tbuckley/cabot-search huggingface dataset:
A framework for advancing our understanding of cancer-associated fibroblasts
Authors: Erik Sahai, Igor Astsaturov, Edna Cukierman, David G. DeNardo, Mikala Egeblad, Ronald M. Evans, Douglas Fearon, Florian R. Greten, Sunil R. Hingorani, Tony Hunter, Richard O. Hynes, Rakesh K. Jain, Tobias Janowitz, Claus Jorgensen, Alec C. Kimmelman, Mikhail G. Kolonin, Robert G. Maki, R. Scott Powers, Ellen Puré, Daniel C. Ramirez, Ruth Scherz-Shouval, Mara H. Sherman, Sheila Stewart, Thea D. Tlsty, David A. Tuveson, Fiona M. Watt, Valerie Weaver, Ashani T. Weeraratna, Zena Werb
Journal: Nature reviews. Cancer (2020)

Abstract Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
Association of Default Electronic Medical Record Settings With Health Care Professional Patterns of Opioid Prescribing in Emergency Departments
Authors: Juan Carlos C. Montoy, Zlatan Coralic, Andrew A. Herring, Eben J. Clattenburg, Maria C. Raven
Journal: JAMA Internal Medicine (2020)

Prescription opioids play a significant role in the ongoing opioid crisis. Guidelines and physician education have had mixed success in curbing opioid prescriptions, highlighting the need for other tools that can change prescriber behavior, including nudges based in behavioral economics.To determine whether and to what extent changes in the default settings in the electronic medical record (EMR) are associated with opioid prescriptions for patients discharged from emergency departments (EDs).This quality improvement study randomly altered, during a series of five 4-week blocks, the prepopulated dispense quantities of discharge prescriptions for commonly prescribed opioids at 2 large, urban EDs. These changes were made without announcement, and prescribers were not informed of the study itself. Participants included all health care professionals (physicians, nurse practitioners, and physician assistants) working clinically in either of the 2 EDs. Data were collected from November 28, 2016, through July 9, 2017, and analyzed from July 16, 2017, through May 14, 2018.Default quantities for opioids were changed from status quo quantities of 12 and 20 tablets to null, 5, 10, and 15 tablets according to a block randomization scheme. Regardless of the default quantity, each health care professional decided for whom to prescribe opioids and could modify the quantity prescribed without restriction.The primary outcome was the number of tablets of opioid-containing medications prescribed under each default setting.A total of 104 health care professionals wrote 4320 prescriptions for opioids during the study period. Using linear regression, an increase of 0.19 tablets prescribed (95% CI, 0.15-0.22) was found for each tablet increase in default quantity. When evaluating each of the 15 pairwise comparisons of default quantities (eg, 5 vs 15 tablets), a lower default was associated with a lower number of pills prescribed in more than half (8 of the 15) of the pairwise comparisons; there was a higher quantity in 1 and no difference in 6 comparisons.These findings suggest that default settings in the EMR may influence the quantity of opioids prescribed by health care professionals. This low-cost, easily implementable, EMR-based intervention could have far-reaching implications for opioid prescribing and could be used as a tool to help combat the opioid epidemic.ClinicalTrials.gov identifier: NCT04155229.
Doxorubicin-polyglycerol-nanodiamond conjugates disrupt STAT3/IL-6-mediated reciprocal activation loop between glioblastoma cells and astrocytes
Authors: Zhuo Chen, Shen-Jun Yuan, Ke Li, Quan Zhang, Tong-Fei Li, Hui-Chao An, Hua-Zhen Xu, Yuan Yue, Min Han, Yong-Hong Xu, Naoki Komatsu, Li Zhao, Xiao Chen
Journal: Journal of Controlled Release (2020)
The mechanism of TNF-stimulated growth of mammary epithelial cells: evidence that NFκB2/p52 can compensate for NFκB1/p50
Authors: Jiping Zhang, Margot M. Ip
Journal: Cancer Research (2006)

