tbuckley/cabot-search huggingface dataset:
A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes
Authors: Anair Graciela Lema Fernandez, Barbara Crescenzi, Valentina Pierini, Valeria Di Battista, Gianluca Barba, Fabrizia Pellanera, Danika Di Giacomo, Giovanni Roti, Rocco Piazza, Emmalee R. Adelman, Maria E. Figueroa, Cristina Mecucci
Journal: Leukemia (2019)

The unbalanced translocation dic(1;7)(q10;p10) in myelodysplastic syndromes (MDS) is originated by centromeric juxtaposition resulting into 1q trisomy and 7q monosomy. More than half of cases arise after chemo/radio-therapy. To date, given the absence of genes within the centromeric regions, no specific molecular events have been identified in this cytogenetic subgroup. We performed the first comprehensive genetic and epigenetic analysis of MDS with dic(1;7)(q10;p10) compared to normal controls and therapy-related myeloid neoplasms (t-MNs). RNA-seq showed a unique downregulated signature in dic(1;7) cases, affecting more than 80% of differentially expressed genes. As revealed by pathway and gene ontology analyses, downregulation of ATP-binding cassette (ABC) transporters and lipid-related genes and upregulation of p53 signaling were the most relevant biological features of dic(1;7). Epigenetic supervised analysis revealed hypermethylation at intronic enhancers in the dicentric subgroup, in which low expression levels of enhancer putative target genes accounted for around 35% of the downregulated signature. Enrichment of Krüppel-like transcription factor binding sites emerged at enhancers. Furthermore, a specific hypermethylated pattern on 1q was found to underlie the hypo-expression of more than 50% of 1q-deregulated genes, despite trisomy. In summary, dic(1;7) in MDS establishes a specific transcriptional program driven by a unique epigenomic signature.
Racial Segregation and Inequality in the Neonatal Intensive Care Unit for Very Low-Birth-Weight and Very Preterm Infants
Authors: Jeffrey D. Horbar, Erika M. Edwards, Lucy T. Greenberg, Jochen Profit, David Draper, Daniel Helkey, Scott A. Lorch, Henry C. Lee, Ciaran S. Phibbs, Jeannette Rogowski, Jeffrey B. Gould, Glenn Firebaugh
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Racial and ethnic minorities receive lower-quality health care than white non-Hispanic individuals in the United States. Where minority infants receive care and the role that may play in the quality of care received is unclear. <h3>Objective</h3> To determine the extent of segregation and inequality of care of very low-birth-weight and very preterm infants across neonatal intensive care units (NICUs) in the United States. <h3>Design, Setting, and Participants</h3> This cohort study of 743 NICUs in the Vermont Oxford Network included 117 982 black, Hispanic, Asian, and white infants born at 401 g to 1500 g or 22 to 29 weeks' gestation from January 2014 to December 2016. Analysis began January 2018. <h3>Main Outcomes and Measures</h3> The NICU segregation index and NICU inequality index were calculated at the hospital level as the Gini coefficients associated with the Lorenz curves for black, Hispanic, and Asian infants compared with white infants, with NICUs ranked by proportion of white infants for the NICU segregation index and by composite Baby-MONITOR (Measure of Neonatal Intensive Care Outcomes Research) score for the NICU inequality index. <h3>Results</h3> Infants (36 359 black [31%], 21 808 Hispanic [18%], 5920 Asian [5%], and 53 895 white [46%]) were segregated among the 743 NICUs by race and ethnicity (NICU segregation index: black: 0.50 [95% CI, 0.46-0.53], Hispanic: 0.58 [95% CI, 0.54-0.61], and Asian: 0.45 [95% CI, 0.40-0.50]). Compared with white infants, black infants were concentrated at NICUs with lower-quality scores, and Hispanic and Asian infants were concentrated at NICUs with higher-quality scores (NICU inequality index: black: 0.07 [95% CI, 0.02-0.13], Hispanic: −0.10 [95% CI, −0.17 to −0.04], and Asian: −0.26 [95% CI, −0.32 to −0.19]). There was marked variation among the census regions in weighted mean NICU quality scores (range: −0.69 to 0.85). Region of residence explained the observed inequality for Hispanic infants but not for black or Asian infants. <h3>Conclusions and Relevance</h3> Black, Hispanic, and Asian infants were segregated across NICUs, reflecting the racial segregation of minority populations in the United States. There were large differences between geographic regions in NICU quality. After accounting for these differences, compared with white infants, Asian infants received care at higher-quality NICUs and black infants, at lower-quality NICUs. Explaining these patterns will require understanding the effects of sociodemographic factors and public policies on hospital quality, access, and choice for minority women and their infants.
