bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the factors underlying adaptive functioning in autism in the EU‐AIMS Longitudinal European Autism Project
Authors: Tillmann Julian , San José Cáceres Antonia , Chatham Chris H. , Crawley Daisy , Holt Rosemary , Oakley Bethany , Banaschewski Tobias , Baron‐Cohen Simon , Bölte Sven , Buitelaar Jan K. , Durston Sarah , Ham Lindsay , Loth Eva , Simonoff Emily , Spooren Will , Murphy Declan G. , Charman Tony ,   the EU‐AIMS LEAP group
Published: February 2019

Scientific Abstract

Individuals with autism spectrum disorder (ASD) exhibit significant impairments in adaptive functioning that impact on their ability to meet the demands of everyday life. A recurrent finding is that there is a pronounced discrepancy between level of cognitive ability and adaptive functioning, and this is particularly prominent among higher‐ability individuals. However, the key clinical and demographic associations of these discrepancies remain unclear. This study included a sample of 417 children, adolescents, and adults with ASD as part of the EU‐AIMS LEAP cohort. We examined how age, sex, IQ, levels of ASD symptom and autistic trait severity and psychiatric symptomatology are associated with adaptive functioning as measured by the Vineland Adaptive Behavior Scales‐Second Edition and IQ‐adaptive functioning discrepancies. Older age, lower IQ and higher social‐communication symptoms were associated with lower adaptive functioning. Results also demonstrate that older age, higher IQ and higher social‐communication symptoms are associated with greater IQ‐adaptive functioning discrepancy scores. By contrast, sensory ASD symptoms, repetitive and restricted behaviors, as well as symptoms of attention deficit/hyperactivity disorder (ADHD), anxiety and depression, were not associated with adaptive functioning or IQ‐adaptive functioning discrepancy scores. These findings suggest that it is the core social communication problems that define ASD that contribute to adaptive function impairments that people with ASD experience. They show for the first time that sensory symptoms, repetitive behavior and associated psychiatric symptoms do not independently contribute to adaptive function impairments. Individuals with ASD require supportive interventions across the lifespan that take account of social‐communicative ASD symptom severity. Autism Res 2019, 12: 645–657. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.

Lay summary

This study investigated key clinical and demographic associations of adaptive functioning impairments in individuals with autism. We found that older age, lower IQ and more severe social‐communicative symptoms, but not sensory or repetitive symptoms or co‐occurring psychiatric symptoms, are associated with lower adaptive functioning and greater ability‐adaptive function discrepancies. This suggests that interventions targeting adaptive skills acquisition should be flexible in their timing and intensity across developmental periods, levels of cognitive ability and take account of social‐communicative ASD symptom severity.
Diffusion tensor imaging of neurocognitive profiles in a community cohort living in marginal housing
Authors: Gicas Kristina M. , Cheng Alex , Rawtaer Iris , Willi Taylor S. , Panenka William J. , Lang Donna J. , Smith Geoff N. , Vila‐Rodriguez Fidel , Leonova Olga , Giesbrecht Chantelle J. , Jones Andrea A. , Barr Alasdair M. , Procyshyn Ric M. , Buchanan Tari , MacEwan G. William , Su Wayne , Vertinsky Alexandra T. , Rauscher Alexander , O’Rourke Norm , Loken Thornton Wendy , Thornton Allen E. , Honer William G.
Published: February 2019

Objective

We investigated white matter differences associated with distinct neurocognitive profiles derived from a large cohort of marginally housed persons with comorbid physical and mental illnesses. Our prior work identified three profile cluster groups: a high functioning group (Cluster 1), a low functioning group with relative strength in decision‐making (Cluster 3), and an intermediary group with a relative decision‐making weakness (Cluster 2). This study extends previous findings of cortical gray matter differences between these groups with evidence for putative neurodevelopmental abnormalities in the low cognitive functioning group (i.e., Cluster 3). We hypothesized that altered white matter diffusion would be associated with the lowest functioning neurocognitive profile and would be associated with previously observed gray matter differences.

Method

Participants from a socially impoverished neighborhood in Vancouver, Canada underwent neurocognitive evaluation and neuroimaging. We performed Tract‐Based Spatial Statistics using diffusion tensor imaging data from 184 participants to examine whole‐brain differences in white matter microstructure between cluster analytically derived neurocognitive profiles, as well as unitary neurocognitive measures. Correlations between frontal gray and white matter were also examined.

Results

Cluster 3 showed increased diffusion in predominately bilateral frontal and interhemisphere tracts (vs. Clusters 1 and 2), with relatively greater diffusion in the left hemisphere (vs. Cluster 1). Differences in radial diffusivity were more prominent compared with axial diffusivity. A weak association between regional frontal fractional anisotropy and previously defined abnormalities in gyrification was observed.

