bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic Glass–Gated 2D Material–Based Phototransistor: MoSe2 over LaF3 as Case Study
Authors: Noumbé Ulrich Nguétchuissi , Gréboval Charlie , Livache Clément , Brule Thibault , Doudin Bernard , Ouerghi Abdelkarim , Lhuillier Emmanuel , Dayen Jean‐Francois
Published: June 2019

Modulating the carrier density of 2D materials is pivotal to tailor their electrical properties, with novel physical phenomena expected to occur at a higher doping level. Here, the use of ionic glass as a high capacitance gate is explored to develop a 2D material–based phototransistor operated with a higher carrier concentration up to 5 × 1013 cm−2, using MoSe2 over LaF3 as an archetypal system. Ion glass gating reveals to be a powerful technique combining the high carrier density of electrolyte gating methods while enabling direct optical addressability impeded with usual electrolyte technology. The phototransistor demonstrates ION/IOFF ratio exceeding five decades and photoresponse times down to 200 µs, up to two decades faster than MoSe2 phototransistors reported so far. Careful phototransport analysis reveals that ionic glass gating of 2D materials allows tuning the nature of the carrier recombination processes, while annihilating the traps' contribution in the electron injection regime. This remarkable property results in a photoresponse that can be modulated electrostatically by more than two orders of magnitude, while at the same time increasing the gain bandwidth product. This study demonstrates the potential of ionic glass gating to explore novel photoconduction processes and alternative architectures of devices.
Brønsted Acid‐Catalyzed Asymmetric Ring‐Closing Alkylation of Inert N‐substituted Pyrroles with α, β‐Unsaturated Ketones
Authors: Wei Zhao , Zhang Jinlong , Yang Huameng , Jiang Gaoxi
Published: June 2019

A Chiral Brønsted acid catalyzed asymmetric intramolecular ring‐closing alkylation of inert pyrroles with α, β‐unsaturated ketones has been developed. This approach gave a wide range of 4‐phenyl‐4,5‐dihydro‐6H‐benzo[f]pyrrolo[1,2‐a]azepin‐6‐ones in high yields with good enantioselectivities under mild reaction conditions.

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Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
Authors: Yu Meng , Duan Xiaohui , Cai Yujun , Zhang Fang , Jiang Shuqi , Han Shisong , Shen Jun , Shuai Xintao
Published: June 2019

Hypoxia leads to up‐regulation of PD‐L1 and decreases T lymphocyte infiltration, thus boosting immunotherapeutic resistance of tumors. Moreover, tumor‐infiltrating myeloid cells such as myeloid‐derived suppressor cells (MDSCs) correlate with potent immune suppressive activity and resistance to the immune checkpoint blocking (ICB) in tumor sites. Here, a multifunctional nanoregulator incorporating MnO2 particles and small molecular IPI549 is developed, which can reshape the tumor immune microenvironment (TIME) to unleash the immune system. The intravenously administered nanoregulator effectively accumulates in tumor sites to alleviate hypoxia via oxygen‐generating reduction of MnO2 and to inhibit PI3Kγ on MDSCs via IPI549 release in the tumor microenvironment (TME), which results in concurrent downregulation of PD‐L1 expression, polarization of tumor associated macrophages (TAMs) toward pro‐inflammatory M1‐like phenotype (tumor‐suppressive), enhanced infiltration of CD4+ helper T lymphocytes (Th cells), and cytotoxic CD8+ T lymphocytes (Tc cells), and suppressed infiltration of regulatory T lymphocytes (Treg cells) for effective tumor immunotherapy. Furthermore, the local generation of Mn2+ in TME allows tumor‐specific magnetic resonance imaging (MRI). More excitingly, the nanoregulator‐reshaped TIME is effectively reserved due to the synergistic effect of hypoxia alleviation and MDSC PI3Kγ inhibition, leading to remarkable post‐medication inhibition of tumor re‐growth and metastasis in an animal study.
Climbing the ladder of decline: Income and acculturation associated with chronic inflammation among Mexican immigrants
Authors: Ablow Measelle Eli , McClure Heather H. , Snodgrass J. Josh , Martinez Charles R. , Jiménez Roberto , Isiordia Laura
Published: June 2019

Objectives

Financial hardship and immigrant status are often associated with poorer health as immigrant groups acculturate to life in the US. Known as the Latino health paradox, studies have shown that Latino/a immigrants in particular often experience declines in health the more they embrace ways of life considered “dominant” by US society. At present, critical biological pathways linking socioeconomic and acculturative processes remain to be better explained. The present study investigates associations among financial strain, acculturation, and chronic inflammation.

Methods

In our study of 129 Mexican‐born immigrants living in the US, we used Pearson's correlations and multiple regression analyses to investigate links among income‐to‐poverty ratio (an indicator of financial strain), English language engagement (acculturation), and C‐reactive protein (CRP), a measure of systemic inflammation.

Results

Results showed that for men, but not women, acculturation as defined by English language engagement moderated the association between an income‐to‐poverty ratio and CRP levels.

