tbuckley/cabot-search huggingface dataset:
Exploring Understanding of “Understanding”: The Paradigm Case of Biobank Consent Comprehension
Authors: Laura M. Beskow, Kevin P. Weinfurt
Journal: The American Journal of Bioethics (2019)

Data documenting poor understanding among research participants and real-time efforts to assess comprehension in large-scale studies are focusing new attention on informed consent comprehension. Within the context of biobanking consent, we previously convened a multidisciplinary panel to reach consensus about what information must be understood for a prospective participant's consent to be considered valid. Subsequently, we presented them with data from another study showing that many U.S. adults would fail to comprehend the information the panel had deemed essential. When asked to evaluate the importance of the information again, panelists' opinions shifted dramatically in the direction of requiring that less information be understood. Follow-up interviews indicated significant uncertainty about defining a threshold of understanding and what should happen when prospective participants are unable to grasp key information. These findings have important implications for urgently needed discussion of whether consent comprehension is an ethical requirement or an ethical aspiration.
Abstract P5-07-09: Withdrawn
Authors: DK Ahirwar, MW Nasser, RK Shukla, K Shilo, RK Ganju
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Ahirwar DK, Nasser MW, Shukla RK, Shilo K, Ganju RK. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-09.
Abstract MS2-1: Overtreatment: First, do no harm
Authors: R Jagsi
Journal: Cancer Research (2019)

Abstract Perhaps more than for any other type of cancer, the management of breast cancer has been supported by a steady trajectory of research that has discovered ways to safely de-escalate therapy and identify patients who may safely forego potentially toxic treatments. This talk will begin with a brief overview of landmark clinical trials that have established the safety of de-escalating breast surgery, axillary surgery, radiotherapy, and systemic therapy for select patients. It will then turn to the research that shows that many women diagnosed with breast cancer today pursue considerably more aggressive treatments than needed to achieve excellent outcomes in terms of survival and recurrence, followed by a focus on the toxicity and costs that can result. Seeking to gain actionable insights on how to prevent shared decision-making from resulting in overtreatment, it will then discuss insights from decision psychology. It will include reflections on the heuristics that can lead patients and physicians alike towards overtreatment, the critical role of patients' underlying proclivities for medical maximizing versus medical minimizing, and the importance of naming and framing to ensure accurate risk communication. Citation Format: Jagsi R. Overtreatment: First, do no harm [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr MS2-1.
Changing the wolf from outside: how microbiota trigger systemic lupus erythematosus
Authors: Isabelle Peene, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2019)

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder affecting multiple organ systems including skin, joint and several internal organs such as kidney, heart or lung. A hallmark of this disease is the development of circulating antibodies against nuclear antigens and immune complex formation. The best-known antibodies are directed against native DNA and are prognostic for development of lupus nephritis. The processes resulting to the cascade of events culminating in the clinical features of SLE are only partially understood and involve among others, defective clearance of apoptotic cells and enhanced DNA damage to ultraviolet irradiation, and netosis1 2 (figure 1). It has also been suggested for a long time that certain microbial triggers could play a role in the onset of SLE, supported by early reports that antibody responses to nucleic acids/nucleoproteins were found in association with certain bacterial infections. More recently, more definitive proof of concept studies using germ-free and reconstituted mice highlighted that intestinal microbiota are able to drive development of systemic autoantibody responses.3 4 However, whether similar processes underlie development of lupus nephritis and anti-DNA antibodies was unclear.



Figure 1 
Integrating intestinal microbiota into systemic lupus erythematosus (SLE) pathogenesis. (A) Exposure to various sterile and/or infectious stimuli can lead to apoptosis or NETosis contributing to release of modified self-antigen (DNA). Genetic susceptibility and/or defective clearance results in presentation of these modified self-antigens to T cells followed by B cell activation and eventually production of anti-DNA antibodies, well-known for their association with lupus nephritis. (B) Dysbiosis in patients with SLE with fivefold overabundance of Ruminococcus g navus (RG) leads to barrier disruption and loss of systemic tolerance …
A useful app for general medicine
Authors: Krishna Anand
Journal: BMJ (2012)

Search online for a medical query and you will probably find that a Medscape article will appear near the top of the list. It is also available in an app format, which offers most of the content available on the website

Medscape is a clinical reference application containing more than 5000 peer reviewed articles written by experts. The topics have a broad range, including anatomy, pathology, and pharmacology. The content is comprehensive, but …
Racial Disparities in Low-Risk Prostate Cancer—Reply
Authors: Brandon A. Mahal, Franklin W. Huang
Journal: JAMA (2019)