Conclusions

In a socially marginalized sample, we established several patterns in the covariation of white matter diffusion and neurocognitive functioning. These patterns elucidate the neurobiological substrates and vulnerabilities that are apt to underlie functional impairments inherent to this complex and heterogeneous population.
Does advertising the green benefits of products contribute to sustainable development goals? A quasi‐experimental test of the dilution effect
Authors: Grolleau Gilles , Mzoughi Naoufel , Sutan Angela
Published: February 2019

Using two studies, we examine the dilution effect for green products, by testing whether advertising green benefits decreases their perceived instrumentality and thus harms sustainable development. We use a between‐subject design and ask participants to evaluate the efficacy of a pen (Study 1) and a dish detergent (Study 2) with and without environmental attributes. Our results are inconsistent with the predictions of the dilution model because the perceived instrumentality of both products does not decrease when environmental benefits are added. Our findings are relevant for eco‐labeling given anecdotal evidence suggesting that adding green information can harm the perceived quality of products.
Customer motivations for sustainable consumption: Investigating the drivers of purchase behavior for a green‐luxury car
Authors: Ali Afzaal , Xiaoling Guo , Ali Adnan , Sherwani Mehkar , Muneeb Farhan Muhammad
Published: February 2019

The purpose of the study is to investigate the effect of status motivation on customers' purchase intention of a green‐luxury car associated with owning a green‐luxury car, and whether materialism and horizontal–vertical individualism/collectivism moderate this relationship. The quantitative research methodology using online survey technique was used to collect cross‐cultural data from respondents (507) from China and Germany. Purposive sampling technique was used to identify and collect data from current and prospective customers of the BMW brand. Collected data were analyzed using structural equation modeling (SEM). The results demonstrated that materialism and cultural value (horizontal–vertical collectivism and vertical individualism) can serve as moderators of the effects of status motivation and purchase intention of the green‐luxury car. Although some studies have explored the factors involved in customer purchasing behaviour for green‐luxury products, our results theoretically and empirically show that materialism, vertical individualism, horizontal collectivism, and vertical collectivism enhance the positive effects of status motivation on customer purchasing behaviour for a green‐luxury car.
Combined prognostic value of the cancer stem cell markers CD47 and CD133 in esophageal squamous cell carcinoma
Authors: Wang Jian‐Hua , Huang Shu‐Ting , Zhang Lan , Liu Zi‐Gang , Liang Rong‐Xin , Jiang Sen‐Wei , Jiang Yi‐Nan , Yu Xing‐Juan , Jiang Yu‐Chuan , Li Xi‐Zhao , Zhang Pei‐Fen , Wen Zhe‐Sheng , Zheng Min
Published: February 2019

Background

Treatments based on the inhibition of pivotal signals of cancer stem cells (CSCs) are on a promising track. Recent studies have shown that targeting CSCs with broader immune‐based therapeutic methods, for example, the anti‐CD47 treatment, may serve as a more potent strategy for eliminating these intractable cells. We aimed to explore the prognostic effects of CD47/CD133 and the potential therapeutic significance of CD47 in esophageal squamous cell carcinoma (ESCC).

Methods

Immunohistochemistry was employed to identify the characteristics of CD47 and CD133 in 26 pairs of tumor tissues and adjacent non‐tumor tissues and 136 ESCC tissues. Kaplan‐Meier analysis and Cox proportional hazards models were built for estimating the prognostic values of CD47 and CD133 expression and their combined stemness index. Sphere formation assays were undertaken to explore the effects of CD47 inhibition on primary human ESCC CSCs.

Results

Results conclude that CD47 and CD133 expression is increased in tumor tissues as compared to adjacent non‐tumor tissues. A positive correlation between CD47/CD133 expression and differentiation was found in 136 ESCC patients. Survival analysis indicated that patients with high CD47 or CD133 expression exhibited poor overall survival and progression‐free survival (PFS). The combination of high CD47 and CD133 expression was a reliable independent prognostic factor for both OS (HR = 1.940, 95% CI = 1.399‐2.690, P < 0.0001) and progression‐free survival (HR = 1.883, 95% CI = 1.384‐2.562, P < 0.0001). Notably, CD47+ CD133+ ESCC cells were observed to possess the characteristics of CSCs, and anti‐CD47 treatment veritably eliminated the CSCs pool.

Conclusions

The stemness index determined by the expression of CD47 and CD133 is a promising prognostic predictor, and CD47 is a potential therapeutic target for CSCs in ESCC patients.
Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma
Authors: Tan Cheng , Liu Liang , Liu Xiaoyang , Qi Ling , Wang Weiyao , Zhao Guifang , Wang Libo , Dai Yimeng
Published: February 2019

Objective

We focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study.

Methods

We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells.

Results

In this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance.

Conclusion

PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.
Docosapentaenoic acid and lung cancer risk: A Mendelian randomization study
Authors: Liu Jiaqing , Zhou Huaqiang , Zhang Yaxiong , Huang Yan , Fang Wenfeng , Yang Yunpeng , Hong Shaodong , Chen Gang , Zhao Shen , Chen Xi , Zhang Zhonghan , Shen Jiayi , Xian Wei , Zhan Jianhua , Zhao Yuanyuan , Hou Xue , Ma Yuxiang , Zhou Ting , Zhao Hongyun , Zhang Li
Published: February 2019

Background

Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method.

Methods

With a two‐sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer.

Results

Our results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01‐fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34‐3.01; P = 7.40 × 10−4). Additionally, lung cancer was not a causal factor for DPA. The results of MR‐Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy.

