tbuckley/cabot-search huggingface dataset:
Combining accurate tumor genome simulation with crowdsourcing to benchmark somatic structural variant detection
Authors: Anna Y. Lee, Adam D. Ewing, Kyle Ellrott, Yin Hu, Kathleen E. Houlahan, J. Christopher Bare, Shadrielle Melijah G. Espiritu, Vincent Huang, Kristen Dang, Zechen Chong, Cristian Caloian, Takafumi N. Yamaguchi, Michael R. Kellen, Ken Chen, Thea C. Norman, Stephen H. Friend, Justin Guinney, Gustavo Stolovitzky, David Haussler, Adam A. Margolin, Joshua M. Stuart, Paul C. Boutros
Journal: Genome biology (2018)

The phenotypes of cancer cells are driven in part by somatic structural variants. Structural variants can initiate tumors, enhance their aggressiveness, and provide unique therapeutic opportunities. Whole-genome sequencing of tumors can allow exhaustive identification of the specific structural variants present in an individual cancer, facilitating both clinical diagnostics and the discovery of novel mutagenic mechanisms. A plethora of somatic structural variant detection algorithms have been created to enable these discoveries; however, there are no systematic benchmarks of them. Rigorous performance evaluation of somatic structural variant detection methods has been challenged by the lack of gold standards, extensive resource requirements, and difficulties arising from the need to share personal genomic information. To facilitate structural variant detection algorithm evaluations, we create a robust simulation framework for somatic structural variants by extending the BAMSurgeon algorithm. We then organize and enable a crowdsourced benchmarking within the ICGC-TCGA DREAM Somatic Mutation Calling Challenge (SMC-DNA). We report here the results of structural variant benchmarking on three different tumors, comprising 204 submissions from 15 teams. In addition to ranking methods, we identify characteristic error profiles of individual algorithms and general trends across them. Surprisingly, we find that ensembles of analysis pipelines do not always outperform the best individual method, indicating a need for new ways to aggregate somatic structural variant detection approaches. The synthetic tumors and somatic structural variant detection leaderboards remain available as a community benchmarking resource, and BAMSurgeon is available at https://github.com/adamewing/bamsurgeon .
The QT Interval
Authors: John R. Giudicessi, Peter A. Noseworthy, Michael J. Ackerman
Journal: Circulation (2019)

