tbuckley/cabot-search huggingface dataset:
TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination
Authors: Benjamin C. Chandler, Leah Moubadder, Cassandra L. Ritter, Meilan Liu, Meleah Cameron, Kari Wilder-Romans, Amanda Zhang, Andrea M. Pesch, Anna R. Michmerhuizen, Nicole Hirsh, Marlie Androsiglio, Tanner Ward, Eric Olsen, Yashar S. Niknafs, Sofia Merajver, Dafydd G. Thomas, Powel H. Brown, Theodore S. Lawrence, Shyam Nyati, Lori J. Pierce, Arul Chinnaiyan, Corey Speers
Journal: Journal of Clinical Investigation (2020)

Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use of radiation therapy (RT); therefore, approaches that result in radiosensitization of basal-like BC are critically needed. Using patients' tumor gene expression data from 4 independent data sets, we correlated gene expression with recurrence to find genes significantly correlated with early recurrence after RT. The highest-ranked gene, TTK, was most highly expressed in basal-like BC across multiple data sets. Inhibition of TTK by both genetic and pharmacologic methods enhanced radiosensitivity in multiple basal-like cell lines. Radiosensitivity was mediated, at least in part, through persistent DNA damage after treatment with TTK inhibition and RT. Inhibition of TTK impaired homologous recombination (HR) and repair efficiency, but not nonhomologous end-joining, and decreased the formation of Rad51 foci. Reintroduction of wild-type TTK rescued both radioresistance and HR repair efficiency after TTK knockdown; however, reintroduction of kinase-dead TTK did not. In vivo, TTK inhibition combined with RT led to a significant decrease in tumor growth in both heterotopic and orthotopic, including patient-derived xenograft, BC models. These data support the rationale for clinical development of TTK inhibition as a radiosensitizing strategy for patients with basal-like BC, and efforts toward this end are currently underway.
Advances and Impact of Antioxidant Hydrogel in Chronic Wound Healing
Authors: Zejun Xu, Shuyan Han, Zhipeng Gu, Jun Wu
Journal: Advanced Healthcare Materials (2020)

Abstract The accelerating and thorough treatment of chronic wounds still represents a major unmet medical need owing to the complex symptoms resulting from metabolic disorder of the wound microenvironment. Although numerous strategies and bioactive hydrogels are developed, an effective and widely used method of chronic wound treatment remains a bottleneck. With the aim to accelerate chronic wound healing, many hydrogel dressings with antioxidant functions have emerged and are proven to accelerate wound healing, especially for chronic wound repair. The new strategy in chronic wound treatment brought by antioxidant hydrogels is of great significance to human health. Here, the application of antioxidant hydrogels in the repair of chronic wounds is discussed systematically, aiming to provide an important theoretical reference for the further breakthrough of chronic wound healing.
Antinuclear antibodies and subclinical interstitial lung disease in community-dwelling adults: the MESA study
Authors: Elana J. Bernstein, John H.M. Austin, Steven M. Kawut, Ganesh Raghu, Eric A. Hoffman, John D. Newell, Jubal R. Watts, P. Hrudaya Nath, Sushilkumar K. Sonavane, R. Graham Barr, David J. Lederer
Journal: European Respiratory Journal (2020)