Conclusions

Genetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.
Synthesis and Characterization of Novel Thiazolo[3,2‐a]pyrimidine Derivatives and Evaluation of Antioxidant and Cytotoxic Activities
Authors: Khalilpour Asieh , Asghari Sakineh , Pourshab Maryam
Published: February 2019

A series of novel thiazolo[3,2‐a]pyrimidines were synthesized and characterized by FT‐IR, 1H, 13C‐NMR and mass techniques. Their antioxidant activities were investigated by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay and the results showed that all the synthesized compounds exhibit good antioxidant activity. In addition, it was found that any substituent on the aromatic ring of the products plays an important role in their antioxidant activity. In vitro cytotoxicity of compounds 4a–4j was investigated using MTT cell viability assay. Among these compounds, 6‐ethyl 2,3‐dimethyl 5‐(4‐chlorophenyl)‐7‐methyl‐2,3‐dihydro‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐2,3,6‐tricarboxylate (4e) bearing a chlorine substituent displayed the highest cytotoxic effect (IC50=6.26±0.6 μm) in comparison with doxorubicin (IC50=0.68±0.1 μm) as a standard after 72 h. Therefore, it is assumed that these compounds could be used as effective antioxidant and cytotoxic agents.
A “Quenchergenic” Chemoselective Protein Labeling Strategy
Authors: Addy Partha Sarathi , Zheng Yunan , Italia James S. , Chatterjee Abhishek
Published: February 2019

Dynamic changes in protein structure can be monitored by using a fluorescent probe and a dark quencher. This approach is contingent upon the ability to precisely introduce a fluorophore/quencher pair into two specific sites of a protein of interest. Despite recent advances, there is continued demand for new and convenient approaches to site‐selectively label proteins with such optical probes. We have recently developed a chemoselectively rapid azo‐coupling reaction (CRACR) for site‐specific protein labeling; it relies on rapid coupling between a genetically encoded 5‐hydroxytryptophan residue and various aromatic diazonium ions. Herein, it is reported that the product of this conjugation reaction, a highly chromophoric biarylazo group, is a potent fluorescence quencher. The absorption properties of this azo product can be tuned by systematically altering the structure of the aryldiazonium species. A particular “quenchergenic” aryldiazonium has been identified that, upon conjugation, efficiently quenches the fluorescence of green fluorescent protein, which is a widely used genetically encoded fluorescent probe that can be terminally attached to target proteins. This fluorophore/quencher pair was used to evaluate the protein‐labeling kinetics of CRACR, as well as to monitor the proteolysis of a fusion protein.
Small‐Molecule Inhibitors of the Proteasome's Regulatory Particle
Authors: Muli Christine S. , Tian Wenzhi , Trader Darci J.
Published: February 2019

Cells need to synthesize and degrade proteins consistently. Maintaining a balanced level of protein in the cell requires a carefully controlled system and significant energy. Degradation of unwanted or damaged proteins into smaller peptide units can be accomplished by the proteasome. The proteasome is composed of two main subunits. The first is the core particle (20S CP), and within this core particle are three types of threonine proteases. The second is the regulatory complex (19S RP), which has a myriad of activities including recognizing proteins marked for degradation and shuttling the protein into the 20S CP to be degraded. Small‐molecule inhibitors of the 20S CP have been developed and are exceptional treatments for multiple myeloma (MM). 20S CP inhibitors disrupt the protein balance, leading to cellular stress and eventually to cell death. Unfortunately, the 20S CP inhibitors currently available have dose‐limiting off‐target effects and resistance can be acquired rapidly. Herein, we discuss small molecules that have been discovered to interact with the 19S RP subunit or with a protein closely associated with 19S RP activity. These molecules still elicit their toxicity by preventing the proteasome from degrading proteins, but do so through different mechanisms of action.
Activating a Cu/ZnO : Al Catalyst – Much More than Reduction: Decomposition, Self‐Doping and Polymorphism
Authors: Frei Elias , Gaur Abhijeet , Lichtenberg Henning , Heine Christian , Friedrich Matthias , Greiner Mark , Lunkenbein Thomas , Grunwaldt Jan‐Dierk , Schlögl Robert
Published: February 2019

The activation of Cu/ZnO‐based catalysts before their application is a key step and sensitive process enabling the development of the entire catalytic potential. Here, we report on a complementary (soft and hard) in‐situ X‐ray absorption spectroscopy (XAS) study investigating in detail the changes of a Cu/ZnO : Al catalyst upon thermal treatment in reducing atmosphere (10 % H2) at ambient pressure. The spectroscopic features of Cu, Zn and Al are investigated. Beyond the reduction event of the Cu moieties, the role of high temperature carbonate and the Al‐dopant is discussed up to the consequences for the ZnO polymorphism. The stability of the observed effects and thus their catalytic relevance are validated by operando XAS under reverse water gas‐shift conditions.
Insulating Polymer‐Hydrogel Nanocomposite Thin Film ‐ Based Catalytic Electrode for Efficient Oxygen Evolution Reaction
Authors: Divya Madhuri U. , Radhakrishnan T. P.
Published: February 2019