BPI19-019: Avoidable Acute Care Use Associated With Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin
Authors: Eric J Roeland, Thomas W. LeBlanc, Kathryn J. Ruddy, Ryan Nipp, Rebecca Clark-Snow, Rita Wickham, Gary Binder, William L. Bailey, Ravi Potluri, Luke M. Schmerold, Eros Papademetriou, Rudolph M. Navari
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Avoiding acute care services can improve cancer care and reduce cost. The US Centers for Medicare and Medicaid Services’ (CMS) new oncology outcome measure (OP-35) defines 30-day post-chemotherapy inpatient (IP) and/or emergency department (ED) events (IP/ED) as “potentially avoidable” if involving any of 10 toxicities, including nausea or vomiting (NV). Evidence demonstrates meaningful gaps in oncologists’ adherence to antiemetic prophylaxis guidelines for highly emetogenic chemotherapy (HEC), and that NV-related IP use costs &gt;$10,000; yet the incidence of avoidable acute care events involving NV is not well studied. Methods: We assessed chemotherapy courses using IBM Explorys electronic health records (4Q 2012–1Q 2018). We identified rates of IP/ED ≤30 days post-chemotherapy, and OP-35 toxicities (NV, anemia, dehydration, diarrhea, fever, neutropenia, pain, pneumonia, or sepsis) by ICD-9, ICD-10, procedure codes, and CMS criteria. We evaluated cisplatin, anthracycline + cyclophosphamide (AC), carboplatin (&gt;14 days apart, as a proxy for AUC ≥4), oxaliplatin (OX), and other non-HEC chemotherapy. We assessed guideline adherence, defined as triple prophylaxis (NK1 RA + 5HT3 RA +dexamethasone) rates at HEC initiation. Results: In 17,609 HEC and 56,624 non-HEC courses, we observed 30-day IP/ED utilization in 29% and 19% of courses, respectively (Table 1). For HEC, 76% of IP/ED use involved ≥1 of the 10 CMS toxicities, most often anemia (42%), pain (41%), dehydration (24%), and NV (24%). Rates of all-cause IP/ED, IP/ED with OP-35 toxicity, and NV-related IP/ED were consistent for HEC and OX. Gaps in triple prophylaxis were common in HEC. Conclusion: Roughly one-third of patients receiving HEC or OX experienced IP/ED events ≤30 days after chemotherapy. Three-quarters of IP/ED events involved ≥1 of 10 OP-35 toxicities linked by CMS to potentially avoidable acute care; of these, one-third involved NV. NV-associated acute care use is considerable, costly, and potentially avoidable with better adherence to antiemesis guidelines.
