bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a platform process for the production and purification of single‐domain antibodies
Authors: Crowell Laura E. , Goodwine Chaz , Holt Carla S. , Rocha Lucia , Vega Celina , Rodriguez Sergio A. , Dalvie Neil C. , Tracey Mary K. , Puntel Mariana , Wigdorovitz Andrés , Parreño Viviana , Love Kerry R. , Cramer Steven M. , Love J. Christopher 
Published: February 2021

AbstractSingle‐domain antibodies (sdAbs) offer the affinity and therapeutic value of conventional antibodies, with increased stability and solubility. Unlike conventional antibodies, however, sdAbs do not benefit from a platform manufacturing process. While successful production of a variety of sdAbs has been shown in numerous hosts, purification methods are often molecule specific or require affinity tags, which generally cannot be used in clinical manufacturing due to regulatory concerns. Here, we have developed a broadly applicable production and purification process for sdAbs in Komagataella phaffii (Pichia pastoris) and demonstrated the production of eight different sdAbs at a quality appropriate for nonclinical studies. We developed a two‐step, integrated purification process without the use of affinity resins and showed that modification of a single process parameter, pH of the bridging buffer, was required for the successful purification of a variety of sdAbs. Further, we determined that this parameter can be predicted based only on the biophysical characteristics of the target molecule. Using these methods, we produced nonclinical quality sdAbs as few as 5 weeks after identifying the product sequence. Nonclinical studies of three different sdAbs showed that molecules produced using our platform process conferred protection against viral shedding of rotavirus or H1N1 influenza and were equivalent to similar molecules produced in Escherichia coli and purified using affinity tags.
Production of high‐quality SARS‐CoV‐2 antigens: Impact of bioprocess and storage on glycosylation, biophysical attributes, and ELISA serologic tests performance
Authors: Castro Rute , Nobre Lígia S. , Eleutério Rute P. , Thomaz Mónica , Pires António , Monteiro Sandra M. , Mendes Sónia , Gomes Ricardo A. , Clemente João J. , Sousa Marcos F. Q. , Pinto Filipe , Silva Ana C. , Freitas Micael C. , Lemos Ana R. , Akpogheneta Onome , Kosack Lindsay , Bergman Marie‐Louise , Duarte Nadia , Matoso Paula , Costa Júlia , Bandeiras Tiago M. , Gomes‐Alves Patricia , Gonçalves Carlos P. , Demengeot Jocelyne , Alves Paula M. 
Published: February 2021

AbstractSerological assays are valuable tools to study SARS‐CoV‐2 spread and, importantly, to identify individuals that were already infected and would be potentially immune to a virus reinfection. SARS‐CoV‐2 Spike protein and its receptor binding domain (RBD) are the antigens with higher potential to develop SARS‐CoV‐2 serological assays. Moreover, structural studies of these antigens are key to understand the molecular basis for Spike interaction with angiotensin converting enzyme 2 receptor, hopefully enabling the development of COVID‐19 therapeutics. Thus, it is urgent that significant amounts of this protein became available at the highest quality. In this study, we produced Spike and RBD in two human derived cell hosts: HEK293‐E6 and Expi293F™. We evaluated the impact of different and scalable bioprocessing approaches on Spike and RBD production yields and, more importantly, on these antigens' quality attributes. Using negative and positive sera collected from human donors, we show an excellent performance of the produced antigens, assessed in serologic enzyme‐linked immunosorbent assay (ELISA) tests, as denoted by the high specificity and sensitivity of the test. We show robust Spike productions with final yields of approx. 2 mg/L of culture that were maintained independently of the production scale or cell culture strategy. To the best of our knowledge, the final yield of 90 mg/L of culture obtained for RBD production, was the highest reported to date. An in‐depth characterization of SARS‐CoV‐2 Spike and RBD proteins was performed, namely the antigen's oligomeric state, glycosylation profiles, and thermal stability during storage. The correlation of these quality attributes with ELISA performance show equivalent reactivity to SARS‐CoV‐2 positive serum, for all Spike and RBD produced, and for all storage conditions tested. Overall, we provide straightforward protocols to produce high‐quality SARS‐CoV‐2 Spike and RBD antigens, that can be easily adapted to both academic and industrial settings; and integrate, for the first time, studies on the impact of bioprocess with an in‐depth characterization of these proteins, correlating antigen's glycosylation and biophysical attributes to performance of COVID‐19 serologic tests.
Prostate‐specific antigen testing among young men: an opportunity to improve value
Authors: Lange Suzanne M. , Ambrose Jacob P. , Flynn Michael C. , Lowrance William T. , Hanson Heidi A. , O’Neil Brock B. 
Published: February 2021

