bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic and molecular insights into PQBP1‐related intellectual disability
Authors: Abdel‐Salam Ghada M. H. , Miyake Noriko , Abdel‐Hamid Mohamed S. , Sayed Inas S. M. , Gadelhak Mohamed I. , Ismail Samira I. , Aglan Mona S. , Afifi Hanan H. , Temtamy Samia A. , Matsumoto Naomichi
Published: September 2018

We report two discordant clinical and imaging features in four male patients from two unrelated families of Egyptian descent with hemizygous pathogenic variants in PQBP1. The three patients of the first family displayed the typical features underlying PQBP1 such as the long triangular face, bulbous nose, hypoplastic malar region, and micrognathia, which were subsequently confirmed using targeted sequence analysis that showed a previously reported nonsense mutation c.586C>T p.R196*. Whole exome sequencing identified a novel missense PQBP1 variant c.530G>A:p.R177H in the second family, in which the index patient presented with intellectual disability and dysmorphic facial features reminiscent of Kabuki‐like syndrome and his brain magnetic resonance imaging revealed partial agenesis of corpus callosum, mild vermis, and brainstem hypoplasia. These imaging features are distinct from the previously described with a well‐known phenotype that is already known for PQBP1. This report expands the phenotypic spectrum of PQBP1‐related disorders and is the second reported missense PQBP1 variant. Further, it highlights the possible role of PQBP1 in hindbrain development.
22q and two: 22q11.2 deletion syndrome and coexisting conditions
Authors: Cohen Jennifer L. , Crowley Terrence B. , McGinn Daniel E. , McDougall Carey , Unolt Marta , Lambert Michele P. , Emanuel Beverly S. , Zackai Elaine H. , McDonald‐McGinn Donna M.
Published: September 2018

22q11.2 deletion syndrome (DS) is the most frequent copy number variant (CNV) affecting ~1/1,000 fetuses and ~1/2,000–4,000 children, resulting in recognizable but variable findings across multiple organ systems. Patients with atypical features should prompt consideration of coexisting diagnoses due to additional genome‐wide mutations, CNVs, or mutations/CNVs on the other allele, unmasking autosomal recessive conditions. Importantly, a dual diagnosis compounds symptoms and impacts management. We previously reported seven patients with 22q11.2DS and: SCID, Trisomy 8 mosaicism, Bernard‐Soulier, and CEDNIK syndromes. Here we present six additional unreported patients with 22q11.2DS and concurrent diagnoses. Records on 1,422 patients with 22q11.2DS, identified via FISH, microarray, or MLPA, followed in our 22q and You Center at the Children's Hospital of Philadelphia (CHOP) were reviewed to identify a dual diagnosis. In addition to our seven previously reported cases, we identified an additional six with 22q11.2DS and another coexisting condition identified via: molecular/cytogenetic studies, newborn screening, coagulation factor studies, or enzyme testing; these include CHARGE syndrome (CHD7 mutation), cystic fibrosis, a maternally inherited 17q12 deletion, G6PD deficiency, von Willebrand disease, and 1q21.1 deletion, resulting in an incidence of dual diagnoses at our center of 0.9%. The range of dual diagnoses identified in our cohort is notable, medically actionable, and may alter long‐term outcome and recurrence risk counseling. Thus, our findings may support testing patients with 22q11.2DS using a combination of microarray, mutational analysis of the other allele/WES, to ensure appropriate personalized care, as formulating medical management decisions hinges on establishing the correct diagnoses in their entirety.
Small 4p16.3 deletions: Three additional patients and review of the literature
Authors: Bernardini Laura , Radio Francesca C. , Acquaviva Fabio , Gorgone Cristina , Postorivo Diana , Torres Barbara , Alesi Viola , Magliozzi Monia , Lonardo Fortunato , Monica Matteo Della , Nardone Anna M. , Cesario Claudia , Mattina Teresa , Scarano Gioacchino , Dallapiccola Bruno , Digilio Maria C. , Novelli Antonio
Published: September 2018

Wolf–Hirschhorn syndrome is a well‐defined disorder due to 4p16.3 deletion, characterized by distinct facial features, intellectual disability, prenatal and postnatal growth retardation, and seizures. Genotype–phenotype correlations based on differently sized deletions have been attempted, and some candidate genes have been suggested. We report on clinical characteristics of three patients with pure interstitial submicroscopic 4p16.3 deletions, ranging in size from 68 to 166 kb, involving WHSCR1 and/or part of WHSCR2, and review published cases with overlapping 4p16.3 losses. The present study highlights a major role ofNSD2gene in the pathogenesis of the WHS main features and predicts that loss‐of‐function mutations affectingNSD2gene could result in microcephaly, prenatal and postnatal growth retardation, psychomotor and language delay, and craniofacial features. Absent seizures in all subjects corroborate the suggestion that this specific feature is causally linked with at least one additional causative gene. Finally, we suggest that mir‐943 could play a role in the pathogenesis of CHD in some of these patients.
Is PNPT1‐related hearing loss ever non‐syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1‐related disorders
Authors: Eaton Alison , Bernier Francois P. , Goedhart Caitlin , Caluseriu Oana , Lamont Ryan E. , Boycott Kym M. , Parboosingh Jillian S. , Innes A. Micheil ,   Care4Rare Canada Consortium
Published: September 2018