Therapeutic Targeting of BRD4 in Head Neck Squamous Cell Carcinoma
Authors: Yaping Wu, Yanling Wang, Pengfei Diao, Wei Zhang, Jin Li, Han Ge, Yue Song, Zhongwu Li, Dongmiao Wang, Laikui Liu, Hongbing Jiang, Jie Cheng
Journal: Theranostics (2019)

The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Methods: Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of publically available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumorigenic roles of BRD4 in HNSCC were evaluated by genetic and pharmacological approach in vitro and in vivo. Therapeutic efficiency of BRD4 targeting by JQ1 was assessed in three preclinical models including xenograft model, 4NQO-induced model and patients-derived xenograft model. Gene candidates responsible for therapeutic effects of JQ1 were identified by transcriptional profiling in HNSCC cells after JQ1 exposure. Results: Significant upregulation of BRD4 was found in primary HNSCC samples and 4NQO-induced HNSCC model. Its overexpression associated with aggressive clinicopathological features and inferior overall and disease-free survival. BRD4 depletion by genetic silencing or pharmacological inhibition impaired cell proliferation, migration and invasion and reduced tumor growth and metastasis in vivo. Transcriptional profiling of HNSCC cells following JQ1 exposure identified hundreds of genes which might mediated its antitumor effects and enriched in cancer-relevant pathways. A novel prognostic risk score derived from JQ1-regulated genes was developed to stratify patients into subgroups with favorable or inferior prognosis. Conclusions: Our findings reveal that BRD4 serves as a novel and critical mediator underlying tumorigenesis and a robust prognostic biomarker in HNSCC. Therapeutic targeting of BRD4 represents a potent and promising strategy against HNSCC.
Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis
Authors: Huan Yang, Ji Wang, Xin Zhang, Yan Zhang, Zi-li Qin, Hua Wang, Xiao-yan Luo
Journal: JAMA Dermatology (2019)

Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy.To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD.Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, Chinese medical databases (Wanfang, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database), ClinicalTrials.gov, and other trial registries from inception to August 15, 2018. No restrictions on languages were placed.Only double-blind randomized clinical trials with topical PDE4 inhibitors vs topical vehicle treatment for patients with mild to moderate AD were included.Two reviewers independently extracted study features, intervention details, and outcomes. A meta-analysis was performed using the random-effects model. The Cochrane Collaboration's risk of bias assessment tool was used to assess the risk of bias. Funnel plots and Egger tests were used to assess the publication bias.Changes from baseline in target lesion score were expressed in terms of standardized mean differences (SMDs) with 95% CIs. Outcomes of investigators' assessment and safety were expressed in terms of relative risk with 95% CIs.Seven studies were identified, which included 1869 patients with mild to moderate AD. Overall, compared with the topical vehicle control, topical application of PDE4 inhibitors was associated with a significant decrease in target lesion score (SMD -0.40; 95% CI, -0.61 to -0.18; P < .001) and a higher response rate in investigators' assessment of clear or almost clear skin (relative risk, 1.50; 95% CI, 1.33-1.70; P < .001). There was no difference in treatment-related adverse events or in adverse events that required discontinuation of therapy. Subgroup analyses indicated that after 14 and 28 days of therapy with PDE4 inhibitors, target lesion score was significantly decreased. However, these beneficial effects were displayed only for the PDE4 inhibitors crisaborole and AN2898 (crisaborole at day 14: SMD, -0.59; 95% CI, -1.15 to -0.02; P = .04; AN2898 at day 14: SMD, -0.76; 95% CI, -1.38 to -0.13; P = .02; crisaborole at day 28: SMD, -0.86; 95% CI, -1.44 to -0.28; P = .004; AN2898 at day 28: SMD, -0.68; 95% CI, -1.30 to -0.05; P = .03). Heterogeneity was not significant across studies.This meta-analysis suggests that topical PDE4 inhibitors are a safe and effective treatment for mild to moderate AD. Current evidence supports the use of crisaborole or AN2898 as the choice of maintenance or sequential therapy for mild to moderate AD.