AbstractIntroductionProstate cancer screening using prostate‐specific antigen (PSA) testing remains widespread. The prevalence of PSA testing in young men is unknown and may be an appropriate target for improving health care by decreasing low‐value testing in this age group. The purpose of this study was to determine PSA testing rates in men younger than current guidelines support.Materials and MethodsHealth Informational National Trends Surveys (HINTS) from 2011 to 2014 and 2017 were analyzed to establish the prevalence of PSA testing in young men and to evaluate the differences in testing rates based on race.ResultsThe combined survey data included 5178 men, with 2393 reporting previous PSA screening. Of men ages 18–39, 7% recalled receipt of PSA testing. Twenty‐two percent of men between the ages of 40 and 44 had been tested. Among men under age 40, PSA testing was more common among black men (14%) compared to white men (7%), Hispanics (6%), and men of Asian descent (8%). Logistic regression modeling demonstrates that black men under the age of 40 were more likely to undergo PSA testing than other racial or ethnic groups (odds ratio 2.14; 95% CI 1.17, 3.93).ConclusionsCurrent guidelines do not recommend routine PSA testing in average‐risk men under the age of 40. This study found that a significant number of young men are exposed to testing, with the greatest risk among black men. This suggests that there is an opportunity to improve the value of PSA testing by decreasing testing in young men.
Electronic Regulation of Bromophenyl Grafted Metal‐Free Carbon Nitride Catalysts for Enhanced Utilization of H2S
Authors: Shen Lijuan , Lei Ganchang , Zheng Yong , Liang Shijing , Liu Fujian , Wang Shuai , Cao Yanning , Xiao Yihong , Jiang Lilong 
Published: February 2021

AbstractDeveloping metal‐free heterogeneous catalysts with high efficiency for the elimination of H2S into eco‐friendly products are very important for both fundamental catalytic science and industrial chemistry. Herein, we design a new modified carbon nitride catalyst engrafted with Br‐substituted aromatic heterocycle (CNU−Br) through a simple copolymerization and exfoliation method. CNU−Br exhibits excellent H2S conversion efficiency, high sulfur selectivity, and outstanding stability in the catalytic desulfurization reaction, which is better than most of the reported catalysts. The experiments and theoretical calculations show that the grafting of bromophenyl groups into the fundamental carbon nitride structural network leads to π‐delocalization, surface modification, as well as enhances the basicity of the structural active N sites. The regulation of the H and S affinity of CNU−Br that mediate the facile cleavage of H2S hydrogen‐sulfur bonds and the release of S atoms in thermodynamics. Furthermore, the superior surface area and mass transfer over CNU−Br accelerate the adsorption and oxidation of H2S in kinetics compared with the ordinary carbon nitride.
Influence of Temperature on Cobalt Hydroxide Precipitation for Recovery from Battery Leachates
Authors: Djoudi Neila , Le Page Mostefa Marie , Muhr Hervé 
Published: February 2021

AbstractAs cobalt is a strategic metal essential for the energy and digital transition, the current research work focuses on cobalt recovery from Li‐ion batteries by precipitation. Simulation results allow determination of the cobalt hydroxide precipitation conditions for a complete cobalt recovery. The experimental results show the high impact of temperature on cobalt hydroxide precipitation kinetics and on particle size distribution. Indeed, cobalt recovery is optimal at 25 °C, with a yield of nearly 100 %. However, the simulation results show that it is necessary to be careful about the chosen temperature to avoid coprecipitation of cobalt with manganese. These promising results allow a better understanding of cobalt hydroxide precipitation for a complete recovery from Li‐ion battery leachates.
Rationale and design of the OPTIMAL‐REPERFUSION trial: A prospective randomized multi‐center clinical trial comparing different fibrinolysis‐transfer percutaneous coronary intervention strategies in acute ST‐segment elevation myocardial infarction
Authors: Chen Zhongxiu , Wang Duolao , Ma Min , Li Chen , Wan Zhi , Zhang Li , Zhu Ye , Wang Mian , Wang Hua , He Sen , Peng Yong , Wei Jiafu , Huang Baotao , He Yong ,   for the OPTIMAL‐REPERFUSION trial investigator
Published: February 2021