PNPT1 is a mitochondrial RNA transport protein that has been linked to two discrete phenotypes, namely isolated sensorineural hearing loss (OMIM 614934) and combined oxidative phosphorylation deficiency (OMIM 614932). The latter has been described in multiple families presenting with complex neurologic manifestations in childhood. We describe adult siblings with biallelic PNPT1 variants identified through WES who presented with isolated severe congenital sensorineural hearing loss (SNHL). In their 40s, they each developed and then followed a nearly identical neurodegenerative course with ataxia, dystonia, and cognitive decline. Now in their 50s and 60s, all have developed the additional features of optic nerve atrophy, spasticity, and incontinence. The natural history of the condition in this family may suggest that the individuals previously reported as having isolated SNHL may be at risk of developing multisystem disease in late adulthood, and that PNPT1‐related disorders may constitute a spectrum rather than distinct phenotypes.
Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis
Authors: Datkhaeva Ilina , Arboleda Valerie A. , Senaratne T. Niroshi , Nikpour Gelareh , Meyerson Cherise , Geng Yipeng , Afshar Yalda , Scibetta Emily , Goldstein Jeffrey , Quintero‐Rivera Fabiola , Crandall Barbara F. , Grody Wayne W. , Deignan Joshua , Janzen Carla
Published: September 2018

Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the PIEZO1 gene diagnosed prenatally using exome sequencing (ES). Two variants in PIEZO1 (c.3206G>A and c.6208A>C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the PIEZO1 subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review PIEZO1 variants as a cause of GLD and discuss the uses of prenatal ES to date.
Phthalorubines: Fused‐Ring Compounds Synthesized from Phthalonitrile
Authors: Zheng Wei , Zhao Yuan , Zhuang Wen‐Hao , Wu Jing‐Jing , Wang Fang‐Zhou , Li Cheng‐Hui , Zuo Jing‐Lin
Published: September 2018

A series of dibenzo[a,f][1,3,5]triazino[2,1,6‐cd] pyrrolizine compounds have been synthesized from phthalonitriles by a facile intramolecular cyclization process using “half‐phthalocyanine” precursors, and they were characterized by X‐ray crystallography, 1H NMR spectroscopy, UV/Vis, and theoretical calculations. These compounds have spectroscopic profiles similar to phthalocyanines and porphyrins, although their inner‐core structures and coordination types are totally different. They can be regarded as a new class of aromatic fused‐ring compounds. The low‐energy absorption of these new fused‐ring compounds are located at around 600 nm. Such a low‐energy π–π* transition is scarce in aromatic compounds having a similar molecular size. According to the nomenclature of phthalocyanines, these types of compounds have been named phthalorubines (Prs).
Stereoselective Synthesis of Mechanically Planar Chiral Rotaxanes
Authors: Jinks Michael A. , de Juan Alberto , Denis Mathieu , Fletcher Catherine J. , Galli Marzia , Jamieson Ellen M. G. , Modicom Florian , Zhang Zhihui , Goldup Stephen M.
Published: September 2018

Chiral interlocked molecules in which the mechanical bond provides the sole stereogenic unit are typically produced with no control over the mechanical stereochemistry. Here we report a stereoselective approach to mechanically planar chiral rotaxanes in up to 98:2 d.r. using a readily available α‐amino acid‐derived azide. Symmetrization of the covalent stereocenter yields a rotaxane in which the mechanical bond provides the only stereogenic element.
Solvent‐Mediated Synthesis of Cyclobutane Isomers in a Photoactive Cadmium(II) Porous Coordination Polymer
Authors: Claassens Isabella E. , Nikolayenko Varvara I. , Haynes Delia A. , Barbour Leonard J.
Published: September 2018

Photochemical [2+2] cycloaddition of 1,4‐bis[2‐(4‐pyridyl)ethenyl]benzene, carried out in a CdII porous coordination polymer (PCP), produces different isomeric products depending on the guest solvent present in the PCP during irradiation. The nature of the included guest influences the conformation of the ligand, and thus the outcome of the cycloaddition reaction. We demonstrate controlled production of the two isomers from the same PCP by simple exchange of solvent.
Synthesis of Elongated Esters from Alkenes
Authors: Miura Tomoya , Funakoshi Yuuta , Nakahashi Junki , Moriyama Daisuke , Murakami Masahiro
Published: September 2018

A convenient method for synthesizing elongated aliphatic esters from alkenes is reported. An (alkoxycarbonyl)methyl radical species is generated upon visible‐light irradiation of an ester‐stabilized phosphorus ylide in the presence of a photoredox catalyst. This radical species adds onto the carbon–carbon double bond of an alkene to produce an elongated aliphatic ester.
Grouping Effect of Single Nickel−N4 Sites in Nitrogen‐Doped Carbon Boosts Hydrogen Transfer Coupling of Alcohols and Amines
Authors: Su Hui , Gao Peng , Wang Meng‐Ying , Zhai Guang‐Yao , Zhang Jun‐Jun , Zhao Tian‐Jian , Su Juan , Antonietti Markus , Li Xin‐Hao , Chen Jie‐Sheng
Published: September 2018

As a new type of heterogeneous catalyst with “homogeneous‐like” activity, single‐site transition‐metal materials are usually treated as integrated but separate active centers. A novel grouping effect is reported for single Ni−N4 sites in nitrogen‐doped carbon (Ni/NC), where an effective ligand‐stabilized polycondensation method endows Ni/NC nanocatalysts with a high content of single‐site Ni up to 9.5 wt %. The enhanced electron density at each single Ni−N4 site promotes a highly efficient hydrogen transfer, which is exemplified by the coupling of benzyl alcohol and aniline into N‐benzylaniline with a turnover frequency (TOF) value of 7.0 molN‐benzylaniline molmetal−1 h−1; this TOF outpaces that of reported stable non‐noble‐metal‐based catalysts by a factor of 2.
Reversible Band Gap Narrowing of Sn‐Based Hybrid Perovskite Single Crystal with Excellent Phase Stability
Authors: Ju Dianxing , Zheng Xiaopeng , Liu Jialiang , Chen Yan , Zhang Jian , Cao Bingqiang , Xiao Hang , Mohammed Omar F. , Bakr Osman M. , Tao Xutang
Published: September 2018