Conclusions

Consistent with the Latino health paradox, more acculturated men with relatively higher income levels (compared with the study sample) had significantly higher levels of CRP.
Cytogenetic profile of patients with clinical spectrum of ambiguous genitalia, amenorrhea, and Turner phenotype: A 21‐year single‐center experience
Authors: Elkarhat Zouhair , Belkady Boutaina , Charoute Hicham , Zarouf Latifa , Razoki Lunda , Aboulfaraj Jamila , Nassereddine Sanaa , Elbakay Chadli , Nasser Boubker , Barakat Abdelhamid , Rouba Hassan
Published: June 2019

The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them with those reported elsewhere. The study was conducted in the Cytogenetic Department of Pasteur Institute of Morocco, and it reports on the patients who were recruited between 1996 and 2016. Cytogenetic analysis was performed according to the standard method. Among 1,415 patients, chromosomal abnormalities were identified in 7.13% (48/673) of patients with AG, 17.39% (28/161) of patients with primary amenorrhea (PA), 4% (1/25) of patients with secondary amenorrhea, and 23.20% (129/556) of patients with Turner phenotype. However, Turner syndrome was diagnosed in 0.89% (6/673) of patients with AG, 10.56% (17/161) of patients with PA, and 19.78% (110/556) of patients with Turner phenotype. In addition, Klinefelter syndrome and mixed gonadal dysgenesis were confirmed in 2.97% and 1.93% of patients, respectively, with AG, while, chimerism, trisomy 8, and trisomy 13 were confirmed only in 0.15% each. Trisomy 21 was confirmed in patients with AG and Turner phenotype (0.15% and 0.36%, respectively). Moreover, 5.60% (9/161) of patients with PA have been diagnosed as having sex reversal. Thus, the frequency of chromosomal abnormalities observed in Moroccan patients with PA is comparable to that reported in Tunisia, Turkey, Iran, and Hong Kong. However, the frequency is significantly less than that identified in India, Malaysia, Italy, and Romania.
Expanding the phenotypic spectrum associated with DPF2: A new case report
Authors: Knapp Karen M , Poke Gemma , Jenkins Danielle , Truter Werner , Bicknell Louise S.
Published: June 2019

Coffin–Siris syndrome (CSS) is a clinically and genetically heterogeneous developmental disorder, linked to disruption of the BAF chromatin‐remodeling complex. Recently, de novo missense and truncating variants have been reported in DPF2 in patients sharing some of the common features of CSS. Here we report a further individual harboring a novel de novo missense DPF2 variant, c.1066T>G, p.Cys356Gly. Structural modeling indicated that the predicted amino acid substitution affects a core residue required for zinc ion coordination and would likely alter the PHD2 domain structure of DPF2. The clinical presentation of Pierre Robin sequence and diaphragmatic hernia did not immediately suggest CSS, with the more common CSS features of hypoplastic toenails and characteristic facial features very subtle. This individual further broadens the phenotypic features of DPF2‐related CSS, as well as CSS more generally.
Expanding the phenotype of intellectual disability caused by HIVEP2 variants
Authors: Goldsmith Heidi , Wells Anna , Sá Maria J. N. , Williams Mark , Heussler Helen , Buckman Melissa , Pfundt Rolph , de Vries Bert B. A. , Goel Himanshu
Published: June 2019

De novo pathogenic variants in the human immunodeficiency virus enhancer type I binding protein 2 (HIVEP2) gene, a large transcription factor predominantly expressed in the brain have previously been associated with intellectual disability (ID) and dysmorphic features in nine patients. We describe the phenotype and genotype of two additional patients with novel de novo pathogenic HIVEP2 variants, who have previously unreported features, including hyperphagia and Angelman‐like features. Exome sequencing was utilized in the investigation of the patients who had previously incurred a rigorous genetic workup for their neurodevelopmental delay, and in whom no genetic cause had been detected. Information pertaining to phenotype and genotype for new patients was collated along with data from previous reports, showing that the phenotypic spectrum of patients with HIVEP2 variants is broader than first noted. Additional characteristics are: an increased body mass index; and features of Angelman‐like syndromes including: ID, limited speech, post‐natal microcephaly, and hypotonia. Dysmorphic features vary between patients. As yet, no clear association between the type of gene aberration and phenotype can be concluded. HIVEP2‐related ID needs to be considered in the differential diagnosis of patients with Angelman‐like phenotypes and hyperphagia, and whole‐exome sequencing should be considered in the genetic diagnostic armamentarium for patients with ID of inconclusive etiology.
Intellectual and developmental disabilities research centers: Fifty years of scientific accomplishments
Authors: Walkley Steven U. , Abbeduto Leonard , Batshaw Mark L. , Bhattacharyya Anita , Bookheimer Susan Y. , Christian Bradley T. , Constantino John N. , de Vellis Jean , Doherty Daniel A. , Nelson David L. , Piven Joseph , Poduri Annapurna , Pomeroy Scott L. , Samaco Rodney C. , Zoghbi Huda Y. , Guralnick Michael J. ,   for the Intellectual and Developmental Disabilities Research Centers Directors Committee
Published: June 2019

Progress in addressing the origins of intellectual and developmental disabilities accelerated with the establishment 50 years ago of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and associated Intellectual and Developmental Disabilities Research Centers. Investigators at these Centers have made seminal contributions to understanding human brain and behavioral development and defining mechanisms and treatments of disorders of the developing brain. ANN NEUROL 2019;86:332–343
The Role of Oil Phase in the Stability and Physicochemical Properties of Oil‐in‐Water Emulsions in the Presence of Gum Tragacanth
Authors: Abdolmaleki Khadije , Mohammadifar Mohammad Amin , Sheikhi Zhian , Matinfar Golshan , Nayebzadeh Kooshan
Published: June 2019

