tbuckley/cabot-search huggingface dataset:
Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia: Exploratory analysis of a series of consecutive patients.
Authors: Bruno Bockorny, Joanna Grabska, Ion Codreanu, Prerna Mewawalla, Joel Silver, Constantin Dasanu
Journal: Journal of Clinical Oncology (2012)

6555 Background: Review of literature suggests certain autoimmune abnormalities to accompany LGL leukemia. The present study was set to identify the prevalence of autoimmune phenomena in LGL leukemia patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=11) with LGL leukemia that had been followed in outpatient setting. Median age was 71 years ( ± 14 years). The presence of associated autoimmune disorders in our cohort was compared to the published prevalence of these conditions in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p value &lt; 0.05 was considered significant. Results: A total of 45% patients in our study were diagnosed with autoimmune conditions. Identified autoimmune disorders included rheumatoid arthritis [RA] (n=3), Hashimoto thyroiditis (n=3), Felty syndrome (n=1), aplastic anemia (n=1), pernicious anemia (n=1), and leukocytoclastic vasculitis (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.044), RA (p=0.003), Felty syndrome (p&lt;0.001), aplastic anemia (p&lt;0.001), pernicious anemia (p&lt;0.001), and leukocytoclastic vasculitis (p&lt;0.001). Statistical difference was also noted for autoimmune serologic abnormalities, with ANA positivity present in 63.6% of the cases (p&lt; 0.001) and RF present in 50% of the patients (p=0.005). Conclusions: Nearly half of LGL leukemia patients in our cohort had autoimmune conditions, thus significantly exceeding the overall prevalence in general population. Statistically significant differences were recorded for RA, Hashimoto thyroiditis, Felty syndrome, aplastic anemia, pernicious anemia, leukocytoclastic vasculitis, ANA and RF positive serologies. The prevalence of Hashimoto thyroiditis and ANA positivity in our patient cohort was significantly higher than the one in existing literature. Given the relatively small size of the analyzed cohort, larger studies are expected to confirm our findings.
A Ribose-Scavenging System Confers Colonization Fitness on the Human Gut Symbiont Bacteroides thetaiotaomicron in a Diet-Specific Manner
Authors: Robert W.P. Glowacki, Nicholas A. Pudlo, Yunus Tuncil, Ana S. Luis, Peter Sajjakulnukit, Anton I. Terekhov, Costas A. Lyssiotis, Bruce R. Hamaker, Eric C. Martens
Journal: Cell Host & Microbe (2019)
Chemotherapy in advanced thymic malignancies
Authors: A.N. Varshney, I. Vanidassane, D. Ramavth, P.S. Malik, S. Khurana, V. Garg, S.P. Vadlamani, K. Kalra, S. Gunasekar, S. Kumar, S. Sethi, M. Yadav, S. Pathy, D. Jain
Journal: Annals of Oncology (2019)
Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
Authors: Christoph Hafemeister, Rahul Satija
Journal: Genome biology (2019)