The counter‐intuitive choice of an insulating polymer for embedding electrocatalysts is shown to facilitate a simple and general strategy to fabricate catalytic electrodes for efficient oxygen evolution reaction (OER) during water splitting. The hydrogel characteristics and appreciable swelling of the polymer in aqueous medium are the key enabling factors; electrolyte absorbed in the polymer matrix is likely to be involved in the electrocatalytic process. Nanocomposite thin films of chitosan spin‐cast on common conducting substrates, with an optimal content of NiO and [Ni,Fe]O nanoplates generated through a facile and simple in situ protocol, are shown to effect OER with excellent overpotentials (down to 240 mV at 10 mA/cm2), low Tafel slope, high Faradaic efficiency, appreciable turn‐over frequency, and extended stability with high current density. Preliminary investigations with a range of catalyst‐polymer combinations illustrate the general applicability of the approach.
Design of Luminescent, Heteroleptic, Cyclometalated PtII and PtIV Complexes: Photophysics and Effects of the Cyclometalated Ligands
Authors: Giménez Nora , Lalinde Elena , Lara Rebeca , Moreno M. Teresa
Published: February 2019

Neutral pentafluorophenyl benzoquinolinyl PtII [Pt(bzq)(HC^N−κN)(C6F5)] (1 a–g) complexes, bearing nonmetalated N‐heterocyclic HC^N ligands [HC^N=2,5‐diphenyl‐1,3,4‐oxadiazole (Hoxd) a, 2‐(2,4‐difluorophenyl)pyridine (dfppy) b, 2‐phenylbenzo[d]thiazole (pbt) c, 2‐(4‐bromophenyl)benzo[d]thiazole (Br‐pbt) d, 2‐phenylquinoline (pq) e, 2‐thienylpyridine (thpy) f, 1‐(2‐pyridyl)pyrene (pypy) g], and heteroleptic bis(cyclometalated) PtIV fac‐[Pt(bzq)(C^N)(C6F5)Cl] (2 b–g, bzq: benzo[h]quinolinyl) derivatives, generated by oxidation of 1 b–g with PhICl2, are reported. The oxidation reaction of 1 a evolved with formation of the bimetallic PtIV complex syn‐[Pt(bzq)(C6F5)Cl(μ‐OH)]2 3. The crystal structures of 1 a,d,f, 2 b,d,e and 3 were corroborated by X‐ray crystallography. A comparative study of the absorption and photoluminescence properties of the two series of complexes PtII (1) and PtIV (2), supported by time‐dependent DFT calculations (TD‐DFT), is presented. The low‐lying transitions (absorption and emission) of PtII complexes 1 a–e [solution and polystyrene (PS) films] were assigned to the IL/MLCT mixture located on the cyclometalated Pt(bzq) unit, with minor IL′/ML′CT/LL′CT contributions involving the non‐metalated ligand. Complex 1 g, bearing the more delocalized pyridyl pyrene (Hpypy) as an ancillary ligand, shows dual 1ππ* and 3ππ* (Hpypy) emission in fluid CH2Cl2 and dual 3IL/3MLCT [Pt(bzq)] and [3ππ*, Hpypy] phosphorescence at 77 K. Upon oxidation, PtIV complexes 2 b–f display (solution, PS) ligand‐based phosphorescence that arises from the bzq in 2 b (3LC) or from the second C^N ligand in 2 c–f (3L′C) with some 3LL′CT in 2 f. Despite metalation of the pyrenyl group, 2 g exhibits dual emission 1ππ*/3ππ* located on the pypy chromophore.
Synthesis of Annulated Indolines by Reductive Fischer Indolization
Authors: Dierks Anna , Schmidtmann Marc , Christoffers Jens
Published: February 2019

Cyclic β‐oxoesters and arylhydrazine derivatives were converted at ambient temperature under modified Fischer indolization conditions to furnish annulated indolines with quaternary bridgehead carbon center. Reaction conditions were Brønsted acidic (with CF3CO2H), but also reductive (with Et3SiH). The latter reduced intermediate iminium ions under formation of the 2,3‐dihydroindole product constitutions. Racemic products (13 examples) were obtained as single diastereoisomers with relative cis‐configuration, which was proved in two cases by single‐crystal X‐ray structure analysis. Conversion of 4‐bromo‐1‐indanone‐2‐carboxylate and 4‐bromophenylhydrazine gave indeno[1,2‐b]indolines with either 1‐bromo, 8‐bromo, or 1,8‐dibromo substitution, which were further diversified by Suzuki coupling reactions with several arylboronic acids (nine examples).
Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near‐Infrared Activated Phototheranostic Agents
Authors: Ortega‐Liebana M. Carmen , Encabo‐Berzosa M. Mar , Casanova Alvaro , Pereboom M. Desiree , Alda J. Octavio , Hueso Jose L. , Santamaria Jesus
Published: February 2019

