Publications by authors named "William Lewis"

382 Publications

A microbial marriage reminiscent of mitochondrial evolution.

Nature 2021 Mar 3. Epub 2021 Mar 3.

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http://dx.doi.org/10.1038/d41586-021-00500-6DOI Listing
March 2021

A Cooperative Photoactive Class-I Hybrid Polyoxometalate With Benzothiadiazole-Imidazolium Cations.

Front Chem 2020 14;8:612535. Epub 2021 Jan 14.

GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, Department of Chemistry, University of Nottingham, Nottingham, United Kingdom.

An organic-inorganic hybrid species based on the Wells-Dawson polyoxotungstate [PWO] and novel fluorescent benzothiadiazole-imidazolium cations, [BTD-4,7-ImH], has been synthesized. X-ray crystallographic analysis shows that the inorganic and organic components form a hydrogen-bonded superstructure and that the cations are revealed to be non-equivalent with varying degrees of rotation between the BTD and imidazolium rings due to competition between weak intra- and intermolecular interactions. The UV-vis diffuse reflectance spectra indicate that the hybrid has a band gap of 3.13 eV, while the solid-state fluorescence properties of the cation are quenched in the hybrid material, suggesting the existence of electron transfer between the inorganic and organic components. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies of the polyoxometalate (POM) and BTD-4,7-ImH precursors, estimated through UV-vis absorption spectroscopy and cyclic voltammetry, indicate that electron transfer from the BTD cations to the POM may occur in the excited state.
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http://dx.doi.org/10.3389/fchem.2020.612535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841050PMC
January 2021

Guideline-Concordant Antiarrhythmic Drug Use in the Get With The Guidelines-Atrial Fibrillation Registry.

Circ Arrhythm Electrophysiol 2021 Feb 8;14(2):e008961. Epub 2021 Jan 8.

Duke Clinical Research Institute (D.N.H., R.A.M., J.P.P.), Durham, NC.

Background: Antiarrhythmic drug (AAD) therapy for atrial fibrillation (AF) can be associated with both proarrhythmic and noncardiovascular toxicities. Practice guidelines recommend tailored AAD therapy for AF based on patient-specific characteristics, such as coronary artery disease and heart failure, to minimize adverse events. However, current prescription patterns for specific AADs and the degree to which these guidelines are followed in practice are unknown.

Methods: Patients enrolled in the Get With The Guidelines-Atrial Fibrillation registry with a primary diagnosis of AF discharged on an AAD between January 2014 and November 2018 were included. We analyzed rates of prescription of each AAD in several subgroups including those without structural heart disease. We classified AAD use as guideline concordant or nonguideline concordant based on 6 criteria derived from the American Heart Association/American College of Cardiology/Heart Rhythm Society AF guidelines. Guideline concordance for amiodarone was not considered applicable, since its use is not specifically contraindicated in the guidelines for reasons such as structural heart disease or renal function. We analyzed guideline-concordant AAD use by specific patient and hospital characteristics, and regional and temporal trends.

Results: Among 21 921 patients from 123 sites, the median age was 69 years, 46% female and 51% had paroxysmal AF. The most commonly prescribed AAD was amiodarone (38%). Sotalol (23.2%) and dofetilide (19.2%) were each more commonly prescribed than either flecainide (9.8%) or propafenone (4.8%). Overall guideline-concordant AAD prescription at discharge was 84%. Guideline-concordant AAD use by drug was as follows: dofetilide 93%, sotalol 66%, flecainide 68%, propafenone 48%, and dronedarone 80%. There was variability in rate of guideline-concordant AAD use by hospital and geographic region.

Conclusions: Amiodarone remains the most commonly prescribed AAD for AF followed by sotalol and dofetilide. Rates of guideline-concordant AAD use were high, and there was significant variability by specific drugs, hospitals, and regions, highlighting opportunities for additional quality improvement.
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http://dx.doi.org/10.1161/CIRCEP.120.008961DOI Listing
February 2021

Procedure characteristics and outcomes of atrial fibrillation ablation procedures using cryoballoon versus radiofrequency ablation: A report from the GWTG-AFIB registry.

