Abstract Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespread and rapidly growing use. In medicine however, it remains a novel approach to reach out to patients. Yet, they have the potential for further improving current health care. Electronic platforms could support therapy adherence and communication between physicians and patients. The power of social media as well as other electronic devices can improve adherence as evidenced by the development...
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Abstract Intergenerational fitness effects on offspring due to the early life of the parent are well studied from the standpoint of the maternal environment, but intergenerational effects owing to the paternal early life environment are often overlooked. Nonetheless, recent laboratory studies in mammals and ecologically relevant studies in invertebrates predict that paternal effects can have a major impact on the offspring's phenotype. These non‐genetic, environment‐dependent paternal effects provide...
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Publication date: Available online 7 August 2019Source: BrachytherapyAuthor(s): Ali-Reza Mehan Haidari, Nelson Miksys, Paul Soubiran, Joanna Ewa Cygler, Oliver Holmes, Gad Perry, Rowan M. ThomsonAbstractPurposePermanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose...
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Publication date: Available online 8 August 2019Source: Sleep MedicineAuthor(s): M. Gorgoni, A. D’Atri, S. Scarpelli, F. Reda, L. De GennaroAbstractSleep has a crucial role in brain functioning and cognition, and several sleep electroencephalography (EEG) hallmarks are associated with intellectual abilities, neural plasticity, and learning processes. Starting from this evidence, a growing interest has been raised regarding the involvement of the sleep EEG in brain maturation and cognitive functioning...
Publication date: Available online 7 August 2019Source: Sleep MedicineAuthor(s): Ahuti Das-Friebel, Anna Gkiouleka, Alexander Grob, Sakari LemolaAbstractObjectivesPreliminary evidence suggests that delaying school start times is an effective tool for improving adolescent sleep duration. Our study assessed whether a policy driven 20-minute delay in school start times led to an increase in adolescents’ weekday bed and wake up times.MethodData collected via school satisfaction surveys concerned 663...
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New England Journal of Medicine, Volume 381, Issue 6, Page 586-587, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 584-585, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 552-565, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 585-586, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 589-590, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 531-542, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 500-502, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 505-507, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 587-589, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 566-566, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 583-583, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, August 2019.
New England Journal of Medicine, Volume 381, Issue 6, Page 567-577, August 2019.
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Familial chylomicronemia syndrome is a rare genetic disorder characterized by reduced or absent lipoprotein lipase (LPL) activity. LPL mediates lipolysis of plasma triglycerides in chylomicrons and other triglyceride-rich lipoproteins, and its absence leads to marked fasting and postprandial…
Pheochromocytoma fascinates and, at times, confounds clinicians. The symptoms due to hypersecretion of catecholamines can mimic more than 30 medical disorders. This rare tumor can be lethal if left undiagnosed. Thus, rapid recognition is vital. Yet selecting a good approach to biochemical testing…
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Abstract Objective The aim of this study is to describe the clinical manifestations and treatment options of patients having dural sinus malformation with giant pouch (DSMGP) in a tertiary pediatric center. Introduction Dural sinus malformation with giant pouch (DSMGP) is a rare vascular malformation affecting fetuses, newborns, and infants. It is characterized...
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Abstract Epithelioid hemangioendotheliomas (EHE) of the liver are rare, low‐malignant vascular tumors whose molecular pathogenesis is incompletely understood. The diagnosis of EHE is challenging, and the course of the disease can be highly variable. Therapeutic options for EHE are limited, including resection of primary and metastatic tumors, organ transplantation and rather ineffective systemic approaches. Driver mutations have been reported (fusion transcripts of either YAP‐TFE3 or WWTR1‐CAMTA1)...
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Abstract Alternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancers. However, the relationship between the DDX family and cancer has not been fully elucidated. In this study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using TCGA dataset of colorectal cancers (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analysis was performed using three...
Abstract Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA‐A24‐ and HLA‐A2‐restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro...
Abstract Lysosomal‐associated protein transmembrane 4 beta (LAPTM4B), a proto‐oncogene, has been demonstrated to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor‐suppressive or oncogenic effects in breast cancer. In this study, miR‐132‐3p, which was predicted by relevant softwares, was confirmed to directly...