Single-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity with technical effects. To address this, we present a modeling framework for the normalization and variance stabilization of molecular count data from scRNA-seq experiments. We propose that the Pearson residuals from "regularized negative binomial regression," where cellular sequencing depth is utilized as a covariate in a generalized linear model, successfully remove the influence of technical characteristics from downstream analyses while preserving biological heterogeneity. Importantly, we show that an unconstrained negative binomial model may overfit scRNA-seq data, and overcome this by pooling information across genes with similar abundances to obtain stable parameter estimates. Our procedure omits the need for heuristic steps including pseudocount addition or log-transformation and improves common downstream analytical tasks such as variable gene selection, dimensional reduction, and differential expression. Our approach can be applied to any UMI-based scRNA-seq dataset and is freely available as part of the R package sctransform, with a direct interface to our single-cell toolkit Seurat.
Association Between Objectively Measured Sleep Duration and Symptoms of Psychiatric Disorders in Middle Childhood
Authors: Bror M. Ranum, Lars Wichstrøm, Ståle Pallesen, Jonas Falch-Madsen, Marte Halse, Silje Steinsbekk
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The long-term association between sleep duration and mental health in children is currently unknown. <h3>Objective</h3> To investigate the prospective associations between sleep duration and symptoms of emotional and behavioral disorders at ages 6, 8, 10, and 12 years. <h3>Design, Setting, and Participants</h3> This population-based cohort study obtained data from the Trondheim Early Secure Study in Trondheim, Norway. A representative, stratified random sample of children born between January 1, 2003, and December 31, 2004, were invited to participate. Participants were followed up biennially from age 4 years (2007-2008) to 12 years (2013-2014). Data analysis was conducted from January 2, 2019, to May 28, 2019. <h3>Main Outcomes and Measures</h3> Sleep duration was assessed with 1 week of continuous use of a triaxial accelerometer. Symptoms of emotional (anxiety and depression) and behavioral (oppositional defiant, conduct, and attention-deficit/hyperactivity) disorders were measured by semistructured clinical interviews (using the Preschool Age Psychiatric Assessment and the Child and Adolescent Psychiatric Assessment) with parents (at all ages) and children (from age 8 years). <h3>Results</h3> The analytical sample comprised 799 children (mean [SD] age at time point 2, 6.0 [0.2] years; 405 [50.7%] boys; and 771 [96.5%] Norwegian). Shorter sleep duration at age 6 years (β [unstandardized regression coefficient] = −0.44; 95% CI, −0.80 to −0.08;<i>P</i> = .02) and 8 years (β = −0.47; 95% CI, −0.83 to −0.11;<i>P</i> = .01) forecasted symptoms of emotional disorders 2 years later. Comparatively short sleep duration at age 8 years (β = −0.65; 95% CI, −1.22 to −0.08;<i>P</i> = .03) and 10 years (β = −0.58; 95% CI, −1.07 to −0.08;<i>P</i> = .02) was associated with symptoms of behavioral disorders 2 years later among boys but not among girls at age 8 years (β = −0.14; 95% CI,− 0.52 to 0.24;<i>P</i> = .48) or 10 years (β = −0.05; 95% CI, = −0.49 to 0.40;<i>P</i> = .84). These associations were statistically significant among boys compared with girls at age 8 years (Δχ<sup>2</sup><sub>1</sub> = 13.26;<i>P</i> &lt; .001) and 10 years (Δχ<sup>2</sup><sub>1</sub> = 10.25;<i>P</i> = .001). Symptoms of psychiatric disorders did not forecast sleep duration at any age. <h3>Conclusions and Relevance</h3> This study found an association between short sleep duration and increased risk of future occurrence of emotional disorder symptoms in both boys and girls and between reduced sleep and behavioral disorder symptoms in boys. These results suggest that improving sleep in children may help protect against the development of symptoms of common psychiatric disorders and may be advantageous in the treatment of such disorders.
Phase II study of short CHOP-rituximab combination with early consolidation with ibritumomab-tiuxetan-Y<sup>90 </sup>(IT-Y<sup>90</sup>) in non-pretreated patients age 65 to 80 with CD20+ diffuse large B-cell lymphoma (DLBCL).
Authors: Frederic Peyrade, Gerard Lepeu, Jocelyn Gal, Christophe Fruchart, Diane Coso, Serge Bologna, Mariano Provencio, Regis Kaphan, Claudine Sohn, Bruno Audhuy, Gomez Codina, Antoine Thyss
Journal: Journal of Clinical Oncology (2012)

6633 Background: IT-Y 90 was approved in follicular lymphoma, and some data indicates that it could be used in DLBCL. It has been reported that early TEP-TDM negativity is associated with a longer survival in DLBCL, which suggest that these patients could benefit of a less intensive protocol. Methods: We conducted an international, open-label, phase II non-randomised study, in patients aged between 65 and 80 with age-adjusted (aa) IPI score of 0 and 1 and CD20+ DLBCL. The primary objective was to evaluate the efficacy of 3 cycles of RCHOP14 followed by, in case of complete response (CR), an injection of IT-Y 90 . Results: Thirty patients (M/F= 1) were included. Median age was 72.6 years (range 65 - 80). Patients had a stage III/IV, elevated LDH and IPI=1 in 38%, 16.6 and 57% respectively. 25 patients received the full treatment. Five obtained an uncomplete FDG-PET response and were excluded after 2 RCHOP cycles. 23 patients received the full IT-Y 90 dosage (0.4mCi/Kg) and two received the attenuated dosage (0.3mCi/Kg). Mean treatment time was 54 days (median 52; min 48-max 69). The CR rate after RCHOP treatment was 85% [95% CI: 65-94]. No treatment-related deaths occurred. Grade III-IV neutropenia and thrombocytopenia was observed in 45% and 4%, respectively. Five patients experienced at least one febrile neutropenia. After IT-Y 90 , mean duration time for platelets &lt;50G/l was 2.08 weeks (median 2; min 0-max 5). Two patients required platelet transfusion. With a median follow-up of 29.5 months [95% CI: 23-39], the estimated 3-year PFS was 90% [95% CI: 80-100] and the 3-year OS was 100% [95% CI: 100-100]. Among patients treated with 90 Y-IT, only 3 relapsed were recorded (at 6, 16 and 24 months). Conclusions: this study suggested the feasibility, and efficacy of a short regimen including one injection of IT-Y 90 for selected DLBCL in complete response after 3 cycles of RCHOP14. This results need to be confirmed by further studies.
Response to: ‘Frequency of MRI changes suggestive of axial spondyloarthritis in the axial in a large population-based cohort of individuals aged &lt;45 years’ by Parperis
Authors: Xenofon Baraliakos, Adrian Richter, Carsten O Schmidt, Juergen Braun
Journal: Annals of the Rheumatic Diseases (2020)