This work describes the synthesis of nitrogen‐doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual‐mode theranostic role as near‐infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions (.O2−) and hydrogen peroxide (H2O2) ROS generated in situ upon NIR irradiation.
A Visibly Observable, Programmable Supramolecular Logic Platform and Its Application in Smart Thiols Sensing
Authors: Chen Jianchi , Yang Shu , Yang Chunrong , Li Jicheng , Huang Dan , Lin Xiao , Guo Chen , Zhou Qiuju , Yang Qianfan , Tang Yalin
Published: February 2019

Molecular computation is increasingly attractive as a tool for medical and biological research because of its programmability and controllability. Herein, a novel visibly observable supramolecular system that can execute multi‐level logic functions on a uniform platform was constructed. By employing some programming factors, we succeeded in not only constructing a whole set of contrary logic pairs, but also building up a logic network that can implement advanced functions. Further, the platform is applied to sense thiols in specific environments. The developed method can efficiently filter signals of thiols in intracellular conditions and measure cysteine levels quantitatively in serum conditions. The visual readout makes the method particularly suitable for point‐of‐care testing. The supramolecule‐based platform illustrates not only an incremental advance for the construction of programmable molecular logic systems, but also viable applications in intelligent thiol analysis.
Glänzend gemacht
Authors: Emden Markus , Engel Simon , Hild Pitt , Kallinna Kirsten , Murer Livia
Published: February 2019

Anliegen der in loser Folge erscheinenden Versuche ist es, Impulse für chemische Experimente zu geben, die sich gefahrlos zu Hause mit haushaltsüblichen Gegenständen durchführen lassen. Sie können damit als Quelle dienen für das gemeinsame Ausprobieren mit Kindern zuhause, in Kindergärten oder an Schulen sowie zur Verwendung bei Tagen der offenen Tür. Ein Stückweit sind sie als Antwort auf den oft gehörten Satz zu verstehen: „Ach, Du bist Chemiker/in? Dann mach doch mal ein Experiment.“
Auf den Leim gegangen
Authors: Tetsch Larissa
Published: February 2019

Stummelfüßer fangen ihre Beute mit Hilfe eines klebrigen Schleims, den sie aus zwei seitlichen Kopfdrüsen abschießen (Abbildung 1). Durch das Zappeln des Opfers entsteht aus dem ehemals flüssigen Sekret ein starres Geflecht mit der Steifigkeit von Nylon®. Dieses lässt sich in Wasser wieder in seine Einzelteile auflösen, die wiederverwertet werden können. Ein Vorbild für die industrielle Synthese von nachhaltig nutzbaren Polymeren?
Fully Automated Synthesis and Evaluation of [18F]BPAM121: Potential of an AMPA Receptor Positive Allosteric Modulator as PET Radiotracer
Authors: Manos‐Turvey Alexandra , Becker Guillaume , Francotte Pierre , Serrano Maria Elisa , Luxen André , Pirotte Bernard , Plenevaux Alain , Lemaire Christian
Published: February 2019

Alzheimer's disease (AD) remains a significant burden on society. In the search for new AD drugs, modulators of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) are of particular interest, as loss of synaptic AMPARs has been linked to AD learning and memory deficits. Previously reported fluorine‐containing BPAM121, an AMPA positive allosteric modulator (pam) with high activity, low toxicity, and slow metabolism, was considered to be a perfect 18F‐labeled candidate for positron emission tomography (PET) AD diagnostic investigations. For the preclinical use of this compound, an automated synthesis avoiding human radiation exposure was developed. The detailed production of [18F]BPAM121 in relatively high quantity using a commercial FASTlab synthesizer from GE Healthcare coupled with a full set of quality controls is presented, along with procedures for the synthesis of the tosylated precursor and the fluorinated reference. To evaluate the clinical usefulness of [18F]BPAM121 as a potential AD diagnostic, some in vivo studies in mice were then realized, alongside blocking and competition studies.
Paraneoplastic syndrome in neuroendocrine breast cancer: A case report
Authors: Levenbaum Erica , Ruffolo Luis I. , Balceniuk Mark D. , Peacock James , Prieto Peter A.
Published: February 2019

Background

Paraneoplastic syndromes are rare manifestations of underlying malignancies, most commonly small cell lung cancer and invasive ductal carcinoma of the breast.

Case

We present a case of anti‐AMPA receptor paraneoplastic limbic encephalitis, a specific paraneoplastic syndrome, in a woman with neuroendocrine breast cancer. Her condition improved with surgical resection and chemotherapy.

Conclusion

This is the first known case of anti‐AMPA receptor paraneoplastic limbic encephalitis in a patient with primary neuroendocrine breast cancer.
Combinatorial BRD4 and AURKA inhibition is synergistic against preclinical models of Ewing sarcoma
Authors: Tomino Laura , Bopp Emily , Felgenhauer Joshua , Selich‐Anderson Julia , Shah Nilay
Published: February 2019

Background

Ewing sarcoma (ES), a bone cancer affecting children, adolescents, and young adults, is driven by the EWS‐FLI1 fusion protein in the majority of cases, but the mechanisms of tumorigenesis are still being elucidated. Consequentially, therapeutic advances have been limited in the last 25 years. Two therapeutic targets have been recently examined. Aurora kinase A (AURKA) promotes cell cycling and posttranslational stabilization of the oncoprotein MYC, while bromodomain‐containing protein 4 (BRD4) promotes gene expression epigenetically. Studies of AURKA and BRD4 inhibitors showed some impairment of tumorigenesis in ES preclinical models, but this efficacy was limited in single‐agent use. AURKA and BRD4 activate common oncogenic pathways through different mechanisms, so we hypothesized dual inhibition would be synergistic against tumorigenesis.

