bluuebunny/crossref_metadata_2025_split huggingface dataset:
The treasure of now and an uncertain future: Delay discounting and health behaviors among cancer survivors
Authors: Sheffer Christine E. , Miller Austin , Bickel Warren K. , Devonish Julia A. , O’Connor Richard J. , Wang Chong , Rivard Cheryl , Gage‐Bouchard Elizabeth A. 
Published: October 2018

BackgroundThe identification of new therapeutic targets to improve health behaviors among cancer survivors (CS) is likely to improve cancer treatment outcomes. Delay discounting (DD) rate is the degree to which one devalues rewards as a function of time to receipt. Lower DD rates (ie, prioritizing long‐term over immediate rewards) are associated with healthier behaviors. CS often experience distress and thoughts of early mortality that can potentially shift priorities to the present and negatively impact DD rates, especially when newly diagnosed. Understanding relations between DD and health behaviors among CS will contribute to the examination of DD as a therapeutic target for improving health behaviors for CS.MethodCS (n = 1001) were recruited from a web panel and administered a web‐based questionnaire. Multivariate models examined relations among DD rate, years since diagnosis, and 10 health behavior indicators. We hypothesized that 1) higher DD rates would be associated with fewer years since diagnosis, and 2) lower DD rates would be associated with healthier behaviors, moderated by years since diagnosis.ResultsIn general, higher DD rates were associated with fewer years since diagnosis. Higher DD rates were associated with more alcohol consumption, cigarette smoking, other tobacco use, tanning booth use, and conversely, greater adherence to annual primary care visits. A significant interaction between DD rate and years since diagnosis was not found.ConclusionLower DD rates are associated with several important healthy lifestyle behaviors. DD rate is a promising therapeutic target for new interventions to improve multiple health behaviors among CS.
A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients
Authors: Stinchcombe Thomas E. , Fan Wen , Schild Steven E. , Vokes Everett E. , Bogart Jeff , Le Quynh‐Thu , Thomas Charles R. , Edelman Martin J. , Horn Leora , Komaki Ritsuko , Cohen Harvey J. , Kishor Ganti Apar , Pang Herbert , Wang Xiaofei 
Published: October 2018

BackgroundPlatinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). Many patients with LS‐SCLC are elderly with comorbidities.MethodsIndividual patient data were collected from 11 phase 2 or 3 trials for LS‐SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression‐free survival (PFS), the rate of severe adverse events, and off‐treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients).ResultsIndividual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18‐1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03‐1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently.ConclusionsElderly patients with LS‐SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.
Reducing DNA damage by formaldehyde in liquid‐based cytology preservation solutions to enable the molecular testing of lung cancer specimens
Authors: Matsuo Yukiko , Yoshida Tsutomu , Yamashita Kazuya , Satoh Yukitoshi 
Published: October 2018

AbstractBackgroundLiquid‐based cytology (LBC) is a useful cytopathological method, and LBC lung adenocarcinoma specimens may be used for genetic analysis in the near future. In the current study, the authors determined whether LBC specimens can be used for epidermal growth factor receptor (EGFR) mutation analysis in human lung adenocarcinoma cell lines.MethodsGenomic DNA was extracted from 3 lung adenocarcinoma cell lines that were fixed in LBC preservation solution using 2 protocols (one for cultured cells and one for tissues) of a DNA extraction kit. Different fixation times were tested for each protocol: 30 minutes, 1 hour, and 1 to 9 days. As controls, cells also were fixed in 10% formalin or 95% ethanol. The authors investigated the effect of fixation time on DNA fragmentation, polymerase chain reaction (PCR) amplification, and EGFR mutation detection.ResultsThe DNA yield of LBC specimens tended to decrease depending on fixation time. When using the DNA extraction protocol for tissues, PCR amplification was successful after 9 days of fixation, although extracted genomic DNA that was fixed for >1 hour demonstrated fragmentation. Mutation analyses using the Cycleave PCR method were successful after 7 days of fixation. The DNA extraction protocol for tissues was appropriate for lung adenocarcinoma cell lines that were stored for >1 day in a preservative solution. The results of the current study demonstrated that EGFR mutations can be detected on day 7 using lung adenocarcinoma cell lines fixed in CytoRich Red preservative.ConclusionsWhen LBC specimens are used for targeted molecular genetic testing, the appropriate preservative solution and extraction protocol first should be determined.
Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models
Authors: Cong Anh , Pimenta Rafaela M. L. , Lee Hong Bok , Mereddy Venkatram , Holy Jon , Heikal Ahmed A. 
Published: October 2018