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Abstract SATB2‐associated syndrome (SAS) is a recently‐identified disorder characterized by neurodevelopmental deficits and craniofacial anomalies. Assessments of speech, language, and feeding‐related issues were conducted among 61 individuals with SAS (median age = 86 months, range = 26 months to 29 years of age). Individuals with SAS were mostly non‐verbal communicators (72.1%) with severe deficits in both language comprehension and expression. The majority of individuals had receptive...
Abstract The PAK family of proteins function as key effectors of RHO family GTPases in mammalian cells to regulate many pathways including Ras/Raf/MEK/ERK and Wnt/β‐catenin, amongst others. Here we report an individual with a novel autosomal dominant disorder characterized by severe regressive autism, intellectual disability, and epilepsy. Exome sequencing of the proband and her parents revealed a de novo variant in the PAK1 gene ([NM_001128620] c.362C > T/p.Pro121Leu). Studies in patient...
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Boy Erased and The Miseducation of Cameron Post, two movies released in 2018, raised awareness of efforts to change people’s sexual orientation, also known as conversion therapy. These films portray the trauma inflicted by such efforts and the patently false science underpinning this debunked…
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Pheochromocytoma fascinates and, at times, confounds clinicians. The symptoms due to hypersecretion of catecholamines can mimic more than 30 medical disorders. This rare tumor can be lethal if left undiagnosed. Thus, rapid recognition is vital. Yet selecting a good approach to biochemical testing…
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Abstract Mesenteric venous thrombosis (MVT) is one of major causes leading to severe mesenteric ischemia. Vascular network plays an important role during the occurrence and development of MVT. However, there lacks an appropriate imaging method, which features advanced volumetric resolving capability, superior sensitivity to hemoglobin, and ultra‐large field‐of‐view (FOV), to investigate vascular response of MVT. In this study, we developed and applied a large‐field‐of‐view optical resolution photoacoustic...
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Pheochromocytoma fascinates and, at times, confounds clinicians. The symptoms due to hypersecretion of catecholamines can mimic more than 30 medical disorders. This rare tumor can be lethal if left undiagnosed. Thus, rapid recognition is vital. Yet selecting a good approach to biochemical testing…
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Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Allergens (NDA) was asked to deliver an opinion on nicotinamide riboside chloride as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including an evaluation of the safety of its use in food supplements as a source of niacin, and the bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. The NF, a synthetic form of nicotinamide riboside, is proposed to...
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You can’t walk into a pediatric intensive care unit (PICU) anywhere in the world without being viscerally struck by sights, smells, and sounds that can easily overwhelm the uninitiated. Every child in a PICU is attached to various monitors that seem to reduce that child’s life to a set of vital…
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To the Editor: In June and July of 2018, Sphingomonas paucimobilis bacteremia occurred in six patients at Roswell Park Comprehensive Cancer Center; the first three cases were diagnosed within 1 week of one another (Table 1). The common source was contaminated hydromorphone that had been…
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Presentation of Case. Dr. Kelsey Hills-Evans (Medicine): A 39-year-old woman with cyclic vomiting syndrome and polysubstance use disorder was seen in the emergency department of this hospital because of abdominal pain and vomiting. Eleven weeks before the current presentation, the patient was…
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Abstract Aymé‐Gripp syndrome is an intellectual disability syndrome characterized by autism spectrum disorder, cataracts, sensorineural hearing loss, skeletal involvement, seizures, cardiac anomalies, and distinctive facial features. The condition is caused by pathogenic variants in MAF. To date, less than 20 cases have been reported, the majority having de novo mutations. Here, we report a patient with classical features of Aymé‐Gripp syndrome who inherited a MAF variant, c.206C>G (p.P69R),...
Abstract Introduction SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. Methods We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features....
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Presentation of Case. Dr. Kelsey Hills-Evans (Medicine): A 39-year-old woman with cyclic vomiting syndrome and polysubstance use disorder was seen in the emergency department of this hospital because of abdominal pain and vomiting. Eleven weeks before the current presentation, the patient was…
Figure 1.
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Attentional and executive function impairments were found in IBS patients, with sustained attentional deficit being a trait characteristics and FMS being an index of bowel symptoms severity. The findings also suggest shared neurocognitive pathology between GAD and IBS. Abstract Background It is unknown whether cognitive dysfunction found in patients with irritable bowel syndrome (IBS) was attributable to the different subtypes, ongoing pathophysiological processes, trait characteristics, or...