The presence of a systemic autoimmune rheumatic disease (ARD) is a well-known risk factor for interstitial lung disease (ILD). For example, 33% of adults with rheumatoid arthritis (RA) have subclinical ILD [1]. Higher serum levels of IgM rheumatoid factor (RF), IgA RF, and anti-cyclic citrullinated peptide antibody 2 are associated with subclinical ILD in community-dwelling adults [2]. It is unknown whether this relationship between autoimmunity and subclinical ILD is limited to RA-related autoantibodies, or extends more broadly to other epitopes. High attenuation areas (HAA) and interstitial lung abnormalities (ILA) are validated quantitative and qualitative subclinical ILD phenotypes, respectively. In community-dwelling adults, greater HAA is associated with reduced forced vital capacity, reduced exercise capacity, elevated serum levels of matrix metalloproteinase-7 and interleukin-6, higher prevalence of ILA on computed tomography (CT) scans of the chest, higher all-cause mortality rate, and an increased risk of developing clinically evident ILD and ILD-specific mortality at 12-year follow-up [3, 4]. ILA has been associated with all-cause mortality in four different longitudinal cohorts [5]. The purpose of this study was to examine the association between antinuclear antibody (ANA) and both HAA and ILA in community-dwelling adults enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Antinuclear antibodies are associated with subclinical interstitial lung disease in community-dwelling adults enrolled in the Multi-Ethnic Study of Atherosclerosis <http://bit.ly/2FIEJpS> The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at [www.mesa-nhlbi.org][1] [1]: http://www.mesa-nhlbi.org
Presacral Anastomotic Sinus After Low Anterior Resection Mimicking Recurrent Rectal Cancer
Authors: Chanwoo Kim, Deog Yoon Kim, Il Ki Hong
Journal: Clinical Nuclear Medicine (2019)

Abstract Presacral anastomotic sinus is recognized as a complication of anastomotic leakage in patients with rectal cancer. Active inflammation in the anastomotic sinus can masquerade as pelvic recurrence of rectal cancer. We present a case of progressive inflammation in anastomotic sinus demonstrated by serial FDG PET/CT scans. Despite its benign nature, increased FDG uptake in this nonnegligible condition, which could lead to further detrimental complications including secondary cancer, may have clinical implications.
Cryoballoon ablation for gastric pouch and/or outlet reduction in patients with weight regain post Roux-en-Y gastric bypass
Authors: Lea Fayad, Arvind J. Trindade, Petros C. Benias, Cem Simsek, Micheal Raad, Dilhana Badurdeen, Christine Hill, Olaya I. Brewer Gutierrez, George Fayad, Margo Dunlap, Anthony N. Kalloo, Mouen A. Khashab, Christopher C. Thompson, Marcia Canto, Vivek Kumbhari
Journal: Endoscopy (2020)

