tbuckley/cabot-search huggingface dataset:
Cumulative Burden of Morbidity Among Testicular Cancer Survivors After Standard Cisplatin-Based Chemotherapy: A Multi-Institutional Study
Authors: Sarah L. Kerns, Chunkit Fung, Patrick O. Monahan, Shirin Ardeshir-Rouhani-Fard, Mohammad I. Abu Zaid, AnnaLynn M. Williams, Timothy E. Stump, Howard D. Sesso, Darren R. Feldman, Robert J. Hamilton, David J. Vaughn, Clair Beard, Robert A. Huddart, Jeri Kim, Christian Kollmannsberger, Deepak M. Sahasrabudhe, Ryan Cook, Sophie D. Fossa, Lawrence H. Einhorn, Lois B. Travis
Journal: Journal of Clinical Oncology (2018)

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among &gt; 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records. A CBM score encompassed the number and severity of AHOs, with ordinal logistic regression used to assess associations with exposures. Nonlinear factor analysis and the nonparametric dimensionality evaluation to enumerate contributing traits procedure determined which AHOs co-occurred. Results Among 1,214 participants, approximately 20% had a high (15%) or very high/severe (4.1%) CBM score, whereas approximately 80% scored medium (30%) or low/very low (47%). Increased risks of higher scores were associated with four cycles of either ifosfamide, etoposide, and cisplatin (odds ratio [OR], 1.96; 95% CI, 1.04 to 3.71) or bleomycin, etoposide, and cisplatin (OR, 1.44; 95% CI, 1.04 to 1.98), older attained age (OR, 1.18; 95% CI, 1.10 to 1.26), current disability leave (OR, 3.53; 95% CI, 1.57 to 7.95), less than a college education (OR, 1.44; 95% CI, 1.11 to 1.87), and current or former smoking (OR, 1.28; 95% CI, 1.02 to 1.63). CBM score did not differ after either chemotherapy regimen ( P = .36). Asian race (OR, 0.41; 95% CI, 0.23 to 0.72) and vigorous exercise (OR, 0.68; 95% CI, 0.52 to 0.89) were protective. Variable clustering analyses identified six significant AHO clusters (χ 2 P &lt; .001): hearing loss/damage, tinnitus (OR, 16.3); hyperlipidemia, hypertension, diabetes (OR, 9.8); neuropathy, pain, Raynaud phenomenon (OR, 5.5); cardiovascular and related conditions (OR, 5.0); thyroid disease, erectile dysfunction (OR, 4.2); and depression/anxiety, hypogonadism (OR, 2.8). Conclusion Factors associated with higher CBM may identify testicular cancer survivors in need of closer monitoring. If confirmed, identified AHO clusters could guide the development of survivorship care strategies.
What Do We Learn From Disciplined Practice Learning?
Authors: Kazim Sheikh
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The study by the Northern New England Cardiovascular Study Group<sup>1</sup>is a good example of the use of disease registry data for an epidemiologic experiment to assess the effectiveness of medical care improvement in changing the outcome. In this study of patients undergoing coronary artery bypass graft (CABG) surgery in 5 medical centers, the investigators compared case-fatality (disease- or procedure-specific in-hospital mortality) rates before and after a set of interventions—feedback of the outcome data to the surgeons, training of the medical and nursing staff, and learning from each other by observing the processes of CABG surgery at each site. After a 16-month intervention period, a 24% to 25% reduction in case fatality over 2 years was attributed to the interventions.<sup>1</sup>However, the usefulness of the study findings was limited due to its weak design and nonspecific interventions. Since it was not a controlled trial, the study could not
Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys
Authors: Yuanyuan Li, Hui Zheng, Qiujun Wang, Chen Zhou, Lei Wei, Xuehui Liu, Wenhao Zhang, Yu Zhang, Zhenhai Du, Xiaowo Wang, Wei Xie
Journal: Genome biology (2018)

