bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme—Crystallographic Study of Glutamate Mutase with Cofactor Homologues
Authors: Gruber Karl , Csitkovits Vanessa , Łyskowski Andrzej , Kratky Christoph , Kräutler Bernhard 
Published: July 2022

AbstractCatalysis by radical enzymes dependent on coenzyme B12 (AdoCbl) relies on the reactive primary 5′‐deoxy‐5′adenosyl radical, which originates from reversible Co−C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 1012‐fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic. As revealed here, a displaced firm adenosine binding cavity in substrate‐loaded glutamate mutase (GM) causes a structural misfit for intact AdoCbl that is relieved by the homolytic Co−C bond cleavage. Strategically interacting adjacent adenosine‐ and substrate‐binding protein cavities provide a tight caged radical reaction space, controlling the entire radical path. The GM active site is perfectly structured for promoting radical catalysis, including “negative catalysis”, a paradigm for AdoCbl‐dependent mutases.
A General and Efficient Solution to Monofluoroalkylation: Divergent Synthesis of Aliphatic Monofluorides with Modular Synthetic Scaffolds
Authors: Wu Bing‐Bing , Xu Jie , Gao Qian , Bian Kang‐Jie , Liu Guo‐Kai , Wang Xi‐Sheng 
Published: July 2022

AbstractMonofluoroalkanes are important in many pharmaceuticals, agrochemicals and functional materials. However, the lack of easily available and transformable monofluoroalkylating reagents that facilitate a broad array of transformations has hampered the application of monofluoroalkylation. Herein, we report a general and efficient method of preparing diverse aliphatic monofluorides with monofluoroalkyl triflate as the synthetic scaffold. Using both nickel‐catalyzed hydromonofluoroalkylation of unactivated alkenes and copper‐catalyzed C−C bond formation, the general diversification of the monofluoroalkylating scaffold has been exhibited. The broad utility of this monofluoroalkylating reagent is shown by concise conversion into various conventional fluoroalkylating reagents and construction of monofluoro‐alkoxy, ‐alkylamino motifs with commercially available heteroatom‐based coupling partners.
Association of 18F‐Fluorodeoxyglucose–Positron Emission Tomography Activity With Angiographic Progression of Disease in Large Vessel Vasculitis
Authors: Quinn Kaitlin A. , Ahlman Mark A. , Alessi Hugh D. , LaValley Michael P. , Neogi Tuhina , Marko Jamie , Novakovich Elaine , Grayson Peter C. 
Published: July 2022

ObjectiveTo assess whether vascular activity seen on 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) scan is associated with angiographic change in large vessel vasculitis (LVV).MethodsPatients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG‐PET imaging. Follow‐up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow‐up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged.ResultsA total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow‐up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG‐PET scan at baseline had no angiographic change over the follow‐up period (787 [99%] of 793). Few territories with baseline FDG‐PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG‐PET activity at baseline. Within the same patient, an arterial territory with baseline FDG‐PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG‐PET activity (odds ratio 19.49 [95% confidence interval 2.44–156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change.ConclusionDevelopment of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG‐PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG‐PET activity.
Denver Water Ensures a Sustainable Future With Its Northwater Treatment Plant
Authors: Mukherjee Sananda , Geiger Lindsey 
Published: July 2022

Key TakeawaysDenver Water's project to upgrade part of its water system involves building a new treatment plant, installing new pipeline, and redeveloping the existing treatment plant.Good stewardship through commitment to protecting the environment, serving current and future populations, and exercising fiscal responsibility is woven into the Northwater Treatment Plant project.The Envision sustainability assessment framework, along with pursuit of the Envision Gold Award, has helped Denver Water achieve its project objectives.
Politics of evidence: Think tanks and the Academies Act
Authors: Kauko Jaakko 
Published: July 2022