Abstract Background Cryoballoon ablation could induce stricture formation to achieve outlet and pouch reduction in patients regaining weight after Roux-en-Y gastric bypass (RYGB). This pilot study aimed to assess technical feasibility and short-term efficacy. Methods A retrospective chart review (January – November 2018) at two academic centers identified patients with weight regain post-RYGB, treated with cryoablation if pouch &gt; 4 cm and/or outlet &gt; 15 mm. Patients were scheduled for surveillance endoscopies at 8 weeks. Results 22 patients presented 10.5 years (SD 4.42) post-RYGB with weight regain of 30.9 kg (SD 13.7). Technical success was 89.5 % for outlet ablation and 93.0 % for pouch ablation. From baseline to 8 weeks, the outlet was reduced from 24.1 mm (95 % confidence interval [CI] 19.8 to 28.5) to 17.1 mm (95 %CI 13.1 to 21.1; P &lt; 0.001), and pouch from 5 cm (95 %CI 4.1 to 5.9) to 3.9 cm (95 %CI 2.6 to 5.1; P &lt; 0.05). Total body weight loss at 8 weeks was 8.1 % (SD 12.8 %). Conclusion Cryoablation appears technically feasible and effective for outlet and/or pouch reduction in the short term.
Letter to the Editor: Portal Pressure in Non‐Cirrhotic Portal Hypertension: To Measure or Not to Measure
Authors: Ashish Kumar, Praveen Sharma, Anil Arora
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To The Editor: We read with interest the article by Da et al.1 on hepatic venous pressure gradient (HVPG) measurement in patients with noncirrhotic portal hypertension (NCPH). The investigators, on the basis of HVPG measurement in a cohort of 53 patients, had concluded that it is not useful in patients suspected to have NCPH. While we commend the investigators for undertaking this important study on this neglected disease entity of NCPH, we disagree with the investigators on their conclusions. In our opinion, HVPG is an excellent modality in differentiating patients of NCPH from compensated Child‐A cirrhosis. In clinical presentation, NCPH closely mimics compensated cirrhosis; however, the prognosis of these two conditions is vastly different. Thus, it is essential to differentiate these two conditions so that patients of NCPH are not unnecessarily labeled as cirrhosis and given a grave prognosis, including advice for need for liver transplantation within a few years. The only method to differentiate these two conditions is liver biopsy; however, HVPG can be used as a reliable alternative. We had found that the biochemical parameters, systemic and pulmonary hemodynamics, and size of esophageal varices were similar in patients of NCPH and compensated cirrhosis. The only parameter that differentiated the two was HVPG, which was significantly lower in NCPH.2 Subsequently, the Asian Pacific Association for the Study of the Liver in their recommendation also suggested that normal or near‐normal HVPG is one of the diagnostic features of NCPH.3 We also do not agree with the investigators that among noninvasive tests transient elastography (TE) is inadequate for diagnosis of NCPH. In our recent study,4 we showed that TE in patients with NCPH was significantly lower compared to patients with cirrhosis, and it correlated well with HVPG. Thus, TE can be a useful noninvasive technique to differentiate between Child's A cirrhosis and NCPH. Thus, we opine that HVPG should routinely be done in patients suspected to have NCPH to differentiate them from patients with compensated cirrhosis. As an alternative to HVPG, TE can also be used reliably for this differentiation. Author Contributions Ashish Kumar contributed to the conception of the article, initiated the draft of the article, and revised the article. Praveen Sharma and Anil Arora edited the article.
Trimethylamine N-Oxide and Adenosine Diphosphate–Induced Platelet Reactivity Are Independent Risk Factors for Cardiovascular and All-Cause Mortality
Authors: Martin Berger, Marcus E. Kleber, Graciela E. Delgado, Winfred März, Meinitzer Andreas, Peter Hellstern, Nikolaus Marx, Katharina A. Schuett
Journal: Circulation Research (2020)
Cooperation Between MYC and β‐Catenin in Liver Tumorigenesis Requires Yap/Taz
Authors: Andrea Bisso, Marco Filipuzzi, Gianni Paolo Gamarra Figueroa, Giulia Brumana, Francesca Biagioni, Mirko Doni, Giorgia Ceccotti, Nina Tanaskovic, Marco Jacopo Morelli, Vera Pendino, Fulvio Chiacchiera, Diego Pasini, Daniela Olivero, Stefano Campaner, Arianna Sabò, Bruno Amati
Journal: Hepatology (2020)

Activation of MYC and catenin beta-1 (CTNNB1, encoding β-catenin) can co-occur in liver cancer, but how these oncogenes cooperate in tumorigenesis remains unclear.We generated a mouse model allowing conditional activation of MYC and WNT/β-catenin signaling (through either β-catenin activation or loss of APC - adenomatous polyposis coli) upon expression of CRE recombinase in the liver and monitored their effects on hepatocyte proliferation, apoptosis, gene expression profiles, and tumorigenesis. Activation of WNT/β-catenin signaling strongly accelerated MYC-driven carcinogenesis in the liver. Both pathways also cooperated in promoting cellular transformation in vitro, demonstrating their cell-autonomous action. Short-term induction of MYC and β-catenin in hepatocytes, followed by RNA-sequencing profiling, allowed the identification of a "Myc/β-catenin signature," composed of a discrete set of Myc-activated genes whose expression increased in the presence of active β-catenin. Notably, this signature enriched for targets of Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz), two transcriptional coactivators known to be activated by WNT/β-catenin signaling and to cooperate with MYC in mitogenic activation and liver transformation. Consistent with these regulatory connections, Yap/Taz accumulated upon Myc/β-catenin activation and were required not only for the ensuing proliferative response, but also for tumor cell growth and survival. Finally, the Myc/β-catenin signature was enriched in a subset of human hepatocellular carcinomas characterized by comparatively poor prognosis.Myc and β-catenin show a strong cooperative action in liver carcinogenesis, with Yap and Taz serving as mediators of this effect. These findings warrant efforts toward therapeutic targeting of Yap/Taz in aggressive liver tumors marked by elevated Myc/β-catenin activity.
Breaking through the surface: more to learn about lipids and cardiovascular disease
Authors: Justin B. Echouffo-Tcheugui, Mohit Jain, Susan Cheng
Journal: Journal of Clinical Investigation (2020)