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Opinion statement Early detection and treatment of cardiotoxicity from cancer therapies is key to preventing a rise in adverse cardiovascular outcomes in cancer patients. Over-diagnosis of cardiotoxicity in this context is however equally hazardous, leading to patients receiving suboptimal cancer treatment, thereby impacting cancer outcomes. Accurate screening therefore depends on the widespread availability of sensitive and reproducible biomarkers of cardiotoxicity, which can...
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Abstract Objectives Body mass estimation from skeletal dimensions is a useful tool when studying archeological human samples. Bony articular surface dimensions of the lower limb have frequently been utilized to estimate body size. In the present study, we investigated the association between knee breadth and body mass in a Northern European population. Our study aimed to confirm both methodology and results presented in earlier studies. Materials and methods The study sample consists of...
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Neuroimaging studies have shown that the anterior cingulate cortex (ACC) is consistently activated by thirst and may underlie the affective motivation of drinking behaviour demanded by thirst. But direct evidence for this hypothesis is lacking. The present study evaluated potential correlations between ACC neuronal activity and drinking behaviour in rats injected with different concentrations of saline. We observed increased number of c‐Fos‐positive neurons in the ACC after injection of hypertonic...
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Technology in Cancer Research &Treatment, Volume 18, Issue , January 2019. Purpose:To develop a fusion imaging system that combines ultrasound and computed tomography for real-time tumor tracking and to validate the accuracy of performing registration via this approach during a specific breathing phase.Materials and Methods:The initial part of the experimental study was performed using iodized oil injection in pig livers and was focused on determining the accuracy of registration. Eight points...
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A hybrid transition metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenylboron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.
Breaking Ground: Reactions in the Photocatalytic Conversion of Tertiary Alcohols on Rutile TiO2(110)
According to textbooks, tertiary alcohols are inert towards oxidation. The photocatalysis of tertiary alcohols under highly defined vacuum conditions on a titania single crystal reveals unexpected and new reactions, which can be described as disproportionation into an alkane and the respective ketone. In contrast to primary and secondary alcohols the absence of an α‐H leads to a C‐C‐bond cleavage instead of the common abstraction of hydrogen. Surprisingly, bonds to methyl groups are not at all cleaved,...
The electronic ground state of the weakly magnetic UIV was studied in great detail for the simple structurally characterized [UF6]2− anion, combining X‐ray absorption spectroscopy, magnetometry, and quantum‐chemical calculations. The decomposition and quantification of the relatively large spin and orbital magnetic moments provide key information for an improved understanding of the complex electronic structures of actinide ions. Abstract The first structurally characterized hexafluorido complex...
Pathogen detection is growing in importance in the global health arena because of the high morbidity and mortality associated with bacterial blood stream infections. The development of rapid, high‐throughput, multiplex, and ultrasensitive methods for the discrimination of pathogens in the early stage of infection is the key to improve the patient survival rates. In this work, we present stochastic DNA walkers in droplets (SDwalker‐Drop), a one‐step, rapid, and super‐multiplex method for ultrahigh‐throughput...
A new balanced donor‐acceptor molecule, namely, benzodithiophene (BDT)‐rhodanine‐[6, 6]‐phenyl‐C71 butyric acid methyl ester (Rh‐PC71BM) comprising two covalently linked blocks, one of p‐type oligothiophene containing BDT based moiety and one of n‐type PC71BM, is designed and synthesized. The single‐component organic solar cell (SCOSC) fabricated from Rh‐PC71BM molecules, showed the power conversion efficiency (PCE) of 3.22% with an open‐circuit voltage (Voc) of 0.98 V. These results rank among the...
Integrating 2D culture of adherent mammalian cells with single‐cell western blotting (in situ scWB) uses microfluidic design to eliminate trypsin release of cells to suspension, prior to single‐cell isolation and protein analysis. To assay HeLa cells from an attached starting state, we culture adherent cells in fibronectin‐functionalized microwells formed in a thin layer of polyacrylamide gel. To integrate the culture, lysis, and assay workflow, we introduce a one‐step copolymerization process that...
