Effect of Aryl Substituents and Fluorine Addition on the Optoelectronic Properties and Organic Solar Cell Performance of a High Efficiency Indacenodithienothiophene‐alt‐Quinoxaline π‐Conjugated Polymer

A series of donor‐acceptor (D‐A) π‐conjugated polymers, based on indacenodithienothiophene (IDTT) as an electron‐donating unit and quinoxaline as an electron‐deficient moiety, are synthesized via a Pd‐catalyzed Stille cross‐coupling polymerization. Molecular characteristics, photovoltaic parameters, and optoelectronic properties are examined through structural differences corresponding to thienyl versus phenyl side group substitutions on the IDTT and the non‐fluorinated versus the monofluoro quinoxaline derivatives. One of the most important outcome is that the power conversion efficiency (PCE) in the studied polymers is more device architecture dependent (conventional vs inverted) rather than chemical structure dependent. From single junction solar cells based on bulk heterojunction polymer:[6,6]‐phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) systems as the active layer, a maximum PCE of 5.33% has been achieved from the polymer containing the thienyl substituent on the IDTT and one fluorine atom on the quinoxaline. This demonstrates that finding the optimum molecular weight of ThIDTT‐QF or introducing the monofluoro‐quinoxaline in a regioregular motif in the polymer backbone significantly higher PCE can be expected versus the fully optimized high performance PhIDTT‐Q conjugated polymer.     

Aerobic fitness is a potential crucial factor in protecting paralympic athletes with locomotor impairments from atherosclerotic cardiovascular risk

Sport Sciences for Health - To test the hypothesis that aerobic fitness is inversely related to the risk of atherosclerotic cardiovascular disease (ACVD) in athletes with locomotor impairments...     

Epidermolytic hyperkeratosis in a Hispanic family resulting from a mutation in the keratin 1 gene

Epidermolytic hyperkeratosis (EHK; bullous congenital ichthyosiform erythroderma) is a genodermatosis resulting from mutations in either the keratin 1 (K1) or keratin 10 (K10) genes. It is characterized by erythroderma and blistering at birth, and the development of ichthyotic hyperkeratosis and palmoplantar keratoderma. A wide variety of mutations within the highly conserved helix initiation and termination motifs of the central rod domains of the K1 or K10 genes correlate with the highly variable phenotypic severity observed in EHK. We report a novel missense mutation designated L214P in a large Hispanic pedigree with EHK. The mutation is located in the highly conserved 1A segment of the alpha-helical rod domain. The presence of this mutation underscores the importance of sequence alterations located in the central rod domain in the pathogenesis of EHK.     

Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes

Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as “writer” of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann–Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein–Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions.Subject terms: Epigenetics, Mutation     

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer

Checkpoint-blockade therapy (CBT) is approved for select colorectal cancer (CRC) patents, but additional immunotherapeutic options are needed. We hypothesized that vaccination with carcinoembryonic antigen (CEA) and Her2/neu (Her2) peptides would be immunogenic and well tolerated by participants with advanced CRC. A pilot clinical trial (NCT00091286) was conducted in HLA-A2⁺ or -A3⁺ Stage IIIC-IV CRC patients. Participants were vaccinated weekly with CEA and Her2 peptides plus tetanus peptide and GM-CSF emulsified in Montanide ISA-51 adjuvant for 3 weeks. Adverse events (AEs) were recorded per NIH Common Terminology Criteria for Adverse Events version 3. Immunogenicity was evaluated by interferon-gamma ELISpot assay of in vitro sensitized peripheral blood mononuclear cells and lymphocytes from the sentinel immunized node. Eleven participants were enrolled and treated; one was retrospectively found to be ineligible due to HLA type. All 11 participants were included in AEs and survival analyses, and the 10 eligible participants were evaluated for immunogenicity. All participants reported AEs: 82% were Grade 1-2, most commonly fatigue or injection site reactions. Two participants (18%) experienced treatment-related dose-limiting Grade 3 AEs; both were self-limiting. Immune responses to Her2 or CEA peptides were detected in 70% of participants. Median overall survival (OS) was 16 months; among those enrolled with no evidence of disease (n = 3), median OS was not reached after 10 years of follow-up. These data demonstrate that vaccination with CEA or Her2 peptides is well tolerated and immunogenic. Further study is warranted to assess potential clinical benefits of vaccination in advanced CRC either alone or in combination with CBT.     

Branched Oligophenylenes with Phenylene–Ethynylene Fragments as Anode Interfacial Layer for Solution Processed Optoelectronics

Two branched oligophenylenethynylenes with phenylene or biphenylene moieties as inter‐nodal fragments are synthesized by the Sonogashira reaction for optoelectronic applications. The branching of polyphenylenethynylenes influences the electro‐optical properties, but cannot be precisely controlled, while its determination is often hardly addressed. The optical investigation, supported by nuclear magnetic resonance (NMR) studies, of oligophenylenethynylenes and the properly synthesized model compounds is performed to get insights on the branching and related effect on the material performance. The proposed branched oligophenylenethynylenes are good ultraviolet emitters in solution, while in solid‐state aggregation phenomena strongly affect emission properties. However, the interactions between π‐electrons on phenylene and ethynylene of neighboring molecules in films enhance intermolecular charge transport (hole mobility = 3.2 × 10^?3 cm² V^?1s^?1) making them optimal candidates as hole transport materials in optoelectronic devices. The insertion of the oligophenylenethynylene film as a hole transporting layer in multilayered solution processes blue, green, and red electroluminescent diodes, enhances OLEDs electro‐optical properties.     

ASO Visual Abstract: Effects of Adjuvant Endocrine Therapy Adherence and Radiation on Recurrence and Survival Among Older Women With Early-Stage Breast Cancer

Annals of Surgical Oncology -     

DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies

PurposeChromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection.MethodsDNA methylation data was generated on extracted blood samples from 129 affected individuals with the Illumina Infinium EPIC arrays and analyzed using an established bioinformatic pipeline.ResultsThe DNA methylation profiles matched and confirmed the sequence findings in both the discovery and validation cohorts. Twenty-five affected individuals carrying a variant of uncertain significance, did not show a methylation profile matching any of the known episignatures. Three additional variant of uncertain significance cases with an identified KDM6A variant were re-classified as likely pathogenic (n = 2) or re-assigned as Wolf-Hirschhorn syndrome (n = 1). Thirty of the 33 Next Generation Sequencing negative cases did not match a defined episignature while three matched Kabuki syndrome, Rubinstein-Taybi syndrome and BAFopathy respectively.ConclusionWith the expanding clinical utility of the EpiSign assay, DNA methylation analysis should be considered part of the testing cascade for individuals presenting with clinical features of Mendelian chromatinopathy disorders.     

Diode Laser Assisted Filament Winding of Thermoplastic Matrix Composites

A new consolidation method for the laser-assisted filament winding of thermoplastic prepregs is discussed: for the first time a diode laser is used, as well as long glass fiber reinforced polypropylene prepregs. A consolidation apparatus was built by means of a CNC motion table, a stepper motor and a simple tensioner. Preliminary tests were performed in a hoop winding configuration: only the winding speed was changed, and all the other process parameters (laser power, distance from the laser focus, consolidation force) were kept constant. Small wound rings with an internal diameter of 25 mm were produced and compression tests were carried out to evaluate the composite agglomeration in dependence of the winding speed. At lower winding speeds, a strong interpenetration of adjacent layers was observed.