bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the phenotype in Adams–Oliver syndrome correlating with the genotype
Authors: Dudoignon Benjamin , Huber Celine , Michot Caroline , Di Rocco Federico , Girard Muriel , Lyonnet Stanislas , Rio Marlène , Rabia Smail Hadj , Daire Valérie Cormier , Baujat Geneviève 
Published: October 2019

AbstractRationaleAdams–Oliver syndrome (AOS) is a genetic disorder characterized by the association of aplasia cutis congenita (ACC), terminal transverse limb defect (TTLD), congenital cardiac malformation (CCM), and minor features, such as cutaneous, neurological, and hepatic abnormalities (HAs). The aim of the study is to emphasize phenotype–genotype correlations in AOS.MethodsWe studied 29 AOS patients. We recorded retrospectively detailed phenotype data, including clinical examination, biological analyses, and imaging. The molecular analysis was performed through whole exome sequencing (WES).ResultsTwenty‐nine patients (100%) presented with ACC, the principal inclusion criteria in the study. Seventeen of twenty‐one (81%) had cutis marmorata telangiectasia congenita, 16/26 (62%) had TTLD, 14/23 (61%) had CCM, 7/20 (35%) had HAs, and 9/27 (33%) had neurological findings. WES was performed in 25 patients. Fourteen of twenty‐five (56%) had alterations in the genes already described in AOS. CCM and HAs are particularly associated with the NOTCH1 genotype. TTLD is present in patients with DOCK6 and EOGT alterations. Neurological findings of variable degree were associated sometimes with DOCK6 and NOTCH1 rarely with EOGT.ConclusionAOS is characterized by a clinical and molecular variability. It appears that degrees of genotype–phenotype correlations exist for patients with identified pathogenic mutations, underlining the need to undertake a systematic but adjusted multidisciplinary assessment.
Behavioral characterization of dup15q syndrome: Toward meaningful endpoints for clinical trials
Authors: DiStefano Charlotte , Wilson Rujuta B. , Hyde Carly , Cook Edwin H. , Thibert Ronald L. , Reiter Lawrence T. , Vogel‐Farley Vanessa , Hipp Joerg , Jeste Shafali 
Published: October 2019

AbstractDuplication of 15q11.2‐q13.1 (dup15q syndrome) is one of the most common copy number variations associated with autism spectrum disorders (ASD) and intellectual disability (ID). As with many neurogenetic conditions, accurate behavioral assessment is challenging due to the level of impairment and heterogeneity across individuals. Large‐scale phenotyping studies are necessary to inform future clinical trials in this and similar ID syndromes. This study assessed developmental and behavioral characteristics in a large cohort of children with dup15q syndrome, and examined differences based on genetic subtype and epilepsy status. Participants included 62 children (2.5–18 years). Across individuals, there was a wide range of abilities. Although adaptive behavior was strongly associated with cognitive ability, adaptive abilities were higher than cognitive scores. Measures of ASD symptoms were associated with cognitive ability, while parent report of challenging behavior was not. Both genetic subtype and epilepsy were related to degree of impairment across cognitive, language, motor, and adaptive domains. Children with isodicentric duplications and epilepsy showed the greatest impairment, while children with interstitial duplications showed the least. On average, participants with epilepsy experienced seizures over 53% of their lives, and half of children with epilepsy had infantile spasms. Parents of children with isodicentric duplications reported more concerns regarding challenging behaviors. Future trials in ID syndromes should employ a flexible set of assessments, allowing each participant to receive assessments that capture their skills. Multiple sources of information should be considered, and the impact of language and cognitive ability should be taken into consideration when interpreting results.
Prenatal and perinatal history in Kabuki Syndrome
Authors: Rosenberg Chen E. , Daly Tara , Hung Christina , Hsueh Irene , Lindsley Andrew W. , Bodamer Olaf 
Published: October 2019