A pentaaryl borole (Ph*C)4BXylF [Ph* = 3,5‐tBu2(C6H3); XylF = 3,5‐(CF3)2(C6H3)] reacts with low‐valent group 13 precursors E(I)Cp* (E = Al, Ga). With [AlCp*]4 the borole reacts as an oxidising agent accepting two electrons. The resulting unprecedented neutral η5‐Cp*,η5‐[(Ph*C)4BXylF] complex of Al(III) was structurally, spectroscopically and computationally probed and revealed a strong ionic bonding interaction. The formation of the heteroleptic borole‐cyclopentadienyl “aluminocene” leads to significant...
Direct addition of Amides to Glycals Enabled by Solvation‐insusceptible 2‐Haloazolium Salt Catalysis
The direct 2‐deoxyglycosylation of nucleophiles with glycals leads to biologically and pharmacologically important 2‐deoxysugar compounds. Although the direct addition of hydroxyl and sulfonamide groups have been well developed, the direct 2‐deoxyglycosylation of amide groups has not been reported to date. Here, we show the first direct 2‐deoxyglycosylation of amide groups using a newly designed Brønsted acid catalyst under mild conditions. Through mechanistic investigations, we discovered that the...
Herein we report the highly diastereo‐ and enantioselective preparation of (E)‐δ‐boryl‐substituted anti‐homoallylic alcohols in two steps from terminal alkynes. Namely, it consists of a cobalt(II)‐catalyzed 1,1‐diboration reaction of terminal alkynes with B2pin2 and a palladium(I)‐mediated asymmetric allylation reaction of the resulting 1,1‐di(boryl)alk‐1‐enes with aldehydes in the presence of a chiral phosphoric acid. Propyne, which is produced as the byproduct during petroleum refining, could be...
Visualization of the nanoscale organization of cell membranes remains challenging because of the lack of appropriate fluorescent probes. Here, we introduce a new design concept for super‐resolution microscopy probes that combines specific membrane targeting, ON/OFF switching, and environment sensing functions. In this design, we propose a functionalization strategy for solvatochromic dye Nile Red that improves its photostability. The dye is grafted to a newly developed membrane‐targeting moiety composed...
The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins are known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, e.g. stability. Herein, we present for the first time an aqueous phase protocol that allows...
A highly diastereoselective copper catalyzed multi‐components tandem cyclization of exocyclic enol ethers/enamines with methylene malonate and aldehydes has been developed to furnish the spiroheterocyclic tetrahydropyrans in high yields with >95/5 dr. This method is very practical that 36 examples reacted smoothly over a very broad range of aldehydes and many different exo‐vinyl heterocycles. By applying the newly developed method, the total synthesis of (+)‐broussonetine G and formal synthesis...
The first enantioselective catalytic C−H functionalization of polyfluoroarenes is reported. This unprecedented asymmetric C−H alkylation of fluoroarenes with alkenes is enabled by using a Ni/NHC catalysis, to furnish chiral fluorotetralins in high efficiency and excellent levels of chemo‐, regio‐, and enantiocontrol. Abstract Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C−H alkylation of polyfluoroarenes with alkenes is described....
Acyl substituted triazoles were synthesized by a copper catalyzed azide alkyne cycloaddition–acylation cascade in good yields. The developed reaction provides an efficient and mild approach towards otherwise difficult‐to‐synthesize complex heterocycles. Abstract Acyl substituted triazoles are valuable scaffolds, but the direct synthesis of these moieties from terminal alkynes by copper catalysis remains unexplored. We report a robust, general, and efficient method using a simple CuI/2,2′‐bipyridine...
Branching out: A direct 13C NMR assay was applied to monitor model biosynthetic intermediates bound to an acyl carrier protein (ACP). This assay was used in conjunction with multienzyme cascades to show how the pattern of β‐branching in the polyketide antibiotic kalimantacin is controlled. Abstract The presence of β‐branches in the structure of polyketides that possess potent biological activity underpins the widespread importance of this structural feature. Kalimantacin is a polyketide antibiotic...