J Cardiovasc Electrophysiol 2021 Feb 6;32(2):248-259. Epub 2021 Jan 6.

Duke Clinical Research Institute, Durham, North Carolina, USA.

Introduction: Cryoballoon ablation (CBA) is an alternative to radiofrequency ablation (RFA) for ablation of atrial fibrillation (AF) and real-world comparisons of this strategy are lacking. As such, we sought to compare patient and periprocedural characteristics and outcomes of CBA versus RFA in the Get With the Guidelines AFIB Registry.

Methods: Categorical variables were compared via the χ test and continuous variables were compared via the Wilcoxon rank-sum test. Adjusted analyses were performed using overlap weighting of propensity scores.

Results: A total of 5247 (1465 CBA, 3782 RFA) ablation procedures were reported from 33 sites. Those undergoing CBA more often had paroxysmal AF (60.0% vs. 48.8%) and no prior AF ablation (87.5% vs. 73.8%). CHA DS -VASc scores were similar. Among de novo ablations, most ablations involved intracardiac echocardiography and electroanatomic mapping, but both were less common with CBA (87.3% vs. 93.9%, p < .0001, and 87.7% vs. 94.6%, p < .0001, respectively). CBA was associated with shorter procedures (129 vs. 179 min, p < .0001), increased fluoroscopy use (19 vs. 11 min, p < .0001), and similar ablation times (27 vs. 35 min, p = .15). Nonpulmonary vein ablation was common with CBA: roof line 38.6%, floor line 20.4%, cavotricuspid isthmus 27.7%. RFA was associated with more total complications compared to CBA (5.4% vs. 2.3%, p < .0001), due to more volume overload and "other" events, although phrenic nerve injury was more common with CBA (0.9% vs 0.1%, p = .0001). In the adjusted model, any complication was less common among CBA cases (odds ratio, 0.45; confidence interval, 0.25-0.79, p = .0056).

Conclusion: CBA was associated with fewer complications, and shorter procedure times, and greater fluoroscopy times, compared to RFA. Nonpulmonary vein ablation and electroanatomic mapping system use was common with CBA.
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http://dx.doi.org/10.1111/jce.14858DOI Listing
February 2021

Structural and electronic studies of substituted m-terphenyl lithium complexes.

Dalton Trans 2021 Jan 21;50(2):722-728. Epub 2020 Dec 21.

School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

The effect of para-substitution upon the structural and electronic properties of a series of m-terphenyl lithium complexes [R-Ar-Li] (R = t-Bu 1, SiMe2, H 3, Cl 4, CF5; where R-Ar = 2,6-{2,6-Xyl}-4-R-CH and 2,6-Xyl = 2,6-MeCH) has been investigated. X-ray crystallography reveals the complexes to be structurally similar, with little variation in C-M-C bond lengths and angles across the series. However, in-depth NMR spectroscopic studies reveal notable electronic differences, showing a linear correlation between the Li{H} NMR chemical shifts of the para-substituted complexes and their Hammett constants. The flanking methyl protons exhibit a similar electronic shift in the H NMR spectra, which has been rationalised by the presence of through-space LiH interactions, as evidenced by two-dimensional Li-H heteronuclear Overhauser spectroscopy (HOESY). In both cases, electron-withdrawing substituents are found to cause an upfield peak shift. A computational analysis is employed to account for these trends.
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http://dx.doi.org/10.1039/d0dt03972aDOI Listing
January 2021

Conformationally adaptable macrocyclic receptors for ditopic anions: analysis of chelate cooperativity in aqueous containing media.

Chem Sci 2020 Jul 18;11(27):7015-7022. Epub 2020 Jun 18.