Previous studies showed that the majority of developmental genes are devoid of DNA methylation at promoters even when they are repressed. Such hypomethylated regions at developmental genes are unusually large and extend well beyond proximal promoters, forming DNA methylation valleys (DMVs) or DNA methylation canyons. However, it remains elusive how most developmental genes can evade DNA methylation regardless of their transcriptional states. We show that DMVs are hypomethylated in development and are highly conserved across vertebrates. Importantly, DMVs are hotspots of regulatory regions for key developmental genes and show low levels of deamination mutation rates. By analyzing a panel of DNA methylomes from mouse tissues, we identify a subset of DMVs that are dynamically methylated. These DMVs are strongly enriched for Polycomb-deposited H3K27me3 when the associated genes are silenced, and surprisingly show elevated DNA methylation upon gene activation. 4C-seq analyses indicates that Polycomb-bound DMVs form insulated and self-interacting chromatin domains. Further investigations show that DNA hypomethylation is better correlated with the binding of Polycomb than with H3K27me3. In support of a role of Polycomb in DMV hypomethylation, we observe aberrant methylation in DMVs in mouse embryonic stem cells deficient in the EED protein. Finally, we show that Polycomb regulates hypomethylation of DMVs likely through ten-eleven translocation (TET) proteins. We show that Polycomb promotes the hypomethylation of DMVs near key developmental genes. These data reveal a delicate interplay between histone modifiers and DNA methylation, which contributes to their division at distinct gene targets, allowing lineage-specifying genes to largely maintain DNA methylation-free at regulatory elements.
Association of adjuvant chemoradiotherapy with survival in patients with resected gallbladder carcinoma: A systematic review and meta-analysis.
Authors: Eui Kyu Chie, Byoung Hyuck Kim, Jeanny Kwon, Kyubo Kim
Journal: Journal of Clinical Oncology (2018)

477 Background: The impact of adjuvant radiotherapy (ART) on survival in gallbladder carcinoma (GBC) remains underexplored, and conflicting results have been reported. We conducted a systematic review and meta-analysis to clarify the impact of ART in GBC. Methods: Systematic literature search was performed in the several databases following the PRISMA guidelines from inception to August 2016. We included the studies which reported survival outcome in the patients with or without ART following curative surgery. Results: Fourteen retrospective studies including 9364 analyzable patients met all inclusion criteria, but most of them had a moderate risk of bias. Generally, ART group had more patients with unfavorable characteristics than the surgery alone group. Nevertheless, pooled results showed that ART significantly reduced the risk of death (HR, 0.54; 95% CI, 0.44-0.67; p &lt; 0.001) and recurrence (HR, 0.61; 95% CI, 0.38-0.98; p = 0.04) compared to the surgery alone group. Exploratory analyses demonstrated that subgroup of patients with lymph node positive disease (HR, 0.61; p &lt; 0.001) and R1 resection (HR, 0.55; p &lt; 0.001) had survival benefit from ART, while those with lymph node negative disease did not (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). Conclusions: This work is the first meta-analysis evaluating the role of ART and provides convincing evidence that ART may offer survival benefit, especially in high risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would most benefit from ART.
20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia
Authors: Jari Tiihonen, Antti Tanskanen, Heidi Taipale
Journal: American Journal of Psychiatry (2018)

It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that after stabilization, antipsychotic treatment should be continued for 1-5 years, and longer exposure should be avoided if possible. However, there is no published evidence to substantiate this view. The authors used nationwide databases to investigate this issue.Prospectively gathered nationwide register data were used to study the risk of treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment. Multivariate Cox regression was used to assess outcomes among all patients hospitalized for the first time with a schizophrenia diagnosis in Finland during the period of 1996-2014 (N=8,719).The lowest risk of rehospitalization or death was observed for patients who received antipsychotic treatment continuously (adjusted hazard ratio=1.00), followed by patients who discontinued antipsychotic use immediately after discharge from the first hospital treatment (hazard ratio=1.63, 95% CI=1.52-1.75), within 1 year (hazard ratio=1.88, 95% CI=1.57-2.24), within 1-2 years (hazard ratio=2.12, 95% CI=1.43-3.14), within 2-5 years (hazard ratio=3.26, 95% CI=2.07-5.13), and after 5 years (a median of 7.9 years) (hazard ratio=7.28, 95% CI=2.78-19.05). Risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years.Whatever the underlying mechanisms, these results provide evidence that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotic treatment is associated with increased survival.
Abstract P198: Diabetes Alters the Association Between High-density Lipoprotein Subfractions and Carotid Intima-media Thickness: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Giuliano Generoso, Isabela J Bensenor, Itamar S Santos, Raul D Santos, Alessandra C Goulart, Steven R Jones, Krishnaji R Kulkarni, Michael J Blaha, Peter P Toth, Paulo A Lotufo, Marcio S Bittencourt
Journal: Circulation (2018)

