bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia
Authors: Noh Hayeon , Jung Su Young , Kwak Jae‐Yong , Kim Sung‐Hyun , Oh Suk Joong , Zang Dae Young , Lee Suhyun , Park Hye Lin , Jo Dae Jin , Shin Jae Soo , Do Young Rok , Kim Dong‐Wook , Lee Jangik I. 
Published: March 2018

AbstractRadotinib is a second‐generation BCR‐ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP‐CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP‐CML, the dose–efficacy as well as dose–safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose‐limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR‐ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12‐month follow‐up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long‐term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP‐CML.
Attitudes toward early palliative care in cancer patients and caregivers: a Korean nationwide survey
Authors: Yoo Shin Hye , Kim Miso , Yun Young Ho , Keam Bhumsuk , Kim Young Ae , Kim Yu Jung , Shim Hyun‐Jeong , Song Eun‐Kee , Kang Jung Hun , Kwon Jung Hye , Lee Jung Lim , Lee Soon Nam , Kim Si‐Young , Kang Eun Joo , Do Young Rok , Choi Yoon Seok , Jung Kyung Hae 
Published: March 2018

AbstractIntegrated early palliative care (EPC) improves quality of life and reduces psychological distress in adult patients with cancer and caregivers, but attitudes toward EPC have been poorly studied. We aimed to investigate attitudes toward EPC in a nationwide survey of patients with cancer and caregivers. From July to October 2016, we administered nationwide questionnaires examining attitudes toward EPC in patients with cancer (n = 1001) and their families (n = 1006) from 12 Korean hospitals. When an individual considered EPC unnecessary, the reasons were collected and analyzed. Factors associated with perception of EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had positive attitudes toward EPC. The most common reasons for deeming EPC unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%; caregivers: 23%; respectively) or that they were not sure if EPC is beneficial (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was more evident in caregivers (23%) than in patients (17%). Male gender, age <50, early stage, intensive care unit admission, and not believing that dying people should prepare to practice charity were associated with patients’ negative attitudes. In caregivers, opposition to EPC was associated with not thinking death should be feared, not thinking people should be remembered, and lower educational level. Our findings showed that significant numbers of patients with advanced cancer and family caregivers showed positive attitudes toward EPC. However, more than 10% of participants did not consider EPC necessary. Physicians’ communication with patients and caregivers and financial support could help overcome the barriers of EPC.
Performance of theUroVysion®FISHassay for the diagnosis of malignant effusions using two cutoff strategies
Authors: Rosolen Débora C. B. , Faria Daniel K. , Faria Caroline S. , Antonangelo Leila 
Published: March 2018

AbstractThe cytological examination of cavity fluids has limited sensitivity in the diagnosis of malignancy. Aneuploidy, which is commonly observed in neoplastic cells, could potentially be used as an ancillary diagnostic tool. To evaluate the detection of aneuploid cells in cavitary effusion samples using the fluorescence in situ hybridization (FISH) assayUroVysion®with some adaptations and two different cutoff strategies. Seventy samples of pleural or peritoneal fluid with positive (n = 40), negative (n = 15), or suspicious (n = 15) oncotic cytology were subjected toFISHassay with the multitargetUroVysion®kit, which is composed of probes that hybridize to the centromeric region of chromosomes 3, 7, and 17 and to the locus 9p21.FISHperformance was evaluated using two different cutoffs: (1) the manufacturer's cutoff (M‐FISH) and 2) a proposed cutoff (P‐FISH). UsingM‐FISH, the diagnostic sensitivity was 57.1%, specificity 87.5%, and accuracy 60.0%; withP‐FISH, the sensitivity was 87.3%, specificity 71.4%, and accuracy 85.7%. When combined with cytology, the sensitivity, specificity, and accuracy were 88.0%, 83.3%, and 87.8%, respectively. Malignant cells presented a predominance of chromosomal gains. TheUroVysion®test using theP‐FISHcutoff was effective in demonstrating aneuploid cells in all malignant effusions, confirming the diagnosis of malignancy even in cases with suspicious cytology.
Cancer risk in patients with alopecia areata: a nationwide population‐based matched cohort study
Authors: Chen Chih‐Chiang , Chang Yun‐Ting , Liu Han‐Nan , Chen Yi‐Ju 
Published: March 2018