AbstractPrimary percutaneous coronary intervention (PPCI), the preferred reperfusion strategy for all acute ST‐segment elevation myocardial infarction (STEMI) patients, is not universally available in clinical practice. Pharmacoinvasive strategy has been proposed as a therapeutic option in patients with STEMI when timely PPCI is not feasible. However, pharmacoinvasive strategy has potential delay between clinical patency and complete myocardial perfusion. The optimal reperfusion strategy for STEMI patients with anticipated PPCI delay according to current practice is uncertain. OPTIMAL‐REPERFUSION is an investigator‐initiated, prospective, multicenter, randomized, open‐label, superiority trial with blinded evaluation of outcomes. A total of 632 STEMI patients presenting within 6 hours after symptom onset and with an expected time of first medical contact to percutaneous coronary intervention (PCI) ≥120 minute will be randomized to a reduced‐dose facilitated PCI strategy (reduced‐dose fibrinolysis combined with simultaneous transfer for immediate invasive therapy with a time interval between fibrinolysis to PCI < 3 hours) or to standard pharmacoinvasive treatment. The primary endpoint is the composite of death, reinfarction, refractory ischemia, congestive heart failure, or cardiogenic shock at 30‐days. Enrollment of the first patient is planned in March 2021. The recruitment is anticipated to last for 12 to 18 months and to complete in September 2023 with 1 year follow‐up. The OPTIMAL‐REPERFUSION trial will help determine whether reduced‐dose facilitated PCI strategy improves clinical outcomes in patients with STEMI and anticipated PPCI delay. This study is registered with the ClinicalTrials.gov (NCT04752345).
Population‐level impact of coronavirus disease 2019 on breast cancer screening and diagnostic procedures
Authors: Nyante Sarah J. , Benefield Thad S. , Kuzmiak Cherie M. , Earnhardt Kathryn , Pritchard Michael , Henderson Louise M. 
Published: February 2021

BACKGROUNDTo understand how health care delays may affect breast cancer detection, the authors quantified changes in breast‐related preventive and diagnostic care during the coronavirus disease 2019 (COVID‐19) pandemic.METHODSEligible women (N = 39,444) were aged ≥18 years and received a screening mammogram, diagnostic mammogram, or breast biopsy between January 1, 2019 and September 30, 2020, at 7 academic and community breast imaging facilities in North Carolina. Changes in the number of mammography or breast biopsy examinations after March 3, 2020 (the first COVID‐19 diagnosis in North Carolina) were evaluated and compared with the expected numbers based on trends between January 1, 2019 and March 2, 2020. Changes in the predicted mean monthly number of examinations were estimated using interrupted time series models. Differences in patient characteristics were tested using least squares means regression.RESULTSFewer examinations than expected were received after the pandemic's onset. Maximum reductions occurred in March 2020 for screening mammography (−85.1%; 95% CI, −100.0%, −70.0%) and diagnostic mammography (−48.9%; 95% CI, −71.7%, −26.2%) and in May 2020 for biopsies (−40.9%; 95% CI, −57.6%, −24.3%). The deficit decreased gradually, with no significant difference between observed and expected numbers by July 2020 (diagnostic mammography) and August 2020 (screening mammography and biopsy). Several months after the pandemic's onset, women who were receiving care had higher predicted breast cancer risk (screening mammography, P < .001) and more commonly lacked insurance (diagnostic mammography, P < .001; biopsy, P < .001) compared with the prepandemic population.CONCLUSIONSPandemic‐associated deficits in the number of breast examinations decreased over time. Utilization differed by breast cancer risk and insurance status, but not by age or race/ethnicity. Long‐term studies are needed to clarify the contribution of these trends to breast cancer disparities.
Local Contact Fluorination of Graphene
Authors: Chilingarov Norbert S. , Skokan Eugene V. , Knot'ko Alexander V. , Eliseev Andrei A. 
Published: February 2021

AbstractA procedure for solid‐phase fluorination of graphene is described that provides fluorine addition at the interfaces of graphene with solid fluorinating reagents. Graphene sheets were formed on a copper substrate (Cu−G) with a specific wave‐like microstructure. A solid fluorinating reagent, {Pt2F6−PtF4} solid solution, was layered on a Pt substrate (Pt−F). Thermally activated fluorination is found to be localized to the linear contacts of the Pt−F surface with the “ridges” of the Cu−G waves, leading to alternating stripes of intact and fluorinated graphene. Thus, the use of specifically profiled substrates for the graphene layer and/or the solid‐phase fluorinating reagent offers a promising approach to create fluorinated zones of the desired shape and size.
Acute heart transplantation from mechanical circulatory support in a human immunodeficiency virus‐positive patient with fulminant myocarditis
Authors: Szakal‐Toth Zsofia , Szlavik Janos , Soltesz Adam , Berzsenyi Viktor , Csikos Gergely , Varga Tamas , Racz Kristof , Kiraly Akos , Sax Balazs , Hartyanszky Istvan , Fintha Attila , Prohaszka Zoltan , Monostory Katalin , Merkely Bela , Nemeth Endre 
Published: February 2021