AbstractKabuki syndrome (KS) is a disorder of epigenetic dysregulation due to heterozygous mutations in KMT2D or KDM6A, genes encoding a lysine‐specific methyltransferase or demethylase, respectively. The phenotype is highly variable, including congenital cardiac and renal anomalies, developmental delay, hypotonia, failure to thrive, short stature, and immune dysfunction. All affected individuals have characteristic facial features. As KS natural history has not been fully delineated, limited information exists on its prenatal and perinatal history. Two tertiary centers collected retrospective data from individuals with KS (N = 49) using a questionnaire followed by review of medical records. Data from 49 individuals (age range: 7 months–33 years; 37% male; 36 with KMT2D mutations, 2 with KDM6A mutations, and 11 diagnosed clinically) were examined. Polyhydramnios affected 16 of 39 (41%) pregnancies. Abnormal quad screens in four out of nine (44%) pregnancies and reduced placental weights also complicated KS pregnancies. These data comprise the first large dataset on prenatal and perinatal history in individuals with confirmed (genetically or clinically) KS. Over a third of pregnancies were complicated by polyhydramnios, possibly secondary to abnormal craniofacial structures and functional impairment of swallowing. The differential diagnosis for polyhydramnios in the absence of intrauterine growth retardation should include KS.
Palladium‐Catalyzed [2+2+1] Spiroannulation via Alkyne‐Directed Remote C−H Arylation and Subsequent Arene Dearomatization
Authors: Zuo Zhijun , Wang Jing , Liu Jingjing , Wang Yaoyu , Luan Xinjun 
Published: October 2019

AbstractPalladium‐catalyzed alkene‐directed cross‐coupling of aryl iodide with another aryl halide through C−H arylation opens a unique avenue for unsymmetrical biaryl‐derived molecules. However, homo‐coupling of aryl iodides often erodes the overall synthetic efficiency. Reported herein is a highly chemoselective Pd0‐catalyzed alkyne‐directed cross‐coupling of aryl iodides with bromophenols, which was subsequently followed by phenol dearomatization to furnish a very attractive [2+2+1] spiroannulation. Notably, possible homo‐coupling of aryl iodides was not observed at all. Mechanistic studies indicated that a five‐membered aryl/vinyl palladacycle most likely accounts for promoting the key step of biaryl cross‐coupling.
Li[LiCs2Cl][Ga3S6]: A Nanoporous Framework of GaS4 Tetrahedra with Excellent Nonlinear Optical Performance
Authors: Liu Bin‐Wen , Jiang Xiao‐Ming , Li Bing‐Xuan , Zeng Hui‐Yi , Guo Guo‐Cong 
Published: October 2019

AbstractA large nonlinear optical (NLO) coefficient and a wide band gap are two crucial but contradictory parameters that are difficult to achieve simultaneously in a single infrared (IR) NLO compound. A salt‐inclusion chalcogenide (SIC), Li[LiCs2Cl][Ga3S6] (1), was prepared that presents a nanosized tunnel framework constructed from monotype chalcogenide tetrahedra. Highly oriented covalent GaS4 tetrahedra in the host lead to a moderate second harmonic generation response (0.7 AgGaS2), and ionic guests effectively broaden the band gap to the widest value (4.18 eV) among all IR NLO chalcogenides, thereby achieving a remarkable balance between NLO efficiency and band gap.
AuNPs composites of gelatin hydrogels crosslinked by ferrocene‐containing polymer as recyclable supported catalysts
Authors: Long Yanru , Song Bin , Shi Chutong , Liu Wentao , Gu Haibin 
Published: October 2019