We agree with the authors of the comment that caution in the interpretation of MRI is needed, though we think this is generally the case for any kind of imaging techniques. Regarding the axial skeleton including the spine and the sacroiliac joints (SIJs) this is particularly critical if identification of patients with axial spondyloarthritis (axSpA) is pursued. In this context our study1 confirms earlier data.2 We conclude that false positive MRI findings account for much of the confusion that has been created in relation to the Assessments in Spondyloarthritis International Society (ASAS) classification criteria.3

However, Dr Parperis has a different issue4 since he proposes …
The “ART” of Epigenetics in Melanoma: From histone “Alterations, to Resistance and Therapies”
Authors: Thomas Strub, Robert Ballotti, Corine Bertolotto
Journal: Theranostics (2020)

Malignant melanoma is the most deadly form of skin cancer.It originates from melanocytic cells and can also arise at other body sites.Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients.However, long-term survival rate for metastatic melanoma patients remains at only 5%.Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations.In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this resistance seems to be non-genetic in nature with a change in transcription programs within cell subpopulations.This change can adapt and escape targeted therapy and immunotherapy cytotoxic effects favoring relapse.Because they are reversible in nature, epigenetic changes are a growing focus in cancer research aiming to prevent or revert the drug resistance with current therapies.As such, the field of epigenetic therapeutics is among the most active area of preclinical and clinical research with effects of many classes of epigenetic drugs being investigated.Here, we review the multiplicity of epigenetic alterations, mainly histone alterations and chromatin remodeling in both cutaneous and uveal melanomas, opening opportunities for further research in the field and providing clues to specifically control these modifications.We also discuss how epigenetic dysregulations may be exploited to achieve clinical benefits for the patients, the limitations of these therapies, and recent data exploring this potential through combinatorial epigenetic and traditional therapeutic approaches.
The application of big data to cardiovascular disease: paths to precision medicine
Authors: Jane A. Leopold, Bradley A. Maron, Joseph Loscalzo
Journal: Journal of Clinical Investigation (2020)

Advanced phenotyping of cardiovascular diseases has evolved with the application of high-resolution omics screening to populations enrolled in large-scale observational and clinical trials. This strategy has revealed that considerable heterogeneity exists at the genotype, endophenotype, and clinical phenotype levels in cardiovascular diseases, a feature of the most common diseases that has not been elucidated by conventional reductionism. In this discussion, we address genomic context and (endo)phenotypic heterogeneity, and examine commonly encountered cardiovascular diseases to illustrate the genotypic underpinnings of (endo)phenotypic diversity. We highlight the existing challenges in cardiovascular disease genotyping and phenotyping that can be addressed by the integration of big data and interpreted using novel analytical methodologies (network analysis). Precision cardiovascular medicine will only be broadly applied to cardiovascular patients once this comprehensive data set is subjected to unique, integrative analytical strategies that accommodate molecular and clinical heterogeneity rather than ignore or reduce it.
Cost-effectiveness analysis of cetuximab and panitumumab as first-line metastatic colorectal cancer therapies in Spain.
Authors: Victor Moreno, Brezo Martinez-Amores, Jorge Barriuso, Laura Mezquita, Inmaculada Ibañez de Cáceres, Angel Ayuso Sacido, Jose Maria Peña, Rosario Perona, Cristobal Belda-Iniesta
Journal: Journal of Clinical Oncology (2012)

