bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold‐Hopping Approach
Authors: Heidmann Bibia , Gatfield John , Roch Catherine , Treiber Alexander , Tortoioli Simone , Brotschi Christine , Williams Jodi T. , Bolli Martin H. , Abele Stefan , Sifferlen Thierry , Jenck François , Boss Christoph 
Published: July 2016

AbstractStarting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold‐hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time‐dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P‐glycoprotein (Pgp)‐mediated efflux. Compound 80 c [{(1S,6R)‐3‐(6,7‐difluoroquinoxalin‐2‐yl)‐3,8‐diazabicyclo[4.2.0]octan‐8‐yl}(4‐methyl‐[1,1′‐biphenyl]‐2‐yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium‐release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep‐promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant.
Comorbid symptoms of emotional distress in adult survivors of childhood cancer
Authors: D'Agostino Norma Mammone , Edelstein Kim , Zhang Nan , Recklitis Christopher J. , Brinkman Tara M. , Srivastava Deokumar , Leisenring Wendy M. , Robison Leslie L. , Armstrong Gregory T. , Krull Kevin R. 
Published: July 2016

BACKGROUNDChildhood cancer survivors are at risk for emotional distress symptoms, but symptom comorbidity has not been previously examined. This study examined distress profiles for adult survivors of childhood cancer diagnosed between 1970 and 1999.METHODSSelf‐reported depression, anxiety, and somatization symptoms from Brief Symptom Inventory 18 were examined in survivors (n = 16,079) and siblings (n = 3085) from the Childhood Cancer Survivor Study. A latent profile analysis identified clusters of survivors with individual and comorbid symptoms. Disease, treatment, and demographic predictors of distress comorbidity patterns were examined with multinomial logistic regressions.RESULTSFour clinically relevant profiles were identified: low distress on all subscales (asymptomatic, 62%), high distress on all subscales (comorbid distress, 11%), elevated somatization (somatic symptoms, 13%), and elevated depression and anxiety (affective distress, 14%). Compared with siblings, fewer survivors were asymptomatic (62% vs 74%, P < .0001), and more had comorbid distress (11% vs 5%, P < .0001). Survivors of leukemia (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.12‐1.61), central nervous system tumors (OR, 1.30; 95% CI, 1.05‐1.61), and sarcoma (OR, 1.26; 95% CI, 1.01‐1.57) had a greater risk of comorbid distress than survivors of solid tumors. Psychoactive medications were associated with comorbid distress (P < .0001), and this suggested that this group was refractory to traditional medical management. Comorbid distress was associated with poor perceived health (OR, 31.7; 95% CI, 23.1‐43.3), headaches (OR, 3.2; 95% CI, 2.8‐3.7), and bodily pain (OR, 4.0; 95% CI, 3.2‐5.0).CONCLUSIONSA significant proportion of survivors are at risk for comorbid distress, which may require extensive treatment approaches beyond those used for individual symptoms. Cancer 2016;122:3215–24. © 2016 American Cancer Society.
Downstream consequences of melanoma screening in a community practice setting: First results
Authors: Weinstock Martin A. , Ferris Laura K. , Saul Melissa I. , Geller Alan C. , Risica Patricia M. , Siegel Julia A. , Solano Francis X. , Kirkwood John M. 
Published: July 2016