Aims

(a) Define the synergistic antineoplastic effects of BRD4 inhibitor I‐BET151 and AURKA inhibitor alisertib against ES cell lines in vitro. (b) Confirm the mechanism of activity of each agent in these cell line models. (c) Define the efficacy of I‐BET 151 and alisertib alone and in combinations with each other, and with the chemotherapeutic drug vincristine against ES tumor xenografts in vivo.

Methods and results

I‐BET151 and alisertib synergistically inhibit viability in ES cell lines SK‐ES, TC71, and ES2 in vitro. Alisertib alone upregulates transcriptional expression of its targets, but combined use of I‐BET151 mitigates that upregulation, likely contributing to the drug synergy and downregulating RNA and protein expression of key oncogenic pathways as shown by RT‐qPCR and western blot. Alisertib and I‐BET151 significantly prolong survival in three ES xenograft models in vivo, and this efficacy is augmented by the addition of vincristine.

Conclusion

Dual targeting of oncogenic drivers in ES epigenetically and posttranslationally, specifically by use of BRD4 and AURKA inhibitors, may have significant clinical efficacy in ES alone and/or in combination with current chemotherapy regimens.
High‐Throughput Yeast One‐Hybrid Screens Using a Cell Surface gLUC Reporter
Authors: Li Zheng , Bonaldi Katia , Kang S. Earl , Pruneda‐Paz Jose L.
Published: February 2019

Gene‐centered yeast one‐hybrid (Y1H) screens using arrayed genome‐wide transcription factor (TF) clone collections provide a simple and effective strategy to identify TF‐promoter interactions using a DNA fragment as bait. In an effort to improve the assay we recently developed a Y1H system that uses a cell surface Gaussia luciferase reporter (gLUC59). Compared to other available methods, this luciferase‐based strategy requires a shorter processing time, enhances the throughput and improves result analysis of gene‐centered Y1H screens. Here, we described the procedure to perform high‐throughput screens using this novel strategy, which involves a protocol for mating two haploid yeast strains carrying an arrayed TF clone collection and a promoter::gLUC59 reporter, respectively, and a protocol for analyzing gLUC59 activity in the resulting diploid cells. © 2019 by John Wiley & Sons, Inc.
Orthodontic screening and treatment timing in preschoolers
Authors: Grippaudo Cristina , Paolantonio Ester Giulia , Luzzi Valeria , Manai Alice , La Torre Giuseppe , Polimeni Antonella
Published: February 2019

Dental and stomatologic problems in childhood need to be diagnosed and managed with multidisciplinary protocols focusing around the children an appropriate prevention, diagnosis, and care program. Therefore, it is paramount to avail of screening tools that provide an indication of in‐depth multidisciplinary diagnostic flow. The aim of this study is to detect and evaluate malocclusion problems and predisposing factors in an Italian preschooler population. Design‐calibrated operators detected data through examination of 1,405 children (706 males and 699 females) aged between 2 and 7 years, in one hospital in Rome and in kindergartens of several Italian cities. Data were collected following Risk of Malocclusion Assessment index criteria. Pearson's chi‐square test (with continuity correction) and Fisher's exact test were the statistical tests conducted (P < 0.05). Grade 2 (49.6%) and 4 (21.7%), followed by grade 1 (17.1%), grade 3 (9.3%), and finally grade 5 (2.3%) are the most represented degrees. 53.6% of the cases have a high risk, whereas 32.2% has a low risk and 14.9% has a moderate risk. The risk‐degree correlation is statistically significant (P < 0.005). Flawed habits and oral breathing are present in more than a quarter of children. Findings of the study highlighted that early multidisciplinary approach, as well as orthodontic visits and screening in childhood, is necessary to promote normal growth and development of the face and the elimination of potential interferences that may harm these processes.
Manganese‐Catalyzed Selective Upgrading of Ethanol with Methanol into Isobutanol
Authors: Liu Yaqian , Shao Zhihui , Wang Yujie , Xu Lijin , Yu Zhiyong , Liu Qiang
Published: February 2019

Isobutanol serves as an ideal gasoline additive owing to its good compatibility with current engine technology, high energy density, and high octane number. Herein, an efficient and selective Mn‐catalyzed upgrading of ethanol with methanol into isobutanol is reported. This is the first example of deoxygenative coupling of lower alcohols to isobutanol by using a homogeneous non‐noble‐metal catalyst. This transformation proceeded at very low catalyst loading with a high turnover number (9233) and up to 96 % isobutanol selectivity.
Electrochemical Reduction of CO2 by SnOx Nanosheets Anchored on Multiwalled Carbon Nanotubes with Tunable Functional Groups
Authors: Zhang Qi , Zhang Yanxing , Mao Jianfeng , Liu Junyu , Zhou Yue , Guay Daniel , Qiao Jinli
Published: February 2019

