bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis
Authors: Curry Edward , Zeller Constanze , Masrour Nahal , Patten Darren K. , Gallon John , Wilhelm-Benartzi Charlotte S. , Ghaem-Maghami Sadaf , Bowtell David D. , Brown Robert 
Published: January 2018

Abstract
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised genes may facilitate changes in transcriptional states after exposure to anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue. Gene sets with proximal bivalent marks defined in this manner were evaluated subsequently as signatures of systematic change in DNA methylation and gene expression, comparing pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. We found that gene sets harboring bivalent chromatin domains at their promoters in tumor tissue, but not normal epithelia, overlapped with Polycomb-repressive complex target genes as well as transcriptionally silenced genes in normal ovarian and tubal stem cells. The bivalently marked genes we identified in tumors before chemotherapy displayed increased promoter CpG methylation and reduced gene expression at relapse after chemotherapy of ovarian cancer. Overall, our results support the hypothesis that preexisting histone modifications at genes in a poised chromatin state may lead to epigenetic silencing during acquired drug resistance.
Significance: These results suggest epigenetic targets for intervention to prevent the emergence of cancer drug resistance. Cancer Res; 78(6); 1383–91. ©2018 AACR.
AMPK–Akt Double-Negative Feedback Loop in Breast Cancer Cells Regulates Their Adaptation to Matrix Deprivation
Authors: Saha Manipa , Kumar Saurav , Bukhari Shoiab , Balaji Sai A. , Kumar Prashant , Hindupur Sravanth K. , Rangarajan Annapoorni 
Published: January 2018

Abstract
Cell detachment from the extracellular matrix triggers anoikis. Disseminated tumor cells must adapt to survive matrix deprivation, while still retaining the ability to attach at secondary sites and reinitiate cell division. In this study, we elucidate mechanisms that enable reversible matrix attachment by breast cancer cells. Matrix deprival triggered AMPK activity and concomitantly inhibited AKT activity by upregulating the Akt phosphatase PHLPP2. The resultant pAMPKhigh/pAktlow state was critical for cell survival in suspension, as PHLPP2 silencing also increased anoikis while impairing autophagy and metastasis. In contrast, matrix reattachment led to Akt-mediated AMPK inactivation via PP2C-α-mediated restoration of the pAkthigh/pAMPKlow state. Clinical specimens of primary and metastatic breast cancer displayed an Akt-associated gene expression signature, whereas circulating breast tumor cells displayed an elevated AMPK-dependent gene expression signature. Our work establishes a double-negative feedback loop between Akt and AMPK to control the switch between matrix-attached and matrix-detached states needed to coordinate cell growth and survival during metastasis.
Significance: These findings reveal a molecular switch that regulates cancer cell survival during metastatic dissemination, with the potential to identify targets to prevent metastasis in breast cancer. Cancer Res; 78(6); 1497–510. ©2018 AACR.
Radioresistant Cervical Cancers Are Sensitive to Inhibition of Glycolysis and Redox Metabolism
Authors: Rashmi Ramachandran , Huang Xiaojing , Floberg John M. , Elhammali Adnan E. , McCormick Michael L. , Patti Gary J. , Spitz Douglas R. , Schwarz Julie K. 
Published: January 2018

Abstract
Highly glycolytic cervical cancers largely resist treatment by cisplatin and coadministered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of glycolysis (2-deoxyglucose, 2-DG) with or without simultaneous inhibition of glutathione and thioredoxin metabolism (BSO/AUR). Intracellular levels of total and oxidized glutathione, thioredoxin reductase activity, and indirect measures of intracellular reactive oxygen species were compared before and after treatment. Highly radioresistant cells were the most sensitive to 2-DG, whereas intermediate radioresistant cells were sensitive to 2-DG plus BSO/AUR. In response to 2-DG/BSO/AUR treatment, we observed increased levels of intracellular oxidized glutathione, redox-sensitive dye oxidation, and decreased glucose utilization via multiple metabolic pathways including the tricarboxylic acid cycle. 2-DG/BSO/AUR treatment delayed the growth of tumors composed of intermediate radioresistant cells and effectively radiosensitized these tumors at clinically relevant radiation doses both in vitro and in vivo. Overall, our results support inhibition of glycolysis and intracellular redox metabolism as an effective alternative drug strategy for the treatment of highly glycolytic and radioresistant cervical cancers.
Significance: This study suggests a simple metabolic approach to strike at an apparent Achilles' heel in highly glycolytic, radioresistant forms of cervical cancers, possibly with broader applications in cancer therapy. Cancer Res; 78(6); 1392–403. ©2018 AACR.
Role of Chromatin Damage and Chromatin Trapping of FACT in Mediating the Anticancer Cytotoxicity of DNA-Binding Small-Molecule Drugs
Authors: Nesher Elimelech , Safina Alfiya , Aljahdali Ieman , Portwood Scott , Wang Eunice S. , Koman Igor , Wang Jianmin , Gurova Katerina V. 
Published: January 2018