Different emulsions based on six types of vegetable oils (sunflower, canola, sesame, olive, coconut, and palm olein) were studied to investigate the role of the oil phase in the stability and physicochemical characteristics of oil‐in‐water emulsions prepared with gum tragacanth. The results indicated that the stability, rheological parameters, and size distribution of emulsions were dependent on the oil type. Based on the interfacial tension value, the type of oil did not have a significant effect on the gum tragacanth‐emulsifying properties. The formulation based on sunflower and coconut oil led to producing more stable emulsion and a sample containing palm olein resulted in an unstable emulsion. Rheological analysis revealed that the sample based on palm olein showed the lowest consistency coefficient (2.10 ± 0.05 Pas
n), elastic modulus (3.90 ± 0.21 Pa), and energy of cohesion (80.87 ± 1.1 J m−3). This study revealed that using oils with lower viscosity and higher density led to the higher stability of the emulsion samples.
Synthesis of homo/3‐ and 4‐armed hydrophilic glycopolymers: To promote aniline to polyaniline‐glycopolymers for fluorescence, electro active material, and electrostatic discharge applications
Authors: Karri Sangam Naidu , Rao Nakka Naga Malleswara , Sesha Sainath Annadanam V. , Palaniappan Srinivasan
Published: June 2019

Preparation of electrically conducting polymer film with homogeneity is very important work for electrical and electronic applications. In order to make homogenous conductive polyaniline film, we selected water soluble glycopolymer (GP), as dopant for polyaniline. Pendant carbohydrates water soluble glycopolymer architectures, such as, homo, 3 and 4 multi‐armed polymers were prepared from methacryl‐2,3,4,6‐tetra‐O‐acetyl‐D‐glucopyranoside (MTAGP) monomer and EBrIB and 3‐ and 4‐aremed initiators via ATRP polymerization followed by deacetylation process. This water soluble glycopolymer was used as dopant for polyaniline salt via the chemical oxidative emulsion polymerization of aniline using glycopolymer and surfactant by ammonium persulfate oxidant. Sulfate and dodecylhydrogen sulfate (DHS) groups are doped on polyaniline system via protonating H+, whereas, glycopolymer involves on polyaniline through hydrogen bonding (PANI‐DHS‐SA‐GP). Coated film of PANI‐DHS‐SA‐GP salt showed resistance in ESD range. PANI‐DHS‐SA‐GP showed fluorescence and Hydrophilicity. Electrochemical performance of PANI‐DHS‐SA‐GP as electrode material in supercapacitor cell was found from charge–discharge measurement. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48043.
The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double‐Blind, Placebo‐Controlled, Randomized Clinical Trial
Authors: Dakin Paula , DiMartino Stephen J. , Gao Haitao , Maloney Jennifer , Kivitz Alan J. , Schnitzer Thomas J. , Stahl Neil , Yancopoulos George D. , Geba Gregory P.
Published: June 2019

Objective

To prospectively assess the efficacy, general safety, and joint safety of fasinumab, an anti–nerve growth factor monoclonal antibody, in osteoarthritis (OA) hip and/or knee pain.

Methods

Patients with moderate‐to‐severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to receive fasinumab (at 1 mg, 3 mg, 6 mg, or 9 mg) or placebo every 4 weeks over 16 weeks and were followed up to week 36. Efficacy end points were the change from baseline to week 16 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and patient global assessment (PGA) of OA. Joints were monitored at scheduled assessments (by plain film radiography and magnetic resonance imaging) during treatment and follow‐up, and if prompted, at the time of active joint symptoms.

Results

Of the 421 patients randomized, 342 completed the 36‐week study. All doses of fasinumab yielded statistically significant and clinically important reductions in pain compared to placebo (least squares mean difference in WOMAC pain subscale scores at week 16 ranging −0.78 to −1.40), without any clear dose dependence. Physical function and PGA scores improved in parallel. Treatment‐emergent adverse event rates were 17% with fasinumab and 10% with placebo, and 4% and 1% of patients, respectively, discontinued treatment. Arthropathies (25 in total, 7% of fasinumab‐treated patients and 1% of placebo‐treated patients) occurred in a dose‐dependent manner, with 2 occurring in patients receiving the lowest dose of fasinumab and 10 in patients receiving the highest dose. Most of the arthropathies (16 of 25) were discovered with scheduled radiographs and not based on symptoms. Destructive arthropathy (in 1 of 337 treated patients) occurred in 1 patient who was receiving 6 mg fasimumab.

Conclusion

Fasinumab provided improvements in OA pain and function, even in those benefitting little from previous analgesics. The observed benefit‐to‐risk relationship favors further clinical development to explore the lowest doses of fasinumab in patients with knee or hip OA.
Control‐oriented modeling and robust nonlinear triple‐step controller design for an air‐feed system for polymer electrolyte membrane fuel cells
Authors: Hu Yunfeng , Chen Huan , Gong Xun , Yu Shuyou , Gao Jinwu , Chen Hong
Published: June 2019

The efficient operation of polymer electrolyte membrane fuel cells (PEMFCs) significantly relies on the reliable control of air‐feed system. The core control objective in air‐feed system is to track a pre‐defined reference of the oxygen excess ratio to avoid oxygen starvation and stack damage. In this paper, we focus on the modeling of the air‐feed system in a PEMFC and the robust nonlinear controller design for the oxygen excess ratio tracking control. To facilitate the subsequent nonlinear controller design, a specific affine‐like, second‐order, control‐oriented model of oxygen excess ratio dynamic behavior is developed, and the modeling uncertainty is estimated and compensated by using an extended state observer (ESO). The control‐oriented model is verified via a high‐fidelity plant model. A nonlinear controller for oxygen excess ratio tracking control is proposed based on the triple‐step technique which is robust against the system disturbances. The tuning rule of the controller parameters is discussed in the scheme of the linear system. Finally, simulations are conducted to demonstrate the effectiveness and advantages of the proposed controller under variant operating conditions compared with baseline controllers.
Using self‐report to explore the relationship between anxiety and quality of life in children on the autism spectrum
Authors: Adams Dawn , Clark Megan , Keen Deb
Published: June 2019