An intriguing reversible band gap narrowing behavior of the lead‐free hybrid perovskite single crystal DMASnI3(DMA=CH3NH2CH3+) from yellow to black is observed without phase transformation. We discuss the transformation mechanism in detail. More interestingly, the transformed samples in black can rapidly self‐heal into yellow ones when exposed to deionized water (DI water). Contrary to other hybrid perovskites, DMASnI3crystals exhibit excellent water phase stability. For example, DMASnI3was immersed in DI water for 16 h and no decomposition was observed. Inspired by its excellent water phase stability, we demonstrate a potential eco‐friendly application of DMASnI3in photo‐catalysis for H2evolution in DI water. We present the first H2evolution rate of 0.64 μmol h−1with good recycling properties for pure DMASnI3crystals. After the narrowing process, the optical band gap of DMASnI3can be lowered from 2.48 eV to 1.32 eV. Systematical characterizations are applied to investigate their structures and optoelectronic properties. The reversible band gap narrowing behavior and outstanding electrical properties, such as higher carrier mobility and long carrier lifetime show that DMASnI3has a great potential for optoelectronic applications.
Copper‐Catalyzed Ring Opening of Benzofurans and an Enantioselective Hydroamination Cascade
Authors: Xu‐Xu Qing‐Feng , Liu Qiang‐Qiang , Zhang Xiao , You Shu‐Li
Published: September 2018

A copper(II) acetate/(R)‐DTBM‐SEGPHOS‐catalyzed ring opening of benzofurans and enantioselective hydroamination cascade with dimethoxymethylsilane (DMMS) and hydroxylamine esters is described. Starting from readily available substituted benzofurans, a series of chiral N,N‐dibenzylaminophenols, which are of high interest in pharmaceutical chemistry, were obtained with excellent enantioselectivities (up to 66 % yield, 94 % ee).
Carbonyl–Olefin Cross‐Metathesis Through a Visible‐Light‐Induced 1,3‐Diol Formation and Fragmentation Sequence
Authors: Pitzer Lena , Sandfort Frederik , Strieth‐Kalthoff Felix , Glorius Frank
Published: September 2018

A visible‐light‐mediated approach to carbonyl–olefin cross‐metathesis is described. Photoinduced hole catalysis was used to promote the formation of 1,3‐diols from aldehydes and styrenes, which were then readily fragmented under acidic conditions to form the cross‐metathesis products. The use of 1,3‐diols as intermediates, rather than the energetically more demanding oxetanes, provides a new, orthogonal mechanistic strategy for carbonyl–olefin cross‐metathesis. Furthermore, this approach does not require any metals, ligands, or additives, and provides the products with high levels of E selectivity. A mechanistic rationale is provided and supported by both theoretical calculations and experiments. Additionally, a practical synthesis of a new acridinium‐based photocatalyst, including full characterization, is presented.
Strategies to Enhance the Photosensitization: Polymerization and the Donor–Acceptor Even–Odd Effect
Authors: Liu Shunjie , Zhang Haoke , Li Yuanyuan , Liu Junkai , Du Lili , Chen Ming , Kwok Ryan T. K. , Lam Jacky W. Y. , Phillips David Lee , Tang Ben Zhong
Published: September 2018

A particular challenge in the design of organic photosensitizers (PSs) with donor–acceptor (D‐A) structures is that it is based on trial and error rather than specific rules. Now these challenges are addressed by proposing two efficient strategies to enhance the photosensitization efficiency: polymerization‐facilitated photosensitization and the D‐A even–odd effect. Conjugated polymers have been found to exhibit a higher 1O2 generation efficiency than their small molecular counterparts. Furthermore, PSs with A‐D‐A structures show enhanced photosensitization efficiency over those with D‐A‐D structures. Theoretical calculations suggest an enhanced intersystem crossing (ISC) efficiency by these strategies. Both in vitro and in vivo experiments demonstrate that the resulting materials can be used as photosensitizers in image‐guided photodynamic anticancer therapy. These guidelines are applicable to other polymers and small molecules to lead to the development of new PSs.
Synthesis of tetramethylquinoline‐2,4‐diamine using FeNi3/KCC‐1/APTPOSS‐supported copper cyclam and salen complex as a reusable catalyst
Authors: Saadati Seyed Mahdi , Zhiani Rahele , Zahedifar Mahboobeh , Sadeghzadeh Seyed Mohsen
Published: September 2018

The potential application of an efficient, easily recoverable and reusable magnetically separable FeNi3/KCC‐1/APTPOSS nanoparticle‐supported Cu(II) cyclam and salen complex catalyst for the synthesis of tetramethylquinoline‐2,4‐diamine was investigated. The FeNi3/KCC‐1/APTPOSS/Cyclam@Salen/Cu(II) magnetic nanoparticles were thoroughly characterized using various techniques. This catalyst was utilized in the direct and selective chemical reaction of 1,3‐dichlorovinamidinium⋅PF6 with aniline for the synthesis of tetramethylquinoline‐2,4‐diamine. The recycled catalyst was analysed using inductively coupled plasma mass spectrometry, which showed only minor changes in the morphology after the reaction, thus confirming the robustness of the catalyst.
Highly resilient polyethylene elastomers prepared using α‐diimine nickel catalyst with highly conjugated backbone
Authors: He Feng , Wang Dan , Wu Anyang , Jiang Baiyu , Zhang Zhen , Cheng Zhenmei , Fu Zhisheng , Zhang Qisheng , Fan Zhiqiang
Published: September 2018