Sn‐based electrocatalysts are promising for the electrochemical CO2 reduction reaction (CO2RR), but suffer from poor activity and selectivity. A hierarchical structure composed of ultrathin SnOx nanosheets anchored on the surface of the commercial multiwalled carbon nanotubes (MWCNTs) is synthesized by a simple hydrothermal process. The electrocatalytic performance can be further tuned by functionalization of the MWCNTs with COOH, NH2, and OH groups. Both SnOx@MWCNTs−COOH and SnOx@MWCNTs−NH2 show excellent catalytic activity for CO2RR with nearly 100 % selectivity for C1 products (formate and CO). SnOx@MWCNTs−COOH has favorable formate selectivity with a remarkably high faradaic efficiency (FE) of 77 % at −1.25 V versus standard hydrogen electrode (SHE) and a low overpotential of 246 mV. However, SnOx@MWCNTs−NH2 manifests increased selectivity for CO with higher current density. Density functional theory calculations and experimental studies demonstrate that the interaction between Sn species and functional groups play an important role in the tuning of the catalytic activity and selectivity of these functionalized electrocatalysts. SnOx@MWCNTs−COOH and SnOx@MWCNTs−NH2 both effectively inhibit the hydrogen evolution reaction and prove stable without any significant degradation over 20 h of continuous electrolysis at −1.25 V versus SHE.
A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population
Authors: Lee Silvia , Brook Emily , Affandi Jacquita , Howson Prue , Tanudjaja Selita Agnes , Dhaliwal Satvinder , Irish Ashley , Price Patricia
Published: February 2019

Objectives

Meta‐analyses have now confirmed that persistent infections with cytomegalovirus (CMV) can accelerate the onset of diseases of ageing, notably cardiovascular pathologies. We address the circumstances in which the association may be strong enough to warrant intervention to reduce the viral burden.

Results

We compare markers of the burden of CMV with established indices of vascular pathology in healthy adults (n = 82) and in renal transplant recipients (RTR; n = 81). Levels of all inflammatory and vascular biomarkers and CMV antibodies were higher in RTR, and flow‐mediated dilation (FMD) values were lower indicating inferior endothelial function. In multivariable regression models without adjustment for estimated glomerular filtration rate (eGFR), CMV antibody levels, age and gender were independently associated with FMD in RTR, whilst only CRP associated with FMD in healthy adults. After adjustment for eGFR, associations between CMV antibody and FMD in RTR were reduced.

Methods

Carotid intima‐media thickness, FMD, eGFR and plasma levels of CMV antibodies (reactive with a lysate, CMV IE‐1 or CMV gB), ICAM‐1, VCAM‐1, P‐selectin, sIFNαR2, sTNFR1, sCD14 and CRP were determined.

Conclusion

Levels of CMV antibody predict declining endothelial health in RTR and not in healthy adults, presumably by reflecting a high burden of CMV. The levels of CMV antibodies were a poor reflection of plasma biomarkers thought to reflect ‘inflammaging’ or vascular damage.
Rate limitable and efficient discovery of path maximum transmission units
Authors: Subbaraman Ramesh R.
Published: February 2019

Path maximum transmission unit discovery (PMTUD) is the protocol by which a host can find the largest packet it can send through an internet protocol (IP) network to a given destination. It relies on intermediary nodes sending “packet too big” (PTB) messages in IPv6 or “datagram too big” messages in IPv4 (both henceforth referred to as PTB for the purposes of this paper). These are often completely blocked by firewalls, presumably due to a fear of PTB floods wasting the bandwidth of network links. This breaks PMTUD, forcing the use of fragmentation in IPv4 and/or suboptimal packet sizes. In IPv6, fragmentation by intermediary nodes is no longer an option. Utilizing a dynamic programming‐based solution to the generalization of a mathematical puzzle, the two‐egg problem, this work presents a family of strategies for a host to discover path MTU while obeying hard limits on the maximum number of incoming PTB messages that may be generated. This allows a firewall to mitigate PTB floods via rate limits. Moreover, these strategies are compliant with the relevant standards on PMTUD and thus can be deployed by merely changing the PMTUD algorithm implementation in TCP/IP stacks on end hosts without changing intermediary nodes' protocol behavior.
Genotyping and cytomorphological subtyping of lung adenocarcinoma based on liquid‐based cytology
Authors: Tanaka Ryota , Sakamoto Norihiko , Suzuki Hitomi , Tachibana Keisei , Ohtsuka Kouki , Kishimoto Koji , Fujiwara Masachika , Kamma Hiroshi , Shibahara Junji , Kondo Haruhiko
Published: February 2019

Background

Liquid‐based cytology (LBC) samples allow immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular testing of nucleic acids to be performed in the remaining fixed cells. The current study aimed to examine the relationship between gene mutational status and cytomorphological features in primary lung adenocarcinoma (ADC) using LBC materials.

Methods

Forty consecutive patients with primary lung ADC underwent surgical resection in our hospital. Cytological material was obtained by scraping the cut‐surface of the lesion, and samples were fixed and stored as LBC materials using CytoRich Red. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma kinase (ALK), and c‐ros oncogene 1 (ROS1) gene rearrangements were detected, and cytomorphological studies were performed.