BACKGROUNDPopulation‐based screening for the early detection of melanoma holds great promise for reducing melanoma mortality, but evidence is needed to determine whether benefits outweigh risks. Skin surgeries and dermatology visits after screening were assessed to indicate potential physical, psychological, and financial consequences.METHODSTargeted primary care providers (PCPs) at the University of Pittsburgh Medical Center were trained to detect early melanoma using the INFORMED (INternet course FOR Melanoma Early Detection) program. The authors analyzed aggregated administrative data describing 3 groups of patients aged ≥35 years who had received an annual physical examination by PCPs: group A1 included patients of PCPs from the group with the highest percentage of INFORMED‐trained providers, group A2 included patients of PCPs from the group with a lower percentage of INFORMED‐trained providers, and group B included patients of PCPs without INFORMED training.RESULTSINFORMED‐trained PCPs screened 1572 of 16,472 patients in groups A1 or A2 and none of the 56,261 patients in group B. In group A1, there was a 79% increase (95% confidence interval, 15%‐138%) in melanoma diagnoses noted; no increase was observed for the other groups, and no substantial increase in skin surgeries or dermatology visits occurred in any group.CONCLUSIONSA large‐scale melanoma screening using the INFORMED program was conducted in Pennsylvania. To the best of the authors' knowledge, the current study is the first analysis of downstream results and the findings indicate increased melanoma diagnoses but little impact on skin surgeries or dermatology visits. This result provides some reassurance that such efforts can be conducted without major adverse consequences, at least as measured by these parameters, and therefore should be considered for more widespread use. Cancer 2016;122:3152–6. © 2016 American Cancer Society.
Lack of harms from community‐based melanoma screening by primary care providers
Authors: Curiel‐Lewandrowski Clara , Swetter Susan M. 
Published: July 2016

Skin cancer screening by primary care physicians results in the increased diagnosis of melanomas without affecting the number of referrals to specialists and surgical procedures. The identification of nonmelanoma skin cancers as part of melanoma screening efforts should not be considered a deleterious effect.See also pages 3152‐6.
Site‐Specific Chemical Surface Functionalization and Electronic Patterning of Graphene by Electrooxidative Lithography
Authors: Liu He , Hoeppener Stephanie , Schubert Ulrich S. 
Published: July 2016

AbstractThe combination of different properties being manipulated on nanomaterials is one of the challenges in nanotechnology research. In particular, the possibility to tailor the electronic and chemical properties offers promising possibilities for the design of functional nanostructures. Herein, we report an approach that permits control of these properties on the basis of electrooxidative lithography to structure reduced graphene oxide functionalized with a self‐assembled monolayer of n‐octadecyltrichlorosilane. The electrochemical oxidation process first induces the formation of polar acid groups on the monolayer, which can be used to covalently bind nanoparticles and molecules and, secondly, also allows the reoxidation of the underlying reduced graphene oxide. As such, the chemical signature as well as the electronic properties of the substrate can be tailored on the micro‐ and nanometer scale. Details on the oxidation of the monolayer as well as thorough characterization of the electronic properties will be presented. Finally, the approach is used to demonstrate the fabrication of a sensitive glucose sensor device.
Extraction and Esterification of Low‐Titer Short‐Chain Volatile Fatty Acids from Anaerobic Fermentation with Ionic Liquids
Authors: Andersen Stephen J. , Berton Jan K. E. T. , Naert Pieter , Gildemyn Sylvia , Rabaey Korneel , Stevens Christian V. 
Published: July 2016

AbstractIonic liquids can both act as a solvent and mediate esterification to valorize low‐titer volatile fatty acids and generate organic solvents from renewable carbon sources including biowaste and CO2. In this study, four phosphonium ionic liquids were tested for single‐stage extraction of acetic acid from a dilute stream and esterification to ethyl acetate with added ethanol and heat. The esterification proceeded with a maximum conversion of 85.9±1.3 % after 30 min at 75 °C at a 1:1 stoichiometric ratio of reactants. Extraction and esterification can be tailored using mixed‐anion ionic liquids; this is demonstrated herein using a common trihexyl(tetradecyl)phosphonium cation and a mixed chloride and bis(trifluoromethylsulfonyl)imide anion ionic liquid. As a further proof‐of‐concept, ethyl acetate was generated from an ionic liquid‐driven esterification of an acetic acid extractant generated using CO2 as the only carbon source by microbial electrosynthesis.
Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models
Authors: Martínez‐Cerdeño Verónica 
Published: July 2016

ABSTRACTDendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size, and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Although there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated through genetic modifications and those non‐genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non‐genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number, as well as an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419–437, 2017
Pivotal effect of early‐winter temperatures and snowfall on population growth of alpineParnassius smintheusbutterflies
Authors: Roland Jens , Matter Stephen F. 
Published: July 2016