Background: Although HDL-C is inversely associated with cardiovascular risk, no causal relationship has been demonstrated. Since HDL comprises a group of heterogeneous subfractions, they might have different effects on atherosclerosis, and its effects may be modified by the presence of diabetes mellitus. Hypothesis: HDL-C subfractions exert different effects on subclinical carotid atherosclerosis, and diabetes modifies these effects. Methods: We evaluated 3,930 individuals between 35 and 74 years (45.6% men) without previous cardiovascular disease not using lipid-lowering drugs. HDL 2 -C and HDL 3 -C were obtained by zonal ultracentrifugation. The relationships between each HDL-C subfraction and cIMT were analyzed by multiple linear regression models. Results: The mean cIMT was 0.796±0.195 mm, the mean total HDL-C was 55.1±14.4 mg/dl, HDL 2 -C was 14.9±6.7, and HDL 3 was 40.1±8.4 mg/dl. Total HDL-C and subfractions, as well as HDL 2 -C/HDL 3 -C ratio were negatively associated with cIMT after adjustment for race/ethnicity, age, and sex (all p&lt;0.001) and further for smoking status, alcohol use, physical activity, LDL-C, systolic blood pressure, waist circumference, fasting serum glucose, body mass index, triglycerides and antihypertensive use (HDL-C: p = 0.003, HDL 2 -C: p = 0.01; HDL 3 -C: p = 0.003; HDL 2 -C/HDL 3 -C ratio: p = 0.02). When stratified by diabetes status, both HDL 2 -C (p=0.03) and HDL 2 -C/HDL 3 -C ratio (p= 0.01) showed a negative association with cIMT in people with diabetes (n=531) after adjusting for confounding variables. These associations were not observed in individuals without diabetes (p = 0.11 and p = 0.30, respectively). Conclusion: HDL 2 -C and HDL 3 -C subfractions, as well as the HDL 2 /HDL 3 -C ratio, are inversely associated with cIMT after adjustment for traditional risk factors. This association of HDL 2 -C/HDL 3 -C ratio and HDL 2 -C is modified by the presence of diabetes, where it is more pronounced.
Chemotherapy-Induced Long Non-coding RNA 1 Promotes Metastasis and Chemo-Resistance of TSCC via the Wnt/β-Catenin Signaling Pathway
Authors: Zhaoyu Lin, Lijuan Sun, Shule Xie, Shanyi Zhang, Song Fan, Qunxing Li, Weixiong Chen, Guokai Pan, Weiwei Wang, Bin Weng, Zhang Zhang, Bodu Liu, Jinsong Li
Journal: Molecular Therapy (2018)

