tbuckley/cabot-search huggingface dataset:
Morphology-Predicted Large-Scale Transition Number in Circulating Tumor Cells Identifies a Chromosomal Instability Biomarker Associated with Poor Outcome in Castration-Resistant Prostate Cancer
Authors: Joseph D. Schonhoft, Jimmy L. Zhao, Adam Jendrisak, Emily A. Carbone, Ethan S. Barnett, Melanie A. Hullings, Audrey Gill, Ramsay Sutton, Jerry Lee, Angel E. Dago, Mark Landers, Samuel F. Bakhoum, Yipeng Wang, Mithat Gonen, Ryan Dittamore, Howard I. Scher
Journal: Cancer Research (2020)

Chromosomal instability (CIN) increases a tumor cell's ability to acquire chromosomal alterations, a mechanism by which tumor cells evolve, adapt, and resist therapeutics. We sought to develop a biomarker of CIN in circulating tumor cells (CTC) that are more likely to reflect the genetic diversity of patient's disease than a single-site biopsy and be assessed rapidly so as to inform treatment management decisions in real time. Large-scale transitions (LST) are genomic alterations defined as chromosomal breakages that generate chromosomal gains or losses of greater than or equal to10 Mb. Here we studied the relationship between the number of LST in an individual CTC determined by direct sequencing and morphologic features of the cells. This relationship was then used to develop a computer vision algorithm that utilizes CTC image features to predict the presence of a high (9 or more) versus low (8 or fewer) LST number in a single cell. As LSTs are a primary functional component of homologous recombination deficient cellular phenotypes, the image-based algorithm was studied prospectively on 10,240 CTCs in 367 blood samples obtained from 294 patients with progressing metastatic castration-resistant prostate cancer taken prior to starting a standard-of-care approved therapy. The resultant computer vision-based biomarker of CIN in CTCs in a pretreatment sample strongly associated with poor overall survival times in patients treated with androgen receptor signaling inhibitors and taxanes. SIGNIFICANCE: A rapidly assessable biomarker of chromosomal instability in CTC is associated with poor outcomes when detected in men with progressing mCRPC.
Airborne transmission of covid-19
Authors: Nick Wilson, Stephen Corbett, Euan Tovey
Journal: BMJ (2020)

In July, 239 scientists signed an open letter "appealing to the medical community and relevant national and international bodies to recognise the potential for airborne spread of covid-19." 1 Although the World Health Organization conceded that "airborne transmission cannot be ruled out," the response was reserved and arguably mistaken in continuing to suggest that airborne and droplet transmission are discrete categories and that airborne transmission occurs only during medical "aerosol generating procedures.
重症监护治疗学基础知识（11）热点问题
Authors: Mervyn, Rod, Little
Journal: BMJ (2001)

临床医学中几乎没有哪个领域能够象重症监护治疗学那样发展迅速。在过去的 10年里 ,有许多方面对重症监护的发展起了重要的作用 ,包括对疾病病理生理学认识的不断深入、技术手段的不断创新、药物的针对性增强、使用专门的计算和评分方法对患者进行分级以及疾病过程的持续监测等。本文主要介绍今后 10年可能对临床医疗产生影响的进展。 预防 应在危重患者出现器官功能衰竭前进行积极预防 ,而不是器官功能衰竭发生后再进行积极的支持治疗 ,对这一点有了越来越深刻的理解。虽然应减少对重症监护的需求以节省资源 ,但预防也可大大节省资源。应强调正确判断患者病情的危险性 ,早期认识患者的生理紊乱并迅速地予以纠正 ,以避
Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study
Authors: Emma C. Robbins, Kate Wooldrage, Iain Stenson, Kevin Pack, Stephen Duffy, David Weller, Theodore Levin, Carol Conell, Suzanne Wright, Claire Nickerson, Jessica Martin, Amanda J. Cross
Journal: Endoscopy (2020)

Abstract Background Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. Methods This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 – 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. Results Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 – 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 – 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 – 1.38). Conclusion As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.
STAT3 and GR Cooperate to Drive Gene Expression and Growth of Basal-Like Triple-Negative Breast Cancer
Authors: Megan E. Conway, Joy M. McDaniel, James M. Graham, Katrin P. Guillen, Patsy G. Oliver, Stephanie L. Parker, Peibin Yue, James Turkson, Donald J. Buchsbaum, Bryan E. Welm, Richard M. Myers, Katherine E. Varley
Journal: Cancer Research (2020)