School of Chemistry , The University of Sydney , NSW 2006 , Australia . Email:

The effect of chelate cooperativity on the binding of several ditopic anions to two tetrathiourea macrocycles has been analysed in competitive solvent mixtures (HO : DMSO 1 : 9 v/v). The semi-flexible receptors bind dicarboxylates with high affinity dependent on the length and flexibility of the guest. Chemical double mutant cycle (DMC) analysis allowed the chelate cooperativity effects to be measured in detail and revealed both positive and negative cooperativity effects which were dependent on guest size, flexibility and spacer interactions between guest and macrocycle. H NMR and crystallographic studies confirmed the macrocycle hosts are adaptable, changing conformation to match their pore size to a selected guest.
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http://dx.doi.org/10.1039/d0sc02533jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690315PMC
July 2020

Water-Soluble α-Amino Acid Complexes of Molybdenum as Potential Antidotes for Cyanide Poisoning: Synthesis and Catalytic Studies of Threonine, Methionine, Serine, and Leucine Complexes.

Inorg Chem 2020 Dec 28;59(24):18190-18204. Epub 2020 Nov 28.

Science Institute, University of Iceland, Dunhagi 3, 107 Reykjavik, Iceland.

Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula K[(L)MoO(μ-S)(S)] (L = leu (), met (), thr (), and ser ()) were synthesized in a reaction of [(DMF)MoO(μ-S)(S)] with deprotonated α-amino acids; leu, met, thr, and ser are the carboxylate anions of l-leucine, l-methionine, l-threonine, and l-serine, respectively. Potassium salts of α-amino acids (leu (), met (), thr (), and ser ()) were prepared as precursors for complexes -, respectively, by employing a nonaqueous synthesis route. The ligand exchange reaction of [MoO(μ-S)(DMF)](I) with deprotonated α-amino acids afforded -α-amino acid complexes, [(L)MoO(μ-S)] (-). A -α-amino acid complex, [(leu)MoO(μ-S)(μ-leu + H)] (; leu + H is the carboxylate anion of l-leucine with the amine protonated), formed in the reaction with leucine. crystallized from methanol with a third weakly bonded leucine as a bridging bidentate carboxylate. An adduct of with SCN coordinated, , crystallized and was structurally characterized. Complexes - are air stable and highly water-soluble chiral molecules. Cytotoxicity studies in the A549 cell line gave IC values that range from 80 to 400 μM. Cyclic voltammetry traces of - show solvent-dependent irreversible electrochemical behavior. Complexes - demonstrated the ability to catalyze the reaction of thiosulfate and cyanide to exhaustively transform cyanide to thiocyanate in less than 1 h.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02672DOI Listing
December 2020

Management of Atrial Fibrillation in Older Patients by Morbidity Burden: Insights From Get With The Guidelines-Atrial Fibrillation.

J Am Heart Assoc 2020 12 26;9(23):e017024. Epub 2020 Nov 26.

Duke Clinical Research Institute Duke University Durham NC.

Background Knowledge is scarce regarding how multimorbidity is associated with therapeutic decisions regarding oral anticoagulants (OACs) in patients with atrial fibrillation. Methods and Results We conducted a cross-sectional study of hospitalized patients with atrial fibrillation using the Get With The Guidelines-Atrial Fibrillation registry from 2013 to 2019. We identified patients ≥65 years and eligible for OAC therapy. Using 16 available comorbidity categories, patients were stratified by morbidity burden. A multivariable logistic regression model was used to determine the odds of receiving OAC prescription at discharge by morbidity burden. We included 34 174 patients with a median (interquartile range) age of 76 (71-83) years, 56.6% women, and 41.9% were not anticoagulated at admission. Of these patients, 38.6% had 0 to 2 comorbidities, 50.7% had 3 to 5 comorbidities, and 10.7% had ≥6 comorbidities. The overall discharge OAC prescription was high (85.6%). The prevalence of patients with multimorbidity increased from 59.7% in 2014 to 64.3% in 2019 ( trend=0.002). Using 0 to 2 comorbidities as the reference, the adjusted odds ratio (95% CI) of OAC prescription were 0.93 (0.82, 1.05) for patients with 3 to 5 comorbidities and 0.72 (0.60, 0.86) for patients with ≥6 comorbidities. In those with ≥6 comorbidities, the most common reason for nonprescription of OACs were frequent falls/frailty (31.0%). Conclusions In a contemporary quality-of-care database of hospitalized patients with atrial fibrillation eligible for OAC therapy, multimorbidity was common. A higher morbidity burden was associated with a lower odds of OAC prescription. This highlights the need for interventions to improve adherence to guideline-recommended anticoagulation in multimorbid patients with atrial fibrillation.
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http://dx.doi.org/10.1161/JAHA.120.017024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763767PMC
December 2020