ABSTRACTTo fabricate a recyclable supported catalyst based on gold nanoparticles (AuNPs) and gelatin hydrogel (HG) composites, a ferrocene (Fc)‐containing tetrablock copolymer [P(NCHO‐b‐NFc‐b‐NTEG‐b‐NCHO)] was used as both reducing and stabilizing agents for AuNPs and as a crosslinker for HG. First, the effects of Fc‐containing polymers, including homopolymer PNFc and copolymer P(NCHO‐b‐NFc‐b‐NTEG‐b‐NCHO), and different solvent systems on the morphology and aggregation of AuNPs were examined by using ultraviolet–visible spectroscopy, transmission electron microscopy, and dynamic light scattering. Second, two strategies (blending and soaking) were applied to prepare different AuNPs/HG composites (AuNPs‐HG), and their structure and properties were studied by using various techniques including scanning electron microscopy, X‐ray diffraction, and thermogravimetry. Finally, the catalytic performance and reusability of AuNPs‐HG‐1 (via blending) and AuNPs‐HG‐2 (via soaking) were evaluated utilizing the model catalytic reduction of 4‐nitrophenol to 4‐aminophenol by NaBH4. Results indicated that P(NCHO‐b‐NFc‐b‐NTEG‐b‐NCHO) dissolved in N,N‐dimethylformamide was the optimal reductant and stabilizer to prepare AuNPs. The in situ reduction of AuIII ions to Au0 particles was very essential for the fabrication of AuNPs‐HG in terms of hydrogel pore size, Au0 distribution and immobilization stability, and hydrogel thermal stability. Due to the stronger interactions among AuNPs, P(NCHO‐b‐NFc‐b‐NTEG‐b‐NCHO), and gelatin molecules in the blending strategy, AuNPs‐HG‐1 showed better mechanical stability and catalytic performance and more reusing cycles than AuNPs‐HG‐2. This work highlights the design and fabrication of robust recyclable supported AuNP catalyst by using eco‐friendly Fc‐containing HGs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48653.
Detection of differentiated changes in gray matter in children with progressive hydrocephalus and chronic compensated hydrocephalus using voxel‐based morphometry and machine learning
Authors: Li Yongxin , Tan Zhen , Wang Ya , Wang Yanfang , Li Ding , Chen Qian , Huang Wenhua 
Published: October 2019

AbstractCurrently, no neuroimaging study has reported the detection of specific imaging biomarkers that distinguish the progressive hydrocephalus (PH) and chronic compensated hydrocephalus (CH). Our main focus is to evaluate the different structural changes in classifying the two types of hydrocephalus children. Twenty‐two children with hydrocephalus (12 PHs and 10 CHs) and 30 age‐matched healthy controls were enrolled and the T1‐weighted imaging was collected in the study. A customized voxel‐based morphometry (VBM) approach and support vector machine (SVM) were combined to investigate the structural changes and group classification. Comparing with the controls and CH, PH groups invariably showed a significant decrease of GM volume in the bilateral hippocampus/parahippocampus, insula, and motor‐related areas. SVM applied to the GM volumes of bilateral hippocampus/parahippocampus, insula, and motor‐related areas correctly identified hydrocephalus children from normal controls with a statistically significant accuracy of 88.46% (p ≤ .001). In addition, SVM applied to GM volumes of the same regions correctly identified PH from CH with a statistically significant accuracy of 77.27% (p ≤ .009). Using VBM analysis, we characterized and visualized the GM changes in children with hydrocephalus. Machine learning results further confirmed that a significant decrease of the bilateral hippocampus/parahippocampus, insula, and motor‐related GM volume can serve as a specific neuroimaging index to distinguish the children with PH from the children with CH and controls at individual. The findings could help to aid the identification of individuals with PH in clinical practice.
A spectrum of approaches to health information interaction: From avoidance to verification
Authors: Costello Kaitlin L. , Veinot Tiffany C. 
Published: October 2019

AbstractPeople respond to illness in a range of ways, and take different approaches to engaging with health information throughout the course of their illness. This study describes and explains the variety of approaches to health information interactions made by patients on hemodialysis. Ethnographic observations (156 hours) were conducted in three hemodialysis clinics, and semistructured interviews about health information were held with 28 patients. Demographic data were collected. Data were analyzed qualitatively. We found a spectrum of five approaches to health information: avoiders, who close themselves off from health information; receivers, who encounter information in the dialysis clinic but do not seek it out; askers, who only pose questions about health to their healthcare providers but otherwise do not seek; seekers, who actively look for health information both in and out of the clinic; and verifiers, who seek information and triangulate it among multiple sources. Trust in healthcare providers and coping sociality differed across approaches. The findings indicate that health information should be provided to patients using strategies tailored to their preferences and existing approaches to information interaction.
Differential contribution of possible pattern‐recognition receptors to advanced glycation end product–induced cellular responses in macrophage‐like RAW264.7 cells
Authors: Watanabe Masahiro , Toyomura Takao , Wake Hidenori , Liu Keyue , Teshigawara Kiyoshi , Takahashi Hideo , Nishibori Masahiro , Mori Shuji 
Published: October 2019