The human lipidome comprises over tens of thousands of distinct lipid species in addition to total cholesterol and the other conventional lipid traits that are routinely measurable in the peripheral circulation. Of the lipid species considered to exhibit bioactive functions, sphingolipids are a class of molecules that have shown relevance to human disease risk and cardiovascular outcomes in particular. In this issue of the JCI, Poss et al. conducted targeted lipidomics in a case-control study involving over 600 individuals and found a sphingolipid profile that predicted coronary artery disease status. In the context of emerging evidence linking sphingolipid biology with cardiovascular pathophysiology, these results suggest the potential utility of serum sphingolipids as cholesterol-independent markers of risk and even future targets for optimizing cardiovascular health.
Gallbladder Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN) Arising in Intracholecystic Papillary Neoplasm: Clinicopathologic and Molecular Analysis of a Case and Review of the Literature
Authors: Amedeo Sciarra, Edoardo Missiaglia, Mounir Trimech, Emmanuel Melloul, Jean-Philippe Brouland, Christine Sempoux, Stefano La Rosa
Journal: Endocrine Pathology (2020)
Filling the Gap: A Correlation between Objective and Subjective Measures of Injectability
Authors: Thomas E. Robinson, Erik A. B. Hughes, Aniruddha Bose, Elizabeth A. Cornish, Jun Y. Teo, Neil M. Eisenstein, Liam M. Grover, Sophie C. Cox
Journal: Advanced Healthcare Materials (2020)

Abstract Various injectable biomaterials are developed for the minimally invasive delivery of therapeutics. Typically, a mechanical tester is used to ascertain the force required to inject these biomaterials through a given syringe‐needle system. However, currently there is no method to correlate the force measured in the laboratory to the perceived effort required to perform that injection by the end user. In this article, the injection force (F) for a variety of biomaterials, displaying a range of rheological properties, is compared with the effort scores from a 50 person panel study. The maximum injection force measured at crosshead speed 1 mm s −1 is a good proxy for injection effort, with an R 2 of 0.89. This correlation leads to the following conclusions: participants can easily inject 5 mL of substance for F &lt; 12 N; considerable effort is required to inject 5 mL for 12 N &lt; F &lt; 38 N; great effort is required and &lt;5 mL can be injected for 38 N &lt; F &lt; 64 N; and materials are entirely non‐injectable for F &gt; 64 N. These values may be used by developers of injectable biomaterials to make decisions about formulations and needle sizes early in the translational process.
Advances in cervical cancer prevention: Efficacy, effectiveness, elimination?
Authors: Karin Sundström, K. Miriam Elfström
Journal: PLoS Medicine (2020)

With major advances in understanding the infectious etiology of cervical cancer, preventive medicine has obtained highly promising new tools. Human papillomavirus (HPV) vaccines, together with a growing arsenal of HPV-based screening tests, have the potential to radically change public health but require diligent, large-scale implementation to reach the final goal: the elimination of cervical cancer. We reflect here upon the state of cervical cancer prevention globally as there have been several recent developments that will inform this implementation process.
A 61-Year-Old Woman With New Pericardial Effusion
Authors: Melissa A. Lyle, Siu-Hin Wan, Fletcher A. Miller
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
A benchmark of batch-effect correction methods for single-cell RNA sequencing data
Authors: Hoa Thi Nhu Tran, Kok Siong Ang, Marion Chevrier, Xiaomeng Zhang, Nicole Yee Shin Lee, Michelle Goh, Jinmiao Chen
Journal: Genome biology (2020)