AbstractPrevious research has identified political ideology as central in the landmark Academies Act (2010). This article further analyses how politics of evidence played its part in the policy process by focusing on long‐term structural changes and preferences among policymakers. The article draws on policymaker interviews after the reform, a mapping of think tanks and a document analysis. The analysis shows that political–ideological preferences were derived from think tanks, and the Conservative manifesto built on skewed Swedish evidence in constructing an argument for the Act. The political choices morphed into fact‐based arguments in the policy process. While think tanks had some reservations, in the Whitehall bureaucracy the argument was reformulated as a rational deliberation. This was possible because of the long‐term change in the significance of think tanks, and how policymakers preferred politically informed opinions instead of research evidence. The conclusion argues that the evidence‐based policy emphasis is an attempt to depoliticise the scope for political arguments. The political dynamic thus results in structurally empowered and layered but depoliticising use of evidence.
LIBS‐ und Elektrolytwiderstands‐Untersuchungen – Bausteine einer vertieften Bauwerksdiagnose bei chloridbelasteten Stahlbetonbauteilen
Authors: Kapteina Gesa , Dauberschmidt Christoph , Vestner Stephan , Langer Christoph 
Published: July 2022

AbstractChloride in Stahlbetonbauteilen können zu einer schädigenden Lochkorrosion der Bewehrung führen, die von außen nicht unbedingt sichtbar ist. Um den Schädigungsgrad der Bauteile und das Schädigungspotenzial auch hinsichtlich der zu wählenden Instandsetzungsvariante möglichst zielgerichtet ermitteln zu können, werden neben den herkömmlichen Methoden der Bauwerksdiagnose auch zunehmend zwei weitere Untersuchungsmethoden angewandt: So können durch gezielte Untersuchungen mit LIBS (Laser induzierte Breakdown Spektroskopie) wertvolle zusätzliche Informationen zur Chloridverteilung innerhalb des Bauwerks generiert werden. Mittels Bestimmung des Elektrolytwiderstands können Bauteile hinsichtlich des Wassergehalts und der Dichtigkeit und damit das Schädigungspotenzial beurteilt werden. Die Anwendungen beider Verfahren bei der Bauwerksdiagnose werden nachfolgend vorgestellt. Abschließend wird dargestellt, wie in Abhängigkeit von den später durchgeführten Instandsetzungsverfahren nach der Technischen Regel „Instandhaltung von Betonbauwerken“ (kurz: TR‐IH) des DIBt unterschiedliche Untersuchungsmethoden unterschiedliche Wichtigkeiten und Wertigkeiten aufweisen. Dies soll in der Praxis eine auf das Instandsetzungsverfahren zugeschnittene Bauwerksdiagnose ermöglichen.
Phage‐free production of artificial ssDNA with Escherichia coli
Authors: Behler Karl L. , Honemann Maximilian N. , Silva‐Santos Ana R. , Dietz Hendrik , Weuster‐Botz Dirk 
Published: July 2022

AbstractArtificial single‐stranded DNA (ssDNA) with user‐defined sequences and lengths up to the kilobase range is increasingly needed in mass quantities to realize the potential of emerging technologies such as genome editing and DNA origami. However, currently available biotechnological approaches for mass‐producing ssDNA require dedicated, and thus costly, fermentation infrastructure, because of the risk of cross‐contaminating manufacturer plants with self‐replicating phages. Here we overcome this problem with an efficient, scalable, and cross‐contamination‐free method for the phage‐free biotechnological production of artificial ssDNA with Escherichia coli. Our system utilizes a designed phagemid and an optimized helper plasmid. The phagemid encodes one gene of the M13 phage genome and a freely chosen custom target sequence, while the helper plasmid encodes the other genes of the M13 phage. The phagemid particles produced with this method are not capable of self‐replication in the absence of the helper plasmid. This enables cross‐contamination‐free biotechnological production of ssDNA at any contract manufacturer. Furthermore, we optimized the process parameters to reduce by‐products and increased the maximal product concentration up to 83 mg L−1 of ssDNA in a stirred‐tank bioreactor, thus realizing up to a 40‐fold increase in maximal product concentration over previous scalable phage‐free ssDNA production methods.
Clinical effect of flunarizine combined with duloxetine in the treatment of chronic migraine comorbidity of depression and anxiety disorder
Authors: Zhu Junliang , Chen Jianhuang , Zhang Kaixue 
Published: July 2022

