tbuckley/cabot-search huggingface dataset:
Diurnal regulation of SDG2 and JMJ14 by circadian clock oscillators orchestrates histone modification rhythms in Arabidopsis
Authors: Qingxin Song, Tien-Yu Huang, Helen H. Yu, Atsumi Ando, Paloma Mas, Misook Ha, Z. Jeffrey Chen
Journal: Genome biology (2019)

Circadian rhythms modulate growth and development in all organisms through interlocking transcriptional-translational feedback loops. The transcriptional loop involves chromatin modifications of central circadian oscillators in mammals and plants. However, the molecular basis for rhythmic epigenetic modifications and circadian regulation is poorly understood. Here we report a feedback relationship between diurnal regulation of circadian clock genes and histone modifications in Arabidopsis. On one hand, the circadian oscillators CCA1 and LHY regulate diurnal expression of genes coding for the eraser (JMJ14) directly and writer (SDG2) indirectly for H3K4me3 modification, leading to rhythmic H3K4me3 changes in target genes. On the other hand, expression of circadian oscillator genes including CCA1 and LHY is associated with H3K4me3 levels and decreased in the sdg2 mutant but increased in the jmj14 mutant. At the genome-wide level, diurnal rhythms of H3K4me3 and another histone mark H3K9ac are associated with diurnal regulation of 20–30% of the expressed genes. While the majority (86%) of H3K4me3 and H3K9ac target genes overlap, only 13% of morning-phased and 22% of evening-phased genes had both H3K4me3 and H3K9ac peaks, suggesting specific roles of different histone modifications in diurnal gene expression. Circadian clock genes promote diurnal regulation of SDG2 and JMJ14 expression, which in turn regulate rhythmic histone modification dynamics for the clock and its output genes. This reciprocal regulatory module between chromatin modifiers and circadian clock oscillators orchestrates diurnal gene expression that governs plant growth and development.
Differing Risk of Mortality in Trauma Patients With Stab Wounds to the Torso
Authors: Miseker Abate, Areg Grigorian, Jeffry Nahmias, Sebastian D. Schubl, Eric Kuncir, Michael Lekawa
Journal: JAMA Surgery (2019)