Clinicopathological features and impact of adjuvant chemotherapy on the long‐term survival of patients with multiple gastric cancers: a propensity score matching analysis
Authors: Jian‐Xian Lin, Zu‐Kai Wang, Jian‐Wei Xie, Jia‐Bin Wang, Jun Lu, Qi‐Yue Chen, Long‐Long Cao, Mi Lin, Ru‐Hong Tu, Ze‐Ning Huang, Ju‐Li Lin, Chao‐Hui Zheng, Chang‐Ming Huang, Ping Li
Journal: Cancer Communications (2019)

Little is known about the correlation between the clinicopathological features, postoperative treatment, and prognosis of multiple gastric cancers (MGCs). In this study, we aimed to investigate the correlation between these features and the impact of postoperative adjuvant chemotherapy on the long-term survival of patients with MGC.The clinical and pathological data of patients diagnosed with gastric adenocarcinoma who had radical gastrectomy from January 2007 to December 2016 were analyzed. Using propensity score matching, the prognostic differences, and the impact of postoperative adjuvant chemotherapy between those with MGC and solitary gastric cancers (SGC) were compared.Among the 4107 patients investigated, the incidence of MGC was 3.2% (133/4107). Before matching, patients with MGC and SGC had disparities in the type of gastrectomy, pathological tumor stage (pT), pathological node stage (pN), and pathological tumor-node-metastasis stage (pTNM). After a 1:4 ratio matching, the clinical data of 133 cases of MGC and 532 cases of SGC were found to be comparable. The 5-year overall survival (OS) rate was 56.6% in the entire matched cohort, 48.1% in the MGC group, and 58.7% in the SGC group (P = 0.013). Multivariate analysis revealed that MGC, age, pT stage, pN stage, and adjuvant chemotherapy were independent predictors of OS (all P < 0.05). Stratified analyses demonstrated that for the cohort of advanced gastric cancer (AGC) patients who did not had adjuvant chemotherapy, the 5-year OS rate of advanced cases of MGC was inferior than that of SGC patients (34.0% vs. 46.1%, respectively; P = 0.025) but there were no significant difference in the 5-year OS rate between advanced MGC and SGC patients who had adjuvant chemotherapy (48.0% vs. 53.3%, respectively; P = 0.292). Further, we found that the 5-year OS rate of advanced MGC who had adjuvant chemotherapy was significantly higher than those who did not had adjuvant chemotherapy (48.0% vs. 34.0%, P = 0.026).Patients with advanced MGC was identified as having a poorer survival as to SGC patients, but the implementation of postoperative adjuvant chemotherapy showed that it had the potential to significantly improve the long-term prognoses of MGC patients.
Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2
Authors: Serena Lucotti, Camilla Cerutti, Magali Soyer, Ana M. Gil-Bernabé, Ana L. Gomes, Philip D. Allen, Sean Smart, Bostjan Markelc, Karla Watson, Paul C. Armstrong, Jane A. Mitchell, Timothy D. Warner, Anne J. Ridley, Ruth J. Muschel
Journal: Journal of Clinical Investigation (2019)

Because metastasis is associated with the majority of cancer-related deaths, its prevention is a clinical aspiration. Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. Thromboxane A2 (TXA2) was the prostanoid product of COX-1 responsible for this antimetastatic effect. Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/macrophages, and diminished the formation of a premetastatic niche. Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis.