AbstractAlopecia areata (AA) is an organ‐specific autoimmune disorder. Defective immune system related disorders are prone to increase the risk of cancer formation. However, the association among AA and variety of cancer types had never been studied. A nationwide population‐based matched cohort study was conducted to evaluate the cancer risk in patients with AA. Records from Taiwan National Health Insurance Research Database were analyzed. Cases of AA from 1997 to 2013 and cancers registered in the catastrophic illness profile from the same time period were collected. The standard incidence ratio (SIR) of each cancer was calculated. In total, 2099 cancers among 162,499 patients with AA and without prior cancers were identified. The overall cancer risks in AA patients were slightly decreased, especially among male subjects (SIR: 0.89). Refer to individual cancer, the cancer risk of nonmelanoma skin cancer (NMSC) (SIR: 0.59), upper GI cancer (SIR: 0.70), liver cancer (SIR: 0.82), uterine, and cervix cancer (SIR: 0.84) were significantly lower in patients with AA. In contrast, AA patients were inclined to have lymphoma, breast cancer, kidney, and urinary bladder cancer with the SIR of 1.55, 2.93, and 2.95, respectively. Age stratified analyses revealed female AA patients younger than 50 years old have even higher risk of breast cancer (SIR: 3.37). Further sensitivity analysis showed similar results after excluding major autoimmune disorders. Cancer risk in AA patients is organ specific, and it is not associated with the underlying autoimmune disorders in patients with AA.
Correlation of infarct size with invasive hemodynamics in patients with ST‐elevation myocardial infarction
Authors: Goins Allie E. , Rayson Robert , Caughey Melissa C. , Sola Michael , Venkatesh Kiran , Dai Xuming , Yeung Michael , Stouffer George A. 
Published: March 2018

AbstractObjectivesTo identify invasive hemodynamic parameters that correlate with infarction size in patients with ST‐elevation myocardial infarction (STEMI).BackgroundInvasive hemodynamics obtained during primary percutaneous coronary intervention (PPCI) are predictive of mortality in STEMI, but which parameters correlate best with the size of the infarction are unknown.MethodsThis is a single‐center study of 405 adult patients with STEMI who had left ventricular end‐diastolic pressure (LVEDP) measured during PPCI. Size of infarction was estimated by peak troponin I level and ejection fraction (LVEF) determined by echocardiography.ResultsThe average (±SD) age was 61 ± 14 years, TIMI STEMI risk score was 3.5 ± 2.7 and Grace score was 157 ± 42. Hemodynamic parameters that correlated best with EF were LVEDP (r = −0.40), PP (r = 0.24), and SBP/LVEDP ratio (r = 0.22) and with peak troponin were SBP/LVEDP ratio (r = −0.41), LVEDP (r = 0.31), and PP (r = −0.29). SBP/LVEDP (AUC = 0.76) and SBP (AUC = 0.77) had a stronger association with in‐hospital mortality than did LVEDP (AUC = 0.66) or PP (AUC = 0.64). Door‐to‐balloon time did not affect the correlations between hemodynamic parameters and infarct size.ConclusionsIn this sample of 405 patients undergoing PPCI, SBP/LVEDP ratio had the strongest correlation with peak troponin levels and LVEDP with EF, whereas SBP/LVEDP and SBP had a strong association with in‐hospital mortality. These results suggest that measurement of LVEDP as well as SBP may help risk stratify patients during PPCI.
Bleachorexia—an addictive behavior to tooth bleaching: a case report
Authors: Lee Denzel Kun‐Tsung , Kastl Cameron , Chan Daniel C. N. 
Published: March 2018