ABSTRACTMost studies using intrinsic NAD(P)H as biomarkers for energy metabolism and mitochondrial anomalies have been conducted in routine two‐dimensional (2D) cell culture formats. Cellular metabolism and cell behavior, however, can be significantly different in 2D cultures from that in vivo. As a result, there are emerging interests in integrating noninvasive, quantitative imaging techniques of NAD(P)H with in vivo‐like three‐dimensional (3D) models. The overall features and metabolic responses of the murine breast cancer cells line 4T1 in 2D cultures were compared with those in 3D collagen matrix using integrated optical micro‐spectroscopy. The metabolic responses to two novel compounds, MD1 and TPPBr, that target metabolism by disrupting monocarboxylate transporters or oxidative phosphorylation (OXPHOS), respectively, were investigated using two‐photon fluorescence lifetime imaging microscopy (2P‐FLIM) of intracellular NAD(P)H in 2D and 3D cultures. 4T1 cells exhibit distinct behaviors in a collagenous 3D matrix from those in 2D culture, forming anastomosing multicellular networks and spherical acini in 3D culture, as opposed to simple flattened epithelial plaques in 2D culture. The cellular NAD(P)H in 3D collagen matrix exhibits a longer fluorescence lifetime as compared with 2D culture, which is attributed to an enhanced population of enzyme‐bound NAD(P)H in the 3D culture. TPPBr induces mitochondrial hyperpolarization in 2D culture of 4T1 cells along with an enhanced free NAD(P)H population, which suggest an interference with OXPHOS. In contrast, 2P‐FLIM of cellular NAD(P)H revealed an enhanced autofluorescence lifetime in 3D 4T1 cultures after MD1 treatment as compared with MD1‐treated 2D culture and the control 3D culture. Physical and chemical microenvironmental signaling are critical factors in understanding how therapeutic compounds target cancer cells by disrupting their metabolic pathways. Integrating 2P‐FLIM of intrinsic NAD(P)H with refined 3D tumor‐matrix in vitro models promises to advance our understanding of the roles of metabolism and metabolic plasticity in tumor growth and metastatic behavior. © 2018 International Society for Advancement of Cytometry
Is routine ECC necessary in patients with HPV16 and normal cytology?
Authors: Ureyen Isin , Toptas Tayfun , Uysal Aysel 
Published: October 2018

BackgroundIn the present study, we primarily aimed to correlate the colposcopy results of patients with human papillomavirus (HPV) positivity and abnormal cervical screening results. Secondarily, we attempted to define the role of endocervical curettage (ECC) in the colposcopic evaluation of patients who had normal cytology and HPV16, which is the most carcinogenic HPV type.MethodsThis was a retrospective study analyzing the data of patients who had colposcopies between January 2015 and May 2016 in the Gynecological Oncology clinic of a single tertiary center. The data were evaluated to identify the pathologies in patients with HPV positivity and abnormal cervical screening results. A Colposcopic examination database was evaluated to obtain information regarding the cervical transformation zone (TZ), which was divided into three types by the International Federation for Cervical Pathology and Colposcopy. The binary variables were reported as counts and percentages.ResultsA total of 1049 patients were included in the analysis. The median age of the patients was 43 (range: 21‐79). Cervical biopsies, ECC results, or both revealed cervical intraepithelial neoplasia 2+ (CIN2+: CIN2, CIN3, and invasive cancer) lesions in 22% (70/322) of the patients with HPV16 positivity, while this ratio was 8% (6/78) for patients with HPV18. CIN2+ lesions were detected in the 2.5% of patients with HPV positivity for types other than 16 and 18, as well as normal cytology. In the group of patients with HPV 16 and normal cytology, CIN2+ results were observed in the ECC of 11% of the patients whose colposcopy was normal regardless of the TZ type. Ten of the patients had invasive cancer.ConclusionThe current study provides evidence for the possible role of routine ECC in patients with HPV16, normal cytology, and a normal colposcopy.
Thiazole‐substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
Authors: Sahin Zafer , Ertas Merve , Bender Ceysu , Bülbül Emre F. , Berk Barkin , Biltekin Sevde N. , Yurttaş Leyla , Demirayak Şeref 
Published: October 2018

Hit, Lead & Candidate Discovery

After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid‐20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic‐framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs.In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N′‐benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%–83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.
Ionic Liquids as Environmentally Benign Electrolytes for High‐Performance Supercapacitors
Authors: Shahzad Suniya , Shah Afzal , Kowsari Elaheh , Iftikhar Faiza Jan , Nawab Anum , Piro Benoit , Akhter Mohammad Salim , Rana Usman Ali , Zou Yongjin 
Published: October 2018