Abstract
Precisely how DNA-targeting chemotherapeutic drugs trigger cancer cell death remains unclear, as it is difficult to separate direct DNA damage from other effects in cells. Recent work on curaxins, a class of small-molecule drugs with broad anticancer activity, shows that they interfere with histone–DNA interactions and destabilize nucleosomes without causing detectable DNA damage. Chromatin damage caused by curaxins is sensed by the histone chaperone FACT, which binds unfolded nucleosomes becoming trapped in chromatin. In this study, we investigated whether classical DNA-targeting chemotherapeutic drugs also similarly disturbed chromatin to cause chromatin trapping of FACT (c-trapping). Drugs that directly bound DNA induced both chromatin damage and c-trapping. However, chromatin damage occurred irrespective of direct DNA damage and was dependent on how a drug bound DNA, specifically, in the way it bound chromatinized DNA in cells. FACT was sensitive to a plethora of nucleosome perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Strikingly, we found that the cytotoxicity of DNA-binding small molecules correlated with their ability to cause chromatin damage, not DNA damage. Our results suggest implications for the development of chromatin-damaging agents as selective anticancer drugs.
Significance: These provocative results suggest that the anticancer efficacy of traditional DNA-targeting chemotherapeutic drugs may be based in large part on chromatin damage rather than direct DNA damage. Cancer Res; 78(6); 1431–43. ©2018 AACR.
Memory Matters: A Case for Granger Causality in Climate Variability Studies
Authors: McGraw Marie C. , Barnes Elizabeth A. 
Published: January 2018

Abstract
In climate variability studies, lagged linear regression is frequently used to infer causality. While lagged linear regression analysis can often provide valuable information about causal relationships, lagged regression is also susceptible to overreporting significant relationships when one or more of the variables has substantial memory (autocorrelation). Granger causality analysis takes into account the memory of the data and is therefore not susceptible to this issue. A simple Monte Carlo example highlights the advantages of Granger causality, compared to traditional lagged linear regression analysis in situations with one or more highly autocorrelated variables. Differences between the two approaches are further explored in two illustrative examples applicable to large-scale climate variability studies. Given that Granger causality is straightforward to calculate, Granger causality analysis may be preferable to traditional lagged regression analysis when one or more datasets has large memory.
Does the MJO Have a Westward Group Velocity?
Authors: Chen Guosen , Wang Bin 
Published: January 2018

AbstractCurrent theoretical studies have a debate on whether the Madden–Julian oscillation (MJO) has a zero or westward group velocity. A recent analysis of the observed Hovmöller diagram of MJO signals suggested that the MJO has a significant westward group velocity. Here it is shown that the observed MJO has a negligibly small group velocity, which is manifested in two aspects. First, on the wavenumber–frequency spectra diagram the precipitation spectra indicate quasi independence of the MJO frequency on wavenumber, suggesting a nearly vanishing group velocity. Second, on the Hovmöller diagram of the regressed intraseasonal daily precipitation, the MJO group velocity is defined by the propagation of the wave envelopes of the precipitation and is shown to be negligibly small for the eastward propagating signals. The causes of the discrepancy between this study and the recent study mentioned above are the calculating method and the data filtering process. The group velocity in the recent study is calculated by the propagation of local convection extrema, which does not necessarily indicate the propagation of the wave envelopes. More importantly, the westward propagation of the local convection extrema is an artifact of the data filtering. The Hovmöller diagram in the recent study was constructed by using only the eastward propagating wavenumber-1–5 signals. This truncation of data onto the planetary scales of the eastward wavenumber domain fails to resolve the Maritime Continent “barrier effect,” causing significant artificial westward propagation of local convection extrema.
Cognitive work hardening for return to work following depression: An intervention study
Authors: Wisenthal Adeena , Krupa Terry , Kirsh Bonnie H. , Lysaght Rosemary 
Published: January 2018

Background. Work absences due to depression are prevalent; however, few interventions exist to address the return-to-work challenges following a depressive episode. Purpose. This mixed-methods study aimed to (a) evaluate the effectiveness of cognitive work hardening in preparing people with depression to return to work and (b) identify key elements of the intervention. Method. A single group ( n = 21) pretest-posttest study design was used incorporating self-report measures (Work Ability Index, Multidimensional Assessment of Fatigue, Beck Depression Inventory II) with interviews at intervention completion and at 3-month follow-up. Descriptive statistics, paired-samples t test, and content analysis were used to analyze the data. Findings. Work ability, fatigue, and depression severity significantly improved postintervention. Participants identified structure, work simulations, realism of simulated work environment, support, and education as key intervention elements. Implications. Findings underscore an occupationally focused return-to-work intervention for people recovering from depression with potential for wider adoption and future research.
The effect of social support, gratitude, resilience and satisfaction with life on depressive symptoms among police officers following Hurricane Katrina
Authors: McCanlies Erin C , Gu Ja Kook , Andrew Michael E , Violanti John M 
Published: January 2018