Results

Twenty cases (50%) were positive for EGFR mutation and four (10%) were positive for KRAS mutation. ALK gene rearrangement was identified in one case (2.5%) by IHC and FISH, and ROS1 gene rearrangement was identified in one case (2.5%) by IHC and real‐time polymerase chain reaction. The KRAS‐positive group included higher proportions of cases with an inflammatory background (100%), predominantly papillary architecture (75%), and papillary‐type ADC pattern (75%) compared with the EGFR‐positive group and the other group, which included ALK and ROS1 gene rearrangements.

Conclusions

LBC material is suitable for use in molecular testing. Differences in major gene aberrations detected by this method might predict specific cytomorphological features.
Metabolic effects and safety of Roux‐en‐Y gastric bypass surgery vs. conventional medication in obese Chinese patients with type 2 diabetes
Authors: Feng Wenhuan , Yin Tingting , Chu Xuehui , Shan Xiaodong , Jiang Can , Wang Yan , Qian Yufen , Zhu Dalong , Sun Xitai , Bi Yan
Published: February 2019

Aim

To assess metabolic effects and safety of Roux‐en‐Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM).

Methods

This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low‐density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed.

Results

After 1‐year follow‐up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high‐density cholesterol (P < 0.001‐ < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non‐alcoholic fatty liver disease (NAFLD) than the CM group during follow‐up. More patients had nutrient deficiency–related diseases in the RYGB group over 1‐year follow‐up.

Conclusions

For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency.
Patients' experiences of brief cognitive behavioral therapy for eating disorders: A qualitative investigation
Authors: Hoskins Jessica I. , Blood Lauren , Stokes Holly R. , Tatham Madeleine , Waller Glenn , Turner Hannah
Published: February 2019

Objective

Although it is important to analyze the effectiveness of new therapies, it is also necessary to consider how patients experience them. This is particularly important if we are to maximize treatment acceptability and reduce attrition. This study examined patient experiences of a new 10‐session cognitive‐behavioral therapy (CBT‐T), using a qualitative approach.

Method

The sample was 17 patients with a diagnosis of bulimia nervosa who had received CBT‐T (including treatment completers and non‐completers) within the previous 2 years. Sample size was determined by saturation of the emergent themes. Responses were analyzed using a six‐step thematic analysis process.

Results

Rated acceptability and effectiveness of CBT‐T were high. Five themes emerged, with subthemes. The key elements of patient experience of the therapy were: the therapeutic relationship; the nature of the therapy; its challenging but beneficial aspects; ending therapy; and the overall experience of CBT‐T (including comparison with other therapies).

Discussion

The findings build on the effectiveness research for CBT‐T, suggesting that it is an acceptable therapy that addresses many of the same themes that matter to patients as other therapies. The findings show that patients were positive about CBT‐T relative to other therapies, and offer suggestions as to how CBT‐T might be delivered to emphasize the importance of the time‐limited nature of the therapy.
Experimental test of birdcall detection by autonomous recorder units and by human observers using broadcast
Authors: Castro Isabel , De Rosa Alberto , Priyadarshani Nirosha , Bradbury Leanne , Marsland Stephen
Published: February 2019

Autonomous recording units are now routinely used to monitor birdsong, starting to supplement and potentially replace human listening methods. However, to date there has been very little systematic comparison of human and machine detection ability.

We present an experiment based on broadcast calls of nocturnal New Zealand birds in an area of natural forest. The soundscape was monitored by both novice and experienced humans performing a call count, and autonomous recording units.

We match records of when calls were broadcast with detections by both humans and machines, and construct a hierarchical generalized linear model of the binary variable of correct detection or not, with a set of covariates about the call (distance, sound direction, relative altitude, and line of sight) and about the listener (age, experience, and gender).

The results show that machines and humans have similar listening ability. Humans are more homogeneous in their recording of sounds, and this was not affected by their individual experience or characteristics. Humans were affected by trial and location, in particular one of the stations located in a small but deep valley. Despite recorders being affected significantly more than people by distance, altitude, and line of sight, their overall detection probability was higher. The specific location of recorders seems to be the most important factor determining what they record, and we suggest that for best results more than one recorder (or at least, microphone) is needed at each station to ensure all bird sounds of interest are captured.
Proposing autotuning image enhancement method using stochastic resonance
Authors: Kojima Noriko , Lamsal Bikash , Matsumoto Naofumi , Yamashiro Mitsuo
Published: February 2019

This paper is associated with an autotuning stochastic resonance (SR) approach for image enhancement on illumination variant images. This new process is being developed based on our previous works related to image enhancement by using SR through the manual tuning process. The process was performed by adding the random noise and threshold 0 in an image. The process works properly in the dark and very low contrast images as well as bright images based and mixed illumination variant images. This system works on the images with the mixture of darkness and brightness. We also present the idea of autotuning of the iteration with random noise and threshold value 0 by using the process related to the histogram calculation or mean and median. We performed various experiments on various types of images including human faces under different conditions and confirmed the effectiveness of our image enhancement technique.