AbstractElectrochemical capacitors (ECs) are a vital class of electrical energy storage (EES) devices that display the capacity of rapid charging and provide high power density. In the current era, interest in using ionic liquids (ILs) in high‐performance EES devices has grown exponentially, as this novel versatile electrolyte media is associated with high thermal stability, excellent ionic conductivity, and the capability to withstand high voltages without undergoing decomposition. ILs are therefore potentially useful materials for improving the energy/power performances of ECs without compromising on safety, cyclic stability, and power density. The current review article underscores the importance of ILs as sustainable and high‐performance electrolytes for electrochemical capacitors.
The association of puerperal sepsis with HIV infection at two tertiary hospitals in Zimbabwe
Authors: Majangara Rumbidzai , Chirenje Zvavahera M. , Gidiri Muchabaiwa F. 
Published: October 2018

AbstractObjectiveTo evaluate the association between HIV infection and puerperal sepsis among women in Zimbabwe.MethodsA subanalysis was performed using data from a prospective cohort study conducted between September 2, 2014, and July 1, 2015, at two tertiary hospitals in Zimbabwe. Eligible participants were consecutive women who met the WHO criteria for puerperal sepsis. Variables assessed included HIV‐infection status and the use of antiretroviral therapy. Severity of immunosuppression was defined by the number of T cells that expressed cluster of differentiation 4 (CD4). Endocervical swabs and blood samples were collected for microbial culture and susceptibility testing.ResultsIn all, 33 (21.9%) of the 151 women included in the present analysis had HIV. Among women with HIV, severe immunosuppression (CD4‐positive T cell count <200/mm3) was associated with a mean hospital stay of 19.0 days versus 10.2 days for mild‐advanced immunosuppression (CD4‐positive T cell count 200–500/mm3) and insignificant immunosuppression (CD4‐positive T cell count >500/mm3; P=0.030). Use of antiretroviral therapy did not independently influence clinical outcomes. Furthermore, infection with HIV did not influence the microorganisms isolated from blood or endocervical samples.ConclusionSevere immunosuppression was associated with increased length of hospitalization among women with HIV who had puerperal sepsis.
Structural VARs and noninvertible macroeconomic models
Authors: Forni Mario , Gambetti Luca , Sala Luca 
Published: October 2018

SummaryWe resume the line of research pioneered by C. A. Sims and Zha (Macroeconomic Dynamics, 2006, 10, 231–272) and make two novel contributions. First, we provide a formal treatment of partial fundamentalness—that is, the idea that a structural vector autoregression (VAR) can recover, either exactly or with good approximation, a single shock or a subset of shocks, even when the underlying model is nonfundamental. In particular, we extend the measure of partial fundamentalness proposed by Sims and Zha to the finite‐order case and study the implications of partial fundamentalness for impulse‐response and variance‐decomposition analysis. Second, we present an application where we validate a theory of news shocks and find it to be in line with the empirical evidence.
Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus
Authors: Sharma Dixit , Sharma Ankita , Verma Shailender Kumar , Singh Birbal 
Published: October 2018

AbstractOrientia tsutsugamushi (Ott)is a causative agent of chigger‐borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique toOttby using high‐throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty‐six proteins were reported to be essential for the pathogen's survival and non‐homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA‐binding, secretory, and outer membrane proteins. Further,in silicoanalysis of 46 proteins showed that 25 proteins were suitable therapeutic targets with known druggable properties. The structural modeling of B3CSG3 (MurA) protein was carried out and catalytic site essential for its functioning was analyzed. Virtual screening of chemical compounds was performed against modeled structure. The docking study by AutodockVina reported compound from PubChem with CID: 16036947 as best and potential inhibitor by means of docking score and binding affinity. The reliability and stability of the MurA‐16036947 complex were confirmed with molecular dynamics simulation. The report will provide insight to understand the mechanism of pathogenesis ofOttand instigate the development of effective treatment strategies against this disease.
Marijuana medusa: The many pulmonary faces of marijuana inhalation in adolescent males
Authors: McGraw Matthew D. , Houser Grace H. , Galambos Csaba , Wartchow Eric P. , Stillwell Paul C. , Weinman Jason P. 
Published: October 2018

AbstractMarijuana use has risen dramatically over the past decade. Over this same time period, pediatric hospitals have seen an increase in presentation of adolescents with acute respiratory symptoms after recent marijuana inhalation. We report a case series of three adolescent males with significant findings of bilateral pulmonary nodules and ground glass opacities on chest imaging associated with recent marijuana inhalation. Lung biopsies in two of the three patients confirmed silica‐induced pneumoconiosis. The third patient was diagnosed with acute hypersensitivity pneumonitis without lung biopsy. Improvement in clinical symptoms and lung function testing were noted in two of three patients after marijuana inhalation cessation. This case series highlights the variety of severe pulmonary presentations in adolescents following recent marijuana inhalation. Future studies are required to assess whether these presenting pulmonary complications are from direct marijuana exposure or indirect associations with marijuana inhalation injuries.
Monochromatic cycle covers in random graphs
Authors: Korándi Dániel , Mousset Frank , Nenadov Rajko , Škorić Nemanja , Sudakov Benny 
Published: October 2018