Anxiety is now recognized as one of the most common conditions that co‐occur with autism. While there has been increased research describing the typical and autism‐specific anxiety symptomatology and assessing the effectiveness of potential interventions, there has been less research exploring the impact that elevated anxiety may have on an individual and their quality of life (QoL). This study aimed to explore the impact of anxiety on the QoL in children on the autism spectrum. Children and young adolescents on the spectrum were invited to participate in a self‐report study measuring anxiety and health‐related QoL (HRQoL). The sample consisted of 71 children, aged 6–13. Children who scored above the cut off for elevated anxiety on the autism‐specific measure of anxiety (ASC‐ASD) had poorer total HRQoL and poorer scores on the social, emotional, physical, and school functioning QoL domains. Regression analyses indicate that children's self‐reported ratings of difficulties with uncertainty on the ASC‐ASD predicted all domains of HRQoL, with higher levels of difficulty with uncertainty predicting poorer HRQoL. Elevated levels of anxious arousal were also predictive of poorer physical functioning. This study highlights the importance of exploring the impact of anxiety on individuals on the spectrum and suggests that using carefully planned interventions to reduce difficulties with uncertainty may be a potential way to work toward improving the QoL of children on the spectrum. Autism Res 2019, 12: 1505–1515. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Research has shown us that individuals on the autism spectrum are more likely to have poor “quality of life” or general well‐being. Because many individuals with a diagnosis on the autism spectrum also receive a diagnosis of anxiety, this study looked at whether a child's autism symptoms or their anxiety have a bigger impact on their quality of life. Children on the autism spectrum completed questionnaires and the results showed us that one factor, difficulty with uncertainty, had the biggest impact on the child's quality of life.
The social ecology of aggression in youths with autism spectrum disorder
Authors: Brown Cynthia E. , Borduin Charles M. , Dopp Alex R. , Mazurek Micah O.
Published: June 2019

This study examined the social‐ecological correlates of aggressive behavior in 120 youths with autism spectrum disorder. Youths were divided into three groups based on caregiver reports of the youth's aggressive acts: youths who engaged in acts of both physical and verbal aggression, youths who engaged only in acts of physical aggression, and nonaggressive youths. Caregivers and youths completed self‐report instruments and behavior rating inventories that assessed youth individual functioning, family relations, and extrafamilial factors (i.e., peer relations, academic performance). Results showed that youths who engaged in both verbal and physical aggression were characterized by poor sleep quality and victimization by peers, and their caregivers evidenced high levels of distress and avoidant coping. In contrast, youths who were physically but not verbally aggressive were distinguished by difficulties in social interaction and communication. In general, each group of youths who were aggressive experienced more problems with repetitive behaviors, family relations, and academic performance than did their nonaggressive counterparts. The implications of these findings for theory, research, and treatment are discussed. Autism Res 2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

The present study demonstrated that youths with autism spectrum disorder may be classified by the types of aggressive behaviors that they exhibit: youths who are verbally and physically aggressive, physically aggressive only, or not aggressive. Compared to the nonaggressive group, both groups of youths who were aggressive experienced difficulties in their individual, family, peer, and academic functioning. Youths with both verbal and physical aggression showed the most problems in their functioning.
Private tutoring in a high socio‐economic secondary school in Israel and pupils’ attitudes towards school learning: A double‐edged sword phenomenon
Authors: Addi‐Raccah Audrey
Published: June 2019

Private tutoring (PT) is a widespread educational phenomenon that blurs the conceptual boundaries of public and private education and can affect the formal school system and teachers’ work. This study examined whether participation in PT and the estimation of private tutors’ contributions are related to pupils’ attitudes towards teachers’ effectiveness. Based on a questionnaire administered to all pupils (n = 855) from Grades 7 to 10 from one secondary school located in an affluent area at the centre of Israel (respondence rate, 83.2%), it was found that overall, there were few differences in students’ attitudes between participants in PT compared to those who did not participate in PT. However, among those who participate in PT, their attitudes towards school teachers are related to the distinction between the academic and social‐affective contribution of private tutors. When PT is related to academic spheres, it enhances positive attitudes towards school teachers and when PT is related to socio‐affective aspects, it increases criticism. The findings highlight the complex interactions of PT with mainstream education and emphasise the challenges school teachers face in view of the trend for more personalised learning approaches.
Marginal hazard ratio estimates in joint frailty models for heart failure trials
Authors: Toenges Gerrit , Jahn‐Eimermacher Antje
Published: June 2019