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
Mucosal-associated invariant T cells and oral microbiome in persistent apical periodontitis
Authors: Haleh Davanian, Rogier Aäron Gaiser, Mikael Silfverberg, Luisa W. Hugerth, Michał J. Sobkowiak, Liyan Lu, Katie Healy, Johan K. Sandberg, Peggy Näsman, Jörgen Karlsson, Leif Jansson, Lars Engstrand, Margaret Sällberg Chen
Journal: International Journal of Oral Science (2019)

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination. Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity. It was recently shown that MAIT cells are present in the oral mucosal tissue, but the involvement of MAIT cells in AP is unknown. Here, comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33, Vα7.2-Jα20, Vα7.2-Jα12, Cα and tumour necrosis factor (TNF), interferon (IFN)-γ and interleukin (IL)-17A transcripts, resembling a MAIT cell signature. Moreover, in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4+ subset. Unlike gingival tissues, the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature. When merged in an integrated view, the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33, Cα, and IL-17A transcript expressions in AP, implying that MAIT cells could play a role in the local defence at the oral tissue barrier. In conclusion, we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place. These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.
AODTU-004 Endoscopic submucosal dissection for colorectal neoplasia: the experience of a uk tertiary referral centre
Authors: A Emmanuel, S Gulati, M Burt, B Hayee, A Haji
Journal: Gut (2017)

Introduction  Despite the advantages of endoscopic submucosal resection (ESD) demonstrated in large series from the far east, the procedure is not commonly practiced in the west and its role in standard practice is still debated. Although limited evidence regarding its efficacy in European practice is emerging, few centres in the United Kingdom perform ESD regularly, if at all. We report the experience of a UK tertiary referral institution using ESD as part of a lesion specific, pragmatic approach to endoscopic resection in a complex patient cohort.  Method  Patients who underwent ESD of colorectal lesions were included. Lesions were assessed with magnification chromoendoscopy, supplemented by colonoscopic ultrasound. to determine morphology, pit pattern, risk of submucosal invasion, and presence of submucosal fibrosis or scarring. ESD was used where en bloc resection was deemed essential, or as part of a hybrid procedure to ensure resection of a dominant nodule or suspicious area of a lesion in one piece, or where fibrosis or scarring would make standard EMR impossible. A resection was designated a hybrid procedure if ESD was used to effect mucosal incision and submucosal dissection to assist subsequent snare resection.  Results  438 colorectal lesions were resected. ESD was used in 97 cases, 49 cases used ESD alone and 48 as part of a hybrid procedure. 74% had 1 or more failed attempts at resection or significant manipulation in the form of ≥6 or more biopsies or tattoo into the lesion prior to referral to our institution. Only 8 of the remaining patients had no prior biopsies performed. The mean lesion size was 63 mm. En bloc resection was achieved in 89.8% where ESD was used alone, with a recurrence rate of 5.3% after a mean follow up of 13.3 months. There were 6 microperforations treated with either endoscopic clips or antibiotics alone with no adverse sequelae, and one clinically significant perforation requiring surgery. However, the lesion in this case contained an adenocarcinoma with deep submucosal invasion. There was no residual tumour in the surgical resection specimen. Post-procedure bleeding occurred in 6 patients, none of whom required additional interventional therapy. 71% of cases were successfully performed as day case procedures. 97% of patients without invasive cancer were free from recurrence and had avoided surgery at last follow up.  Conclusion  ESD can be safely and effectively incorporated into European practice as an essential adjunct in the treatment of a particularly complex patient cohort. As a result of large lesion size and very high rates of previous significant manipulation of lesions by the time of referral, a pragmatic, lesion-specific approach in choosing the resection technique is recommended.  Disclosure of Interest  None Declared
Aurora Kinase A Inhibition Provides Clinical Benefit, Normalizes Megakaryocytes, and Reduces Bone Marrow Fibrosis in Patients with Myelofibrosis: A Phase I Trial
Authors: Naseema Gangat, Christian Marinaccio, Ronan Swords, Justin M. Watts, Sandeep Gurbuxani, Alfred Rademaker, Angela J. Fought, Olga Frankfurt, Jessica K. Altman, Qiang Jeremy Wen, Noushin Farnoud, Christopher A. Famulare, Akshar Patel, Roberto Tapia, Rangit R. Vallapureddy, Stephanie Barath, Amy Graf, Amy Handlogten, Darci Zblewski, Mrinal M. Patnaik, Aref Al-kali, Yvonne Trang Dinh, Kristen Englund Prahl, Shradha Patel, Juan Carlos Nobrega, Dalissa Tejera, Amber Thomassen, Juehua Gao, Peng Ji, Raajit K. Rampal, Francis J. Giles, Ayalew Tefferi, Brady Stein, John D. Crispino
Journal: Clinical Cancer Research (2019)