Increasing evidence has shown that chemo-resistance is related to the process of epithelial-mesenchymal transition (EMT) and increased invasiveness by tongue squamous cell carcinoma (TSCC) cells. Long non-coding RNAs (lncRNAs) play pivotal roles in tumor metastasis and progression. However, the roles and mechanisms of lncRNAs in cisplatin-resistance-induced EMT and metastasis are not well understood. In this study, a chemotherapy-induced lncRNA 1 (CILA1) was discovered by using microarrays and was functionally identified as a regulator of chemo-sensitivity in TSCC cells. Upregulation of CILA1 promotes EMT, invasiveness, and chemo-resistance in TSCC cells, whereas the inhibition of CILA1 expression induces mesenchymal-epithelial transition (MET) and chemo-sensitivity, and inhibits the invasiveness of cisplatin-resistant cells both in vitro and in vivo. We also found that CILA1 exerts its functions via the activation of the Wnt/β-catenin signaling pathway. High CILA1 expression levels and low levels of phosphorylated β-catenin were closely associated with cisplatin resistance and advanced disease stage, and were predictors of poor prognosis in TSCC patients. These findings provided a new biomarker for the chemo-sensitivity of TSCC tumors and a therapeutic target for TSCC treatment. Increasing evidence has shown that chemo-resistance is related to the process of epithelial-mesenchymal transition (EMT) and increased invasiveness by tongue squamous cell carcinoma (TSCC) cells. Long non-coding RNAs (lncRNAs) play pivotal roles in tumor metastasis and progression. However, the roles and mechanisms of lncRNAs in cisplatin-resistance-induced EMT and metastasis are not well understood. In this study, a chemotherapy-induced lncRNA 1 (CILA1) was discovered by using microarrays and was functionally identified as a regulator of chemo-sensitivity in TSCC cells. Upregulation of CILA1 promotes EMT, invasiveness, and chemo-resistance in TSCC cells, whereas the inhibition of CILA1 expression induces mesenchymal-epithelial transition (MET) and chemo-sensitivity, and inhibits the invasiveness of cisplatin-resistant cells both in vitro and in vivo. We also found that CILA1 exerts its functions via the activation of the Wnt/β-catenin signaling pathway. High CILA1 expression levels and low levels of phosphorylated β-catenin were closely associated with cisplatin resistance and advanced disease stage, and were predictors of poor prognosis in TSCC patients. These findings provided a new biomarker for the chemo-sensitivity of TSCC tumors and a therapeutic target for TSCC treatment.
The impact of research presented at annual gastrointestinal cancers symposium.
Authors: Amikar Sehdev, Neelakanta Dadi, David Andrew Haggstrom, Leonidas George Koniaris, Bert H. O'Neil
Journal: Journal of Clinical Oncology (2018)

757 Background: The Gastrointestinal (GI) Cancers Symposium provides a multidisciplinary forum to both present research and gain expertise in the management of GI cancers. We conducted a study to understand the research trends, publication rate and the overall impact of research presented. Methods: A bibliometric review of the conference proceedings of the Symposium from 2013-2015 was undertaken. Data collected on each abstract included author number, demographic information of the presenting author, presentation type, cancer type, research focus (multidisciplinary treatment; prevention, diagnosis and screening; translational research) and research design. A PubMed search was used to determine overall and specific publication data. Descriptive statistics were compiled. Chi-square was used to compare groups. Results: The number of abstracts presented has increased (584 in 2013, 652 in 2014 and 794 in 2015). Fraction of oral presentations by year were similar (2.0%, 2.1% and 1.8%). Median number of authors per abstract was 9 (range 1-20). The subject area in all three years was dominated by multidisciplinary treatment (mean 58.6%), followed by translational research (mean 25.5%) and lastly Prevention, Diagnosis and Screening (mean 15.8%). The most common study design was observational (mean 43.5%), followed by case series (mean 27%), clinical trial (mean 19.8%) and other (mean 9.2%). Overall, 51.5%, 46.9% and 40.4% of the abstracts presented in 2013, 2014 and 2015 were published. The median time to publication was 14.5 months (range 0-49 months). The majority of published abstracts were published in journals with impact factor (IF) &lt; 5 (mean 66.5%) and a small percentage (mean 8.4%) of abstracts were published in high impact journals (IF &gt; 10). Abstracts selected for oral presentation were associated with publication in a journal with high IF (p &lt; 0.001). The presenting author was more commonly male (70%) and a medical oncologist (61.5%). Conclusions: Overall participation is increasing in the Symposium. Selection for oral presentation appeared to be a good marker for both publication and higher impact. Prevention, diagnosis, and screening studies were under-represented and clinical trials were also relatively uncommon.
Safety and Efficacy of ventilation delivered by a full automated mode (Intellivent-ASV): a randomized controlled study
Authors: Emilie Bialais, L Vignaux, Xavier Wittebole, D Novotni, J Meyer, M Wysocki, Thibaut Sottiaux, Gregory Reychler, Jean Roeseler, Pierre-François Laterre, Philippe Hantson
Journal: Intensive Care Medicine (2013)
Evaluation of the Direct Antiglobulin Test (DAT) in the Setting of <i>Mycoplasma pneumoniae</i> Infection
Authors: Brady Stein, Nicole DeCredico, Luke Hillman
Journal: JAMA (2018)