AbstractBackgroundMigraine is common in primary headaches, and with the development of social economy and the increase in living pressure, the prevalence of migraine has an upward trend.ObjectiveTo observe the clinical effect of flunarizine combined with duloxetine in the treatment of chronic migraine with comorbid depression and anxiety disorders and to provide a reference for clinical treatment.MethodsA total of 118 patients with chronic migraine complicated with depression and anxiety disorder admitted to our hospital from June 2018 to August 2020 were selected and divided into two groups according to treatment methods, 59 cases in each group. The control group was treated with flunarizine combined with loxoprofen sodium, and the observation group was treated with flunarizine combined with duloxetine. The changes of electroneurophysiological indexes, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), high sensitivity‐C reactive protein (hs‐CRP), Hamilton depression scale (HAMD) score, and Hamilton anxiety scale (HAMA) score before and after treatment in the two groups were recorded, and the total effective rate of clinical treatment in the two groups was counted.ResultsAfter treatment, TNF‐α, IL‐6, and hs‐CRP in the two groups decreased gradually (p < .05). Further comparison between groups showed that TNF‐α, IL‐6, and hs‐CRP in the observation group were lower than those in the control group (p < .05). After treatment, the HAMD score and the HAMA score of the two groups decreased gradually (p < .05). Further comparison between the two groups showed that HAMD score and HAMA score of the observation group were lower than those of the control group (p < .05).ConclusionFlunarizine combined with duloxetine in the treatment of chronic migraine with depression and anxiety disorder can effectively improve neuroelectrophysiological indexes, reduce inflammation, and reduce depression and anxiety.
Theoretical Perspectives in Organocatalysis
Authors: Melnyk Nika , Iribarren Iñigo , Mates‐Torres Eric , Trujillo Cristina 
Published: July 2022

AbstractIt is clear that the field of organocatalysis is continuously expanding during the last decades. With increasing computational capacity and new techniques, computational methods have provided a more economic approach to explore different chemical systems. This review offers a broad yet concise overview of current state‐of‐the‐art studies that have employed novel strategies for catalyst design. The evolution of the all different theoretical approaches most commonly used within organocatalysis is discussed, from the traditional approach, manual‐driven, to the most recent one, machine‐driven.
Universal Trends between Acid Dissociation Constants in Protic and Aprotic Solvents
Authors: Busch Michael , Ahlberg Elisabet , Laasonen Kari 
Published: July 2022

AbstractpKa values in non‐aqueous solvents are of critical importance in many areas of chemistry. Our knowledge is, despite their relevance, still limited to the most fundamental properties and few pKa values in the most common solvents. Taking advantage of a recently introduced computationally efficient procedure we computed the pKa values of 182 compounds in 21 solvents. This data set is used to establish for the first time universal trends between all solvents. Our computations indicate, that the total charge of the molecule and the charge of the acidic group combined with the Kamlet‐Taft solvatochromic parameters are sufficient to predict pKa values with at least semi‐ quantitative accuracy. We find, that neutral acids such as alcohols are strongly affected by the solvent properties. This is contrasted by cationic acids like ammonium ions whose pKa is often almost completely independent from the choice of solvent.
Molecular Insights of Non‐fused Ring Acceptors for High‐Performance Non‐fullerene Organic Solar Cells
Authors: Li Yibin , Yu Jiangsheng , Zhou Yinhua , Li Zhong'an 
Published: July 2022