AbstractGeographic range shifts in species’ distributions, due to climate change, imply altered dynamics at both their northern and southern range limits, or at upper and lower elevational limits. There is therefore a need to identify specific weather or climate variable(s), and life stages or cohorts on which they act, and how these affect population growth. Identifying such variables permits prediction of population increase or decline under a changing climate, and shifts in a species’ geographic range. For relatively well studied groups, such as butterflies, geographic range shifts are well documented, but weather variables and mechanisms causing those shifts are not well known. The Holarctic butterfly genusParnassius(Papilionidae) inhabits northern and alpine environments subject to variable and extreme weather. As such,Parnassiusspecies are vulnerable not only to long‐term changes in average conditions but especially to short‐term extreme weather events. We use population growth estimates for the alpine butterfly,Parnassius smintheus, from 21 populations in the Rocky Mountains of Canada over a 20‐yr interval combined with techniques of machine learning (randomForests) and parametric modeling to identify the important weather variables determining population growth. We do this to determine the seasons and life stages ofP. smintheusmost affected by climate change. Extreme minimum and maximum temperatures in November, in combination with November snowfall, affect annual population growth most, more so than do mean temperatures in November, and more so than weather at any other time of year. Populations decline both in years with low extreme minimum temperatures in November and especially in years with high extreme maximum temperatures in November, indicating that overwintering eggs are particularly vulnerable to early‐winter weather. Snowfall ameliorates the negative effects of extreme temperatures, particularly for extreme warm events. Results provide insight into biological mechanisms by which overwintering eggs might be affected by early winter weather. Short‐term extreme weather in November, acting on a single pivotal life stage (egg) is a far better predictor of population change of alpineP. smintheusbutterflies than is the general index of climate, the Pacific Decadal Oscillation.
A Sensitive Sensor Based on CuTSPc and Reduced Graphene Oxide for Simultaneous Determination of the BHA and TBHQ Antioxidants in Biodiesel Samples
Authors: Sousa Carvalho Rita Maria , Yotsumoto Neto Sakae , Carvalho Silva Fernando , Santos Damos Flavio , de Cássia Silva Luz Rita 
Published: July 2016

AbstractA novel and sensitive electrochemical sensor was developed for the simultaneous determination of the butylated hydroxyanisole (BHA) and tert‐butylhydroquinone (TBHQ) antioxidants in biodiesel samples employing the differential pulse voltammetry (DPV). In this sense, a glassy carbon electrode (GCE) modified with copper (II) tetrasulfonated phthatocyanine immobilized on reduced graphene oxide (CuTSPc/rGO) allowed the detection of BHA and TBHQ at potentials lower than those observed at unmodified electrodes. The sensor was characterized by cyclic voltammetry (CV) and linear scan voltammetry (LSV). After optimization of the experimental parameters, the analytical curves for simultaneous determination of BHA and TBHQ by DPV technique demonstrated an excellent linear response from 0.1 to 500 µmol L−1 with detection limit of 0.045 µmol L−1 for TBHQ and 0.036 µmol L−1 for BHA. Finally, the proposed method was successfully applied in the simultaneous determination of BHA and TBHQ in six biodiesel samples, and the results obtained were found to be similar to those obtained using the HPLC method with agreement at 95 % confidence level.
Voltammetry at a Hanging Mercury Drop Electrode as a Tool for the Study of the Interaction of Double‐stranded DNA with Genotoxic 4‐Nitrobiphenyl
Authors: Horakova Eva , Barek Jiri , Vyskocil Vlastimil 
Published: July 2016

AbstractDifferential pulse voltammetry, cyclic voltammetry, alternating current voltammetry, and chronocoulometry at a hanging mercury drop electrode (HMDE) and DNA modified HMDE were used for the study of the interaction of 4‐nitrobiphenyl (4‐NBP) with double‐stranded DNA and for the detection of DNA damage caused by its interaction with 4‐NBP. Moreover, the interaction of DNA with intermediates of the 4‐NBP reduction and with 4‐aminobiphenyl, a metabolite of 4‐NBP, was investigated. The mechanism of the electrochemical reduction of 4‐NBP was investigated using CV, too. It was found that the reduction of 4‐NBP is controlled by both diffusion and adsorption. The rate constant of the reduction and the diffusion coefficient were calculated as well.
Potentiometric Anion Selectivity and Analytical Applications of Polymer Membrane Electrodes Based on Novel Mn(III)‐ and Mn(IV)‐Salophen Complexes
Authors: Abdel‐Haleem Fatehy M. , Badr Ibrahim H. A. , Rizk Mahmoud S. 
Published: July 2016