Patients were prescribed a median of 100 OMEs (interquartile range, 100-150 OMEs).There was significant variability in prescription quantity between clinicians, with a median value that ranged from 75 to 200 OMEs between physicians (Figure).Prescriptions were written by surgical trainees, house staff, or fellow-level physicians, none of whom received formal education or guidelines for analgesia prescribing.Fellow-level physicians prescribed higher opioid quantities than resident physicians did, with a mean (SD) of 143 (77) OMEs prescribed by fellow physicians and 123 (54) OMEs prescribed by resident physicians (P = .01).On regression analysis adjusted for operative time, there remained a significant difference in the quantity of opioids prescribed, with an estimated increase by 17.8 (95% CI, 1.6-34.0)OMEs (P = .004)for fellow-level physicians compared with resident physicians.There was no association between OMEs prescribed and actual opioid use.Discussion | In this study, which is, to our knowledge, the first of its kind for endocrine surgery, most patients did not require opioid medications after cervical endocrine surgery, even though most were prescribed them.Prescribing patterns were variable between clinicians, perhaps owing to a paucity of evidence-based guidelines.The lack of association between the quantity of opioids prescribed and the need for opioid medications suggests that prescribers are poor judges of pain requirements postoperatively.Based on these results, an endocrine surgery optimal analgesia-prescribing toolkit was developed at the study institution.This includes preoperative patient education around pain expectations and effective medications for postsurgery analgesia, with an emphasis on multimodal analgesia.Also included are standardized postsurgery prescribing recommendations for routine cervical endocrine procedures that use acetaminophen and ibuprofen, with no opioid prescriptions.Importantly, the toolkit was developed by clinicians working as a team, and all endocrine surgery clinicians agreed with the recommendations.The institution now monitors patients closely to ensure adequate pain control and satisfaction.Through patient engagement and collaborative team-based approaches, we appear to have begun to reduce unnecessary variation in practice and stem the flow of opioids into the community.
Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis
Authors: Daniel Aletaha, Jen-fue Maa, Su Chen, Sung-Hwan Park, Dave Nicholls, Stefan Florentinus, Daniel Furtner, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA). Methods Associations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses. Results In the larger study (N=207), a greater number of prior DMARDs (&gt;2 vs 0–1) was associated with smaller improvements in DAS28(CRP) (–1.8 vs –2.2), SDAI (–22.1 vs –26.9) and HAQ-DI (–0.43 vs –0.64) from baseline to week 24. RA duration of &gt;10 years versus &lt;1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings. Conclusions Number of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.
AB0181 Epidemiology study about osteoporosis in postmenopausal women about 1000 case
Authors: S Quennesson, E Quennesson, PM Preux, C Scotto Di Fazano, D Coyral, P Vergne, C Bonnet, P Bertin, R Treves
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteoporosis is a bone disease who concerns above all postmenopausal women. It's characterised by bone loss and associated fractures. In France, in 1995 it's 1% hospital cost. We realised a transversal study about osteoporosis and risk factors with 1000 women. <h3>Objectives</h3> We excluded women with hormonal substitutive treatment and secondary osteoporosis. The study group was randomised. All patients were interviewed about risk factor and bone mineral density was measured by dual energy X ray. One woman was excluded for myeloma. <h3>Methods</h3> We compared risk factor between osteoporosis group and non osteoporosis group determined by densitometry OMS criteria, with student t test or chi2. Finally a multivarious analysis includes all significative risk factor.(p &lt; 0,05). <h3>Results</h3> In our study, there was 25%osteoporotic patients. The univarious analysis find a significant relation between osteoporosis and study level, the age at menopause, thyroid disease, body mass index, calcium intake, milk drink, fresh water consumption, white cheese. The multivarious analysis shows a significant relation between osteoporosis and age (odds ratio = 1,1 per year), the level study (odds ratio = 0,34 between; after first grade diploma and no education), Body Mass Index (odds ratio = 0,86 per unity), milk drinks (odds ratio = 0,7). The discriminant analysis after further adjustment for confounding factors allows to diagnose 67% of osteoporotic women. <h3>Conclusion</h3> In our population, we find some usual risk factor of literature. The interview is not sufficient to diagnose osteoporosis certainly but allow to purpose bone density. The results of this bone density with clinical information is necessary to start the best treatment.
In pregnant women, the pregnancy-adapted YEARS algorithm ruled out PE, with a low rate of VTE at 3 months
Authors: Kenneth Chan, Eddy Lang
Journal: Annals of Internal Medicine (2019)

Source Citation van der Pol LM, Tromeur C, Bistervels IM, et al; Artemis Study Investigators. Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. N Engl J Med. 2019;380:1139-49. 30893534
AB0113 Analysis of clinical manifestations in patients with crest variant of scleroderma
Authors: BM Kecman-Prunic, NZ Pilipovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of the study was to ascertain frequency of clinical manifestations in patients with CREST variant related to skin involvement in SSc. <h3>Methods</h3> Since 1993 we have treated 184 patients with systemic sclerosis (SSc) at the Institute of Rheumatology in Belgrade. Within this group there were 51 (27.7%) – 49 females and 2 males, with complete clinical manifestations of CREST variant. Mean age of patients was 55.7 years and disease duration 10.9 years. Thirty-four patients (66.7%) had limited cutaneous SSc (lSSc) and 17 (33.3%) diffuse cutaneous SSc (dSSc). <h3>Results</h3> Our results are in following Table 1: <h3>Conclusion</h3> According our results, visceral involvement in systemic sclerosis does not depend on distribution of skin sclerosis. So we think that CREST variant of SSc can be classified as separate form of scleroderma.
Write to recover: The impact of group led creative writing on behavioral health outcomes in cancer patients.
Authors: Darya Nesterova, Junjia Zhu, Courtney Kramer, Monali K. Vasekar, Jolene Collins, Cristina I. Truica, Aditya Joshi, Michael Hayes, Erika Saunders, Joseph J. Drabick, Monika Joshi
Journal: Journal of Clinical Oncology (2019)