3649  Nuclear factor kappaB (NFκB) is important in mammary gland development and breast cancer. We previously demonstrated that TNF stimulated the growth of rat mammary epithelial cells (MEC) and rat mammary tumor cells in a physiologically relevant 3D primary culture system, accompanied by enhanced DNA-binding of the NFκB p50 homodimer. Recently, we found that expression of cyclin D1 mRNA and protein was also increased by TNF in MEC. To determine if NFκB1/p50 was required for TNF-stimulated growth and up-regulation of cyclin D1, the TNF responsiveness of MEC including cell growth, activation of NFκB and cyclin D1 expression was compared between NFκB1/p50 null and wild type mice in MEC primary culture. TNF stimulated growth and induced the expression of cyclin D1 in MEC from both p50 null and wild type mice. No p50 protein was detected in either mammary gland tissue or cultured MEC of p50 null mice. However, a TNF-inducible NFκB DNA-binding protein complex was seen in the nuclear extract of cultured MEC from p50 null mice by electrophoresis mobility shift assay. This complex migrated at the same position as the upper band of the two NFκB-binding complexes detected in wild type MEC. Supershift analysis showed that the NFκB-binding complex in p50 null MEC was composed of NFκB2/p52 and RelB, while the two complexes in the wild type mice were the p65/p50 heterodimer, and the p50 homodimer. Additionally, NFκB2/p52 as well as its precursor p100 was increased by TNF in whole cell lysates of MEC from both p50 null and wild type mice. These data provide the first evidence that in the absence of p50, its close homologue p52 can functionally compensate. Although we demonstrate that the p50 protein itself is not critical in TNF-stimulated proliferation and up-regulation of cyclin D1 in MEC, the similar sensitivity of MEC to TNF in p50 null and wild type mice and the substitution of p52 for p50 highly suggest that NFκB-mediated transactivation and transcription are important in MEC responsiveness to TNF. The data further suggest that therapeutic approaches that target the NFκB pathway will have to take into consideration the individual proteins that make up the NFκB complex and the partial redundancy of the protein components within the complex. Supported by NIH CA77656.
Photo-curing 3D printing technique and its challenges
Authors: Haoyuan Quan, Ting Zhang, Hang Xu, Shen Luo, Jun Nie, Xiaoqun Zhu
Journal: Bioactive Materials (2020)

In recent ten years, 3D printing technology has been developed rapidly. As an advanced technology, 3D printing has been used to fabricate complex and high-precision objects in many fields. 3D printing has several technologies. Among these technologies, photo-curing 3D printing was the earliest and most mature technology. In 1988, the first 3D printing machine which was based on photo-curing and called Stereo lithography Appearance (SLA) technology was produced by 3D system Corp. After 30 years of development, many new technologies based on photocuring mechanism emerged. Based on the different principle of pattern formation and character of printing technology, numerous photocuring 3D printing techniques, such as SLA, DLP, LCD, CLIP, MJP, two-photon 3D printing, holographic 3D printing and so on, have been developed. Photo-curing 3D printing has many advantages, such as high precision, smooth surface of printing objects, rapid printing speed and so on. Here, we would introduce five industrial photocuring 3D printing technologies, which are SLA, DLP, LCD, CLIP and MJP. The characters of the materials and the progress of the application of the technique in the biomedical field is also overviewed. At last, the difficulties and challenges of photo-curing 3D printing are also discussed.
A41 EO1001: A First-in-Class Irreversible Pan-ErbB Inhibitor with Excellent Brain Penetration
Authors: W. Shen, J. Bacha, S. Kanekal, N. Sankar, W. ZhenZhong, Y. Yoshida, T. Ozawa, T. Yao, A. Parsa, J. Raizer, S. Cheng, A. Stegh, F. Giles, H. Pedersen, J. Sakaria, N. Butowski, C. James, D. Brown
Journal: Journal of Thoracic Oncology (2020)
Reply to Alberto Ferlin’s Letter to the Editor, re: Taylor P. Kohn, Jaden R. Kohn, Ryan C. Owen, R. Matthew Coward. The Prevalence of Y-chromosome Microdeletions in Oligozoospermic Men: A Systematic Review, Meta-analysis of European, North American Studies. Eur Urol 2019, 76:626–36. Indication for Y Chromosome Microdeletion Analysis in Infertile Men Should Not be, Based Merely on Sperm Concentration
Authors: Taylor P. Kohn, Jaden R. Kohn, Ryan C. Owen, R. Matthew Coward
Journal: European Urology (2020)
Muco-Obstructive Lung Diseases
Authors: Rosemary J Boyton, Daniel M Altmann
Journal: New England Journal of Medicine (2019)