Tetrapodal Anion Transporters.

Molecules 2020 Nov 6;25(21). Epub 2020 Nov 6.

School of Chemistry (F11), The University of Sydney, Sydney 2006, Australia.

Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an undesired side effect of facilitating proton transport via interacting with fatty acids present in the membrane. To address the limitation, we here report the use of a new tetrapodal scaffold to maximize the selective interaction with spherical chloride over binding the carboxylate headgroup of fatty acids. One of the new transporters demonstrated a high selectivity for chloride uniport over fatty acid-induced proton transport while being >10 times more active in chloride uniport than strapped calixpyrroles that were previously the only class of compounds known to possess similar selectivity properties.
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http://dx.doi.org/10.3390/molecules25215179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664440PMC
November 2020

Innovations to culturing the uncultured microbial majority.

Nat Rev Microbiol 2020 Oct 22. Epub 2020 Oct 22.

Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands.

Despite the surge of microbial genome data, experimental testing is important to confirm inferences about the cell biology, ecological roles and evolution of microorganisms. As the majority of archaeal and bacterial diversity remains uncultured and poorly characterized, culturing is a priority. The growing interest in and need for efficient cultivation strategies has led to many rapid methodological and technological advances. In this Review, we discuss common barriers that can hamper the isolation and culturing of novel microorganisms and review emerging, innovative methods for targeted or high-throughput cultivation. We also highlight recent examples of successful cultivation of novel archaea and bacteria, and suggest key microorganisms for future cultivation attempts.
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http://dx.doi.org/10.1038/s41579-020-00458-8DOI Listing
October 2020

Porous Metal-Organic Polyhedra: Morphology, Porosity, and Guest Binding.

Inorg Chem 2020 Nov 12;59(21):15646-15658. Epub 2020 Oct 12.

School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.

Designing porous materials which can selectively adsorb CO or CH is an important environmental and industrial goal which requires an understanding of the host-guest interactions involved at the atomic scale. Metal-organic polyhedra (MOPs) showing permanent porosity upon desolvation are rarely observed. We report a family of MOPs , , ), which derive their permanent porosity from cavities between packed cages rather than from within the polyhedra. Thus, for , the void fraction outside the cages totals 56% with only 2% within. The relative stabilities of these MOP structures are rationalized by considering their weak nondirectional packing interactions using Hirshfeld surface analyses. The exceptional stability of enables a detailed structural investigation into the adsorption of CO and CH using X-ray and neutron diffraction, coupled with DFT calculations. The primary binding sites for adsorbed CO and CH in are found to be the open metal sites and pockets defined by the faces of phenyl rings. More importantly, the structural analysis of a hydrated sample of reveals a strong hydrogen bond between the adsorbed CO molecule and the Cu(II)-bound water molecule, shedding light on previous empirical and theoretical observations that partial hydration of metal-organic framework (MOF) materials containing open metal sites increases their uptake of CO. The results of the crystallographic study on MOP-gas binding have been rationalized using DFT calculations, yielding individual binding energies for the various pore environments of .
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http://dx.doi.org/10.1021/acs.inorgchem.0c01935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610226PMC
November 2020

-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-]pyrazine-Based Antimalarials.

J Org Chem 2020 11 13;85(21):13438-13452. Epub 2020 Oct 13.

School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, U.K.