he core vital signs including heart rate, respiratory rate, body temperature, and blood pressure can be assessed rapidly and provide critical, objective, and quantitative insights into the state of the body's essential functions.Although these traditional vitals will almost certainly remain a cornerstone of medical practice, a wealth of readily available biometric data, facilitated by mobile health technologies, is transforming age-old approaches to assessment and monitoring in both health and disease.As such, it appears increasingly likely that novel vital signs will emerge from the current precision medicine revolution.In the recent past, many new vital signs, ranging from subjective pain scales to oxygen saturation to health literacy, have been proposed.Although each has some merit, most provide redundant information and fail to meet the benchmark of a true vital sign (ie, a rapid, objective, and quantifiable assessment of life-sustaining function[s]).Until recently, the heart rate-corrected QT interval (QTc), which represents a dynamic measurement of the time required to reset the heart's electric system, fell squarely into this latter category.However, with the present availability of cardiac monitors equipped with automated QTc monitoring, and the more recent availability of Food and Drug Administration (FDA)-approved consumer mobile ECG devices that appear capable of accurately detecting QTc prolongation (reported sensitivity and specificity for a QTc >500 ms of 64% and 97%, respectively) 1 in settings where obtaining a traditional 12-lead ECG is simply not feasible or fiscally possible, the technology to enable the QTc to enter the vital sign debate is finally emerging.To this end, a prolonged QTc, defined as a QTc value >450 ms in males and >460 ms in females measured preferably in lead II or V 5 on a standard 12-lead ECG, predisposes to functional reentry, torsades de pointes, and sudden cardiac death (SCD), and represents a widely accepted, easily measured, and quantifiable risk factor for adverse outcomes. 2,3An otherwise unexplained baseline QTc >500 ms should prompt clinical suspicion for the possible presence of a potentially lethal, highly treatable condition known as congenital long-QT syndrome (LQTS).In addition, acute QTc increases (ie, ΔQTc >60 ms) are indicative of the exaggerated QTc response that accompanies increased risk of torsades de pointes/SCD in drug-induced LQTS. 3,4It is interesting to note that even modest QTc prolongation, perhaps mediated by elevated sympathetic tone, subclinical atherosclerosis, and electrolyte/metabolic abnormalities, is associated with an increased risk of cardiovascular events, stroke, and all-cause mortality, often independent of traditional risk factors, in a variety of patient populations. 2ollectively, this body of evidence illustrates that a prolonged QTc value, whether secondary to genetics, drugs, electrolyte perturbations, or systemic disease, represents a critical barometer of the heart's electric system capable of
THU0579 CHEMOKINE AND CYTOKINE TEARS PROFILE OF PATIENTS WITH IGG4-RELATED DISEASE
Authors: Eduardo Martin-Nares, Luis Llorente, Isela Chan-Campos, Diego Hernández-Ramírez, Guadalupe Lima, Vanessa Saavedra-González, Gabriela Hernandez-Molina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The lacrimal gland is frequently involved in both IgG4-related disease (IgG4-RD) and Sjögren's syndrome (SS) and presents with swelling and/or dry eye symptoms. Although a distinct chemokine and cytokine tear profile might distinguish SS from idiopathic dry eye, as of today no study has assessed this issue in IgG4-RD. <h3>Objectives:</h3> To evaluate and compare a set of chemokine/cytokine in the tears of patients with IgG4-RD and primary SS. <h3>Methods:</h3> We included 11 patients with IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD and 17 with primary SS according the AECG criteria, who attended a tertiary referral center in Mexico City. Schirmer-I test were performed using two standardized sterile tear strips, and then immediately frozen at -86°C until assayed. Once defrosted, the tears were extracted from the strips using a buffer containing 0.5 M NaCl and 0.5% Tween-20. Then, the amount (pg/mL) of the following selected chemokines and cytokines were measured by Luminometry: CCL11, G-CSF, IFN-γ, IL-12p40, IL-12p70, IL-13, IL-17A, IL-1α, IL-1β, IL-4, IL-7, CXCL10, CCL2, CCL3, CCL4 and TNF-α. <h3>Results:</h3> Patients with IgG4-RD were younger (51.3±14.7 vs. 55.7±10.6) and more frequently men (45.5% vs. 5.9%) than SS patients. Regarding the IgG4-RD group, 7 (63.6%) had lacrimal gland involvement, 5 (45.5%) dry eye symptoms and 6 (54.5%) positive Schirmer-I test. We observed multi-organic involvement in 9 patients (81.8%), median number of involved organs of 5, 9 (81.8%) patients had active disease, median IgG4-RD responder index of 6 points, 8 (72.7%) patients had high IgG4 serum levels, and 9 (81.8%) biopsy proven diagnosis. We found higher levels of IL-7 and CCL2, and a trend for G-CSF in the IgG4-RD group. Conversely, primary SS patients had higher levels of IL-12p40, IL-1α, IL-1β, CCL3 and CCL4. At the logistic regression analysis, the variables that remained associated with IgG4-RD were IL-7 (OR 1.43 95% CI 1.06-1.93, p=0.01) and IL12p40 (OR 0.92, 95% CI 0.84-0.99, p=0.01). In a sensitivity analysis, including only 7 IgG4-RD patients with dacryoadenitis, we also observed higher levels of IL-7 and G-CSF in the IgG4-RD group vs primary SS. <h3>Conclusion:</h3> The chemokine and cytokine profile of tears of patients with IgG4-RD is characterized by a mixed immune response (Th1/Th2/Th17) compare with a predominantly Th1 response in primary SS. Our results also suggest a possible role of IL-7 in the pathogenesis of IgG4-RD. <h3>References:</h3> [1] Hernández-Ruiz M, Zlotnik A, Llorente L, Hernandez-Molina G. Markedly high salivary and lacrimal CXCL17 levels in primary Sjögren's syndrome. Joint Bone Spine. 2018May;85(3):379-380. <h3>Disclosure of Interests:</h3> None declared
Decision Aids for Prostate Cancer Screening—The True Potential Remains Unknown
Authors: Laura D. Scherer, Grace Lin
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
AB1320 NEUTROPHIL-TO-LYMPHOCYTE RATIO AND PLATELET-TO-LYMPHOCYTE RATIO ARE ASSOCIATED WITH DISEASE ACTIVITY IN POLYMYALGIA RHEUMATICA
Authors: Ju-Yang Jung, Jiwon Kim, Chang-Hee Suh, Hyoun-Ah Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Polymyalgia rheumatica (PMR) is a systemic inflammatory disorder, which develops inflammatory pain and stiffness of large joints. There is no specific serological marker or test to differentiate PMR. <h3>Objectives:</h3> In this study, we compared the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) among patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), and explored possible associations with clinical features, disease activity, and prognosis in PMR. <h3>Methods:</h3> A total of 94 PMR and 242 RA patients who were initially diagnosed at the rheumatology clinic of a university-based tertiary hospital were enrolled. Symptoms, physical examination, and medical histories were collected with the results of laboratory tests. <h3>Results:</h3> NLR (4.5 ± 3.3 vs. 2.8 ± 1.8), PLR (222.7 ± 115.5 vs. 159.7 ± 78.1), and MLR (0.4 ± 0.3 vs. 0.3 ± 0.2) were higher in patients with PMR compared with patients with RA (all p &lt; 0.001). NLR, PLR, and MLR were correlated with specific serological values, including CRP and albumin, in patients with PMR. After disease activity resolved, NLR (2.95 ± 2.32, p &lt; 0.001), PLR (137.5 ± 82.3, p &lt; 0.001), and MLR (0.26 ± 0.16, p &lt; 0.001) decreased significantly. By comparing patients according to the disease course, swollen joint counts were higher in the chronic course group compared with the remission group (p = 0.03), while NLR, PLR, and MLR levels were similar. <h3>Conclusion:</h3> This study found that NLR, PLR, and MLR in patients with PMR were higher than in those with RA. Furthermore, NLR, PLR, and MLR levels were associated with disease activity and specific clinical features, although they could not predict prognosis in patients with PMR. <h3>References:</h3> [1] van der Geest KS, Abdulahad WH, Rutgers A, Horst G, Bijzet J, Arends S, et al. Serum markers associated with disease activity in giant cell arteritis and polymyalgia rheumatica. Rheumatology (Oxford). 2015;54(8):1397-402. [2] Erre GL, Paliogiannis P, Castagna F, Mangoni AA, Carru C, Passiu G, et al. Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis. Eur J Clin Invest. 2018:e13037 <h3>Disclosure of Interests:</h3> Ju-Yang Jung: None declared, Jiwon Kim: None declared, Chang-Hee Suh Consultant for: Celltrion, Inc, Hyoun-Ah Kim: None declared
What I Learned From My Childhood as a Patient
Authors: Amy D. Robertson
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
PB2225 ARTIFICIAL INTELLIGENCE AIDING IN DIAGNOSIS OF JAK2 V617F NEGATIVE PATIENTS WITH WHO DEFINED ESSENTIAL THROMBOCYTHEMIA
Authors: T. Belcic, P. Cernelc, M. Sever
Journal: HemaSphere (2019)