An α‐diimine nickel catalyst (Cat‐1) with highly conjugated acenaphthylene backbone was synthesized and used in ethylene polymerization. Compared with typical Brookhart catalyst B‐Cat, Cat‐1 could produce polyethylene with both higher molecular weight (up to 5.1 × 105 g mol−1) and branching density (up to 135 branches per 1000 carbons) in good polymerization activity. The polyethylene prepared using Cat‐1 with higher molecular weight and branching density possessed exceptional mechanical properties (ultimate tensile strength and elongation at break could reach 12.08 MPa and 1148%) and outstanding elastomeric recovery as compared with the polymer prepared using B‐Cat. Cat‐1 was synthesized using a simple reaction route and the polymerization conditions were suitable for the industrial polymerization process. The novel nickel catalyst Cat‐1 is promising for producing highly resilient polyethylene elastomers industrially.
Synthesis, spectroscopic characterization, x‐ray crystal structures, thermal behavior and antimicrobial activity of copper(II) complexes with the novel (3,5‐dimethyl‐1H‐pyrazol‐1‐yl)(morpholin‐4‐yl)methanethione
Authors: El‐Samanody El‐Sayed A.
Published: September 2018

The new (3,5‐dimethyl‐1H‐pyrazol‐1‐yl)(morpholin‐4‐yl) methanethione ligand (L) and its copper(II) chelates Cu(L)Br2 (1), Cu(L)Cl2 (2) and [Cu(L)2OH(H2O)]ClO4·1.5H2O (3) have been prepared. The coordination behavior of the ligand and the properties of the chelate compounds have been investigated by several physico‐chemical techniques. The structures of (L), (1), and (2) have been characterized by x‐ray single crystal diffraction. The ligand (L) crystalizes in the monoclinic P21/n space group, a = 11.2632(4), b = 7.9959(2), c = 13.4337(5) Å, α = 90, β = 106.3080(14), γ = 90°. The copper(II) complexes (1) and (2) show a distorted square‐planar geometries, with the ligand behaves as a bidentates NS chelating agent, coordinating to the copper(II) ions through the N atom of the pyrazolyl ring and the thione S atom, the third and fourth coordination sites are occupied by two halogen (Br− or Cl−) ions. The ESR spectra of the prepared complexes are consistent with d(x2‐y2)1 ground state with axial symmetry. The thermal analysis data of the Cu(II) complexes (1 and 2) indicated that they have similar thermal degradation pathways. The complexes displayed antimicrobial activity against various pathogenic bacteria and fungi higher than that of the free organic ligand. The reaction of Cu(L)Cl2 (2) with pyridine (py) in ethanol at room temperature does not form mixed‐ligand complex, but leads to complete substitution of the ligand (L). The product of the substitution reaction was characterized based on elemental analyses and FT‐IR measurements.
HDPE/UHMWPE composite foams prepared by compression molding with optimized foaming capacity and mechanical properties
Authors: Sun P. , Qian T. Y. , Ji X. Y. , Wu C. , Yan Y. S. , Qi R. R.
Published: September 2018

High‐density polyethylene (HDPE) foams have attracted increasing interest because of their excellent toughness, chemical stability, and low cost. However, the low melt strength and narrow foaming window usually lead to poor foaming capacity and performances prepared by compression molding under high temperature for HDPE. Herein, ultra high‐molecular weight polyethylene (UHMWPE) is used to improve the melt strength, melting temperature, mechanical properties, and foaming capacity of HDPE. The HDPE/UHMWPE composite foams are fabricated by the single‐stage compression molding with dicumyl peroxide (DCP) as a crosslinking agent and azodicarbonamide (ADC) as a foaming agent. The effects of UHMWPE, DCP, and ADC on the cellular morphology, foaming density, and mechanical properties have also been investigated. The results show that UHMWPE can enhance the foaming capacity and physical properties of HDPE and make it feasible to prepare HDPE foams with a wide density range just by adjusting the content of foaming agent. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 46768.
Role of isophorone diisocyanate in the optimization of adhesion tendency of polyurethane pressure sensitive adhesives
Authors: Akram Nadia , Zia Khalid Mahmood , Saeed Muhammad , Usman Muhammad , Khan Waheed Gul
Published: September 2018

The present work describes the role of accurate selection of diisocyanate on the adhesion strength of polyurethanes (PUs). The concentration of diisocyanate induces the hard segment (HS) in the main architecture of PUs which decides the viscoelastic properties of the polymers. A balanced ratio of viscoelastic properties ultimately determines the adhesion strength. The composition of the polymers consists of a blend of macrodiol of hydroxyl‐terminated polybutadiene and polypropylene glycol with different molecular weights. Isophorone diisocyanate (IPDI) is used to develop the urethane linkages by maintaining its contribution from 28 to 67% as HS contents. It determines the adhesion strength of the final product. The adhesion strength is evaluated by texture analyzer and 180° peel test. The probe tack analysis shows maximum adhesion energy of 156.2 J cm−2 and 180° peel test shows 18.80 N/25 mm peel force. The glass‐transition (T
g) values obtained through differential scanning calorimetry are in good agreement with theoretically calculated Flory–Fox temperature. The proportion of the loss tangent to the storage modulus (tan δ/E′) shows the optimum value of 2.80 MPa−1. The ideal concentration of IPDI results to achieve better adhesion properties of PU pressure sensitive adhesives. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47124.
Effects of inactivation of the cyAbrB2 transcription factor together with glycogen synthesis on cellular metabolism and free fatty acid production in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Kodama Yuta , Kawahara Akihito , Miyagi Atsuko , Ishikawa Toshiki , Kawai‐Yamada Maki , Kaneko Yasuko , Takimura Yasushi , Hihara Yukako
Published: September 2018