We have discovered and studied a -substitution reaction in a biologically important heterocyclic ring system. Conditions that favor the -substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base or the use of softer nucleophiles, less polar solvents, and larger halogens on the electrophile. Using results from X-ray crystallographic and isotope labeling experiments, a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the active antiplasmodium compounds of Series 4 of the Open Source Malaria consortium.
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http://dx.doi.org/10.1021/acs.joc.0c01045DOI Listing
November 2020

Procedural Patterns and Safety of Atrial Fibrillation Ablation: Findings From Get With The Guidelines-Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 09 23;13(9):e007944. Epub 2020 Jul 23.

Duke Clinical Research Institute (Z.L., D.N.H., R.A.M., J.P.P.), Duke University Medical Center.

Background: Catheter ablation is an increasingly used treatment for symptomatic atrial fibrillation (AF). However, there are limited prospective, nationwide data on patient selection and procedural characteristics. This study describes patient characteristics, techniques, treatment patterns, and safety outcomes of patients undergoing AF ablation.

Methods: A total of 3139 patients undergoing AF ablation between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation registry from 24 US centers were included. Patient demographics, medical history, procedural details, and complications were abstracted. Differences between paroxysmal and patients with persistent AF were compared using Pearson χ and Wilcoxon rank-sum tests.

Results: Patients undergoing AF ablation were predominantly male (63.9%) and White (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and patients with persistent AF had more comorbidities than patients with paroxysmal AF. Drug refractory, paroxysmal AF was the most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radiofrequency ablation with contact force sensing was the most common ablation modality (70.5%); 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations; the most common adjunctive lesions included left atrial roof or posterior/inferior lines, and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases.

Conclusions: More than 98% of AF ablations among participating sites are performed for class I or class IIA indications. Contact force-guided radiofrequency ablation is the dominant technique and pulmonary vein isolation the principal lesion set. In-hospital complications are uncommon and rarely life-threatening.
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http://dx.doi.org/10.1161/CIRCEP.119.007944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502261PMC
September 2020

A transition metal-gallium cluster formed via insertion of "GaI".

Chem Commun (Camb) 2020 Jul;56(58):8139-8142

School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

The reaction between a two-coordinate Co(ii) diaryl complex and "GaI" affords 2,6-Pmp2C6H3CoGa3I5, in a new geometry for a heavier group 13-transition metal cluster. Experimental and computational investigations show that this compound is best described as a nido metalla-group 13 cluster.
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http://dx.doi.org/10.1039/d0cc03559aDOI Listing
July 2020

Stimuli-Responsive Cycloaurated "OFF-ON" Switchable Anion Transporters.

Angew Chem Int Ed Engl 2020 09 11;59(40):17614-17621. Epub 2020 Aug 11.

School of Chemistry, The University of Sydney, Sydney, New South Wales, 2006, Australia.

Anion transporters have shown potential application as anti-cancer agents that function by disrupting homeostasis and triggering cell death. In this research article we report switchable anion transport by gold complexes of anion transporters that are "switched on" in situ in the presence of the reducing agent GSH by decomplexation of gold. GSH is found in higher concentrations in tumors than in healthy tissue and hence this approach offers a strategy to target these systems to tumors.
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http://dx.doi.org/10.1002/anie.202006392DOI Listing
September 2020

Reversible single crystal-to-single crystal double [2+2] cycloaddition induces multifunctional photo-mechano-electrochemical properties in framework materials.

Nat Commun 2020 06 4;11(1):2808. Epub 2020 Jun 4.

School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.

Reversible structural transformations of porous coordination frameworks in response to external stimuli such as light, electrical potential, guest inclusion or pressure, amongst others, have been the subject of intense interest for applications in sensing, switching and molecular separations. Here we report a coordination framework based on an electroactive tetrathiafulvalene exhibiting a reversible single crystal-to-single crystal double [2 + 2] photocyclisation, leading to profound differences in the electrochemical, optical and mechanical properties of the material upon light irradiation. Electrochemical and in situ spectroelectrochemical measurements, in combination with in situ light-irradiated Raman spectroscopy and atomic force microscopy, revealed the variable mechanical properties of the framework that were supported using Density Functional Theory calculations. The reversible structural transformation points towards a plethora of potential applications for coordination frameworks in photo-mechanical and photoelectrochemical devices, such as light-driven actuators and photo-valves for targeted drug delivery.
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http://dx.doi.org/10.1038/s41467-020-15510-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272394PMC
June 2020

Frontal sinus abscess with cutaneous fistula secondary to .