To the Editor: The review article by Boucher (May 16 issue) 1 does not include a discussion of asthma as a muco-obstructive lung disease.In a subgroup of patients with asthma, clinically significant mucus plugging is detected on highresolution computed tomographic imaging.This condition is characterized clinically by severe airflow obstruction and a lack of response to both bronchodilators and systemic glucocorticoids. 2 Mucus-derived obstruction is an important asthma phenotype because it may predict more persistent obstruction than that which is usually encountered and involve a treatment approach that is similar to that for other mucoobstructive diseases.Furthermore, overall mucin concentrations have been found to be higher both in patients with stable asthma and in those with asthma exacerbations than in healthy persons, although the predominant mucin in patients with asthma is MUC5AC, 3 and goblet-cell hyperplasia has been associated with neutrophilic asthma, which shares many similarities with chronic obstructive pulmonary disease (COPD). 4 Finally, hypertonic saline, which is frequently used in patients with other muco-obstructive lung diseases, has been shown to increase ciliary clearance in patients with asthma and is an underused therapy in this population. 5
Knockout of the Murine Ortholog to the Human 9p21 Coronary Artery Disease Locus Leads to Smooth Muscle Cell Proliferation, Vascular Calcification, and Advanced Atherosclerosis
Authors: Yoko Kojima, Jianqin Ye, Vivek Nanda, Ying Wang, Alyssa M. Flores, Kai-Uwe Jarr, Pavlos Tsantilas, Liang Guo, Aloke V. Finn, Renu Virmani, Nicholas J. Leeper
Journal: Circulation (2020)
IA13 Targeting Myeloid Cells that Define the Tumor Immune Microenvironment in NSCLC
Authors: T.U. Marron, A. Leader, Y. Lavin, B. Maier, M. Casanova-Acebes, A. Wolf, R. Flores, M. Beasley, A. Rahman, E. Kenigsberg, M. Merad
Journal: Journal of Thoracic Oncology (2020)
Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial
Authors: Xavier Roblin, Nicolas Williet, Gilles Boschetti, Jean-Marc Phelip, Emilie Del Tedesco, Anne-Emmanuelle Berger, Philippe Vedrines, Gerard Duru, Laurent Peyrin-Biroulet, Stéphane Nancey, Bernard Flourie, Stephane Paul
Journal: Gut (2020)

In patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies: either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period.Consecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn's disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level >250 µg/g stool and for UC as a Mayo score >5 with endoscopic subscore >1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay).Ninety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p<0.001; median time of clinical failure since randomisation 18 vs >24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p<0.001 for both) in monotherapy versus combination therapy. Only the use of combination therapy was associated with favourable outcomes after anti-TNF switch.In case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF.03580876.
TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial
Authors: Per Pfeiffer, Mette Yilmaz, Sören Möller, Daniela Zitnjak, Merete Krogh, Lone Nørgård Petersen, Laurids Østergaard Poulsen, Stine Braendegaard Winther, Karina Gravgaard Thomsen, Camilla Qvortrup
Journal: The Lancet Oncology (2020)
Replacing what’s lost: a new era of stem cell therapy for Parkinson’s disease
Authors: Yong Fan, None Winanto, Shi-Yan Ng
Journal: Translational Neurodegeneration (2020)