11536 Background: The diagnosis of cancer can adversely affect mental wellbeing. In addition to treating cancer, the emotional wellbeing of patients must simultaneously be addressed. A previous pilot exploring the feasibility of creative writing workshop (CWW) in cancer patients showed apositive effect on patients’ mental health. Methods: To longitudinally evaluate the efficacy of CWW on mood, we conducted a phase II study with cancer patients (any stage, any cancer type); randomized 2:1 to CWW vs. active control (AC). Patients in the CWW arm attended at least 4, 1.5-hour bi-monthly CWW x 8 wks, whereas AC patients completed independent writing at home with the help of a book (bi-monthly x 8wks). We used validated tools, [Emotional Thermometer Scales (ETS), PHQ-9, GAD-7] to assess changes in overall mood, depression, and anxiety. Primary end point: a) ETS scores before and after intervention b) Changes in depression and anxiety based on PHQ-9 and GAD-7 scores. We present results from ETS scores. Descriptive statistics were generated for these quantitative scales measured in each group, pre and post intervention. Comparisons between groups (gp) were made using Wilcoxon Rank-sum tests. All tests were two sided and the statistical significance level used was 0.05. Results: Amongst evaluable patients, N of 50 (demographics in table below), twenty-six patients in the CWW gp attended at least one class and 19 attended at least 4 classes. Patients in CWW showed significant mood improvement vs. AC when comparing the final overall ETS (p=0.0063). Three of the five sub-scale ETS scores were significantly lower for the CWW vs. AC gp: anxiety (p=0.0027), depression (p=0.0009), and anger (p=0.0027). Conclusions: Group led CWW have a positive effect on mood. Our results suggest potential therapeutic benefit of this intervention on the emotional wellbeing of cancer patients. Larger studies are needed to evaluate the effect of CWW in cancer patients. Clinical trial information: NCT03536702. [Table: see text]
Frequency of rare cytogenetic abnormalities at relapse in acute myeloid leukemia (AML) with FLT3 internal tandem duplication (ITD) and normal karyotype at diagnosis: Evidence for genomic instability?
Authors: Theodore Stewart Gourdin, Yi Ning, Feyruz Rassool, Michael Tidwell, Vu Duong, Ashkan Emadi, Maria R. Baer
Journal: Journal of Clinical Oncology (2013)

7049 Background: FLT3-ITD mutations are present in AML in 30% of patients, most commonly with a normal karyotype, and are associated with short disease-free survival. In vitro and in vivo studies of FLT3-ITD cell lines and patient samples have demonstrated DNA double-strand break repair by an alternative highly error-prone form of non-homologous end-joining (ALT NHEJ), resulting in illegitimate ligation of non-contiguous DNA breaks, causing DNA deletions and translocations that may contribute to disease progression. To look for clinical evidence of genomic instability, we reviewed cytogenetic changes at relapse. Methods: Charts of patients with cytogenetically normal AML with FLT3-ITD treated at the University of Maryland Greenebaum Cancer Center were reviewed along with metaphase analysis results at diagnosis and relapse. Results: Cytogenetic data were available from first and, when applicable, subsequent relapses for 12 patients with cytogenetically normal AML with FLT3-ITD who relapsed, including 5 following allogeneic hematopoietic stem cell transplantation (allo HSCT). Ten patients acquired cytogenetic changes, many of them rare translocations and inversions (Table). Conclusions: AML with FLT3-ITD and normal karyotype at diagnosis has a high frequency of rare cytogenetic abnormalities at relapse, providing clinical evidence for genomic instability. These data may support the potential therapeutic role of inhibitors of ALT NHEJ repair proteins, such as PARP1 and DNA ligase IIIa, in AML with FLT3-ITD. [Table: see text]
Automated classification of gastric neoplasms in endoscopic images using a convolutional neural network
Authors: Bum-Joo Cho, Chang Seok Bang, Se Woo Park, Young Joo Yang, Seung In Seo, Hyun Lim, Woon Geon Shin, Ji Taek Hong, Yong Tak Yoo, Seok Hwan Hong, Jae Ho Choi, Jae Jun Lee, Gwang Ho Baik
Journal: Endoscopy (2019)