Symmetric diaziridines underwent N−N bond ring opening in a formal [3+3] desymmetrization cycloaddition with enol diazo compounds. A chiral copper(I) complex catalyzes the enantioselective variant of this process. The use of donor–acceptor‐substituted cyclopropenes as the metalloenolcarbene precursors in the presence of the same chiral CuI/bisoxazoline complex delivered various chiral 1,5‐diazabicyclo[n.3.1]non‐2‐enes with better enantioselectivity. Abstract A chiral copper(I) complex catalyzes...
Thioamide biosynthesis: Closthioamide (CTA) is a thioamide‐containing nonribosomal peptide (NRP). The thioamide synthetase responsible for six sulfur insertions in CTA assembly was identified and characterized in vitro, shedding new light on the thiotemplated assembly of this unusual antibiotic. Bioinformatic analyses indicate that anaerobic bacteria may represent an untapped source for thioamidated NRPs. Abstract Thioamide‐containing nonribosomal peptides (NRPs) are exceedingly rare. Recently...
Single out: A stereospecific 1,4‐metallate rearrangement leads to single‐geometry ketoximes from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. Abstract Reported herein is a stereospecific 1,4‐metallate rearrangement for single‐geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction...
Core strengthening: Reduction of singly NHC‐stabilized 1,2‐diamino‐1,2‐dihalodiboranes with Na2[Fe(CO)4] has resulted in the first examples of metal complexes with aminoborylene‐stabilized aminoborylenes, which display bond‐strengthening backdonation to the B−B π‐bond upon loss of an ancillary ligand. Reduction with KC8 in the presence of a nucleophile results in rearrangement to B,B‐diaminoborylborylenes. Abstract Singly NHC‐coordinated (aminoboryl)aminoborenium salts react with Na2[Fe(CO)4]...
Ligand K‐edge X‐ray absorption spectroscopy studies were used to quantify the interdependence of metal–ligand covalency and bond distance in metal–phosphorus and metal–chloride bonds. The results establish a quantitative framework to assess changes in metal–ligand covalency using bond distances from readily‐available crystallographic data. Abstract Bond distance is a common structural metric used to assess changes in metal–ligand bonds, but it is not clear how sensitive changes in bond distances...
Tuning molecular weight distributions can substantially affect the properties of synthesised polymeric materials. Photoinduced atom transfer radical polymerisation (photo‐ATRP) was used to control the dispersity of homopolymers and block copolymers by varying the concentration of copper complex. A wide range of monomodal molecular weight distributions are obtained where Mn and Mw can be tuned upon demand. Abstract Dispersity significantly affects the properties of polymers. However, current...
Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry, and provide attractive bioisosteres for sulfonamides. However, there remain few operationally simple methods for their preparation. Here, for the first time the synthesis of NH‐sulfonimidamides is achieved directly from sulfenamides, themselves readily formed in 1 step from amines and disulfides. A highly chemoselective and one‐pot NH and O transfer is developed, mediated by PhIO in iPrOH, using ammonium carbamate as the...
A bifunctional oxygen electrode composed of hybrid spinel Co2FeO4 nanoparticles grown on N‐doped carbon nanotubes is a promising candidate for zinc–air batteries. Theoretical calculations and magnetic measurements reveal that the introduction of Fe cations into the Co3O4 network causes Co 3d electron delocalization and spin‐state transition, resulting in the enhanced catalytic activity of the as‐prepared spinel Co2FeO4. Abstract Bimetallic cobalt‐based spinel is sparking much interest, most...
Domino process: A RhIII‐catalyzed domino annulation of simple olefins with diazo oxindoles generates spirooxindole dihydropyrrole products. This reaction can be formally viewed as the result of a C−H activation, carbene insertion, and Lossen rearrangement, and was applied to the late‐stage diversification of drug molecules. Abstract A rhodium(III)‐catalyzed domino annulation of simple olefins with diazo oxindoles to give spirooxindole pyrrolone products is described. This reaction can be formally...
The pyrolysis of PIM‐1‐derived carbon molecular sieve membranes in an H2‐included environment results in well‐defined “mid‐sized” micropores and a drastic increase in p‐xylene permeability with a little loss in p‐xylene/o‐xylene selectivity. Abstract Carbon molecular sieve (CMS) membranes are candidates for the separation of organic molecules due to their stability, ability to be scaled at practical form factors, and the avoidance of expensive supports or complex multi‐step fabrication processes....
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