Background: Smart Blood Analytics (SBA) is an artificial intelligence program using machine learning algorithm in order to provide a list of most probable disease diagnosis in numerical order based on patient's blood test results. It was successfully tested in diagnosing hematological diseases and is especially targeted for medical doctors without detailed knowledge in the field of hematology. Aims: Our aim was to determine the applicability of SBA algorithm in patients with suspected essential thrombocythemia (ET). Methods: We analyzed 237 patients that presented at UMC Ljubljana between 04/2011 and 09/2016 with the referral diagnosis of ET. Based on the presence of CALR or MPL mutation and bone marrow examination we defined patients with true ET according to WHO 2008 or modified WHO criteria. All 237 patients were subsequently analyzed by SBA algorithm in order to determine the most probable hematologic diagnosis based on patients’ blood test results obtained at the time of referral. The diagnosis of interest according to ICD10 classification was D47 describing other neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue, including ET. We defined sensitivity and specificity of ET diagnosis by using SBA machine learning algorithm. Results: 10.5% (25/237) of patients were diagnosed with ET according to WHO 2008 or modified WHO criteria. 22 patients were CALR positive, 1 patient was MPL positive and 3 patients were triple negative. 89.4% (212/237) of patients were diagnosed with either secondary thrombocythemia or other neoplastic disease, such as myelodysplastic syndrome. The sensitivity of SBA algorithm to detect patients with ET was 100% and the specificity was 50.4%. Summary/Conclusion: The number of patients with true ET referred to our center was low. An improved referral and diagnostic approach for patients with thrombocythemia should be used. The SBA machine learning algorithm could be useful, especially in circumstances where hematologic consultation is not available. Further development of SBA machine learning algorithm is warranted.
Athlete autonomy, supportive interpersonal environments and clinicians’ duty of care; as leaders in sport and sports medicine, the onus is on us: the clinicians
Authors: Jane S Thornton
Journal: British Journal of Sports Medicine (2019)

Excellence for elite athletes demands painstaking attention to detail to all aspects of health, well-being and performance. Researcher and Olympic Taekwondo Gold Medalist Lauren Burns and coauthors1 use the power of the athlete story to argue strongly and convincingly that central to achieving excellence is durable interpersonal support.