Myelofibrosis is characterized by bone marrow fibrosis, atypical megakaryocytes, splenomegaly, constitutional symptoms, thrombotic and hemorrhagic complications, and a risk of evolution to acute leukemia. The JAK kinase inhibitor ruxolitinib provides therapeutic benefit, but the effects are limited. The purpose of this study was to determine whether targeting AURKA, which has been shown to increase maturation of atypical megakaryocytes, has potential benefit for patients with myelofibrosis.Twenty-four patients with myelofibrosis were enrolled in a phase I study at three centers. The objective of the study was to evaluate the safety and preliminary efficacy of alisertib. Correlative studies involved assessment of the effect of alisertib on the megakaryocyte lineage, allele burden, and fibrosis.In addition to being well tolerated, alisertib reduced splenomegaly and symptom burden in 29% and 32% of patients, respectively, despite not consistently reducing the degree of inflammatory cytokines. Moreover, alisertib normalized megakaryocytes and reduced fibrosis in 5 of 7 patients for whom sequential marrows were available. Alisertib also decreased the mutant allele burden in a subset of patients.Given the limitations of ruxolitinib, novel therapies are needed for myelofibrosis. In this study, alisertib provided clinical benefit and exhibited the expected on-target effect on the megakaryocyte lineage, resulting in normalization of these cells and reduced fibrosis in the majority of patients for which sequential marrows were available. Thus, AURKA inhibition should be further developed as a therapeutic option in myelofibrosis.See related commentary by Piszczatowski and Steidl, p. 4868.
Abstract 71: Mutational analysis forIDH1andIDH2in pediatric leukemia
Authors: Mitsuteru Hiwatari, Junko Takita, Riki Nishimura, Jun Okubo, Kentaro Oki, Masashi Sanada, Manabu Sotomatsu, Akira Kikuchi, Takashi Igarashi, Yasuhide Hayashi, Seishi Ogawa
Journal: Cancer Research (2012)

Abstract Recently, mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that NADP+dependent isocitrate dehydrogenase (IDH)1/2-mutated AMLs display global DNA hypermethylation and a specific hypermethylation signature, suggesting a shared proleukemogenic effect. To explore the involvements of IDH1/2 in the pathogenesis in pediatric hematological malignancies. We analyzed mutations that involve the activation sites of IDH1/2 using polymerase chain reaction amplification/sequencing in a total of 244 samples of pediatric myeloid malignancies as well as infantile leukemia including 17 AML-derived cell lines, 115 primary cases of AML, 28 primary cases of MDS, 15 primary cases of juvenile myelomonocytic leukaemia (JMML), 6 chronic myeloid leukemia (CML)-derived cell line, 18 primary cases of CML and 45 infantile leukemia(6 AML and 39 acute lymphoblastic leukemia (ALL) patients). Moreover, to assess whetherIDH1/2 mutations overlap with known gene abnormalities, such as FLT3, c-KIT, and NPM1 mutations, mutational analyses of FLT3, c-KIT, and NPM1 were also performed. The common IDH2 R140Q mutation was detected in a single AML case, whereas no IDH1 mutation was detected in samples of myeloid malignancies. Although no IDH2 mutation was detected in infantile leukemias, novel P127S, H133I and I130V of IDH1 mutations were detected in 4 of 45 (8.9%) infantile ALL cases. No IDH1 and IDH2 mutations were detected in the JMML, MDS, or CML samples examined. Six AML samples including one cell line had c-KIT mutations (D816V, N822K, or D419fs), 12 AML cases had FLT3-ITD and 10 infantile leukemia cases had FLT3 mutations (D835E or I836). The NPM1 mutation was detected in 2 of 132 AML samples. The AML case harboring the IDH2 mutation, Case 39 was a 12-year-old boy diagnosed as AML-M2 according to the French-American-British cooperative group classification system having t(8;21)(q22;q22), showed no abnormalities of NPM1, c-KIT, and FLT3. Remarkably, among 4 infantile ALL cases with IDH1 mutations, 3 cases showed mixed lineage leukemia(MLL) rearrangements with t(4;11). The FLT3-D835 mutation was found in 1 of 4 patients with IDH1 mutations. These results suggest that although the involvements of IDH1/2 mutations in the pathogenesis of pediatric myeloid malignancies are extremely rare, closely positioned to near activation site, R132 IDH1, these IDH1 mutations are the candidate second genetic events in a subset of MLL-leukemia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 71. doi:1538-7445.AM2012-71
Suicidality and risk of suicidality in psoriasis: a critical appraisal of two systematic reviews and meta‐analyses
Authors: U. Matterne, S.E. Baumeister, C.J. Apfelbacher
Journal: British Journal of Dermatology (2019)