Stem cells hold tremendous promise for regenerative medicine because they can be expanded infinitely, giving rise to large numbers of differentiated cells required for transplantation. Stem cells can be derived from fetal sources, embryonic origins (embryonic stem cells or ESCs) or reprogrammed from adult cell types (induced pluripotent stem cells or iPSCs). One unique property of stem cells is their ability to be directed towards specific cell types of clinical interest, and can mature into functional cell types in vivo. While transplantations of fetal or ESC-derived tissues are known to illicit a host immunogenic response, autologous transplantations using cell types derived from one's own iPSCs eliminate risks of tissue rejection and reduce the need for immunosuppressants. However, even with these benefits, cell therapy comes with significant hurdles that researchers are starting to overcome. In this review, we will discuss the various steps to ensure safety, efficacy and clinical practicality of cell replacement therapy in neurodegenerative diseases, in particular, Parkinson's disease.Parkinson's disease (PD) results from a loss of dopaminergic neurons from the substantia nigra and is an ideal target for cell replacement therapy. Early trials using fetal midbrain material in the late 1980s have resulted in long term benefit for some patients, but there were multiple shortcomings including the non-standardization and quality control of the transplanted fetal material, and graft-induced dyskinesia that some patients experience as a result. On the other hand, pluripotent stem cells such as ESCs and iPSCs serve as an attractive source of cells because they can be indefinitely cultured and is an unlimited source of cells. Stem cell technologies and our understanding of the developmental potential of ESCs and iPSCs have deepened in recent years and a clinical trial for iPSC-derived dopaminergic cells is currently undergoing for PD patients in Japan. In this focused review, we will first provide a historical aspect of cell therapies in PD, and then discuss the various challenges pertaining to the safety and efficacy of stem cell-based cell transplantations, and how these hurdles were eventually overcome.With the maturity of the iPSC technology, cell transplantation appears to be a safe and effective therapy. Grafts in non-human primates survive and remain functional for more than 2 years after transplantation, with no signs of tumorigenesis, indicating safety and efficacy of the treatment. However, immunosuppressants are still required because of the lack of "universal stem cells" that would not evoke an immune response. The results of ongoing and upcoming trials by a global consortium known as GForce-PD would be highly anticipated because the success of these trials would open up possibilities for using cell therapy for the treatment of PD and other degenerative diseases.
Targeting necroptosis in anticancer therapy: mechanisms and modulators
Authors: Ying Wu, Guoqiang Dong, Chunquan Sheng
Journal: Acta Pharmaceutica Sinica B (2020)