Background: Police officers in the New Orleans geographic area faced a number of challenges following Hurricane Katrina. Aim: This cross-sectional study examined the effect of social support, gratitude, resilience and satisfaction with life on symptoms of depression. Method: A total of 86 male and 30 female police officers from Louisiana participated in this study. Ordinary least-square (OLS) regression mediation analysis was used to estimate direct and indirect effects between social support, gratitude, resilience, satisfaction with life and symptoms of depression. All models were adjusted for age, alcohol intake, military experience and an increase in the number of sick days since Hurricane Katrina. Results: Mean depressive symptom scores were 9.6 ± 9.1 for females and 10.9 ± 9.6 for males. Mediation analyses indicates that social support and gratitude are directly associated with fewer symptoms of depression. Social support also mediated the relationships between gratitude and depression, gratitude and satisfaction with life, and satisfaction with life and depression. Similarly, resilience mediated the relationship between social support and fewer symptoms of depression. Conclusion: Social support, gratitude and resilience are associated with higher satisfaction with life and fewer symptoms of depression. Targeting and building these factors may improve an officer’s ability to address symptoms of depression.
The Prediction Value of the Systemic Inflammation Score for Oral Cavity Squamous Cell Carcinoma
Authors: Eltohami Yousif I. , Kao Huang‐Kai , Lao William Wei‐Kai , Huang Yenlin , Abdelrahman Mohamed , Liao Chun‐Ta , Yen Tzu‐Chen , Chang Kai‐Ping 
Published: January 2018

ObjectivesThis study aimed to investigate the potential prognostic role of the oral cancer systemic inflammation score (SIS) based on serum albumin levels and the lymphocyte‐to‐monocyte ratio in patients with oral squamous cell carcinoma (OSCC) after treatment.Study DesignA retrospective cohort study.SettingTertiary care center.Subjects and MethodsThe study involved 613 patients who were treated for OSCC between September 2005 and December 2014. The association of the oral cancer SIS with various clinicopathological features was investigated. A nomogram based on different clinicopathological features and SIS was established to predict prognosis.ResultsHigher SIS was significantly associated with older age (P =. 0013), advanced tumor status (P <. 0001), tumor depth (P <. 0001), advanced overall pathologic stage (P <. 0001), and extranodal extension (P =. 0045), as well as the presence of perineural invasion (P =. 0341). Higher SIS, older age, overall stage, and extranodal extension were demonstrated to be independent prognostic indicators for shorter overall survival (P <. 0001). A nomogram comprising SIS, TNM stage, and the degree of cell differentiation, as well as perineural invasion and extranodal extension, was developed to predict the prognosis of these patients. The c‐index of the nomogram model based on TNM staging only was 0.688 and could be increased to 0.752 if SIS and several other clinicopathological parameters were incorporated.ConclusionsHigher SIS is associated with many poor prognosticators, and the nomogram that was established and based on the incorporation of SIS might strengthen the prediction of prognosis in patients with OSCC.
Perineural Invasion in Parotid Gland Malignancies
Authors: Huyett Phillip , Duvvuri Umamaheswar , Ferris Robert L. , Johnson Jonas T. , Schaitkin Barry M. , Kim Seungwon 
Published: January 2018

ObjectivesTo investigate the clinical predictors and survival implications of perineural invasion (PNI) in parotid gland malignancies.Study DesignCase series with chart review.SettingTertiary care medical center.Subjects and MethodsPatients with parotid gland malignancies treated surgically from 2000 to 2015 were retrospectively identified in the Head and Neck Cancer Registry at a single institution. Data points were extracted from the medical record and original pathology reports.ResultsIn total, 186 patients with parotid gland malignancies were identified with a mean follow‐up of 5.2 years. Salivary duct carcinoma (45), mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most common histologic types. A total of 46.2% of tumors were found to have PNI. At the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P <. 001) and facial pain (OR, 3.7; P =. 002) but not facial paresthesia or anesthesia (OR, 2.8, P =. 085) were predictive of PNI. Malignancies with PNI were significantly more likely to be of advanced T and N classification, be high‐risk pathologic types, and have positive margins and angiolymphatic invasion. PNI positivity was associated with worse overall (hazard ratio, 2.62; P =. 001) and disease‐free survival (4.18; P <. 001) on univariate Cox regression analysis. However, when controlling for other negative prognosticators, age, and adjuvant therapy, PNI did not have a statistically significant effect on disease‐free or overall survival.ConclusionsPNI is strongly correlated with more aggressive parotid gland malignancies but is not an independent predictor of worse survival. Facial paresis and pain were predictive of PNI positivity, and facial paresis correlated with worse overall and disease‐free survival.
Physicians’ Perceptions of Hope and How Hope Informs Interactions With Patients: A Qualitative, Exploratory Study
Authors: Wolf Airin , Garlid Catherine F. , Hyrkas Kristiina 
Published: January 2018