Key Clinical MessageBleachorexia, addiction to tooth bleaching, is a behavioral disorder similar to anorexia. The patient feels that their teeth are always not white enough and continues to use whiteners to obtain a “perfect” smile. Such behavior falls under the category of a body dysmorphic disorder and may need medical counseling.
Photoregulating Antifouling and Bioadhesion Functional Coating Surface Based on Spiropyran
Authors: Yu Leixiao , Schlaich Christoph , Hou Yong , Zhang Jianguang , Noeske Paul‐Ludwig Michael , Haag Rainer 
Published: March 2018

AbstractDynamic regulation of the interactions between specific molecules on functional surfaces and biomolecules, for example, proteins or cells, is critical for biosensor and biomedical devices. Herein, we present a spiropyran (SP)‐based light‐responsive surface coating, hPG (hyperbranched polyglycerol)‐SP, to control the adsorption of proteins and adhesion of cells. In the normal state, the SP groups on the coating surface were in hydrophobic ring‐closed form, which promotes the nonspecific protein adsorption and cell adhesion. Under UV irradiation, the grafted SP groups were dynamically isomerized into hydrophilic/zwitterionic merocyanine. Both hydrophilicity and zwitterions support the formation of a hydrated layer and hence the resulting hPG‐MC coatings highly resist protein adsorption and cell adhesion. Moreover, the presented hPG also provided a robust bioinert background to suppress the nonspecific protein adsorption and cells adhesion. Therefore, this functionalized coating exhibited a good photoregulated antifouling behavior. Moreover, the detachment of adsorbed proteins and adhered cells from the coating surface was also realized.
Enantioselective complexation of 1‐phenylethanol with chiral compounds bearing urea moiety
Authors: Cuřínová Petra , Dračínský Martin , Jakubec Martin , Tlustý Martin , Janků Kristýna , Izák Pavel , Holakovský Roman 
Published: March 2018

AbstractA detailed study of diastereomeric complexes of chiral ureido‐1,1′‐binaphthalene derivatives with chiral 1‐phenylethanol showed that a derivative bearing only one urea unit makes five times more stable complex with (S)‐enantiomer than with (R)‐enantiomer of the alcohol. This phenomenon could be used in chiral discrimination processes. The influence of individual parts of the structure on the complexation properties is shown. The probable structure of diastereomeric complexes based on experimental results and computational methods is proposed.
Minimizing Real Driving Emissions of Heavy Duty Vehicles – Exhaust Systems and Legislation
Authors: von Pyschow Christian , Geißelmann Andreas , Beidl Christian 
Published: March 2018

AbstractTrotz sich stetig verbessernder Luftqualität werden die gesetzlich vorgeschriebenen Immissionsziele in urbanen Gebieten noch nicht eingehalten. Deshalb sind im Automobilbereich – auch im Bereich der Nutzfahrzeuge – weitere Verschärfungen der Grenzwerte und vor allem der Testprozeduren zur Überprüfung in Betrieb befindlicher Fahrzeuge angedacht bzw. bereits verabschiedet. Für Nutzfahrzeuge werden Verfahren zur Bestimmung von Realemissionen und anstehende Verschärfungen der gesetzlichen Prozeduren vorgestellt sowie mögliche Maßnahmen zur Einhaltung dieser strengeren Auflagen.
Electrocardiographic predictors of validated right ventricular outflow tract septal pacing for correct localization of transthoracic echocardiography
Authors: Wei Huiqiang , Tang Jiaojiao , Chen Dongli , Zhang Qianhuan , Liang Yuanhong , Liu Lie , Wu Shulin , Lin Chunying , Yang Zhiming , Chai Chanjuan 
Published: March 2018