AbstractNew Mn(III)‐L and Mn(IV)‐L complexes were prepared from the highly lipophilic salophen ligand (L): phenol 2,2′‐[(4,5‐dimethyl‐1,2‐phenylene)bis[(E)‐nitrilomethylidyne]]bis[4,6‐bis(1,1‐dimethylethyl). The prepared complexes were fully characterized and used for the construction of thiocyanate membrane electrodes. Optimized membrane electrodes contained 33.0 mg PVC, 66.0 mg o‐nitrophenyloctylether, 50 or 5 (mole %) tetrakis(trifluoromethyl)phenyl borate and 1 mg Mn(III)‐L (sensor 2) or Mn‐(IV)‐L (sensor 12), respectively. Such electrodes exhibited linear responses toward thiocynate in a concentration range of 10−1–10−5 M and detection limits of 8.3×10−6, 8.9×10−6 M for sensor 2 and 12, respectively. Optimized membrane electrodes exhbited high selectivty toward thiocayante compared to more lipophilic anions. The observed thiocyanate selectivity of the optimized membranes was confirmed by formation constant calculations for Mn(III)‐L and Mn(IV)‐L with SCN−, β=1014.1 and 1012.5, which was measured potentiometrically using the sandwich membrane method. Furthermore, computational study using DFT calculations was performed to at DFT/B3LYP level of theory to confirm the observed selectivity data. The response times were 3 and 0.5 min for low and high concentrations. The lifetimes of the optimized electrodes were ∼4–6 weeks. The analytical utility of the optimized membrane electrodes was demonstrated by the analysis of thiocyanate level in different saliva samples.
Reaction of Pyridoxal with Hydrophosphoryl Compounds
Authors: Kibardina Lyudmila K. , Trifonov Alexey V. , Dobrynin Alexey B. , Pudovik Michael A. , Burilov Alexander R. , Sinyashin Oleg G. 
Published: July 2016

AbstractThe products of carbonyl phosphonylation of pyridoxal with dialkylphosphinous acid, alkylphosphinic acid ethyl esters, and phosphorous acid dialkyl (or diphenyl) esters have been obtained for the first time. In some cases, the products of addition are hydrolytically unstable and stabilized by forming internal betaine structures. The reaction of pyridoxal with phosphorous acid in alcohol solutions gives alkoxyfuropyridines possessing the iminium nitrogen atom. The structure and composition of the prepared compounds have been established by 31P and 1H NMR spectroscopy, mass spectrometry (MALDI‐TOF), and X‐ray analysis.
Effective Synthesis of N‐Arylformamide from α‐Halo‐N‐arylacetamides
Authors: Chiang Kun‐Heng , Lu Shi‐Han , Yen Wan‐Ping , Uramaru Naoto , Tseng Wei‐Siou , Chang Te‐Wei , Wong Fung Fuh 
Published: July 2016

AbstractA convenient synthetic method for N‐arylformamide derivatives was successfully developed by reacting α‐iodo‐N‐arylacetamides with formamide. This method was applicable to α‐iodo‐N‐arylacetamide substrates bearing electron‐donating or electron‐withdrawing groups, N‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐iodoacetamide, 2‐iodo‐N‐(pyridin‐2‐yl)acetamide, and 2‐iodo‐N‐(naphthalen‐4‐yl)acetamide to give the corresponding N‐arylformamides in moderate to excellent yields (65–94%). A plausible mechanism was proposed to account for the new transformation.
“They Didn't Teach Us Well”: Mexican‐Origin Students Speak Out About Their Readiness for College Literacy
Authors: Murillo Luz A. , Schall Janine M. 
Published: July 2016