Necroptosis, a genetically programmed form of necrotic cell death, serves as an important pathway in human diseases. As a critical cell-killing mechanism, necroptosis is associated with cancer progression, metastasis, and immunosurveillance. Targeting necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy, which has the advantage to bypass the apoptosis-resistance and maintain antitumor immunity. Therefore, a better understanding of the mechanism of necroptosis and necroptosis modulators is necessary to develop novel strategies for cancer therapy. This review will summarize recent progress of the mechanisms and detecting methods of necroptosis. In particular, the relationship between necroptosis and cancer therapy and medicinal chemistry of necroptosis modulators will be focused on.
Assessment of the Predictive Value of Outpatient Smartphone Videos for Diagnosis of Epileptic Seizures
Authors: William O. Tatum, Lawrence J. Hirsch, Michael A. Gelfand, Emily K. Acton, W. Curt LaFrance, Robert B. Duckrow, David K. Chen, Andrew S. Blum, John D. Hixson, Joe F. Drazkowski, Selim R. Benbadis, Gregory D. Cascino
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Misdiagnosis of epilepsy is common. Video electroencephalogram provides a definitive diagnosis but is impractical for many patients referred for evaluation of epilepsy. <h3>Objective</h3> To evaluate the accuracy of outpatient smartphone videos in epilepsy. <h3>Design, Setting, and Participants</h3> This prospective, masked, diagnostic accuracy study (the OSmartViE study) took place between August 31, 2015, and August 31, 2018, at 8 academic epilepsy centers in the United States and included a convenience sample of 44 nonconsecutive outpatients who volunteered a smartphone video during evaluation and subsequently underwent video electroencephalogram monitoring. Three epileptologists uploaded videos for physicians from the 8 epilepsy centers to review. <h3>Main Outcomes and Measures</h3> Measures of performance (accuracy, sensitivity, specificity, positive predictive value, and negative predictive value) for smartphone video–based diagnosis by experts and trainees (the index test) were compared with those for history and physical examination and video electroencephalogram monitoring (the reference standard). <h3>Results</h3> Forty-four eligible epilepsy clinic outpatients (31 women [70.5%]; mean [range] age, 45.1 [20-82] years) submitted smartphone videos (530 total physician reviews). Final video electroencephalogram diagnoses included 11 epileptic seizures, 30 psychogenic nonepileptic attacks, and 3 physiologic nonepileptic events. Expert interpretation of a smartphone video was accurate in predicting a video electroencephalogram monitoring diagnosis of epileptic seizures 89.1% (95% CI, 84.2%-92.9%) of the time, with a specificity of 93.3% (95% CI, 88.3%-96.6%). Resident responses were less accurate for all metrics involving epileptic seizures and psychogenic nonepileptic attacks, despite greater confidence. Motor signs during events increased accuracy. One-fourth of the smartphone videos were correctly diagnosed by 100% of the reviewing physicians, composed solely of psychogenic attacks. When histories and physical examination results were combined with smartphone videos, correct diagnoses rose from 78.6% to 95.2%. The odds of receiving a correct diagnosis were 5.45 times greater using smartphone video alongside patient history and physical examination results than with history and physical examination alone (95% CI, 1.01-54.3;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> Outpatient smartphone video review by experts has predictive and additive value for diagnosing epileptic seizures. Smartphone videos may reliably aid psychogenic nonepileptic attacks diagnosis for some people.
High prevalence of Bordetella pertussis in young hospitalized infants with acute respiratory infection in the south of China: age- and season-dependent effects
Authors: Heping Wang, Yuejie Zheng, Ronald de Groot, Yonghong Yang, Dimitri A. Diavatopoulos, Yunsheng Chen, Marien I. de Jonge, Jikui Deng
Journal: Journal of Infection (2020)
A30 Tumor-Infiltrating Lymphocytes (TILs) Found Elevated in Lung Adenocarcinomas (LUAD) Using Automated Digital Pathology Masks Derived from Deep-Learning Models
Authors: M.I. Jaber, L. Beziaeva, S.C. Benz, S.K. Reddy, S. Rabizadeh, C.W. Szeto
Journal: Journal of Thoracic Oncology (2020)
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Authors: Steven M. Corsello, Rohith T. Nagari, Ryan D. Spangler, Jordan Rossen, Mustafa Kocak, Jordan G. Bryan, Ranad Humeidi, David Peck, Xiaoyun Wu, Andrew A. Tang, Vickie M. Wang, Samantha A. Bender, Evan Lemire, Rajiv Narayan, Philip Montgomery, Uri Ben-David, Colin W. Garvie, Yejia Chen, Matthew G. Rees, Nicholas J. Lyons, James M. McFarland, Bang T. Wong, Li Wang, Nancy Dumont, Patrick J. O’Hearn, Eric Stefan, John G. Doench, Caitlin N. Harrington, Heidi Greulich, Matthew Meyerson, Francisca Vazquez, Aravind Subramanian, Jennifer A. Roth, Joshua A. Bittker, Jesse S. Boehm, Christopher C. Mader, Aviad Tsherniak, Todd R. Golub
Journal: Nature Cancer (2020)
The cost of arthralgia ‘pretreatment’ to prevent rheumatoid arthritis
Authors: Bruce M Rothschild
Journal: Annals of the Rheumatic Diseases (2020)

The article by Helm-van Mil and Landewe1 represents the tip of the iceberg. Justifying initiation of medications, in the absence of clinical or radiological evidence because an individual might at some time develop a particular disease is a speculative approach. We are now in an era of evidence-based medicine and such evidence is currently lacking for recognition of who will develop rheumatoid arthritis (RA). Actually, even controlled …
Risk of Inflammatory Arthritis After a New Diagnosis of Hidradenitis Suppurativa
Authors: Maria C. Schneeweiss, Seoyoung C. Kim, Sebastian Schneeweiss, David Rosmarin, Joseph F. Merola
Journal: JAMA Dermatology (2020)

form was interpreted by respondents without the context of a connected clinical visit.Conclusions | While transparency is a worthy goal, it cannot be realized by simply sharing health information without offering context.Efforts should be made to redesign pathology reports to be easier for patients to interpret; for example, they could include autogenerated definitions, bold titles, and clearer lay language.Without such changes, providing patients access to interprofessional communications may lead to confusion, heightened anxiety, and an increased administrative burden.We hope this study inspires conversation regarding thoughtful ways to provide transparency to patients desiring accessibility to their health data while avoiding unintended consequences.