts-Giele, Kris G. Samsom, Guido M.J. M. Roemen, Jan H. von der Thüsen, Erik Thunnissen, Isabelle C. Meijssen, Hein F.B. M. Sleddens, Winand N.M. Dinjens, Mirjam C. Boelens, Karin Weijers, Ernst Jan M. Speel, Stephen P. Finn, Cathal O’Brien, Tom van Wezel, Danielle Cohen, Kim Monkhorst, Paul Roepman, H.J. Dubbink
Journal: Journal of Thoracic Oncology (2021)

RET gene fusions are established oncogenic drivers in 1% of NSCLC. Accurate detection of advanced patients with RET fusions is essential to ensure optimal therapy choice. We investigated the performance of fluorescence in situ hybridization (FISH) as a diagnostic test for detecting functional RET fusions.Between January 2016 and November 2019, a total of 4873 patients with NSCLC were routinely screened for RET fusions using either FISH (n = 2858) or targeted RNA next-generation sequencing (NGS) (n = 2015). If sufficient material was available, positive cases were analyzed by both methods (n = 39) and multiple FISH assays (n = 17). In an independent cohort of 520 patients with NSCLC, whole-genome sequencing data were investigated for disruptive structural variations and functional fusions in the RET and compared with ALK and ROS1 loci.FISH analysis revealed RET rearrangement in 48 of 2858 cases; of 30 rearranged cases double tested with NGS, only nine had a functional RET fusion. RNA NGS yielded RET fusions in 14 of 2015 cases; all nine cases double tested by FISH had RET locus rearrangement. Of these 18 verified RET fusion cases, 16 had a split signal and two a complex rearrangement by FISH. By whole-genome sequencing, the prevalence of functional fusions compared with all disruptive events was lower in the RET (4 of 9, 44%) than the ALK (27 of 34, 79%) and ROS1 (9 of 12, 75%) loci.FISH is a sensitive but unspecific technique for RET screening, always requiring a confirmation using an orthogonal technique, owing to frequently occurring RET rearrangements not resulting in functional fusions in NSCLC.
Effect of race and ethnicity on influenza vaccine uptake among older US Medicare beneficiaries: a record-linkage cohort study
Authors: Salaheddin M Mahmud, Liou Xu, Laura Lee Hall, Gary Puckrein, Edward Thommes, Matthew M Loiacono, Ayman Chit
Journal: The Lancet Healthy Longevity (2021)

Seasonal influenza vaccine (SIV) uptake among US adults aged 65 years or older remains suboptimal and stagnant. Further, there is growing concern around racial and ethnic disparities in uptake. We aimed to assess racial and ethnic disparities in overall SIV and in high-dose vaccine (HDV) uptake among Medicare beneficiaries during the 2015-16 influenza season and sought to identify possible mediators for observed disparities.We did a historical record-linkage cohort study using Medicare (a US national health insurance programme) databases, which included all older adults (≥65 years) enrolled in Medicare during the study period (July 1, 2015, to June 30, 2016). We excluded beneficiaries of Medicare Part C (managed care offered by private companies), and residents of long-term care facilities. The primary outcome was SIV receipt during the study period, classified into receipt of HDV and standard-dose vaccines (SDVs, representing all other SIVs). SIV uptake probabilities were estimated using competing-risk survival analysis methods. Mediation analyses were done to investigate potential mediators of the association between race and ethnicity and uptake.During the study period, of 26·5 million beneficiaries in the study cohort, 47·4% received a SIV, 52·7% of whom received HDV. Compared with white beneficiaries (49·4%), Hispanic (29·1%), Black (32·6%), and Asian (47·6%) beneficiaries were less likely to be vaccinated and, when vaccinated, were less likely to receive HDV (37·8% for Hispanic people, 41·1% for Black people, and 40·3% for Asian people, compared with 53·8% of white people who received HDV). Among those vaccinated, after accounting for region, income, chronic conditions, and health-care use, minority groups were 26-32% less likely to receive HDV, relative to white people (odds ratio [OR] 0·68 [95% CI 0·68-0·69] for Black people; OR 0·71 [0·71-0·72] for Asian people; and OR 0·74 [0·73-0·74] for Hispanic people).Substantial racial and ethnic disparities in SIV uptake among Medicare beneficiaries aged 65 years or older are evident. New legislative, fiscal, and educational strategies are urgently needed to address these inequities.Sanofi Pasteur.
Short-term outcomes of complete mesocolic excision versus D2 dissection in patients undergoing laparoscopic colectomy for right colon cancer (RELARC): a randomised, controlled, phase 3, superiority trial
Authors: Lai Xu, Xiangqian Su, Zirui He, Chenghai Zhang, Junyang Lu, Guannan Zhang, Yueming Sun, Xiaohui Du, Pan Chi, Ziqiang Wang, Ming Zhong, Aiwen Wu, Anlong Zhu, Fei Li, Jianmin Xu, Liang Kang, Jian Suo, Haijun Deng, Yingjiang Ye, Kefeng Ding, Tao Xu, Zhongtao Zhang, Minhua Zheng, Yi Xiao, Lai Xu, Xiangqian Su, Zirui He, Chenghai Zhang, Junyang Lu, Lei Chen, Guannan Zhang, Bo Feng, Lu Zang, Junjun Ma, Yueming Sun, Yifei Feng, Dongjian Ji, Xiaohui Du, Changzheng He, Ze Fu, Pan Chi, Ying Huang, Weizhong Jiang, Ziqiang Wang, Qingbin Wu, Ming Zhong, Minhao Yu, Aiwen Wu, Pengju Chen, Anlong Zhu, Wenlong Guan, Bin Wu, Fei Li, Ang Li, Jianmin Xu, Guodong He, Liang Kang, Xiaowen He, Jian Suo, Daguang Wang, Haijun Deng, Yanan Wang, Yingjiang Ye, Kai Shen, Guole Lin, Hongwei Yao, Huizhong Qiu, Kefeng Ding, Tao Xu, Zhiyong Liang, Weixun Zhou, Huadan Xue, Bin Li, Zhongtao Zhang, Minhua Zheng, Yi Xiao
Journal: The Lancet Oncology (2021)
Cancer Cell-Specific Major Histocompatibility Complex II Expression as a Determinant of the Immune Infiltrate Organization and Function in the NSCLC Tumor Microenvironment
Authors: Amber M. Johnson, Jennifer M. Boland, Julia Wrobel, Emily K. Klezcko, Mary Weiser-Evans, Katharina Hopp, Lynn Heasley, Eric T. Clambey, Kimberly Jordan, Raphael A. Nemenoff, Erin L. Schenk
Journal: Journal of Thoracic Oncology (2021)
Abstract 11421: A Metabolomic Pattern Predicts Incident Coronary Heart Disease: Findings From the Atherosclerosis Risk in Communities Study
Authors: Zhe Wang, Cong Zhu, Alanna C Morrison, Aaron R Folsom, Christie M Ballantyne, Eric Boerwinkle, Bing Yu
Journal: Circulation (2018)

Background: Metabolic changes may be detectable in at-risk individuals prior to the onset of coronary heart disease (CHD). Identifying a pattern of metabolites associated with CHD may provide novel...