‘If we look at an athlete as a whole person, there is a fundamental duty of care to ensure they are supported to become their best, most resilient self, both on and off the field. Athletes therefore need to be encouraged to seek interpersonal support that evolves as they move along their development pathway’.

These sentences, both important, appear sequentially; but I will make one distinction—the onus to create a supportive environment should not rest primarily on athletes.

Where then does the duty of care lie?

According to Fisher et al ’s heuristic model,2 the power differential in sport particularly positions coaches to hurt or help their athletes, and as such coaches are responsible for athlete’s welfare.

Those, …
PB1738 NUCLEOPHOSMIN‐1 GENE MUTATION DETECTION: COMPARATIVE IMMUNO‐STAINING STUDY FOR BONE MARROW (BM) BIOPSY VERSUS BM ASPIRATE &amp; BM CLOT IN DE NOVO ADULT ACUTE MYELOID LEUKEMIA PATIENTS AMONG EGYPTIANS
Authors: B. Elgamal, M. El Gammal, R. Badawy, E. Abdelghaffar, E. Rasheed, M. Elkafoury, M. Hamdy
Journal: HemaSphere (2019)

Background: NPM1 gene mutation is a well‐known prognostic marker in AML, probably related to its cytoplasmic localization. NPM1 gene mutation detection could be done by either molecular genetics or its protein product by immunohistochemical staining of bone marrow (BM) biopsy. Aims: This study aimed to compare the detection rate of the immuno‐staining technique for mutated nucleophosmin‐1 gene when applied on the standard BM biopsy versus BM aspirate or BM clot biopsy in adult de novo patients of acute myeloid leukemia. Methods: Forty adult patients (18‐60 years) with newly diagnosed AML were enrolled into this study. Detection of nucleophosmin localization either nucleolar or cytoplasmic was performed using monoclonal mouse anti‐human nucleophosmin (clone 376) by conventional immunohistochemical technique on BM biopsy, BM aspirate &amp; BM clot biopsy. Results: The study included 40 AML patients, 23 males, 17 females. The complete remission (CR) rate was 70%. Median overall survival (OS) was 2.5 month (0.1‐40 months). Median disease free survival was 6 month (0.2‐39). NPM1 was detected in 11/40 patients by conventional immunohistochemical technique on BM biopsy, 11/39 patients by BMA technique, and 9/29 by BM clot technique. The BMA technique had Sensitivity of 100%, Specificity of 78.6%, positive predictive value of 64.7%, negative predictive value of 100%, and diagnostic accuracy of 84.6%. The BM clot technique had sensitivity of 77.8%, specificity of 90.0%, and positive predictive value of 77.8%, negative predictive of 90.0%, and diagnostic accuracy 86.2%. Summary/Conclusion: The BMA technique had good sensitivity and so could be used as a cheap screening method even in patients with profound thrombocytopenia. BM clot technique had good specificity. Both BMA and BM clot techniques could be a reasonable cheap option if combined together in cases in which BM biopsy could not be done. image
Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age
Authors: J. Ariana Noel, Sarah E. Bota, William Petrcich, Amit X. Garg, Juan Jesus Carrero, Ziv Harel, Navdeep Tangri, Edward G. Clark, Paul Komenda, Manish M. Sood
Journal: JAMA Internal Medicine (2019)

Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use.To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age.Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level.Dispensed sodium polystyrene sulfonate in an outpatient setting.The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription.From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury.The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.
SP0194 WHEN AND HOW TO USE AND NOT USE IMAGING FOR DIAGNOSIS?
Authors: Floris A. van Gaalen
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Since axial spondyloarthritis (axSpA) has no single shared distinguishing feature that distinguishes the disease from other causes of back pain, diagnosis of axSpA requires recognition by the clinician of a pattern of features that taken together are characteristic of axSpA. Information from patient history and physical examination, laboratory, and imaging findings may all aid in recognition of axSpA and the diagnosis of axSpA requires exclusion of other potential causes for these abnormalities/differences. Traditionally, plain radiography is used to assess sacroiliac and spinal involvement of disease. A weakness of radiography in assessing sacroiliac involvement - apart from its inability to detect early disease - is reader variability. Additionally, involvement of the spine (i.e detection of syndesmophytes) is very uncommon in early disease. The use of MRI in diagnosing axSpA has increased over the past ten years and MRI greatly facilitates earlier diagnosis of axSpA. However, it has also become increasingly clear that MRI detectable lesions associated with SpA -including bone marrow edema and fatty lesions- may also occur in patients without axSpA. The aim of this presentation is to provide insight into the pitfalls of imaging in diagnosing SpA, with a particular focus on false positives in imaging as well as the importance of interpretation of the clinical context. <h3>Disclosure of Interests:</h3> None declared