Deletion of the cyAbrB2 (Sll0822) transcription factor in Synechocystis sp. PCC 6803 causes aberrant accumulation of glycogen. We previously tried to redirect the excess carbon stored as glycogen in the
cyabrB2‐disrupted (∆
cyabrB2) mutant by knockout of the
glgC (slr1176) gene encoding glucose‐1‐phosphate adenylyltransferase. However, complete knockout could not be attained, suggesting that accumulation of glycogen is essential for the Δ
cyabrB2 mutant. In this study, we introduced the
cyabrB2 gene fused to the copper‐inducible
petE promoter into the ∆
cyabrB2 mutant. After complete knockout of
glgC in the presence of copper, expression of P
petE‐
cyabrB2 was turned off by copper removal to examine the effect of the double knockout of
cyabrB2 and
glgC. Metabolome analysis and electron microscopic observation revealed that the double knockout causes a large decrease of sugar phosphates in glycolytic and oxidative pentose phosphate pathways and an increase of organic acids in the tricarboxylic acid cycle, amino acids and storage compounds such as polyhydroxybutyrate. When the ability of production of free fatty acids was conferred, synergetic positive effects of knockout of
cyabrB2 and
glgC on productivity were observed by removal of both copper and nitrogen. The P
petE‐
cyabrB2Δ
glgC strain will further serve as a platform for studies on carbon allocation and metabolic engineering.
Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis
Authors: Bellei Elisa , Monari Emanuela , Ozben Serkan , Koseoglu Bitnel Mesrure , Topaloglu Tuac Selma , Tomasi Aldo , Bergamini Stefania
Published: September 2018

Objectives

Restless legs syndrome (RLS) can lead to severe clinical consequences, thus negatively impacts on patients’ overall health and quality of life. Nevertheless, the pathophysiology of RLS is still unclear, resulting in underestimate, incorrect, or ignored diagnosis and in limited management and treatment. The aim of this study was to compare the plasma proteome of RLS patients and healthy controls, in the search of diagnostic biomarkers related to the disease severity.

Materials and Methods

Two‐dimensional gel electrophoresis coupled with liquid chromatography‐mass spectrometry was employed to analyze plasma samples of 34 patients with primary RLS, divided into two subgroups according to the disease severity: MMS group (mild‐moderate symptoms) and HS group (severe and very severe symptoms), and 17 age‐ and sex‐matched control subjects. Sleep quality, daytime sleepiness, and the level of depression were also evaluated.

Results

We identified eight upregulated spots, corresponding to five unique proteins, in both RLS group vs. controls (alpha‐1B‐glycoprotein, alpha‐1‐acid glycoprotein 1, haptoglobin, complement C4‐A, and immunoglobulin kappa constant); five increased spots, consistent with three unique proteins, only in HS‐RLS (kininogen‐1, immunoglobulin heavy constant alpha 1, and immunoglobulin lambda constant 2); one downregulated spot in both patient's groups (complement C3) and another one only in HS‐RLS (alpha‐1‐antitrypsin).

Conclusions

The significantly different plasma proteins detected in RLS were mainly associated with inflammation, immune response, and cardiovascular disorders. Particularly, the gradual increasing in immunoglobulins could be indicative of the disease severity and evolution. Accordingly, these proteins may represent a valid set of useful biomarkers for RLS diagnosis, progression and treatment.
Can business‐oriented managers be effective leaders for corporate sustainability? A study of integrative and instrumental logics
Authors: Joseph Jay , Orlitzky Marc , Gurd Bruce , Borland Helen , Lindgreen Adam
Published: September 2018

This qualitative study investigates whether the views of managers need to be congruent with the corporate sustainability (CS) logics—either integrative or instrumental—of their employing organization. We assessed the CS performance of 25 organizations within the Australian forestry and wood products industry and analyzed the CS orientations of 32 senior managers within these companies to explore whether their individual CS views were consistent with organizational CS logics. The findings indicate that, in general, better performing organizations are led by managers that hold the integrative view, whereas poorer performing organizations are more likely to have managers with an instrumental view of CS. Nonetheless, there were noteworthy exceptions to this conclusion. The findings indicate that, under certain industry conditions, managers who hold an instrumental view may be able to generate ecological and social organizational outcomes that are at least equal to those produced by integrative managers.
Coronary bifurcation bench test using multimodality imaging: Impact of stent strut link location on stent deformity and jailed side‐branch orifices during re‐proximal optimizing technique
Authors: Kume Teruyoshi , Yamada Ryotaro , Koyama Terumasa , Tamada Tomoko , Imai Koichiro , Fukuhara Kenzo , Goryo Yutaka , Kawamura Ai , Okamoto Hiroshi , Neishi Yoji , Uemura Shiro
Published: September 2018

Objectives

The purpose of this study was to compare the stent deformation, obstruction of stent struts at a jailed side branch (SB) ostium, and stent strut malapposition after a repetitive proximal optimizing technique (re‐POT) sequence between bifurcation lesions with and without stent links at SB ostia in ex vivo experimental setting.

Methods

A flexible urethane coronary bifurcation bench model was used, and crossover single stent implantation was performed from main branch (MB) with re‐POT sequence. Under videoscope observation, presence (link group, n = 12) or absence (no‐link group, n = 12) of stent link at distal semicircle of SB ostium was intentionally set, and rewiring was performed through distal cell in four different stent platforms.