Breast cancers are divided into subtypes with different prognoses and treatment responses based on global differences in gene expression. Luminal breast cancer gene expression and proliferation are driven by estrogen receptor alpha, and targeting this transcription factor is the most effective therapy for this subtype. By contrast, it remains unclear which transcription factors drive the gene expression signature that defines basal-like triple-negative breast cancer, and there are no targeted therapies approved to treat this aggressive subtype. In this study, we utilized integrated genomic analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. Glucocorticoid receptor (GR) and STAT3 bind to the same genomic regulatory regions, which were specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperated to regulate expression of hundreds of genes in the basal-like gene expression signature, which were associated with poor prognosis. Combination treatment with small-molecule inhibitors of both transcription factors resulted in synergistic decreases in cell growth in cell lines and patient-derived organoid models. This study demonstrates that GR and STAT3 cooperate to regulate the basal-like breast cancer gene expression program and provides the basis for improved therapy for basal-like triple-negative breast cancer through rational combination of STAT3 and GR inhibitors. SIGNIFICANCE: This study demonstrates that GR and STAT3 cooperate to activate the canonical gene expression signature of basal-like triple-negative breast cancer and that combination treatment with STAT3 and GR inhibitors could provide synergistic therapeutic efficacy.
Randomized study of antiseptic application technique in healthy volunteers before vascular access insertion (TApAS trial)
Authors: Yolène Carre, Bertrand Moal, Christine Germain, Eric Frison, Marielle Dubreuil, Céline Chansel, Valérie Berger, Hélène Boulestreau, Agnès Lasheras-Bauduin, Anne-Marie Rogues
Journal: Journal of Infection (2020)
Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release
Authors: Juan-Vicente Bou, Rafael Sanjuán
Journal: Molecular Biology and Evolution (2020)

Abstract Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by full-genome ultra-deep sequencing. Specifically, using site-directed mutagenesis, we showed that substitution N63H in the viral capsid protein VP3 reduced the ratio of membrane-associated to free viral particles by 2 orders of magnitude. These findings open new avenues for understanding the mechanisms and implications of membrane-associated viral transmission.
Rare Extramedullary Cardiac Involvement of Recurrent Multiple Myeloma Suspected on 18F-FDG and Confirmed on 18F-Fluorocholine
Authors: Jules Zhang-Yin, Laurent Garderet, Suella Martino, Françoise Montravers, Jean-Noël Talbot
Journal: Clinical Nuclear Medicine (2020)

Abstract A man experienced pain in the right hemithorax 6 months after a first-line therapy for multiple myeloma (MM). FDG PET/CT showed a large extramedullary extent in the right hemithorax, which was biopsy proven. During the second-line treatment, FDG PET/CT showed no response as well as a suspected myocardium spread, a rare extramedullary location in MM. 18 F-Fluorocholine PET/CT and then MRI confirmed myocardium lesions. This case confirms that 18 F-fluorocholine PET/CT is able to detect MM recurrence and may be used to complete FDG PET/CT in difficult cases such as suspicion of cardiac MM.
Evaluation for SARS-CoV-2 in Breast Milk From 18 Infected Women
Authors: Christina Chambers, Paul Krogstad, Kerri Bertrand, Deisy Contreras, Nicole H. Tobin, Lars Bode, Grace Aldrovandi
Journal: JAMA (2020)

Oscar Martínez-Perez, MD, PhD; Manon Vouga, MD, PhD; Sara Cruz Melguizo, MD, PhD; Laura Forcen Acebal, MD; Alice Panchaud, PhD; Mar Muñoz-Chápuli, MD; David Baud, MD, PhD
Role of LA Shape in Predicting Embolic Cerebrovascular Events in Mitral Stenosis
Authors: Maria Carmo P. Nunes, Mark D. Handschumacher, Robert A. Levine, Marcia M. Barbosa, Vinicius T. Carvalho, William A. Esteves, Xin Zeng, J. Luis Guerrero, Hui Zheng, Timothy C. Tan, Judy Hung
Journal: JACC. Cardiovascular imaging (2014)
Self-management interventions to reduce healthcare use and improve quality of life among patients with asthma: systematic review and network meta-analysis
Authors: Alexander Hodkinson, Peter Bower, Christos Grigoroglou, Salwa S Zghebi, Hilary Pinnock, Evangelos Kontopantelis, Maria Panagioti
Journal: BMJ (2020)