BackgroundElectrocardiographic (ECG) characteristics of true right ventricular outflow tract (RVOT) septal pacing have not been clearly demonstrated.HypothesisWe hypothesized that ECG parameters would help operators differentiate true RVOT septum from non‐septal septum.MethodsWe analyzed 151 patients who underwent pacemaker implantation with a ventricular lead in the RVOT. Transthoracic echocardiographic (TTE) determination of pacing sites was applied in all patients after implantation. A 12‐lead ECG was recorded during forced ventricular pacing.ResultsAccording to TTE orientation, pacing at the RVOT septum was achieved in 94 patients (62.3%). Compared with nonseptal pacing, septal pacing had significantly shorter QRS duration (139.2 ± 18.5 ms vs 155.5 ± 14.7 ms; P < 0.001). More frequent negative or isoelectric QRS vector in lead I (76% vs 32%; P < 0.001), lead II/III R‐wave amplitude ratio < 1 (52% vs 25%; P = 0.001), and aVR/aVL QS‐wave amplitude ratio < 1 (59% vs 32%; P = 0.001) were observed in septal pacing. Transitional zone (TZ) score (3.8 ± 0.96 vs 4.2 ± 0.90; P = 0.004) and TZ index (0.3 ± 0.5 vs 0.6 ± 0.7; P = 0.008) were significantly lower in septal pacing than in nonseptal pacing, respectively. In multivariate analysis, paced QRS duration and negative or isoelectric QRS vector in lead I independently predicted RVOT septal pacing (P < 0.001). At ROC curve analysis, paced QRS duration ≤145 ms identified RVOT septal pacing with 85.1% sensitivity and 78.9% specificity.ConclusionsThis study reveals the heterogeneity of lead placement within the RVOT. Narrower paced QRS duration and negative or isoelectric QRS vector in lead I independently predict RVOT septal pacing.
Identifying Small‐Molecule Binding Sites for Epigenetic Proteins at Domain–Domain Interfaces
Authors: Bowkett David , Talon Romain , Tallant Cynthia , Schofield Chris , von Delft Frank , Knapp Stefan , Bruton Gordon , Brennan Paul E. 
Published: March 2018

AbstractEpigenetics is a rapidly growing field in drug discovery. Of particular interest is the role of post‐translational modifications to histones and the proteins that read, write, and erase such modifications. The development of inhibitors for reader domains has focused on single domains. One of the major difficulties of designing inhibitors for reader domains is that, with the notable exception of bromodomains, they tend not to possess a well‐enclosed binding site amenable to small‐molecule inhibition. As many of the proteins in epigenetic regulation have multiple domains, there are opportunities for designing inhibitors that bind at a domain–domain interface which provide a more suitable interaction pocket. Examination of X‐ray structures of multiple domains involved in recognising and modifying post‐translational histone marks using the SiteMap algorithm identified potential binding sites at domain–domain interfaces. For the tandem plant homeodomain–bromodomain of SP100C, a potential inter‐domain site identified computationally was validated experimentally by the discovery of ligands by X‐ray crystallographic fragment screening.
A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer
Authors: Pishvaian Michael J. , Slack Rebecca S. , Jiang Wei , He A. Ruth , Hwang Jimmy J. , Hankin Amy , Dorsch‐Vogel Karen , Kukadiya Divyesh , Weiner Louis M. , Marshall John L. , Brody Jonathan R. 
Published: March 2018