This work is motivated by clinical trials in chronic heart failure disease, where treatment has effects both on morbidity (assessed as recurrent non‐fatal hospitalisations) and on mortality (assessed as cardiovascular death, CV death). Recently, a joint frailty proportional hazards model has been proposed for these kind of efficacy outcomes to account for a potential association between the risk rates for hospital admissions and CV death. However, more often clinical trial results are presented by treatment effect estimates that have been derived from marginal proportional hazards models, that is, a Cox model for mortality and an Andersen–Gill model for recurrent hospitalisations. We show how these marginal hazard ratios and their estimates depend on the association between the risk processes, when these are actually linked by shared or dependent frailty terms. First we derive the marginal hazard ratios as a function of time. Then, applying least false parameter theory, we show that the marginal hazard ratio estimate for the hospitalisation rate depends on study duration and on parameters of the underlying joint frailty model. In particular, we identify parameters, for example the treatment effect on mortality, that determine if the marginal hazard ratio estimate for hospitalisations is smaller, equal or larger than the conditional one. How this affects rejection probabilities is further investigated in simulation studies. Our findings can be used to interpret marginal hazard ratio estimates in heart failure trials and are illustrated by the results of the CHARM‐Preserved trial (where CHARM is the ‘Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity’ programme).
Structure and Mechanism of Surfactin Peptide from Bacillus velezensis Antagonistic to Fungi Plant Pathogens
Authors: Park Gwansik , Nam Jiyoung , Kim Jueun , Song Jaekyeong , Kim Pyoung Il , Min Hye Jung , Lee Chul Won
Published: June 2019

Bacillus velezensis GH1‐13 was recently isolated and showed to promote plant growth and strong antagonistic effects against phytopathogenic fungi including Gibberella moniliformis, Fusarium fujikuroi, Bipolaris oryzae, and Colletotrichum gloeosporioides. In this study, the antifungal substances produced by the GH1‐13 strain were purified by ethyl acetate solvent partitioning and solid phase extraction using Sep‐Pak C18 cartridge. The pure antifungal substances were finally purified by preparative reversed phase‐high performance liquid chromatography. We investigated the structure of the purified antifungal compounds using liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. These compounds were identified as surfactin‐type cyclic lipopeptides having an ELLVDLL amino acid sequence with different lengths of lipid chains. The surfactin lipopeptides effectively inhibited the growth of fungal mycelium, suggesting that the GH1‐13 strain will be a potential biocontrol agent against plant pathogenic fungi.
Metabonomics study on the effect of Siwu Decoction for blood deficiency syndrome in rats using UPLC–Q/TOF–MS analysis
Authors: He Yao , Gao Tianhui , Li Jie , Chen Zhejie , Wang Lijuan , Zhang Jinming , Gao Fei , Fu Chaomei
Published: June 2019

Siwu decoction (SWD), a traditional Chinese medicinal formula with over 1000 years of clinical history, is widely used for gynecological disease, especially blood deficiency syndrome, which is similar to anemia in modern medicine. In view of metabonomics being useful approach to investigate the potential mechanisms of action from the point of view of systems biology, in this study an ultra‐performance liquid chromatography–quadrupole‐time of flight mass spectrometry method was employed for a holistic evaluation of SWD on a blood‐deficiency rat model induced by N‐acetylphenylhydrazine and cyclophosphamide via plasma metabonomics study. Routine blood examination results showed that SWD could significantly improve the declining hemogram indices. Meanwhile, the plasma metabonomics profiles in different groups were analyzed and differentiating metabolites were primarily visualized through chemometric analysis. Seven biomarkers were identified in plasma samples of blood‐deficiency rat model compared with the normal group. Five main metabolism pathways were suggested using the Kyoto Encyclopedia of Genes and Genomes Pathway Analysis and Pathway Activity Profiling algorithm analysis. This indicated that SWD played a therapeu role in blood deficiency by regulating the aberrant endogenous metabolites. To sum up, this study provides clear evidence that a metabonomics study could serve as a useful tool to elucidate the systematic therapeutic profiles and mechanisms for blood deficiency syndrome of Chinese herbal medicines.
Derivation and identification of a mechanistic model for a branched enzyme‐catalyzed carboligation
Authors: Ohs Rüdiger , Fischer Konrad , Schöpping Marie , Spiess Antje C.
Published: June 2019

The kinetic description of enzyme‐catalyzed reactions is a core task in biotechnology and biochemical engineering. In particular, mechanistic kinetic models help from the discovery of the biocatalyst throughout its application. Chemo‐ or enantioselective enzyme reactions often undergo two alternative pathways for the release of two different products from a central intermediate. For these types of reaction, no explicit reaction equations have been derived so far. To this end, we extend the commonly used Cleland's notation for branched reaction pathways and explicitly derive the rate expressions for two‐coupled ordered bi–uni reactions. This mechanism also leads to a ping‐pong bi–bi mechanism for a transfer reaction between the two products via the same central intermediate of the reaction system. Using the cross‐ligation of benzaldehyde and propanal catalyzed by the thiamine diphosphate‐dependent enzyme benzaldehyde lyase from Pseudomonas fluorescens yielding (R)‐2‐hydroxy‐1‐phenylbutan‐1‐one as a case study, we performed model‐based experimental analysis to show that such a reaction mechanism can be modeled mechanistically and leads to reasonable kinetic parameters.
Prognosis and cure of long‐term cancer survivors: A population‐based estimation
Authors: Dal Maso Luigino , Panato Chiara , Guzzinati Stefano , Serraino Diego , Francisci Silvia , Botta Laura , Capocaccia Riccardo , Tavilla Andrea , Gigli Anna , Crocetti Emanuele , Rugge Massimo , Tagliabue Giovanna , Filiberti Rosa Angela , Carrozzi Giuliano , Michiara Maria , Ferretti Stefano , Cesaraccio Rosaria , Tumino Rosario , Falcini Fabio , Stracci Fabrizio , Torrisi Antonietta , Mazzoleni Guido , Fusco Mario , Rosso Stefano , Tisano Francesco , Fanetti Anna Clara , Sini Giovanna Maria , Buzzoni Carlotta , De Angelis Roberta ,   AIRTUM Working group
Published: June 2019

Background

Increasing evidence of cure for some neoplasms has emerged in recent years. The study aimed to estimate population‐based indicators of cancer cure.