AbstractA classic result of Erdős, Gyárfás and Pyber states that for every coloring of the edges of Kn with r colors, there is a cover of its vertex set by at most vertex‐disjoint monochromatic cycles. In particular, the minimum number of such covering cycles does not depend on the size of Kn but only on the number of colors. We initiate the study of this phenomenon in the case where Kn is replaced by the random graph . Given a fixed integer r and , we show that with high probability the random graph has the property that for every r‐coloring of the edges of G, there is a collection of monochromatic cycles covering all the vertices of G. Our bound on p is close to optimal in the following sense: if , then with high probability there are colorings of such that the number of monochromatic cycles needed to cover all vertices of G grows with n.
Cervical Medial Branch Block Volume Dependent Dispersion Patterns as a Predictor for Ablation Success: A Cadaveric Study
Authors: Wahezi Sayed E. , Molina Jocelin J. , Alexeev Edward , Georgy John S. , Haramati Nogah , Erosa Stephen A. , Shah Jay M. , Downie Sherry 
Published: October 2018

BackgroundNeck pain is one of the most common causes of chronic pain and the fourth leading cause of disability worldwide; it is estimated that between 36% and 67% of this pain is due to facet arthropathy. For patients who have pain refractory to conservative treatments literature supports management with diagnostic cervical medial branch blocks (MBBs) to identify the associated facet innervation as the source of pain followed by therapeutic radiofrequency ablation (RFA) of the identified nerves. Cervical RFA has good published outcomes; however, the procedure is dependent upon the specificity of the diagnostic block to achieve maximal success. Currently, this prerequisite test has false positive rates between 27% and 63% and recent studies have shown that this may, in part, be a consequence of currently accepted injection volumes of 0.50 mL or more, which may decrease the sensitivity of MBBs.ObjectiveTo evaluate the possible differences in volume dispersion between 0.25 and 0.50 mL of injectate during cervical MBBs.Study DesignCadaveric study.SettingAn academic medical center in the United States.PatientsNot applicable.MethodsThis was a cadaveric study in which six subjects were chosen with intact cervical spines. Cervical MBB were performed bilaterally at the midcervical spine, using a posterior approach under fluoroscopic guidance. 0.25 or 0.50 mL of a 9:1 solution of Omnipaque 180 mg iodine/mL and 1% medical grade methylene blue were administered on the left and right sides, respectively. Postinjection computed tomography (CT) imaging and gross dissection were performed to assess injectate spread.Main Outcome MeasuresOutcome measures after using commonly injected volumes for cervical MBB, included visualized and measured spread (by CT and gross dissection) of cervical medial branch blocks, coating adjacent structures not targeted by RFA.ResultsPostinjection CT imaging and cadaveric dissection demonstrated that, although both volumes adequately coated the medial branches, the 0.50 mL cohort reliably spread dorsally to superficial muscles (splenius) and nerves distant from the targeted nerves (dorsal motor branches to splenius), whereas the 0.25 mL injectate cohort was contained in the deep and intermediate muscular cervical layers directly juxtaposed to the targeted cMBBs.ConclusionResults suggest that 0.50 mL injections of local anesthetic during cervical MBBs contacts many nonintended targets, thus decreasing the specificity of a targeted diagnostic cervical MBB. Furthermore, we demonstrated that 0.25 mL of injectate reliably bathed the cervical medial branches without extensive extravasation. This indicates that there would potentially be fewer local anesthetic effects on distant tissues, increasing the specificity of cervical MBBs and likely improving RFA planning.
Retrieval of Englacial Firn Aquifer Thickness From Ice‐Penetrating Radar Sounding in Southeastern Greenland
Authors: Chu W. , Schroeder D. M. , Siegfried M. R. 
Published: October 2018

AbstractAn extensive perennial firn aquifer was previously mapped in Helheim Glacier, Southeast Greenland. However, critical constraints on aquifer thickness have been so far unobtainable without expensive field observations. Here we present a novel method that combines very high frequency airborne deep ice radar and ice sheet modeling to retrieve aquifer thickness and its evolution at Helheim Glacier. Using 2012–2014 radar measurements, we identify three aquifers of 4–25 m thick, with a total area of 1,934 km2 and water storage of 2.2 ± 1.5 Gt, about half the volume of previous estimates. The aquifer system is dynamic, and its thickness varies interannually at a rate similar to changes in surface mass balance. The rapid upstream migration of the saturated aquifer implies that this feature has the potential to increase its storage potential in upper Greenland. Together, a combination of very high‐ and ultra high frequency radar sounding provides a powerful tool to characterize englacial firn aquifers.