BACKGROUNDPoly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA‐damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects.METHODSA single‐arm, open‐label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients received temozolomide (150 mg/m2/d) on days 1 to 5 and veliparib (40 mg twice daily) on days 1 to 7 of each 28‐day cycle. Another 5 patients with mismatch repair–deficient (dMMR) tumors were also enrolled. Twenty additional patients were then treated with temozolomide at 200 mg/m2/d. Archived tumor specimens were used for immunohistochemistry to assess mismatch repair, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O(6)‐methylguanine‐DNA methyltransferase (MGMT) protein expression levels.RESULTSThe combination was well tolerated, although some patients required dose reductions for myelosuppression. The primary endpoint was successfully met with a DCR of 24% and 2 confirmed partial responses. The median progression‐free survival was 1.8 months, and the median overall survival was 6.6 months. PTEN protein expression and MGMT protein expression were not predictors of DCR. There was also a suggestion of worse outcomes for patients with dMMR tumors.CONCLUSIONSIn this heavily pretreated mCRC population, a combination of veliparib and temozolomide was well tolerated with temozolomide doses up to 200 mg/m2/d, and it was clinically active. PARP inhibitor–based therapy merits further exploration in patients with mCRC. Cancer 2018;124:2337‐46. © 2018 American Cancer Society.
Long‐term safety and survival with gefitinib in select patients with advanced non–small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP)
Authors: Hirsch Fred R. , Sequist Lecia V. , Gore Ira , Mooradian Meghan , Simon George , Croft Elisabeth F. , DeVincenzo Diana , Munley Jiefen , Stein Dara , Freivogel Klaus , Sifakis Frangiscos , Bunn Paul A. 
Published: March 2018

BACKGROUNDThis is the first report of long‐term (>10 years) safety, tolerability, and survival data on patients with non–small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.METHODSPatients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data.RESULTSSeventy‐five of 191 patients (39%) remained on long‐term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib‐related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never‐smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR‐mutation‐positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10‐year and 15‐year survival rates of 86% and 59%, respectively, from the initiation of therapy.CONCLUSIONSA subset of long‐term NSCLC survivors who were receiving gefitinib had an excellent long‐term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long‐term survival. Cancer 2018;124:2407‐14. © 2018 American Cancer Society.
Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results
Authors: Hu Jiyi , Bao Cihang , Gao Jing , Guan Xiyin , Hu Weixu , Yang Jing , Hu Chaosu , Kong Lin , Lu Jiade J. 
Published: March 2018

BACKGROUNDReirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC) after a definitive dose of radiotherapy (RT) is challenging and usually associated with severe toxicities. Intensity‐modulated carbon ion RT (IMCT) offers physical/biologic advantages over photon‐based intensity‐modulated RT. Herein, the authors report their initial experience of IMCT in previously irradiated patients with locoregionally recurrent NPC.METHODSPatients with locoregionally recurrent, poorly differentiated or undifferentiated NPC who underwent salvage therapy with IMCT at the Shanghai Proton and Heavy Ion Center between May 2015 and August 2017 were included in the current study. The IMCT doses were 50 to 66 Gray equivalent (GyE) (2.0‐3.0 GyE/daily fraction), delivered via raster scanning technology. The 1‐year overall survival, disease‐specific survival, progression‐free survival (PFS), local recurrence‐free survival, regional recurrence‐free survival, and distant metastasis‐free survival were calculated. Univariate and multivariate analyses of PFS were performed to identify possible predictive factors.RESULTSAmong the 75 patients included, 4 patients, 14 patients, 29 patients, and 28 patients, respectively, had recurrent American Joint Committee on Cancer stage I, stage II, stage III, and stage IVA/B disease. With a median follow‐up of 15.4 months (range, 2.6‐29.7 months), the 1‐year overall survival, disease‐specific survival, PFS, local recurrence‐free survival, regional recurrence‐free survival, and distant metastasis‐free survival rates were 98.1%, 98.1%, 82.2%, 86.6%, 97.9%, and 96.2%, respectively. A higher fraction size of 3 GyE (vs <3 GyE) or a higher biological equivalent dose significantly improved the PFS rate on univariate analysis, but not on multivariate analysis. No patient developed acute toxicity of grade ≥2 during IMCT. Late treatment‐induced severe (grade 3 or 4) toxicities were infrequent, but included mucosal necrosis (9.3%), xerostomia (1.3%), and temporal lobe necrosis (1.3%).CONCLUSIONSThis initial experience in the first 75 patients with locoregionally recurrent NPC was encouraging. Carbon ion RT could provide promising survival rates with infrequent severe toxicities for patients with locoregionally recurrent NPC. Cancer 2018;124:2427‐37. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.