Methods

Information on more than half a million cancer patients aged 15‐74 years collected by population‐based Italian cancer registries and mixture cure models were used to estimate the life expectancy of fatal tumors (LEFT), proportions of patients with similar death rates of the general population (cure fraction), and time to reach 5‐year conditional relative survival (CRS) >90% or 95% (time to cure).

Results

Between 1990 and 2000, the median LEFT increased >1 year for breast (from 8.1 to 9.4 years) and prostate cancers (from 5.2 to 7.4 years). Median LEFT in 1990 was >5 years for testicular cancers (5.8) and Hodgkin lymphoma (6.3) below 45 years of age. In both sexes, it was ≤0.5 years for pancreatic cancers and NHL in 1990 and in 2000. The cure fraction showed a 10% increase between 1990 and 2000. It was 95% for thyroid cancer in women, 94% for testis, 75% for prostate, 67% for breast cancers, and <20% for liver, lung, and pancreatic cancers. Time to 5‐year CRS >95% was <10 years for testis, thyroid, colon cancers, and melanoma. For breast and prostate cancers, the 5‐year CRS >90% was reached in <10 years but a small excess remained for >15 years.

Conclusions

The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.
Facile Access to Challenging ortho‐Terphenyls via Merging Two Multi‐Step Domino Reactions in One‐Pot: A Joint Experimental/Theoretical Study
Authors: Grau Benedikt W. , Bönisch Simon , Neuhauser Alexander , Hampel Frank , Görling Andreas , Tsogoeva Svetlana B.
Published: June 2019

ortho‐Terphenyls are of high interest for medicinal chemistry and materials science, but they are difficult to access. Herein, we demonstrate a straightforward and sustainable synthesis of highly functionalized ortho‐terphenyls via joining an organocatalyzed two‐step domino reaction (Knoevenagel/vinylogous Michael) with a DABCO/CuBr2 co‐catalyzed three‐step domino reaction (cyclization/tautomerization/aromatization) in a one‐pot process. Overcoming necessity to isolate intermediate products leads to a reduction of energy, costs and waste for a broad scope of reactions. DFT calculations have been performed to investigate the thermodynamics of this one‐pot process towards ortho‐terphenyls and to study the reaction profile of the vinylogous Michael reaction under inclusion of solvent effects. Role of London dispersion forces in this transformation has been elucidated. It is shown that reaction kinetics and thermodynamics are slightly influenced by dispersion interactions. Furthermore, the addition of dispersion energy donors leads to small changes of reaction energies in some cases.
Carbidisation of Pd Nanoparticles by Ethene Decomposition with Methane Production
Authors: Jones Wilm , Wells Peter. P. , Gibson Emma K. , Chutia Arunabhiram , Silverwood Ian P. , Catlow C. Richard A. , Bowker Michael
Published: June 2019

In the presence of oxygenated organic molecules pure Pd, which is widely used in chemicals processing and the pharmaceutical industry, tends to defunctionalise and dehydrogenate such molecules to H2, CO and surface/bulk carbon, in the form of a palladium carbide. We have investigated the formation of this carbide by ethene adsorption using a variety of techniques, including pulsed flow reaction measurements, XAS and DFT calculations of the lattice expansion during carbidisation. These experiments show that two main reactions take place above 500 K, that is, both total dehydrogenation, but also disproportionation to methane and the carbide, after which the activity of the Pd is completely lost. We estimate the value of x in PdCx to be 0.28 (±0.03), and show by computer modelling that this fits the lattice expansion observed by XAFS, and that there is charge transfer to C from Pd of around 0.2–0.4 e.
An Eco‐Friendly Nitrogen Source for the Preparation of Vanadium Nitride/Nitrogen‐Doped Carbon Nanocomposites for Supercapacitors
Authors: Jiang Xin , Lu Wei , Li Yunfeng , Yu Yang , Zhou Xuanbo , Liu Xianchun , Xing Yan
Published: June 2019

It is highly urgent to find an eco‐friendly nitrogen source for the preparation of metal nitrides as an electrode material for supercapacitors (SCs). Herein, vanadium nitride/N‐doped carbon (VN/NC) nanocomposites were prepared from the nitrogen source of g‐C3N4 by a facile one‐step annealing process. VN NPs, with an average particle size of 7 nm, make an important contribution to the capacitance of the composites. N‐doped carbon (NC), with an advanced sheet‐like structure and high nitrogen content provides a large surface area and effective electrolyte penetration, leading to more exposed VN active sites and a good electrical conductivity. As a supporting substrate, NC nanosheets (NCS) prevent VN NPs from aggregation, thereby a favorable cycling stability of the composite electrode was achieved. In addition, as the (−) 0.04‐VN/NCS2//NiCo2S4 (+) asymmetric device is assembled, favorable specific capacitance, high energy, and power density can also be obtained.
A Porous Carbon Polyhedron/Carbon Nanotube Based Hybrid Material as Multifunctional Sulfur Host for High‐Performance Lithium‐Sulfur Batteries
Authors: Ren Juan , Song Zhicui , Zhou Xuemei , Chai Yuru , Lu Xiaoli , Zheng Qiaoji , Xu Chenggang , Lin Dunmin
Published: June 2019