AbstractThis study reports on Mexican‐origin university students' perceptions of their K–12 literacy experiences and preparation for college‐level reading. Participants were first‐generation college students from Spanish‐dominant homes enrolled in a reading‐intensive course at a four‐year Hispanic‐serving institution. The study was conducted as part of an initiative to assist predominantly low‐income, Latino/Hispanic students enrolled in entry‐level reading‐intensive courses, with the goal of improving postsecondary persistence. Data consisted of individual interviews and participants' language and literacy autobiographies and were analyzed from an ecology‐of‐literacy perspective. Findings included contrasts between home and school literacy forms and practices, differences between high school and college as learning environments, linguistic discrimination experienced at school, and negative ideologies associated with Spanish as a barrier to the development of strong literacy skills in English. Suggestions are offered for improving academic literacy instruction for Mexican‐origin youths.
The Relationship between the Methylated Septin‐9 DNA Blood Test and Stool Occult Blood Test for Diagnosing Colorectal Cancer in Taiwanese People
Authors: Chen Chung‐Hung , Yan Sheng‐Lei , Yang Tsung‐Hsun , Chen Shih‐Feng , Yeh Yung‐Hsiang , Ou Jing‐Jim , Lin Chien‐Hua , Lee Yueh‐Tsung , Chen Chien‐Hua 
Published: July 2016

BackgroundColorectal cancer (CRC) is a common and lethal disease in the world. There is an increasing number of cases in Taiwan and a higher rate at advanced stages. The immune fecal occult blood test (iFOBT) has been used as a screening method in Taiwan for years. A new novel diagnostic tool, the Methylated Septin‐9 (MS‐9) DNA blood test, had been reported to have high sensitivity and specificity for CRC detection. There are no available data in Taiwan, so we conducted this prospective randomized trial to investigate the relationship among the MS‐9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people.MethodsFrom July 1, 2012 to December 31, 2013, we prospectively selected 60 plasma samples from patients who were diagnosed with CRC and otherwise, the healthy group by colonoscopy in our hospital. Patients were divided into the CRC group and healthy group. CRC stages 0, I, II and stages III and IV were separately analyzed. We calculated the sensitivity and specificity of each group to determine the relationship among the MS‐9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people.ResultsThe results of the MS‐9 DNA blood test for the 60 samples were divided into three groups, and the sensitivity as well as the specificity of the MS‐9 DNA blood test to detect CRC were 47% and 89%, respectively. The results of iFOBT were also divided into three groups, and had higher sensitivity (84%) but lower specificity (55%) using iFOBT to detect CRC. Higher rates could be predicted to detect CRC if both the tests were positive.ConclusionsA combined MS‐9 DNA blood test and iFOBT may help in a higher detection rate of CRC. It could be offered to individuals who are unwilling or unable to undergo colonoscopy. Further large prospective, randomized studies are needed in the future.
Comparison of the effects of three types of aminobutyric acids on the control of Penicillium expansum infection in pear fruit
Authors: Fu Da , Sun Yu , Yu Chen , Zheng Xiaodong , Yu Ting , Lu Huangping 
Published: July 2016

AbstractBACKGROUNDAminobutyric acids were reported to have inhibitory effects on postharvest fungal diseases. The effects of α‐aminobutyric acid (AABA), β‐aminobutyric acid (BABA) and γ‐aminobutyric acid (GABA) on the control of Penicillium expansum infection in pear fruit were compared in the present study.RESULTSBABA and GABA reduced the disease incidence of P. expansum infection in pear fruit when applied at an appropriate concentration and with a suitable treatment time. The efficacy of GABA was superior to BABA, whereas AABA had no inhibition effect. Three types of aminobutyric acids almost had no direct antifungal activity against P. expansum in vitro and in vivo, although BABA and GABA inhibited spore germination of P. expansum in vivo at a concentration of 100 mg L−1 when P. expansum was inoculated 24 h after treatment. Moreover, BABA and GABA enhanced catalase activity and all three aminobutyric acids enhanced peroxidase activity in pear fruit after being challenged by P. expansum, although BABA and GABA were more forceful than AABA.CONCLUSIONThe position of the amino group in aminobutyric acids may be associated with the effects of aminobutyric acids on the control of postharvest fungal diseases. © 2016 Society of Chemical Industry