Abstract Objective To compare the different self-management models (multidisciplinary case management, regularly supported self-management, and minimally supported self-management) and self-monitoring models against usual care and education to determine which are most effective at reducing healthcare use and improving quality of life in asthma. Design Systematic review and network meta-analysis. Data sources Medline, the Cochrane Library, CINAHL, EconLit, Embase, Health Economics Evaluations Database, NHS Economic Evaluation Database, PsycINFO, and ClinicalTrials.gov from January 2000 to April 2019. Review methods Randomised controlled trials involving the different self-management models for asthma were included. The primary outcomes were healthcare use (hospital admission or emergency visit) and quality of life. Summary standardised mean differences (SMDs) and 95% credible intervals were estimated using bayesian network meta-analysis with random effects. Heterogeneity and publication bias were assessed. Results From 1178 citations, 105 trials comprising 27 767 participants were included. In terms of healthcare use, both multidisciplinary case management (SMD –0.18, 95% credible interval −0.32 to −0.05) and regularly supported self-management (–0.30, −0.46 to −0.15) were significantly better than usual care. For quality of life, only regularly supported self-management (SMD 0.54, 0.11 to 0.96) showed a statistically significant benefit compared with usual care. For trials including adolescents/children (age 5-18 years), only regularly supported self-management showed statistically significant benefits (healthcare use: SMD –0.21, −0.40 to −0.03; quality of life: 0.23, 0.03 to 0.48). Multidisciplinary case management (SMD –0.32, −0.50 to −0.16) and regularly supported self-management (–0.32, −0.53 to −0.11) were most effective at reducing healthcare use in patients with symptoms of severe asthma at baseline. Conclusions This network meta-analysis indicates that regularly supported self-management reduces the use of healthcare resources and improves quality of life across all levels of asthma severity. Future healthcare investments should provide support that offer reviews totalling at least two hours to establish self-management skills, reserving multidisciplinary case management for patients with complex disease. Systematic review registration PROSPERO number CRD42019121350.
Multidisciplinary Update on Genital Hidradenitis Suppurativa
Authors: Judy Hamad, Benjamin J. McCormick, Christopher J. Sayed, Karina Paci, Matthew Overton, Thomas Daubert, Bradley D. Figler
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a predilection for the genital region. Genital HS requires medical and surgical management as well as close collaboration among a multidisciplinary team. <h3>Observations</h3> Hidradenitis suppurativa is a disease of the hair follicles that results in recurrent nodules, abscesses, and tunneling sinus tracts. Medical treatment mainstays include antibiotics and retinoids, but the evolving class of biologic medications has gained traction in the treatment of moderate and severe disease. Many of the medical therapies come with adverse effects requiring clinical and laboratory monitoring over the course of treatment. When lesions are refractory to therapy or are too large for medical therapy alone, surgical intervention is required. Surgical procedures can include treatment of affected areas with deroofing or excision of affected skin. When large portions of genital skin are removed, reconstruction is necessary to restore function and aesthetics of the genitals. We describe a variety of reconstructive techniques based on the size and location of the skin deficiency. <h3>Conclusions and Relevance</h3> Effective management of genital hidradenitis suppurativa requires a thorough understanding of medical and surgical techniques for prevention, treatment, and reconstruction of genital defects.
Tumor bed irradiation enhances sensitivity of A431 tumor xenografts to C225 anti-EGFR antibody
Authors: Oliver Riesterer, Jessica Pickett, Nalini Patel, Uma Raju, Daniel Hicklin, Kian Ang, Luka Milas
Journal: Cancer Research (2008)