Orbit 2021 Apr 27;40(2):171. Epub 2020 Apr 27.

Department of Ophthalmology, California Pacific Medical Center , San Francisco, CA, USA.

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http://dx.doi.org/10.1080/01676830.2020.1760314DOI Listing
April 2021

General Method for the Asymmetric Synthesis of N-H Sulfoximines via C-S Bond Formation.

Org Lett 2020 Apr 16;22(7):2776-2780. Epub 2020 Mar 16.

Department of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.

A versatile method for the synthesis of enantioenriched N-H sulfoximines is reported. The approach stems from the organomagnesium-mediated ring opening of novel cyclic sulfonimidate templates. The reactions proceed in high yield and with excellent stereofidelity with alkyl, aryl, and heteroaryl Grignard reagents. The chiral auxiliary is readily removed from the resultant sulfoximines via an unusual oxidative debenzylation protocol that utilizes molecular oxygen as the terminal oxidant. This provides a general strategy for the synthesis of highly enantioenriched N-H sulfoximines.
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http://dx.doi.org/10.1021/acs.orglett.0c00761DOI Listing
April 2020

Modular bismacycles for the selective C-H arylation of phenols and naphthols.

Nat Chem 2020 03 27;12(3):260-269. Epub 2020 Feb 27.

GSK Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Nottingham, UK.

Given the important role played by 2-hydroxybiaryls in organic, medicinal and materials chemistry, concise methods for the synthesis of this common motif are extremely valuable. In seeking to extend the lexicon of synthetic chemists in this regard, we have developed an expedient and general strategy for the ortho-arylation of phenols and naphthols using readily available boronic acids. Our methodology relies on in situ generation of a uniquely reactive Bi(V) arylating agent from a bench-stable Bi(III) precursor via telescoped B-to-Bi transmetallation and oxidation. By exploiting reactivity that is orthogonal to conventional metal-catalysed manifolds, diverse aryl and heteroaryl partners can be rapidly coupled to phenols and naphthols under mild conditions. Following arylation, high-yielding recovery of the Bi(III) precursor allows for its efficient re-use in subsequent reactions. Mechanistic interrogation of each key step of the methodology informs its practical application and provides fundamental insight into the underexploited reactivity of organobismuth compounds.
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http://dx.doi.org/10.1038/s41557-020-0425-4DOI Listing
March 2020

Influence of molecular design on radical spin multiplicity: characterisation of BODIPY dyad and triad radical anions.

Phys Chem Chem Phys 2020 Feb;22(8):4429-4438

School of Chemistry, University of Nottingham, University Park, NG7 2RD, UK.

A strategy to create organic molecules with high degrees of radical spin multiplicity is reported in which molecular design is correlated with the behaviour of radical anions in a series of BODIPY dyads. Upon reduction of each BODIPY moiety radical anions are formed which are shown to have different spin multiplicities by electron paramagnetic resonance (EPR) spectroscopy and distinct profiles in their cyclic voltammograms and UV-visible spectra. The relationship between structure and multiplicity is demonstrated showing that the balance between singlet, biradical or triplet states in the dyads depends on relative orientation and connectivity of the BODIPY groups. The strategy is applied to the synthesis of a BODIPY triad which adopts an unusual quartet state upon reduction to its radical trianion.
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http://dx.doi.org/10.1039/c9cp06427cDOI Listing
February 2020

Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.

Eur Heart J 2020 03;41(10):1132-1140

Department of Clinical Cardiology, St George's University of London, Blackshaw Road, Tooting, London SW17 0QT, UK.

Aims: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings.

Methods And Results: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set.

Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF.
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http://dx.doi.org/10.1093/eurheartj/ehz871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060456PMC
March 2020

Strict Versus Lenient Versus Poor Rate Control Among Patients With Atrial Fibrillation and Heart Failure (from the Get With The Guidelines - Heart Failure Program).

Am J Cardiol 2020 03 30;125(6):894-900. Epub 2019 Dec 30.

Duke Clinical Research Institute, Durham, North Carolina; Duke University Medical Center, Durham, North Carolina.

Randomized data suggest lenient rate control (resting heart rate <110 beats/min) is noninferior to strict rate control (resting heart rate <80 beats/min) in patients with atrial fibrillation (AF). However, the optimal rate control strategy in patients with AF and heart failure (HF) remains unknown. Accordingly, we performed an observational analysis using data from the Get With The Guidelines-HF Program linked with Medicare data from July 1, 2011, to September 30, 2014. Of 13,981 patients with AF and HF, 9,100 (65.0%) had strict rate control, 4,617 (33.0%) had lenient rate control, and 264 (1.9%) had poor rate control by resting heart rate on the day of discharge. After multivariable adjustment, compared with strict rate control, lenient rate control was associated with higher adjusted risks of death (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.11 to 1.33, p <0.001), all-cause readmission (HR 1.09, 95% CI 1.03 to 1.15, p <0.002), death or all-cause readmission (HR 1.11, 95% CI 1.05 to 1.18, p <0.001), but not cardiovascular readmission (HR1.08, 95% CI 1.00 to 1.16, p = 0.051) at 90 days. Associations were comparable in patients with poor rate control and with heart rate modeled as a continuous variable. The presence or absence of reduced ejection fraction did not impact the magnitude of most observed associations. In conclusion, in patients with HF and AF, 2 of 3 patients had a heart rate that met strict-control goals at discharge. Heart rates >80 beats/min were associated with adverse outcomes irrespective of left ventricular ejection fraction.
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http://dx.doi.org/10.1016/j.amjcard.2019.12.025DOI Listing
March 2020

Ground and Excited States of Bis-4-Methoxybenzyl-Substituted Diketopyrrolopyrroles: Spectroscopic and Electrochemical Studies.

Chempluschem 2019 Sep 31;84(9):1413-1422. Epub 2019 Jul 31.

GSK Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Triumph Road, Nottingham, NG7 2TU, United Kingdom.

A series of symmetrically bis-4-methoxybenzyl (4MB) N-substituted 1,4-diketopyrrolo[3,4-c]pyrrole (DPP) derivatives have been synthesized. The 4MB unit makes the DPP core soluble, and shows subtle modification of up to 0.2 eV in ground and excited states of the core when compared with related alkyl derivatives. Absorption and emission spectroscopy, as well as electrochemical and computational methods have been employed to prove the importance of the peripheral aryl units on the donor/ acceptor properties of the molecules. The 4MB products are highly fluorescent (quantum yields approaching 100 % in solution), with a unique distribution of frontier states shown by spectroelectrochemistry. The solid-state fluorescence correlates with the X-ray crystal structures of the compounds, a Stokes shift of approximately 80 nm is seen for two of the compounds. The frontier energy levels show that this subtle substitutional change could be of future use in molecular energy level tailoring in these, and related, materials for organic (opto)electronics.
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http://dx.doi.org/10.1002/cplu.201900286DOI Listing
September 2019

Lymphoma: Diagnosis and Treatment.

Am Fam Physician 2020 01;101(1):34-41

West Virginia University Eastern Division, Harpers Ferry, WV, USA.

Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.
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January 2020

Convergent Evolution of Hydrogenosomes from Mitochondria by Gene Transfer and Loss.

Mol Biol Evol 2020 02;37(2):524-539

Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-Upon-Tyne, United Kingdom.