Results

There were no significant differences in the rate of malapposed struts and in SB jailing ratio after the re‐POT sequence between the link and no‐link groups. SB jailing ratio increased significantly from 8.0% to 9.6% during the second POT procedure (P < 0.001). SB jailing ratio after the second POT procedure differed among stent platforms.

Conclusions

The presence of a stent link at an SB ostium was not associated with a rate of malapposed struts and SB jailing ratio after the re‐POT sequence. SB jailing ratio was significantly increased after second POT procedure, but was different among stent platforms. The Xience stent might minimize the change of SB jailing ratio and be suitable for coronary bifurcation stenting using re‐POT sequence.
Twelve‐month outcomes of patients unsuitable for prolonged DAPT presenting with an acute coronary syndrome and treated with polymer‐free biolimus A9 drug‐coated stents
Authors: Kinnaird Tim , Abdul Fairoz , Hailan Ahmed , Sheikh Azeem , Hinton Jonathan , Yazji Khaled , Elangovan Senthil , Yousef Adnan , Gallagher Sean , Choudhury Anirban , Anderson Richard , O'Kane Peter , Smith David
Published: September 2018

Introduction

Prolonged dual anti‐platelet therapy (DAPT) is undesirable in certain patients. The biolimus‐A9 drug‐coated stent (BA9‐DCS) has a rapid drug‐elution profile allowing shortened DAPT.

Methods

The demographics, procedural data, and clinical outcomes for 505 patients presenting with an ACS to three UK centres and treated with a BA9‐DCS stent (PCI‐DCS) were collected, and compared to a consecutive ACS cohort of unselected patients treated in the same period with drug‐eluting stents (PCI‐DES).

Results

PCI‐DCS patients were older, more often female with hypertension, chronic kidney disease, severe LV dysfunction, and peripheral vascular disease more frequent than the PCI‐DES cohort. PCI‐DCS patients had a much higher Mehran bleed risk score (21.5 ± 7.7 vs. 15.9 ± 7.7, P < 0.0001). Baseline disease burden was greater in the PCI‐DCS cohort with more left main and three vessel disease. During PCI, more stents (1.91 ± 1.1 vs. 1.57 ± 0.94, P < 0.0001), total stent length (38.2 ± 20.8 vs. 31.4 ± 20.3, P < 0.0001) and longer stents (38.2 ± 20.8 vs. 31.4 ± 20.3 mm, P < 0.0001) were used in the PCI‐DCS cohort with rotational atherectomy also used more frequently. Physician‐recommended DAPT duration was 2.9 ± 3.9 months for PCI‐DCS patients and 11.3 ± 2.4 months for PCI‐DES patients (P < 0.0001). At 12‐month follow‐up, definite stent thrombosis (0.6% vs. 1.1%) and TLR (3.2% vs. 2.7%) rates were similar between the two groups. After adjustment for baseline differences, there were no statistically significant differences in death and combined MACE rates at 12 months.

Conclusions

The outcomes of patients treated with polymer‐free BA9 drug‐coated stent who present with an ACS and who were deemed unsuitable for prolonged DAPT are encouraging. Further studies are warranted.
Fracture in drug‐eluting stents increases focal intimal hyperplasia in the atherosclerosed rabbit iliac artery
Authors: Conway Claire , Desany Gerard J. , Bailey Lynn R. , Keating John H. , Baker Brian L. , Edelman Elazer R.
Published: September 2018

Objectives

Drug‐eluting stent (DES) strut fracture (SF) is associated with higher incidence of In‐stent restenosis (ISR)—return of blockage in a diseased artery post stenting—than seen with bare metal stents (BMS). We hypothesize that concomitance of drug and SF leads to greater neointimal response.

Background

Controlled release of therapeutic agents, such as sirolimus and its analogs, or paclitaxel from has reduced tissue based DES failure modes compared to BMS. ISR is dramatically reduced and yet the implications of mechanical device failure is magnified.

Methods

Bilateral Xience Everolimus‐eluting stents (EES) were implanted in 20 New Zealand White rabbits on normal (n = 7) or high fat (HF)/high cholesterol (HC) (n = 13) diets. Implanted stents were intact or mechanically fractured. Everolimus concentration was as packaged or pre‐eluted. After 21 days, stented vessels were explanted, resin embedded, MicroCT scanned, and analyzed histomorphometrically.

Results

Fractured EES were associated with significant (P < 0.05) increases in arterial stenosis and neointimal formation and lower lumen‐to‐artery area ratios compared to intact EES. Hyperlipidemic animals receiving pre‐eluted EES revealed no significant difference between intact and fracture groups.

Conclusions

SF increases intimal hyperplasia, post EES implant, and worse with more advanced disease. Pre‐eluted groups, reflective of BMS, did not show significant differences, suggesting a synergistic effect of everolimus and mechanical injury, potentially explaining the lack of SF reports for BMS. Here, we report that ISR has a higher incidence with SF in EES, the clinical implication is that patients with SF after DES implantation merit careful follow‐up.
Autologous blood reinfusion during iatrogenic acute hemorrhagic cardiac tamponade: Safety and feasibility in a cohort of 30 patients
Authors: Fiocca Luigi , Cereda Alberto F. , Bernelli Chiara , Canova Paolo A. , Serino Federica , Niglio Tullio , Musumeci Giuseppe , Guagliumi Giulio , Vassileva Angelina , Senni Michele , Valsecchi Orazio
Published: September 2018

Background

Iatrogenic hemorrhagic pericardial tamponade (IHPT) represents a life‐threating condition requiring emergency pericardiocentesis. In this clinical context, reinfusion of pericardial blood can stabilize the patient and sustain hemodynamic conditions.