AbstractNon‐fullerene acceptors with fused‐ring structures have rapidly improved the performance of organic solar cells over the past five years, but they still suffer from synthetic complexity and thus high material costs, one of the major obstacles of hindering their commercialization process. The construction of non‐fused ring acceptors (NFRAs) has recently been regarded as a feasible solution due to their facile synthesis and satisfactory device performances. Thus in this concept, we highlight the important progress of NFRAs in recent years, and discuss the key relationship between molecular design strategies and device performance. Finally, we provide some potential molecular insights for the future design of high‐performance NFRAs.
Clinical activity of checkpoint inhibitors in angiosarcoma: A retrospective cohort study
Authors: Ravi Vinod , Subramaniam Aparna , Zheng Jing , Amini Behrang , Trinh Van A. , Joseph Jocelyn , Mennel Robert G. , Bishop Andrew J. , Sturgis Erich M. , Goepfert Ryan P. , Yalamanchili Sudha , Botello Gilberto , Stephen Bettzy , Piha‐Paul Sarina A. , Patel Anisha B. , Lazar Alexander J. , Conley Anthony P. , Benjamin Robert S. , Patel Shreyaskumar R. , Futreal Phillip A. , Somaiah Neeta , Naing Aung 
Published: July 2022

BackgroundSystemic treatments for angiosarcoma remains an area of unmet clinical need. The authors conducted this retrospective study to assess the clinical activity of checkpoint inhibitors in patients with angiosarcoma. The primary objective was to assess the objective response rate, and the secondary objective was to assess the progression‐free and overall survival durations and disease control rate.MethodsPatient data were obtained using The University of Texas MD Anderson Cancer Center Tumor Registry database. The final study population was refined to only include patients who had undergone pembrolizumab monotherapy. The objective response rate was evaluated using RECIST/irRECIST version 1.1. Progression‐free survival and overall survival were defined as the time from the initiation of immunotherapy to disease progression or recurrence, death, or last follow‐up and to death or last follow‐up, respectively.ResultsThe final cohort comprised 25 patients. Most patients had metastatic disease (72%) and had undergone at least two lines of systemic therapy (80%) before starting pembrolizumab. The objective response rate was 18%, whereas the disease control rate was 59%. The median progression‐free survival duration was 6.2 months and was not significantly different between the cutaneous (4.7 months) and visceral angiosarcoma (6.2 months) groups (p = .42). The median overall survival duration was 72.6 months. Toxicities were recorded for eight patients, with fatigue, anemia, constipation, and rash being the most common.ConclusionsPembrolizumab shows durable clinical activity in angiosarcoma. These findings suggest that checkpoint inhibition as monotherapy or combination therapy is likely to have a high probability of success.© 2022 American Cancer Society.Lay summary

This is the largest retrospective study to assess the clinical activity of checkpoint inhibitor monotherapy in angiosarcomas.

The study includes an adequate number of patients with visceral angiosarcoma that enabled to obtain meaningful clinical insights that were previously unavailable.

Our findings indicate an improvement in progression‐free survival with pembrolizumab that is comparable to other active agents in angiosarcoma.

Pembrolizumab monotherapy in angiosarcomas also has a favorable tolerability profile.

Our findings emphasize the need for prospective studies to evaluate the activity of pembrolizumab monotherapy and combination therapy.
Characteristics and outcomes of pediatric oncology patients at risk for guardians declining transfusion of blood components
Authors: Stevenson Jason , DeGroote Nicholas P. , Keller Frank , Brock Katharine E. , Bergsagel D. John , Miller Tamara P. , Cornwell Patricia , Fasano Ross , Chonat Satheesh , Castellino Sharon M. 
Published: July 2022