AbstractAdvanced glycation end products (AGEs) are considered to be related to the pathogenesis of some inflammatory diseases. AGEs were reported to stimulate the receptor for AGEs (RAGE), which causes inflammatory reactions. However, recently, toll‐like receptors (TLRs), in addition to RAGE, have been reported to be related to AGE‐mediated cellular responses, and it remains unclear which receptor is responsible for AGE recognition. To reveal the role of pattern‐recognition receptors, including TLRs and/or RAGE, in AGE‐mediated cellular responses, we generated macrophage‐like RAW264.7 knockout (KO) cells lacking these receptors by genome editing using the CRISPR/Cas9 system and assessed AGE‐stimulated changes in these cells. Comparison of the established clones suggested that RAGE partially affects the expression of TLRs. In the KO clone lacking TLR4 and TLR2, AGE‐stimulated tumor necrosis factor alpha (TNF‐α) expression and phosphorylation of IκBα, p38, and extracellular signal‐regulated kinase (ERK) were significantly attenuated, suggesting that AGE‐mediated responses are largely dependent on TLRs. On the other hand, on comparison of the AGE‐stimulated responses between the KO clone lacking TLR4 and TLR2, and the clone lacking TLR4, TLR2, and RAGE, RAGE played little role in AGE‐stimulated TNF‐α transcription and ERK phosphorylation. Taken together, this study suggested that AGE‐stimulated inflammatory responses occur mainly through TLRs rather than RAGE.
A carbon footprint assessment of multi‐output biorefineries with international biomass supply: a case study for the Netherlands
Authors: Vera Ivan , Hoefnagels Ric , van der Kooij Aldert , Moretti Christian , Junginger Martin 
Published: October 2019

AbstractThe efficient use of lignocellulosic biomass for the production of advanced fuels and bio‐based materials has become increasingly relevant. In the EU, regulatory developments are stimulating the mobilization and production of bio‐based chemicals / materials and biofuels from lignocellulosic biomass. We used an attributional life‐cycle assessment approach based on region‐specific characteristics to determine the greenhouse gas emissions (GHG) performance of different supply‐chain configurations with internationally sourced lignocellulosic biomass (stem wood, forest residues, sawmill residues, and sugarcane bagasse) from the USA, the Baltic States (BS), and Brazil (BR) for the simultaneous production of lactide and ethanol in a biorefinery located in the Netherlands (NL). The results are compared with a biorefinery that uses locally cultivated sugar beets. We also compared GHG emissions savings from the supply‐chain configurations with the minimum GHG saving requirements in the revised Renewable Energy Directive (RED II) and relevant fossil‐based counterparts for bio‐based materials. The GHG emissions ‘from cradle to factory gate’ vary between 692 g CO2eq/kglactide
(sawmill residues pellets from the BS) and 1002 g CO2eq/kglactide
(sawmill chips from the USA) for lactide and between 15 g CO2eq/MJethanol
(sawmill residues pellets from the BS) and 28 g CO2eq/MJethanol
(bagasse pellets from BR) for ethanol. Upstream GHG emissions from the conversion routes have a relatively small impact compared with biomass conversion to lactide and ethanol. The use of woody biomass yields better GHG emissions performance for the conversion system than sugarcane bagasse or sugar beets as result of the higher lignin content that is used to generate electricity and heat internally for the system. Only the sugar beet from the NL production route is able to comply with RED II GHG savings criteria (65% by 2021). The GHG savings from polylactide acid (a derivate of lactic acid) are high and vary depending on choice of fossil‐based counterpart, with the highest savings reported when compared to polystyrene (PS). These high savings are mostly attributed to the negative emission credit from the embedded carbon in the materials. Several improvement options along the conversion routes were explored. Efficient feedstock supply chains (including pelletization and large ocean vessels) also allow for long‐distance transportation of biomass and conversion in large‐scale biorefineries close to demand centers with similar GHG performance to biorefineries with a local biomass supply. © 2019 The Authors. Biofuels, Bioproducts, and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.
Synergistic effects of flow and interfaces on antibody aggregation
Authors: Grigolato Fulvio , Arosio Paolo 
Published: October 2019