e14093 Background: Current practice of clinical oncology is a challenge where increased efficacy of new-targeted therapies is counteracted by increasing costs. International financial crisis forces national health systems to optimize all therapeutic strategies maintaining clinical outcomes. Personalized medicine tries to select specific subpopulation of patients by biomarkers to refine therapeutic algorithms. We have performed a cost-effectiveness analysis to assess incremental cost-effectiveness ratio (ICER) per radiological response (RR) for cetuximab or panitumumab based scheduled as 1st line therapies for mCRC patients in Spain. Methods: Efficacy data were computed from all randomized trials (RT) that guided on-label uses of bevacizumab (K-Ras mut), panitumumab and cetuximab. Non- significant outcomes and toxicity as predictor of efficacy were excluded. Prices for drugs in Spain were assumed to represent the best-value for each drug including all possibilities to reduce pharmacy costs. For 1st line, median duration of therapy reported by RT was used to calculate the final budget. 70kg and 1.7 m were used as reference for patient dose calculations. Results: We simulated 3 main scenarios based on the possibilities of therapy for K-Ras wt patients assuming that all patients harboring a K-Ras mut. tumor received bevacizumab based chemotherapy. So, in scenario A K-Ras wt patients received weekly cetuximab combined with FOLFOX, ORR reaches 54% and global cost per RR sums €36,964. Scenario B: administering panitumumab-FOLFOX yields 51% ORR and € 38,880 per RR. Scenario C: cetuximab biweekly combined with FOLFOX yields 54% and €36,474. ICER for scenario A vs B is estimated at €4,394 per additional response. ICER for scenario C vs B yields a negative value of €4,432 per additional response. Conclusions: 1st line oxalipatin combinations of biweekly cetuximab for wt and bevacizumab for mutated patients optimize cost per additional response rate rather than panitumumab based schedules. Marginal cost differences between cetuximab and panitumumab therapies are exceeded by efficacy gap as measured by response rates in RT.
Evaluation of Trends of Near-Real-Time Urine Drug Test Results for Methamphetamine, Cocaine, Heroin, and Fentanyl
Authors: Robert K. Twillman, Eric Dawson, Leah LaRue, Maria G. Guevara, Penn Whitley, Angela Huskey
Journal: JAMA Network Open (2020)

Jacob J. Wainwright, MPH; Meriam Mikre, MPH; Penn Whitley, BA; Eric Dawson, PharmD; Angela Huskey, PharmD; Andrew Lukowiak, PhD; Brett P. Giroir, MD
Pilocytic astrocytomas in adults: A retrospective study of 125 patients.
Authors: Brett James Theeler, Zsila Sousan Sadighi, Benjamin Ellezam, Vinay K. Puduvalli
Journal: Journal of Clinical Oncology (2012)

2022 Background: Pilocytic astrocytomas (PAs) are rare primary brain tumors in adults. The natural history is poorly defined with the largest published series including only 30-40 patients. To better define clinical characteristics of adult PAs, we present an analysis of adult PAs at MD Anderson Cancer Center. Methods: We conducted an IRB-approved, retrospective chart review of patients ≥18 years diagnosed with PAs from 1990-2011 at our institution. Results: We identified 125 patients with a median age of 29 (range 18-72y), female to male ratio of 1.7:1, and median follow-up of 62 months. The most common anatomic locations were brainstem 22%, cerebellum 14%, intraventricular 14%, and cortical/lobar 14% (36% other locations). 21% of cases had an initial pathologic diagnosis discordant with neuropathologic review at our institution. Comorbidities included neurofibromatosis type 1 (5 pts) and a history of asthma or autoimmune disease (14%). 38 patients had a gross total (GTR), 55 a sub-total resection (STR) and the remainder a biopsy. 62 patients were treated with radiotherapy (RT): 45 as adjuvant (adj), 17 at recurrence; 2 received RT in both adj and recurrent settings. 73 (58%) patients were stable after initial treatment (surgery +/- adj RT). Median progression free survivals (mPFS) based on upfront treatment as follows: GTR only (n=30) - not been reached, STR only (n=32) 226.6 months, GTR plus adj RT (n=8) 13.2 months, STR plus adj RT (n=23) is 52.4 months (p=0.026, logrank test for trend). At last follow-up, 77% of all patients were stable and 13% were deceased. Conclusions: This is the largest series of adult PAs reported to date. Extracerebellar location, slight female predominance, and history of allergic/autoimmune disease were associations found in this cohort. Neuropathologic review is essential to avoid misdiagnosis. A significant subset of adult PAs behave more aggressively than expected for a grade I tumor with over 40% of patients experiencing recurrence after initial treatment. Adj RT following GTR or STR did not improve PFS, and a trend towards worse PFS with adj RT was observed although these analyzed subgroups were small. These results may help provide a framework for prospective studies in this tumor type.
Stereotactic Ablative Radiotherapy for the Management of Spinal Metastases
Authors: Rachel M. Glicksman, Michael C. Tjong, Wellington F. P. Neves-Junior, Daniel E. Spratt, Kevin L. M. Chua, Alireza Mansouri, Melvin L. K. Chua, Alejandro Berlin, Jeff D. Winter, Max Dahele, Ben J. Slotman, Mark Bilsky, David B. Shultz, Marcos Maldaun, Nicholas Szerlip, Simon S. Lo, Yoshiya Yamada, Francisco Emilio Vera-Badillo, Gustavo N. Marta, Fabio Y. Moraes
Journal: JAMA Oncology (2020)

Rising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application.To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies.The MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases.Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease.These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.