A young adult with community-acquired Mycoplasma pneumonia was found to have new-onset anemia, thrombocytosis, positive direct antiglobulin testing for anti-C3, and red blood cell agglutination at 4°C and at room temperature. How would you interpret these results?
Phosphine Exposure Among Emergency Responders — Amarillo, Texas, January 2017
Authors: Emily M. Hall, Ketki Patel, Kerton R. Victory, Geoffrey M. Calvert, Leticia M. Nogueira, Heidi K. Bojes
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Phosphine is a highly toxic gas that forms when aluminum phosphide, a restricted-use pesticide* typically used in agricultural settings, reacts with water. Acute exposure can lead to a wide range of respiratory, cardiovascular, and gastrointestinal symptoms, and can be fatal (1). On January 2, 2017, the Texas Department of State Health Services (DSHS) was notified by the Texas Panhandle Poison Center of an acute phosphine exposure incident in Amarillo, Texas. DSHS investigated potential occupational phosphine exposures among the 51 on-scene emergency responders; 40 (78.4%) did not use respiratory protection during response operations. Fifteen (37.5%) of these 40 responders received medical care for symptoms or as a precaution after the incident, and seven (17.5%) reported new or worsening symptoms consistent with phosphine exposure within 24 hours of the incident. Emergency response organizations should ensure that appropriate personal protective equipment (PPE) is used during all incidents when an unknown hazardous substance is suspected. Additional evaluation is needed to identify targeted interventions that increase emergency responder PPE use during this type of incident.
We must look further upstream to enable planetary health-literate urban development
Authors: Daniel Black, Gabriel Scally, Alistair Hunt, Judy Orme
Journal: The Lancet Planetary Health (2018)

The gap between academic research and real-world practice in urban planning and development is a major barrier to planetary health.1 By exploring uncertainty and complexity further upstream, we might be able to narrow that gap, and make progress in tackling the urban health crisis.
Incorrect Conclusions of a Secondary Analysis
Authors: Udo Hoffmann, Maros Ferencik, James Udelson
Journal: JAMA Internal Medicine (2018)

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Abstract 1931: Impact of Insulin Resistance on Elevation of Post-procedural Cardiac Biomarker and Long-term Clinical Outcomes in Patients Underwent Elective Coronary Intervention
Authors: Tadayuki Uetani, Tetsuya Amano, Soichiro Kumagai, Hirohiko Ando, Kosuke Arai, Kiminobu Yokoi, Masataka Kato, Nobuyuki Marui, Michio Nanki, Tatsuaki Matsubara, Hideki Ishii, Hideo Izawa, Toyoaki Murohara
Journal: Circulation (2007)

Background: Recently, some trials demonstrated that the presence of insulin resistance and metabolic syndrome was associated with short-term and long-term outcomes after percutaneous coronary intervention (PCI). The aim of this study is to evaluate potential association between homeostatic indices of insulin resistance (HOMA-IR) and post-procedural myocardial injury and clinical outcome after PCI. Methods: From January 2005 to December 2006, 230 consecutive patients who underwent elective stent implantations and evaluation of insulin resistance were enrolled in this study. Blood samples were collected from venous blood after overnight fasting. HOMA-IR was calculated according to the homeostasis model assessment as follows: HOMA-IR = fasting glucose (mg/dL) × fasting insulin (mU/L)/405. Patients were divided into two groups according 50 percentile (2.11) for HOMA-IR. Post-procedural myocardial injury was evaluated by analysis of troponin-T(TnT)and CK-MB 18 hours after PCI. Cardiac event was defined as the composite end-point of death of any cause, MI and revascularization of new lesion. Results: Post-procedural TnT and CK-MB were significantly higher in patients with higher HOMA-IR compared to those with lower HOMA-IR(0.05±0.09 vs 0.15±0.40, p&lt;0.01 and 14.8±6.5 vs 19.9±20.7, p&lt;0.05, respectively). Multivariate linear regression analysis demonstrated that HOMA-IR independently correlated with TnT. In Kaplan-Meier analyses, higher HOMA-IR was associated with worse clinical outcomes (Figure ). Conclusions: These results indicated an impact of insulin resistance on post-procedural cardiac biomarkers and worse clinical outcome after elective PCI.