Hydrogenosomes are H2-producing mitochondrial homologs found in some anaerobic microbial eukaryotes that provide a rare intracellular niche for H2-utilizing endosymbiotic archaea. Among ciliates, anaerobic and aerobic lineages are interspersed, demonstrating that the switch to an anaerobic lifestyle with hydrogenosomes has occurred repeatedly and independently. To investigate the molecular details of this transition, we generated genomic and transcriptomic data sets from anaerobic ciliates representing three distinct lineages. Our data demonstrate that hydrogenosomes have evolved from ancestral mitochondria in each case and reveal different degrees of independent mitochondrial genome and proteome reductive evolution, including the first example of complete mitochondrial genome loss in ciliates. Intriguingly, the FeFe-hydrogenase used for generating H2 has a unique domain structure among eukaryotes and appears to have been present, potentially through a single lateral gene transfer from an unknown donor, in the common aerobic ancestor of all three lineages. The early acquisition and retention of FeFe-hydrogenase helps to explain the facility whereby mitochondrial function can be so radically modified within this diverse and ecologically important group of microbial eukaryotes.
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http://dx.doi.org/10.1093/molbev/msz239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993867PMC
February 2020

The ACS National Surgical Quality Improvement Program-Inflammatory Bowel Disease Collaborative: Design, Implementation, and Validation of a Disease-specific Module.

Inflamm Bowel Dis 2019 10;25(11):1731-1739

Department of Surgery, Cleveland Clinic Florida, Weston, MA, USA.

Background: Surgery for inflammatory bowel disease (IBD) involves a complex interplay between disease, surgery, and medications, exposing patients to increased risk of postoperative complications. Surgical best practices have been largely based on single-institution results and meta-analyses, with multicenter clinical data lacking. The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) has revolutionized the way in which large-volume surgical outcomes data have been collected. Our aim was to employ the ACS-NSQIP to collect disease-specific variables relevant to surgical outcomes in IBD.

Study Design: A collaborative of 13 high-volume IBD surgery centers was convened to collect 5 IBD-specific variables in NSQIP. Variables included biologic and immunomodulator medications usage, ileostomy utilization, ileal pouch anastomotic technique, and colonic dysplasia/neoplasia. A sample of the Surgical Clinical Reviewer collected data was validated by a colorectal surgeon at each institution, and kappa's agreement statistics generated.

Results: Over 1 year, data were collected on a total of 956 cases. Overall, 41.4% of patients had taken a biologic agent in the 60 days before surgery. The 2 most commonly performed procedures were laparoscopic ileocolic resections (159 cases) and subtotal colectomies (151 cases). Overall, 56.8% of cases employed an ileostomy, and 134 ileal pouches were constructed, of which 92.4% used stapled technique. A sample of 214 (22.4%) consecutive cases was validated from 8 institutions. All 5 novel variables were shown to be reliably collected, with excellent agreement for 4 variables (kappa ≥ 0.70) and very good agreement for the presence of colonic dysplasia (kappa = 0.68).

Conclusion: We report the results of the initial year of implementation of the first disease-specific collaborative within NSQIP. The selected variables were demonstrated to be reliably collected, and this collaborative will facilitate high-quality, large case-volume research specific to the IBD patient population.
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http://dx.doi.org/10.1093/ibd/izz044DOI Listing
October 2019

Culturing the uncultured.

Nat Biotechnol 2019 11;37(11):1278-1279

Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Wageningen, the Netherlands.

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http://dx.doi.org/10.1038/s41587-019-0300-2DOI Listing
November 2019

Rhodium-catalyzed arylative cyclization of alkynyl malonates by 1,4-rhodium(i) migration.

Chem Commun (Camb) 2019 Sep;55(76):11366-11369

The GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Jubilee Campus, Triumph Road, Nottingham, NG7 2TU, UK.

The synthesis of functionalized 1-tetralones by the rhodium(i)-catalyzed reaction of alkynyl malonates with arylboronic acids is described. These arylative cyclizations proceed via an alkenyl-to-aryl 1,4-Rh(i) migration as a key step. Preliminary results of an enantioselective variant of these reactions are also presented.
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http://dx.doi.org/10.1039/c9cc05205dDOI Listing
September 2019