To develop high‐performance lithium‐sulfur (Li−S) batteries, designing and exploring an advanced sulfur cathode with a conductive and polar robust framework is highly significant to suppress the “shuttle effect” of polysulfides and enhance the utilization of active sulfur. Herein, a multifunctional conductive nanohybrid, which acts as a sulfur host, is rationally constructed by inserting/intertwining carbon nanotubes (CNTs) onto Co‐embedded N‐doped porous dual carbon polyhedrons derived from a resorcinol‐formaldehyde (RF) polymer layer enwrapping ZIF‐67 metal‐organic frameworks (MOFs) (Co, N−C@RFC/CNTs). The porous carbon polyhedrons can accommodate a high amount of sulfur owing to their large inner void space; the RF coating carbon layer and the CNTs effectively increase the conductivity and build a network for providing smooth ions/e− pathways; In addition, the polar Co particles and electronegative N heteroatoms synergistically strengthen the chemical adsorption of polysulfides and accelerate the redox reaction of the sulfur cathode. Benefiting from these advantages, the as‐fabricated Co, N−C@RFC/CNTs/S cathode delivers a high reversible capacity of 1373.7 mAh g−1 at 0.1 C, an impressive rate performance with 659.2 mAh g−1 at 2.0 C, and an outstanding cycling stability with an ultralow capacity decay rate of 0.041 % per cycle for 500 cycles at 1.0 C. This work provides a facile and high‐efficiency approach to fabricating excellent‐performance storage materials based on an MOF precursor.
Direct Synthesis of N‐Heterocyclic Carbene‐Stabilized Copper Nanoparticles from an N‐Heterocyclic Carbene–Borane
Authors: Frogneux Xavier , Hippolyte Laura , Mercier Dimitri , Portehault David , Chanéac Corinne , Sanchez Clément , Marcus Philippe , Ribot François , Fensterbank Louis , Carenco Sophie
Published: June 2019

N‐Heterocyclic carbene (NHC)‐stabilized copper nanoparticles (NPs) were synthesized from an NHC–borane adduct and mesitylcopper(I) under thermal conditions (refluxing toluene for 2.5 h). NPs with a size distribution of 11.6±1.8 nm were obtained. The interaction between Cu NPs and NHC ligands was probed by X‐ray photoelectron spectroscopy, which showed covalent binding of the NHC to the surface of the NPs. Mechanistic studies suggested that NHC–borane plays two roles: contributing to the reduction of [CuMes]2 to release Cu0 species and providing NHC ligands to stabilize the copper NPs.
Cover Picture: Benzene Triimides: Facile Synthesis and Self‐Assembly Study (Chin. J. Chem. 7/2019)
Authors: Tuo De‐Hui , He Qing , Wang Qi‐Qiang , Ao Yu‐Fei , Wang De‐Xian
Published: June 2019

The cover picture shows an efficient one‐pot condensation of maleimide derivatives in the presence of acetic acid and water to afford a series of benzene triimides (BTIs). The structure, physicochemical properties and electrochemistry behavior of BTIs were systematically investigated. Owing to the planar structure and unique electron‐deficient nature, BTIs can self‐assemble into different motifs. More details are discussed by Wang et al. on page 684–688.

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Inside Cover: From Reactivity and Regioselectivity to Stereoselectivity: An Odyssey of Designing PIP Amine and Related Directing Groups for C—H Activation (Chin. J. Chem. 7/2019)
Authors: Zhang Qi , Shi Bing‐Feng
Published: June 2019

The inside cover picture shows the journey of developing PIP amine directing group for C—H activation, from controlling the reactivity and diastereoselectivity to enantioselectivity. In the presence of Pd or base metal catalysts, PIP amine enabled the activation of inert C—H bonds to form diverse C—C and C—heteroatom bonds. Its tuneable structure has triggered the design of chiral auxiliaries for diastereoselective C—H activation. More recently, enantioselective activation of unbiased methylene C—H bonds has been achieved by cooperative effects between PIP amine and axial chiral ligands. More details are discussed in the article by Shi et al. on page 647–656.

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Composts Containing Natural and Mg‐Modified Zeolite: The Effect on Nitrate Leaching, Drainage Water, and Yield
Authors: Taheri‐Soudejani Hajar , Heidarpour Manouchehr , Shayannejad Mohammad , Shariatmadari Hossein , Kazemian Hossein , Afyuni Majid
Published: June 2019

The growing demand for environmental protection and sustainable food production requires the efficient use of organic and slow‐release fertilizers in agriculture. In this study, co‐composting of municipal solid waste (MSW) + three different ratios of natural and Mg‐modified zeolites (5, 10, and 15% on a wet weight basis) is conducted to improve the MSW compost quality. The effects of soil amendment with MSW compost containing natural zeolite (CNZ) and Mg‐modified zeolite (CMZ) on the corn yield, moisture content, leaching volumes, and NO3‐N concentrations are investigated. Compared to the control (zeolite‐free compost), the CNZ15 and CMZ15 treatments show 39.9 and 49.3% reduction in electrical conductivity and an increase of 64.5 and 110% in NH4‐N retention, respectively. By using the composts containing zeolite, the moisture content in the surface layer of soil is increased up to 12.6%. Nitrogen uptake and water use efficiency in the CNZ treatment are enhanced by 34.6 and 40.0%, respectively. The increase of the nitrogen uptake and water use efficiency of the CMZ treatment is 54.5 and 55.6%, respectively. Compared to the control, the amount of total NO3‐N leached from CNZ and CMZ treatments is decreased by 21.0 and 28.9%, respectively. The use of the MSW compost modified with Mg‐zeolite is, therefore, an environmentally friendly solution to prevent surface and groundwater pollution. The modified compost could be also used for the improvement of the physicochemical properties of sandy loam soils.
Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA‐negative Hispanics with breast cancer
Authors: Weitzel Jeffrey N. , Neuhausen Susan L. , Adamson Aaron , Tao Shu , Ricker Charité , Maoz Asaf , Rosenblatt Margalit , Nehoray Bita , Sand Sharon , Steele Linda , Unzeitig Gary , Feldman Nancy , Blanco Amie M. , Hu Donglei , Huntsman Scott , Castillo Danielle , Haiman Christopher , Slavin Thomas , Ziv Elad
Published: June 2019