Aims and Methods

We reviewed all cases of IHPT occurred at our hospital over a 10 years span. In all patient autologous blood reinfusion through a femoral vein was performed.

Results

In our clinical experience of 30 consecutive patients with hemorrhagic cardiac tamponade, this technique was successful to limit blood transfusions, to prevent further clinical worsening and bridge patients with intractable bleeding, to cardiac surgery. No major adverse reactions were directly related to blood autotransfusion.

Conclusion

In the complex clinical scenario of acute tamponade occurring during catheter‐based cardiac procedures, autotransfusion of pericardial blood through a femoral vein is safe and effective. It can be a useful trick up the sleeve of the interventional cardiologist.
Open sesame technique in percutaneous coronary intervention for ST‐elevation myocardial infarction
Authors: Kimura Toshio , Nishibori Yoshiharu , Miki Kojiro , Maruyama Takao
Published: September 2018

In patients with ST‐elevation myocardial infarction (STEMI), delays in reperfusion attenuate the benefit of primary percutaneous coronary intervention (PCI) and associate with higher mortality rates. Although PCI operators are making their best effort in time saving for reperfusion, it is sometimes challenging and takes time to pass the guide wire across the target lesions. A totally occluded lesion in which a side branch was bifurcating at the proximal end of the occluded segment is one of the most technically challenging anatomies of the target lesion because it is difficult to identify the entry point of the occluded segment. A side branch technique, termed “Open Sesame Technique” (OST), has been previously introduced for chronic total occlusion (CTO) lesion in which a side branch was bifurcating at the proximal end of the occluded segment. We herein present two cases applying this technique in STEMI with totally occluded lesions at bifurcation as a culprit lesion, in which the entry point was not identified on the initial angiography. PCI were performed successfully using the OST in both cases, which resulted in saving procedural time and contrast volume without any complications. This technique can be effective not only in PCI for CTO lesions but also in primary PCI for STEMI cases with occluded bifurcation lesions.
Acute and long‐term outcomes after polytetrafluoroethylene or pericardium covered stenting for grade 3 coronary artery perforations: Insights from G3‐CAP registry
Authors: Pavani Marco , Cerrato Enrico , Latib Azeem , Ryan Nicola , Calcagno Simone , Rolfo Cristina , Ugo Fabrizio , Ielasi Alfonso , Escaned Javier , Tespili Maurizio , Conrotto Federico , Mancone Massimo , Colombo Antonio , Varbella Ferdinando
Published: September 2018

Background

Covered stent (CS) implantation is considered a useful device in the setting of Grade III Coronary Perforation (G3CP), one of the most harmful PCI complication. However, data regarding efficacy of this device and clinical outcomes are still limited.

Methods and results

From 1993 to 2015, among 97,779 patients from 9 European centres undergoing PCI, 224 patients had G3CP (0.23%), and 102 patients were managed with CS implantation (96 with PTFE, 6 with pericardium). Device oriented composite endpoint (DOCE), a composite of cardiac death, target lesion revascularization, and stent thrombosis (ST) in‐hospital and at long term follow‐up were evaluated. G3‐CP perforations were successfully sealed with CS in 88 patients (86.3%) with need of intraprocedural pericardiocentesis in one‐third of cases. Protamine as heparin reversal agent was administered in 36 (35%) of cases. The cumulative incidence of in‐hospital DOCE were 16.6% (17/102): death 14.7%, TLR 2.9%, ST 3.9%. At long‐term follow‐up (mean 42 ± 38 months), DOCE rates occurred in 19.7%: death 7.4%, TLR 11%, and ST 6.2%. Indication to Dual Antiplatelet Therapy (DAPT) was lifelong in 20% of cases, 1 to 6 months in 22.5% and 12‐months in 57.5% without differences in long‐term DOCE before and after DAPT interruption (8.0 vs. 6.6%, respectively, P = 0.20).

Conclusions

Use of CS was successful in sealing grade 3 coronary artery perforations in the majority of cases. Beside the high rate of clinical events at short and long‐term, ST remains the leading cause of device failure.
Day‐case percutaneous left atrial appendage occlusion—Safety and efficacy
Authors: Williams Timothy , Alsanjari Osama , Parker Jessica , Gannaway Alex , Thomson Catherine , Gomes Arionilson , Hildick‐Smith David
Published: September 2018

Objectives

We evaluated the safety and efficacy of percutaneous left atrial appendage (LAA) occlusion performed as a day case procedure.

Background

LAA occlusion has been shown to be safe and effective for stroke prevention in patients with atrial fibrillation. It has not been shown if the procedure can safely be performed on a day‐case basis.

Methods

Retrospective analysis was made of 117 LAA occlusion procedures in a single large teaching hospital in the UK. Procedural success, procedural complications, length of stay, and readmission data were examined.

Results

Successful deployment of a device was possible in all but one patient (whose appendage was too large). Major in‐hospital complications occurred in 1.7% of patients (both femoral vascular). Same‐day discharge was made in 66% of patients overall. Since January 2016, only 3 of 59 patients (5%) have remained in hospital overnight following LAAO. Echocardiography 2–4 hr postprocedure was undertaken prior to discharge. One patient was readmitted within 7 days but this readmission would not have been prevented by overnight stay.