AbstractDuring the manufacturing process, solutions of protein‐based drugs are exposed to hydrodynamic forces, which can potentially affect protein stability and aggregation. Despite being an area of extensive investigation, the effect of hydrodynamic flow on protein aggregation is still controversial. In this study, we designed an experimental setup that allowed us to investigate flow‐ and interface‐induced protein aggregation of two model immunoglobulins in the presence of well‐defined flow stresses and solid–liquid interfaces. Within the range of shear rates typically encountered in bioprocessing (), we observed that increasing the shear rate by three orders of magnitude had a negligible effect on protein aggregation. By contrast, changes in the materials of the syringe barrels had a dramatic effect on the monomer loss, demonstrating the key role of solid–liquid interfaces in flow‐induced aggregation. This finding was confirmed by the observed inverse dependence of the aggregation rate on the initial protein concentration, which is inconsistent with mechanisms of protein aggregation in bulk solution. Overall, our results reveal the presence of a synergistic effect of interfaces and hydrodynamic flow in flow‐induced protein aggregation, which arises from the formation of protein particles or films on interfaces followed by displacement by flow or mechanical scraping.
Biocatalytic properties of cell surface display laccase for degradation of emerging contaminant acetaminophen in water reclamation
Authors: Wu Ying , Chen Yingying , Wei Na 
Published: October 2019

AbstractThe surface display laccase (SDL) biocatalyst, where the enzyme laccase is displayed on the surface of biological cells through synthetic biology, provides a new opportunity to develop sustainable technologies for removal of emerging contaminants from wastewater. This study vigorously characterized biocatalytic properties of the SDL in comparison to free laccase in removing emerging contaminant acetaminophen (APAP), with the aim to understand the effect of surface display on enzyme functionality and identify the strategy to overcome the potential limitation. The SDL could effectively remove APAP. Adding redox mediators substantially improved the removal efficiency. The Michaelis–Menten kinetic analysis showed that the redox mediator 2,2‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonate could overcome the limitation of APAP accessing the active site of laccase in the SDL biocatalyst. The APAP removal rate catalyzed by the SDL in real secondary wastewater effluent was higher than that in acetate buffer; comprehensive enzyme kinetic analysis provided clear evidence that there were redox mediating compounds in the wastewater. Analysis of transformation products revealed that surface display did not change laccase functionality in terms of APAP transformation mechanism. In addition, the SDL retained 88% of the initial activity after six repeated APAP biotransformation reactions. Results from this study provide a scientific basis for developing and implementing SDL as an innovative biocatalytic material for contaminant treatment applications.
Decision-making by the NICE Interventional Procedures Advisory Committee
Authors: Carroll C , Dickson R , Boland A , Houten R , Walton M 
Published: October 2019

Abstract

Background
This study explored the evidence base for recommendations by the National Institute of Health and Care Excellence (NICE) Interventional Procedures Advisory Committee, the only NICE committee not to consider cost. The four potential recommendations are: Standard Arrangements (can be performed as routine practice in the NHS); Special Arrangements (can be done under certain conditions); Research Only; and Do Not Do.

Methods
Quantitative content analysis of data extracted from all published Interventional Procedure Guidance (IPG) for 2003–2018 (n = 496) was undertaken. All data were extracted independently by two researchers; disagreements were clarified by consensus. Data were tabulated, descriptive statistics produced, and regression analyses performed.

Results
The proportion of IPGs by recommendation was: 50·0 per cent Standard Arrangements; 37·2 per cent Special Arrangements; 11·1 per cent Research Only; and 1·6 per cent Do Not Do. There was a clear trend over time: the proportion of recommendations for Standard Arrangements decreased, whereas the evidence threshold increased. Adjusted mean numbers of patients in the evidence base by recommendation type were: Standard, 4867; Special, 709; Research Only, 386. Regression analyses confirmed that the year of recommendation, numbers of patients and levels of evidence all affected the likely recommendation.

Conclusion
This study suggests that the likelihood of achieving the most positive recommendation (Standard Arrangements) is decreasing, and that this is most likely due to evidential requirements becoming more demanding. These findings are distinct from those reported for other NICE committees, for which the cost and statistical superiority of new therapies are among the drivers of recommendations.