Objectives: Today some studies of physicians’ perceptions of hope are available, but not studies of how hope informs patient care. The objectives of this qualitative study were to describe the ways physicians conceptualize hope and how these may inform interactions with their patients. Methods: Ten physicians working in a large tertiary care teaching hospital were interviewed. They represented palliative care, oncology, and 7 other specialties. Minimal amount of background information was collected. In-depth interviews were conducted during spring of 2016. Open coding and the constant comparison method were used to identify emerging themes from the transcribed data. Validation method included member checking. Results: Hope was defined as an abstract, evolving concept characterized by future-oriented wishes; offering possibilities for reframing and shaping new meaning; an attitude of positivity or optimism; an attribute of the human condition with emotional and relational roots; and as a response to the existential inevitability of suffering and death. Three themes describing hope emerged: “assessing hope,” “fostering and sustaining hope,” and “attributes and outcomes of hope.” Conclusions: The findings show how physicians conceptualize hope and how these conceptions differ in the empirical light of the study. Physicians’ perceptions of “hope” may evolve when entering into a therapeutic relationship exploring the needs and desires of patients. Physicians’ perspectives about “hope” may at times not be solely their own but are those of their patients and thus resulting in an amalgamation, or a rebuilding/rekindling of hope amidst hopelessness, that suits a particular relationship.
Latissimus Dorsi Flap in Breast Reconstruction
Authors: Sood Rachita , Easow Jeena M. , Konopka Geoffrey , Panthaki Zubin J. 
Published: January 2018

Background: Surgeons employ the latissimus dorsi flap (LDF) for reconstruction of a large variety of breast cancer surgery defects, including quadrantectomy, lumpectomy, modified radical mastectomy, and others. The LDF may be used in delayed or immediate reconstruction, in combination with tissue expanders for a staged reconstruction, with implant-based immediate reconstruction, or alone as an autogenous flap. Methods: The authors discuss the historical uses and more recent developments in the LDF. More recent advancements, including the “scarless” approach and augmentation with the thoracodorsal artery perforator flap, are discussed. Results: The LDF is a reliable means for soft tissue coverage providing form and function during breast reconstruction with acceptable perioperative and long-term morbidities. Conclusions: When there is a paucity of tissue, the LDF can provide tissue volume in autologous reconstruction, as well as a reliable vascular pedicle for implant-based reconstruction as in the setting of irradiated tissue.
Bacterial Colonization of Chronic Hemodialysis Catheters: Evaluation with Endoluminal Brushes and Heparin Aspirate
Authors: Koch M. , Coyne D. , Hoppe-Bauer J. , Vesely T. M. 
Published: January 2018

Tunneled catheters serve as interim access during maturation of a graft or fistula, or as a permanent vascular access in those patients who have exhausted their traditional access sites. However, bacteremia rates are high in patients with chronic catheters and indiscriminate removal of catheters during bacteremia increases morbidity and costs. A method to identify whether a catheter was colonized with the offending bacteria, without requiring catheter removal is desirable. We compared endoluminal brushing and heparin aspiration, to detect catheter colonization, in 24 asymptomatic patients undergoing elective tunneled hemodialysis catheter removal. The incidence of catheter colonization was highly correlated with catheter duration of ≥ 30 days (p=0.03). Staphylococcus epidermidis represented 68% of the organisms isolated. No other organism accounted for more than 7% of the total. Fifteen (62.5%) of the 24 catheters had positive cultures. Eleven of the catheters were positive by culture of heparin aspirate and eight were positive by endoluminal brushing. Only four of the catheters were positive by both methods. The arterial lumen was more likely to have positive cultures than the venous lumen using either method. In this prospective investigation of tunneled hemodialysis catheters in asymptomatic patients we have demonstrated that a heparin aspirate sample is more likely to detect catheter colonization than a sample obtained using an endoluminal brush. Furthermore, 75% of catheters present for more than 30 days were colonized. Further study is needed to determine if the heparin aspirate method could be used in patients with bacteremia to accurately identify catheters that need removal.