Abstract Background Visual inspection, lesion detection, and differentiation between malignant and benign features are key aspects of an endoscopist’s role. The use of machine learning for the recognition and differentiation of images has been increasingly adopted in clinical practice. This study aimed to establish convolutional neural network (CNN) models to automatically classify gastric neoplasms based on endoscopic images. Methods Endoscopic white-light images of pathologically confirmed gastric lesions were collected and classified into five categories: advanced gastric cancer, early gastric cancer, high grade dysplasia, low grade dysplasia, and non-neoplasm. Three pretrained CNN models were fine-tuned using a training dataset. The classifying performance of the models was evaluated using a test dataset and a prospective validation dataset. Results A total of 5017 images were collected from 1269 patients, among which 812 images from 212 patients were used as the test dataset. An additional 200 images from 200 patients were collected and used for prospective validation. For the five-category classification, the weighted average accuracy of the Inception-Resnet-v2 model reached 84.6 %. The mean area under the curve (AUC) of the model for differentiating gastric cancer and neoplasm was 0.877 and 0.927, respectively. In prospective validation, the Inception-Resnet-v2 model showed lower performance compared with the endoscopist with the best performance (five-category accuracy 76.4 % vs. 87.6 %; cancer 76.0 % vs. 97.5 %; neoplasm 73.5 % vs. 96.5 %; P &lt; 0.001). However, there was no statistical difference between the Inception-Resnet-v2 model and the endoscopist with the worst performance in the differentiation of gastric cancer (accuracy 76.0 % vs. 82.0 %) and neoplasm (AUC 0.776 vs. 0.865). Conclusion The evaluated deep-learning models have the potential for clinical application in classifying gastric cancer or neoplasm on endoscopic white-light images.
Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC
Authors: Yoshihiro Ohue, Koji Kurose, Takahiro Karasaki, Midori Isobe, Takaaki Yamaoka, Junichiro Futami, Isao Irei, Takeshi Masuda, Masaaki Fukuda, Akitoshi Kinoshita, Hirokazu Matsushita, Katsuhiko Shimizu, Masao Nakata, Noboru Hattori, Hiroyuki Yamaguchi, Minoru Fukuda, Ryohei Nozawa, Kazuhiro Kakimi, Mikio Oka
Journal: Journal of Thoracic Oncology (2019)

IntroductionProgrammed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti–PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.MethodsWe conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti–PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing.ResultsIn the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti–PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti–PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004).ConclusionsOur results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti–PD-1 therapy for NSCLC and probably for other cancers.
In compensated cirrhosis with portal hypertension, β-blockers reduced a composite of decompensation or death
Authors: Jacob Korula
Journal: Annals of Internal Medicine (2019)

Source Citation Villanueva C, Albillos A, Genesca J, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2019;393:1597-1608. 30910320
A mouse model for cancer immunoediting with renal cell carcinoma to explore mechanisms of immune escape.
Authors: Elizabeth Bigger, Michael Quigley, Yiping Yang
Journal: Journal of Clinical Oncology (2013)

11074 Background: Cancer immunosurveillance is the immune system's ability to recognize and destroy newly arising malignant cells. Recent data suggests that the immune system functions also to apply a selective pressure, leading to growth of less immunogenic tumors, a process termed cancer immunoediting. However, direct experimental evidence to support this hypothesis has been lacking. Methods: We examined the interaction between tumor and tumor-specific CD8 T cells in vivo with a model tumor antigen, influenza hemagglutinin (HA), in a renal cell carcinoma cell line (Renca-HA) and studied the HA-specific CD8 T cell response to Renca-HA in vivo. Naïve HA-specific CD8 T cells (Thy1.1 + ) purified from HA-TCR transgenic mice that recognize a K d -restricted HA epitope were transferred into congenic Thy1.2 + recipients inoculated the day prior with Renca-HA or wild type Renca (Renca-WT). At subsequent time points, recipient lymphocytes and pulmonary tumors were harvested and analyzed. Results: Four days after transfer, vigorous proliferation of HA-specific CD8 T cells was detected in Renca-HA inoculated mice, but not Renca-WT inoculated mice, leading to activation and effector differentiation of HA-specific T cells. HA-specific CD8 T cell activation resulted in destruction of Renca-HA in vivo, causing a significant (p &lt;0.001) reduction of tumor burden and prolongation of survival. However, a small fraction of Renca-HA tumor cells survived immune-mediated killing and evaded immune surveillance. Microarray technology identified upregulation of transforming growth factor β-3 (TGF-β3) expression in edited Renca-HA, but not in unedited Renca-HA, compared with Renca-WT, confirmed by real-time quantitative PCR. Functional abrogation of TGF-β3 signaling on tumor-specific CD8 T cells delayed Renca HA tumor growth in vivo. Conclusions: These data provide direct evidence for the cancer immunosurveillance and immunoediting processes, and suggest that tumor induction of TGFβ-3 during the immunoediting process suppresses tumor-specific CD8 T cell function in vivo, allowing tumor immune escape. Our results provide mechanistic insights as well as potential strategies to block cancer immune evasion.