AbstractBackgroundTransfusion of blood products is a necessary part of successful delivery of myelosuppressive regimens in pediatric cancer. There is a paucity of literature characterizing outcomes or management of pediatric patients with cancer when transfusion is declined.AimsThe objective of this paper is to describe the clinical characteristics, care, and outcomes of patients with cancer at risk for declining transfusion.Methods and ResultsA retrospective cohort of patients aged 0–21 years with cancer managed at Children's Healthcare of Atlanta between 2006 and 2020 and with ICD‐9 codes indicating risk of “transfusion refusal” or Jehovah's witness (JW) religion was identified. Demographics, disease, and management were abstracted. Descriptive statistics were performed to examine associations with transfusion receipt. Among 35 eligible patients identified as at risk for declining transfusion, 89% had primary guardians who identified as JW, and 45.7% identified as Black, non‐Hispanic. Only 40% of guardians actively declined transfusion. Transfusion recipients had significantly lower hemoglobin (g/dl) and platelet counts (1000/μl) at initial presentation (9.6 vs. 11.9, p < .002 and 116.0 vs. 406.5, p = .001, respectively) and at nadir (5.9 vs. 8.7, p < .001 and ≤ 10 vs. 154, p < .001, respectively) than non‐recipients. Legal intervention was required in 36.4% of those who ultimately received a transfusion.ConclusionAmong pediatric cancer patients whose medical record initially indicated a preference for no transfusion, 60% of guardians accepted blood products when prescribed for oncology care. Guidelines for systematic management and transfusion sparing approaches are needed to honor guardian's preferences when possible yet while maintaining equitable cancer outcomes in this population.
Treatment outcomes of standard (high dose) cisplatin and non‐standard chemotherapy for locally advanced head and neck cancer
Authors: Alamgeer Muhammad , Coleman Andrew , McDowell Lachlan , Giddings Charles , Safdar Adnan , Sigston Elizabeth , Wang Yang , Subramaniam Ashwin 
Published: July 2022

AbstractIntroductionConcurrent chemoradiotherapy with high‐dose (HD) cisplatin is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA‐HNSCC). Due to the higher treatment‐related adverse effects with standard therapy, alternative regimens (non‐standard therapy), namely, lower dose weekly cisplatin, carboplatin/paclitaxel, or cetuximab are considered. There is, however, no consensus on non‐standard regimens. We aimed to investigate the efficacy and safety profile of these regimens.MethodsThis single centre retrospective cohort study included all consecutive adult patients with newly diagnosed LA‐HNSCC treated with either standard or non‐standard regimens between January 2016 and April 2021. The primary outcome was 2‐year failure‐free survival (FFS). The secondary outcomes included acute toxicities, hospitalisation rates, dose modifications, treatment failure rates (TFR), and overall survival.ResultsAbout 235 patients were included in the final analysis; median age was 61 years (IQR 55–67), and 87% were male. Most had oropharyngeal tumours (85.5%) and p16‐positivity was frequent (80%). About 56% received non‐standard regimens: weekly cisplatin = 79 and non‐cisplatin = 48. These patients had higher Charlson Comorbidity Index (CCI; p < .001) and lower European Cooperative Oncology Group (ECOG)‐0 (p = .003). There was no difference in 2‐year FFS (hazard ratio [HR] = 1.16; 95% confidence interval – [CI] 0.65–2.05), hospitalisation and grade‐3 toxicity rates between the two regimens. Nausea and vomiting were lower in the non‐standard regimen (3.0% vs. 16%, p < .001). Dose reductions, adjusted for age, sex, and CCI, were less likely in the non‐standard regimen (OR = 2.36; 95%‐CI: 1.01–5.49, p = .007).ConclusionsWe demonstrated similar efficacy of lower dose weekly cisplatin and carboplatin/paclitaxel regimens and better safety profile of weekly cisplatin compared to standard HD cisplatin regimens for LA‐HNSCC. Multicenter randomised control trials are required in HD cisplatin‐ineligible patients.
Applications of Viologens in Organic and Inorganic Discoloration Materials
Authors: Yu Shuang , Ying Jun , Tian Aixiang 
Published: July 2022

AbstractViologen derived from 4,4’‐bipyridine has attracted much attention because of its color changing properties with electron transfer, unique redox stability and structural diversity. These characteristics have led to its successful use in various applications, in particular in color‐changing materials. In the past few years, researchers have been working on the syntheses of viologen‐based color‐changing functional materials, and such materials have been widely used in many fields. In photochromic materials, it is used as anti‐counterfeiting material; in thermochromic, it is used as memory storage material, and in electrochromic, it is used as a battery material. This Review discusses the progress of viologen in organic and inorganic discoloration materials in recent years. The syntheses of viologen and its derivatives are summarized, and its application in the field of discoloration materials is introduced.