Conclusions

LAA occlusion can be safely performed as a day case procedure with acceptable complication rates and no increment of complications related to the lack of routine overnight stay.
Left atrial hemodynamics and left ventricular remodeling –predictors of outcomes after Transcatheter mitral valve repair with the MitraClip device
Authors: Lazkani Mohamad , Sawant Abhishek C. , Taase Alicia , Khan Sahoor , Fang Kenith , Iyer Vijay , Pershad Ashish
Published: September 2018

Background

Increased afterload and reduced left ventricular (LV) performance are sequela of mitral valve repair. However, hemodynamic left atrial and ventricular parameters that can predict outcome following mitral valve repair remain elusive.

Methods

One hundred and two consecutive patients undergoing MitraClip procedure from 2014 to 2017 at Banner University Medical Center were enrolled in this study. All patients underwent pre‐procedure echocardiograms and intra‐procedure invasive left atrial (LA) pressure monitoring. Clinical, laboratory, and procedural parameters were collected. The primary end‐point was the composite outcome of all‐cause mortality and repeat hospitalization within 90 days.

Results

The mean age was 77 ±10 years, the majority were Caucasians (93, 91.2%) and 47 (46.1%) were males. Thirty‐two patients (31.4%) had diabetes, 39 (38.2%) had renal insufficiency, and 38 (37.3%) had a history of congestive heart failure. The median society of thoracic surgeons score was 6.7% (Interquartile range [IQR]: 3.9, 10.2). Immediately post‐procedure there was a significant reduction in the LA pressure (Mean 12.0 vs. 18.6 mmHg, P < 0.001) and pulmonary artery systolic pressure (43.5 vs. 53.2 mmHg, P = 0.001) compared to baseline. LA pressure was an independent predictor of the composite outcome in an unadjusted (OR = 1.07, 95% CI: 1.00–1.13, P = 0.03) and adjusted (OR = 1.07, 95% CI: 1.00–1.14, P = 0.03) analysis respectively.

Conclusion

LA pressure drop is an independent predictor of outcome after the MitraClip procedure. This finding has implications for early identification of patients at risk of poor outcomes and instituting aggressive medical therapy and close follow‐up for avoiding hospitalizations for heart failure decompensation.
Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: Insights from the TRANSLATE ACS study
Authors: Ibrahim Homam , Kaltenbach Lisa A. , Hess Connie N. , Recchia Tammy , Effron Mark B. , Stone Gregg W. , Wang Tracy Y.
Published: September 2018

Introduction

Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y12 inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y12 inhibitors are unclear.

Methods and results

We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010–2012). We used propensity matching to compare 6‐week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI.

Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P < 0.001) than those without planned GPI use. Planned GPI was used less often with prasugrel/ticagrelor versus clopidogrel (37.1% vs. 43.3%), or when any P2Y12 inhibitor was given >6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99–1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13–1.59).

Conclusion

Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE.
Impact of left atrial compliance improvement on functional status after percutaneous mitral valvuloplasty
Authors: Athayde Guilherme Rafael Sant'Anna , Nascimento Bruno Ramos , Elmariah Sammy , Lodi‐Junqueira Lucas , Soares Juliana Rodrigues , Saad Gabriel Prado , da Silva Jose Luiz Padilha , Tan Timothy C. , Hung Judy , Palacios Igor F. , Levine Robert A. , Nunes Maria Carmo Pereira
Published: September 2018

Background

Conventional hemodynamic parameters may not accurately predict symptomatic improvement after percutaneous mitral valvuloplasty (PMV). Changes in left heart chamber compliance following adequate relief o0066 mitral stenosis (MS) may be useful in determining functional capacity after PMV. This study aims to determine the acute effects of PMV on compliance of the left heart and whether its changes relate to the patient's functional capacity.

Methods

One‐hundred thirty‐seven patients with severe MS undergoing PMV were enrolled. Left atrial (Ca) and left ventricular (Cv) compliance were invasively estimated and net atrioventricular compliance (Cav) was calculated before and immediately after the procedure. B‐type natriuretic peptide (BNP) levels were obtained before and 24 hr after the procedure. The primary endpoint was functional status at 6‐month follow‐up, and the secondary endpoint was a composite of death, mitral valve (MV) replacement, repeat PMV, new onset of atrial fibrillation, or stroke in patients in whom PMV was successful.

Results

The mean age was 43 ± 12 years, and 119 patients were female (87%). After PMV, Ca and Cav improved significantly from 5.3 [IQR 3.2–8.2] mL/mmHg to 8.7 [5.3–19.2] mL/mmHg (P < 0.001) and 2.2 [1.6–3.4] to 2.8 [2.1–4.1] mL/mmHg (P < 0.001), respectively, whereas Cv did not change (4.6 [3.2–6.8] to 4.4 [3.1–5.6]; P = 0.637). Plasma BNP levels significantly decreased after PMV, with no correlation between its variation and changes in left chamber compliance. At 6‐month follow‐up, NYHA functional class remained unchanged in 32 patients (23%). By multivariable analyses, changes in Ca immediately after PMV (adjusted OR 1.42; 95% CI 95% 1.02 to 1.97; P = 0.037) and younger age (adjusted OR 0.95; CI 95% 0.92–0.98; P = 0.004), predicted improvement in functional capacity at 6‐month follow‐up, independent of postprocedural data. The secondary endpoint were predicted by post‐PMV mean gradient (adjusted HR 1.363; 95% CI 95% 1.027–1.809; P = 0.032), and lack of functional improvement at 6‐month follow‐up (adjusted HR 4.959; 95% 1.708–14.403; P = 0.003).

Conclusions

Ca and Cav increase significantly after PMV with no change in Cv. The improvement of Ca is an important predictor of functional status at 6‐month follow up, independently of other hemodynamic data. Postprocedural mean gradient and lack of short‐term symptomatic improvement were predictors of adverse outcome.