Background

Breast cancer (BC) is the most common cancer and related cause of mortality among Hispanics, yet susceptibility has been understudied. BRCA1 and BRCA2 (BRCA) mutations explain less than one‐half of hereditary BC, and the proportion associated with other BC susceptibility genes is unknown.

Methods

Germline DNA from 1054 BRCA‐mutation–negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51‐70 years with ≥2 first‐degree or second‐degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high‐penetrance and moderate‐penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C‐terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53).

Results

Forty‐nine (4.6%) pathogenic or likely pathogenic variants (PVs) in 47 of 1054 participants (4.5%), including 21 truncating frameshift, 20 missense, 5 nonsense, and 4 splice variants, were identified in CHEK2 (n = 20), PALB2 (n = 18), ATM (n = 5), TP53 (n = 3), BRIP1 (n = 2), and CDH1 and NF1 (both n = 1) and none were identified in NBN, PTEN, STK11, RAD51C, or RAD51D. Nine participants carried the PALB2 c.2167_2168del PV (0.85%), and 14 carried the CHEK2 c.707T>C PV (1.32%).

Conclusions

Of 1054 BRCA‐negative, high‐risk Hispanic women, 4.5% carried a PV in a cancer susceptibility gene, increasing understanding of hereditary BC in this population. Recurrent PVs in PALB2 and CHEK2 represented 47% (23 of 49) of the total, suggesting a founder effect. Accurate classification of variants was enabled by carefully controlling for ancestry and the increased identification of at‐risk Hispanics for screening and prevention.
Does race predict survival for women with invasive breast cancer?
Authors: Walsh Siún M. , Zabor Emily C. , Stempel Michelle , Morrow Monica , Gemignani Mary L.
Published: June 2019

Background

Black women with breast cancer have lower survival rates and higher recurrence rates in comparison with white women. This study compared treatment and survival outcomes for black and white women at a highly specialized tertiary care cancer center.

Methods

An institutional review board–approved, retrospective institutional database review was performed to identify all black women treated for invasive breast cancer between 2005 and 2010. Women with a prior history of breast cancer, stage IV cancer, or bilateral breast cancer were excluded. White women had similar exclusion criteria applied and were then matched to black women 1:1 by age and diagnosis year. Clinicopathologic and treatment variables were compared by race. Kaplan‐Meier methodology was used to estimate overall survival (OS) and disease‐free survival (DFS); a multivariable analysis was conducted with Cox regression models.

Results

The study group consisted of 1332 women (666 black). The median tumor size was larger in black women (1.6 vs 1.3 cm; P < .001). Black women had more nodal disease (41.1% vs 32%; P < .001) and had tumors that were more frequently an estrogen receptor–negative (32.9% vs 15%; P < .001), progesterone receptor–negative (47.1% vs 30.2%; P < .001), or triple‐negative (TN) subtype (24% vs 8.9%; P < .001) in comparison with white women. Black women also had inferior DFS and OS; race was not an independent prognostic indicator in the multivariable analysis.

Conclusions

Black women had more advanced disease and adverse prognostic indicators at diagnosis, but race was not an independent predictor of outcome. Black women were significantly more likely to have TN breast cancer. Further research is necessary to understand the differences in tumor biology associated with race.
In Situ Synthesis of Well‐Ordered Magnetic Palladium Catalyst Triggered by Supramolecular Chaotropic Effect of Boron Cluster
Authors: Qi Bin , Wu Chenchen , Liu Jun , Zhang Haibo
Published: June 2019

Supramolecular chaotropic effect is a new topic in the field of nanocomposites (NCs) fabrication. Herein, this strategy was applied to prepare magnetic Fe3O4@γ‐CD‐boron cluster (SSAs)@Pd NCs in situ via a facile two‐step process, involving a supramolecular assembly process on Fe3O4 NPs and in situ formation of Pd nanoparticles. Boron clusters ([closo‐B12H12]2−) played a dual role in this synthetic process, and were used as a superchaotropic anion to interact with γ‐CD to form supramolecular self‐assemblies (SSAs), as well as efficient reductant to in situ reduce Pd(II) to Pd(0). Ascribed to the electrostatic attraction of boron clusters and capping effect of γ‐CD, ultrafine Pd nanoparticles were successfully coated on the Fe3O4@SSAs composites to fabricate Fe3O4@SSAs@Pd NCs. A combination of UV spectra, Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, transmission electron microscopy, X‐ray diffraction, and energy dispersive X‐ray spectroscopy was used to verify the formation of these magnetic Pd NCs. The ultrafine metallic Pd NPs imparted the magnetic composites with great potential in catalysis, especially for Suzuki coupling reactions. Remarkably, the obtained Fe3O4@SSAs@Pd NCs showed good catalytic performance, high stability and easy recycling via an external magnet.