Chi et al.1 and Singh et al.2 each conducted a systematic review and meta‐analysis of observational studies examining the relationship between suicidality and psoriasis. Chi et al. included only cohort studies while Singh et al. included cohort, cross‐sectional and case–control studies. The primary outcome, suicidality, was assessed in people with psoriasis (exposure) and people without psoriasis. Analyses were separated for suicidal ideation and behaviour. Chi et al. included five population‐based cohort studies that were considered to be of high quality according to the Newcastle–Ottawa Scale (NOS). They found no significant increase in the risk of suicide [risk ratio (RR) 1·13, 95% confidence interval (CI) 0·87–1·46], suicide attempt (RR 1·25, 95% CI 0·89–1·75) or suicidality (RR 1·26, 95% CI 0·97–1·64) among people with psoriasis. Singh et al. included 18 studies that were rated to be of medium quality to high quality according to the NOS. They found a pooled odds ratio (OR) of 2·05 (95% CI 1·54–2·74) for suicidal ideation among patients with psoriasis. For suicidal behaviours (combined attempted and completed suicides) a pooled OR of 1·26 (95% CI 1·13–1·40) was obtained, suggesting a higher risk of these behaviours in people with psoriasis. Subgroup analysis showed that patients with psoriasis were more likely to attempt suicide (OR 1·32, 95% CI 1·14–1·54) and complete suicide (OR 1·20, 95% CI 1·04–1·39) than those without psoriasis. Singh et al. concluded that patients with psoriasis have a significantly higher risk of suicidal ideation, suicide attempts and completed suicides, while Chi et al. concluded that the available, limited, very low‐quality evidence does not support the notion of an association between psoriasis on the one hand, and suicide, suicidal ideation and suicide attempts on the other.
Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection
Authors: Chinnakkaruppan Adaikkan, Steven J. Middleton, Asaf Marco, Ping-Chieh Pao, Hansruedi Mathys, David Nam-Woo Kim, Fan Gao, Jennie Z. Young, Ho-Jun Suk, Edward S. Boyden, Thomas J. McHugh, Li-Huei Tsai
Journal: Neuron (2019)
Abstract P6-20-15: Characterization of a novel prognostic and targetable modulator of the Wnt/β-catenin signaling pathway in breast cancers
Authors: N Bunnag, Y Yuan, W Cai, J Suresh, L Young Bok, K Deog Joong, N Tolwinski, AP Kumar
Journal: Cancer Research (2019)

Abstract Mortality in metastatic triple negative breast cancer (TNBC) remains high due to a lack of targeted therapy options. Consequently, there is a pressing need to identify prognostic markers and therapeutic targets for TNBC. Our group identified the DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene enriched in TNBC. Aberrant Wnt/β-catenin signaling has been implicated for driving growth and metastasis of many cancers, like TNBC. Our studies found that the depletion of DP103 in metastatic TNBC cells resulted in decreased Wnt activity and expression of downstream Wnt target genes such as Axin2 and c-Myc. In addition, stimulation of the Wnt pathway via GSK3β inhibition or Wnt-3a recombinant protein significantly increased the transcriptional expression of DP103, indicating a possible positive feedback loop. To validate this new role for DP103 in regulating the Wnt/β-catenin signaling pathway in vivo, we developed a novel Drosophila stem cell and tumor model by generating a genetic mosaic of oncogenic Ras and β-catenin in Drosophila. The co-expression of these oncogenes caused benign tumor formation in Drosophila larval tissue that were visualized and used to identify key genetic modifiers necessary for growth and invasion into neighboring tissues. RX-5902, a novel Wnt/β-catenin modulator preventing the nuclear translocation of β-catenin via phosphorylated p68 decreased the transcriptional expression of DP103 and inhibited tumor formation as observed in our Drosophila model. Interestingly, overexpression of DP103 abrogated the effects of RX-5902, suggesting a requirement for RX-5902-mediated downregulation of DP103 to bring about anti-tumorigenic effects. Collectively, our data suggests a novel regulatory role for DP103 in the Wnt/β-catenin signaling pathway that is targetable by drugs like RX-5902. Citation Format: Bunnag N, Yuan Y, Cai W, Suresh J, Young Bok L, Deog Joong K, Tolwinski N, Kumar AP. Characterization of a novel prognostic and targetable modulator of the Wnt/β-catenin signaling pathway in breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-15.