CLO19-048: Effects of Acupuncture on Cutaneous Microcirculation by Infrared Thermography in Cancer Patients
Authors: Namie Okino Sawada, Bruna Franciely Toneti, Liyoko Okino, Juliana Maria de Paula Avelar, Amanda Fonseca Baviera, Luana Okino Sawada
Journal: Journal of the National Comprehensive Cancer Network (2019)

Objectives: The objective of this case series was to describe the experience of the use of infrared thermography to evaluate the effects of acupuncture on cutaneous microcirculation of cancer patients. Methods: The method is a cross-sectional survey, descriptive of a series of cases of a sample for convenience. The data collection procedure had a total duration of 30 minutes, being captured images at different times during the procedure: before the needling (T0); first minute (T0a); second minute (T0b); third minute (T0c); forth minute (T0d); fifth minute (T1); tenth minute (T2); and after 15 minutes (T3) of needling. Body temperature was evaluated by infrared camera, brand FLIR, series A. The FLIR Tools software version 5.9 was used to perform the calculation of the temperatures with subsequent descriptive analysis of the data. The choice of the PC6, BP10, R6, and B62 bilateral acupoints was because of the anatomic location and energetic actions on the blood circulation. The PC6 acupoint (Neiguan) is located in the meridian of the pericardium, lies on the anterior face of the forearm approximately 2 cm (0.79 inches) below the wrist and between the flexor tendons. This acupoint is responsible for sending signals to the central nervous system, which results in the reduction of sympathetic activity. Results: According to the ANOVA test, considering P value less than or equal to .05, there were statistically significant differences in the time intervals evaluated, with P value of .004. There was a 1.7% increase in the mean temperature of the interval between T3 and T0 in the sample, that is, between the time before and after 15 minutes of needling. Conclusion: This series of cases showed the viability of the method of evaluating the effects of acupuncture on cutaneous microcirculation by infrared thermography in the rehabilitation of cancer patients. The results showed statistically significant differences in the time intervals evaluated, demonstrating the importance of the evaluation at 15 minutes after needling to accurately verify the variation of cutaneous temperature by thermography in the acupoints. It was noticed that the increase of the cutaneous temperature occurred, mainly, in the first 5 minutes after the needling, with a reduction after this time interval.
Kidney Disease Quality of Life 36-Item Short Form Survey (KDQOL-36) Normative Values for the United States Dialysis Population and New Single Summary Score
Authors: John D. Peipert, Devika Nair, Kristi Klicko, Dorian R. Schatell, Ron D. Hays
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Reliable, valid, and interpretable patient-reported outcome measures for kidney patients are needed for patient monitoring and use as outcomes in clinical trials. The Kidney Disease Quality of Life 36-item short form survey (KDQOL-36) is often used with patients on dialysis, but improvements are needed to facilitate interpretability of its scores. The authors calculate normative values for the KDQOL-36 scales referenced to the United States dialysis population, which allow comparison of group means and individual scores with national averages, such as by dialysis centers when fulfilling their required annual assessment of patients’ quality of life. The authors also created the KDQOL-36 Summary Score (KSS), a composite of items from the KDQOL-36’s kidney-targeted scales, which may be useful when kidney-targeted health-related quality of life needs to be summarized in a single score. Background The Kidney Disease Quality of Life 36-item short form survey (KDQOL-36) is a widely used, patient-reported outcome measure for patients on dialysis. Efforts to aid interpretation are needed. Methods We used a sample of 58,851 dialysis patients participating in the Medical Education Institute (MEI) KDQOL Complete program, and 443,947 patients from the US Renal Data System (USRDS) to develop the KDQOL-36 Summary Score (KSS) for the kidney-targeted KDQOL-36 scales (Burdens of Kidney Disease [BKD], Symptoms and Problems of Kidney Disease [SPKD], and Effects of Kidney Disease [EKD]). We also used the MEI and USRDS data to calculate normative values for the Short Form-12 Health Survey’s Physical Component Summary (PCS) and Mental Component Summary (MCS), and the KDQOL-36’s BKD, SPKD, and EKD scales for the United States dialysis population. We used confirmatory factor analysis (CFA) models for KDQOL-36 kidney-targeted items, evaluated model fit with the comparative fit index (CFI; &gt;0.95 indicates good fit) and root-mean-squared error of approximation (RMSEA; &lt;0.06 indicates good fit), and estimated norms by matching the joint distribution of patient characteristics in the MEI sample to those of the USRDS sample. Results A bifactor CFA model fit the data well (RMSEA=0.046, CFI=0.990), supporting the KSS ( α =0.91). Mean dialysis normative scores were PCS=37.8 and MCS=50.9 (scored on a T-score metric); and KSS=73.0, BKD=52.8, SPKD=79.0, and EKD=74.1 (0–100 possible scores). Conclusions The KSS is a reliable summary of the KDQOL-36. The United States KDQOL-36 normative facilitate interpretation and incorporation of patient-related outcome measures into kidney disease care.