1318  Introduction: C225 strongly enhances tumor radioresponse when given concurrently with radiotherapy. Recently we reported that maintenance therapy with C225 after radiotherapy further increases tumor radiocurability in A431 tumor xenografts (Milas IJROBP 67, 568, 2007). Among mechanisms considered responsible for this effect was an enhanced response of irradiated vasculature of tumor bed to the antiangiogenic actions of C225. To determine the involvement of this mechanism, the present study assessed whether C225 exerts stronger antitumor effect on tumors that grow in pre-irradiated than in unirradiated tumor bed. Tumors bed effect denotes slower growth of tumors transplanted into irradiated tissue.  Material and Methods: The right hind legs of nude mice were irradiated with a single dose of 20 Gy γ-rays, and one day later A431 tumor cells were injected sc to generate tumors. Tumors were also generated in unirradiated mouse legs. When tumors grew to 5 mm in diameter, the mice were treated ip with 3 doses of 1 mg C225 per mouse given 3 days apart. Tumor doubling time (TDT) was defined as time (days) for tumors to grow from 5 to 10 mm. At 6 days after the 1st dose of C225 tumor tissue was taken for immunohistochemistry (IM). The Ki-67 labeling index (LI) was defined as the percentage of positive nuclei out of 103 cells counted. Tumor necrotic area was determined on H&E stained slides by image analysis.  Results: Tumor bed irradiation delayed tumor take and slowed the growth of established tumors, indicating a pronounced tumor bed effect. Treatment withC225 greatly reduced tumor take, which was more pronounced in the irradiated tumor bed. C225 only modestly delayed the growth of established tumors in the unirradiated tumor bed, but it dramatically reduced tumor growth in the irradiated tumor bed (TDT: control 7d, C225 10d, tumor bed irradiation 48d, C225 after tumor bed irradiation 98d). IM analysis showed a more pronounced antiproliferative effect of C225 against A431 tumor cells in the irradiated tumor bed than in the unirradiated tumor bed (Ki-67 LI: 12% vs 39%). Also, C225 increased the percentage of necrosis much more in tumors grown in the irradiated than in unirradiated tumor bed: 68% vs 5%.  Conclusion: C225 strongly enhanced tumor bed effect, which at the cellular level was accompanied by decreased tumor cell proliferation and increased tumor cell necrosis. These findings imply that irradiated tumor bed blood vessels exhibit increased sensitivity to antiangiogenic actions of C225, and thereby further support the concept of C225 maintenance after completion of radiotherapy we previously advanced.
First Tobacco Product Receives “Reduced Exposure” Authorization
Authors: Mary Chris Jaklevic
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Association of Acyl-Ghrelin With Posttraumatic Stress Disorder in Adolescents Who Experienced Severe Trauma
Authors: Muhammad Omar Malik, Mohsin Shah, Muhammad Irfan ul Akbar Yousufzai, Najeeb Ullah, JoColl A. Burgess, Ki Ann Goosens
Journal: JAMA Network Open (2020)

This cross-sectional study examines acyl-ghrelin levels in Pakistani adolescents who experienced severe trauma and have posttraumatic stress disorder (PTSD) compared with adolescents who have not experienced severe trauma.
A Solitary Skull Base Plasmacytoma Mimicking Paraganglioma on 68Ga-DOTATATE PET/CT
Authors: Jiaqiong Wang, Russ Kuker
Journal: Clinical Nuclear Medicine (2020)

The patient was a 61-year-old man with a history of neck pain starting around October 2019. CT of the neck showed a lytic lesion at the right skull base. Subsequent MRI demonstrated an enhancing destructive mass in the right skull base centered in the occipital bone and condyle involving the jugular foramen and hypoglossal canal. An F-FDG PET/CT was performed showing increased FDG uptake in the right jugular foramen tumor. In addition, a PET/CT with Ga-[DOTA-Tyr3]-octreotate (Ga-DOTATATE) demonstrated a Ga-DOTATATE-avid lesion in the right jugular foramen eroding the adjacent osseous structures. Biopsy revealed a plasmacytoma and not paraganglioma.
Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer
Authors: Chiara Cremolini, Carlotta Antoniotti, Alexander Stein, Johanna Bendell, Thomas Gruenberger, Daniele Rossini, Gianluca Masi, Elena Ongaro, Herbert Hurwitz, Alfredo Falcone, Hans-Joachim Schmoll, Massimo Di Maio
Journal: Journal of Clinical Oncology (2020)

A proper estimation of the magnitude of the overall survival (OS) benefit from infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab versus doublets + bevacizumab is lacking because all trials that have investigated this regimen had primary end points other than OS. To test OS with higher power and to explore the interaction of treatment effect with main patient and disease characteristics, we performed an individual patient data (IPD) meta-analysis.
Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma
Authors: Jean-François Martini, Elizabeth R. Plimack, Toni K. Choueiri, David F. McDermott, Igor Puzanov, Mayer N. Fishman, Daniel C. Cho, Ulka Vaishampayan, Bradley Rosbrook, Kathrine C. Fernandez, Jamal C. Tarazi, Saby George, Michael B. Atkins
Journal: Clinical Cancer Research (2020)

Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS).Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS.With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.