Abstract Background Large-scale single-cell transcriptomic datasets generated using different technologies contain batch-specific systematic variations that present a challenge to batch-effect removal and data integration. With continued growth expected in scRNA-seq data, achieving effective batch integration with available computational resources is crucial. Here, we perform an in-depth benchmark study on available batch correction methods to determine the most suitable method for batch-effect removal. Results We compare 14 methods in terms of computational runtime, the ability to handle large datasets, and batch-effect correction efficacy while preserving cell type purity. Five scenarios are designed for the study: identical cell types with different technologies, non-identical cell types, multiple batches, big data, and simulated data. Performance is evaluated using four benchmarking metrics including kBET, LISI, ASW, and ARI. We also investigate the use of batch-corrected data to study differential gene expression. Conclusion Based on our results, Harmony, LIGER, and Seurat 3 are the recommended methods for batch integration. Due to its significantly shorter runtime, Harmony is recommended as the first method to try, with the other methods as viable alternatives.
The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas
Authors: Ricardo Gargini, Berta Segura-Collar, Beatriz Herránz, Vega García-Escudero, Andrés Romero-Bravo, Felipe J. Núñez, Daniel García-Pérez, Jacqueline Gutiérrez-Guamán, Angel Ayuso-Sacido, Joan Seoane, Angel Pérez-Núñez, Juan M. Sepúlveda-Sánchez, Aurelio Hernández-Laín, María G. Castro, Ramón García-Escudero, Jesús Ávila, Pilar Sánchez-Gómez
Journal: Science Translational Medicine (2020)

TAU is expressed in the less aggressive gliomas where it impairs the mesenchymal transdifferentiation of tumor cells and normalizes the vasculature.
Gerald Weissmann: Inflammation in rheumatic disease
Authors: Bruce N Cronstein, Jill P Buyon, Steven B Abramson
Journal: Annals of the Rheumatic Diseases (2020)

Gerald Weissmann (1930–2019), former President of the American College of Rheumatology (ACR), was at the forefront of a generation of rheumatologists/scientists who transformed the study of the rheumatic diseases from a largely descriptive effort to a hypothesis-driven scientific endeavour. Born in Vienna, his family left Austria in 1938, during the rise of Nazism in Europe, and settled in New York City, where his father resumed his practice of medicine. Through his remarkable scientific career, Gerry Weissmann carved an indelible mark on the field of rheumatology serving as chief of the Division of NYU’s Langone Medical Center (1973–2000), training scores of physicians and scientists. To all, he was an exemplar of scientific rigour and unbounded enthusiasm for scholarship, whose legacy continues to influence numerous disciples throughout the world. For all of these attributes, Gerald Weissmann is an academic ‘hero’.

Over his 50-year scientific career students, clinicians and scientists sought out Dr Weissmann as a mentor. With his scientific rigour, creativity and, on occasion, acerbic wit, Dr Weissmann introduced a generation of students to the practice of experimental science. He was an inspiration to many aspiring rheumatologists; the excitement of his scientific approach and the changes and developments in the clinic attracted a large number of able trainees. He influenced both at bench and bedside, the latter enforcing on medical rounds the relevance of ear cartilage resilience to general health. Many of us fondly recall Dr Weissmann’s trademark purple magic marker which repeatedly circled all the nouns we mistakenly used as adjectives. Surely as his mentees we will always be indebted …
Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland
Authors: Anita Jeyam, Stuart J. McGurnaghan, Luke A.K. Blackbourn, John M. McKnight, Fiona Green, Andrew Collier, Paul M. McKeigue, Helen M. Colhoun
Journal: Diabetes Care (2020)

OBJECTIVE To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications. RESEARCH DESIGN AND METHODS We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications. RESULTS The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21–1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37–2.03]), and worse renal function (1.96 [1.03–3.74] for estimated glomerular filtration rate levels &amp;lt;30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66–0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78–2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications. CONCLUSIONS Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.