AbstractSince the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus‐positive heart transplant recipients' survival is similar to non‐infected patients. We present the case of a 40‐year‐old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus‐positive patients even in case of new onset, irreversible acute heart failure.
Pharmacotherapy for heart failure with reduced ejection fraction and health‐related quality of life: a systematic review and meta‐analysis
Authors: Turgeon Ricky D. , Barry Arden R. , Hawkins Nathaniel M. , Ellis Ursula M. 
Published: February 2021

AbstractAimsThe aim of this study was to synthesize the evidence on the effect of heart failure with reduced ejection fraction (HFrEF) pharmacotherapy on health‐related quality of life (HRQoL).Methods and resultsWe searched MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform in June 2020. Randomized placebo‐controlled trials evaluating contemporary HFrEF pharmacotherapy and reporting HRQoL as an outcome were included. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias and GRADE certainty of evidence. The primary outcome was HRQoL at last available follow‐up analysed using a random‐effects model. We included 37 studies from 5770 identified articles. Risk of bias was low in 10 trials and high/unclear in 27 trials. High certainty evidence from meta‐analyses demonstrated improved HRQoL over placebo with sodium–glucose co‐transporter 2 (SGLT2) inhibitors [standardized mean difference (SMD) 0.16, 95% confidence interval (CI) 0.08–0.23] and intravenous iron (SMD 0.52, 95% CI 0.04–1.00). Furthermore, high certainty evidence from ≥1 landmark trial further supported improved HRQoL with angiotensin receptor blockers (ARBs) (SMD 0.09, 95% CI 0.02–0.17), ivabradine (SMD 0.14, 95% CI 0.04–0.23), hydralazine–nitrate (SMD 0.24, 95% CI 0.04–0.44) vs. placebo, and for angiotensin receptor–neprilysin inhibitor (ARNI) compared with an angiotensin‐converting enzyme (ACE) inhibitor (SMD 0.09, 95% CI 0.02–0.17). Findings were inconclusive for ACE inhibitors, beta‐blockers, digoxin, and oral iron based on low‐to‐moderate certainty evidence.ConclusionARBs, ARNIs, SGLT2 inhibitors, ivabradine, hydralazine–nitrate, and intravenous iron improved HRQoL in patients with HFrEF. These findings can be incorporated into discussions with patients to enable shared decision‐making.
Diagnostic scores predict morbidity and mortality in patients hospitalized for heart failure with preserved ejection fraction
Authors: Verbrugge Frederik H. , Reddy Yogesh N.V. , Sorimachi Hidemi , Omote Kazunori , Carter Rickey E. , Borlaug Barry A. 
Published: February 2021

AimsTo investigate the prognostic value of diagnostic scores for heart failure (HF) with preserved ejection fraction (HFpEF).Methods and resultsConsecutive patients with HFpEF admitted for unequivocal decompensated HF treated with intravenous loop diuretics were evaluated (n = 443; mean age 78 ± 12 years; 60% women). The HFA‐PEFF and H2FPEF scores were calculated for all patients with echocardiography data available within 1 year and the population was stratified according to HFA‐PEFF scores 2–4 (n = 79), 5 (n = 93), or 6 (n = 271) and H2FPEF score probabilities <90% (n = 80), 90–95% (n = 61), and 96–100% (n = 293). HF readmission rates (95% confidence intervals) increased from 28.9 (22.7–35.0) per 100 patient‐years in HFA‐PEFF 2–4 to 46.0 (38.5–53.5) in HFA‐PEFF 5 and 45.0 (40.1–49.8) in HFA‐PEFF 6. Similarly, HF readmission rates increased with increasing H2FPEF probability: <0.90 [31.8 (25.3–38.2) per 100 patient‐years], 0.90–0.95 [41.5 (32.9–50.1)], and 0.96–1.00 [45.9 (41.2–50.6]. Median survival was 65 months (36–89 months) in HFA‐PEFF score 2–4, 45 months (26–59 months) in HFA‐PEFF score 5, and 28 months (22–42 months) in HFA‐PEFF score 6 (P < 0.001), while the hazard ratio (95% confidence interval) for all‐cause mortality was 1.16 (1.02–1.32) per 0.10 increase in H2FPEF probability.ConclusionsAmong patients hospitalized with HFpEF, higher HFpEF probability according to diagnostic scores is associated with increased risk of subsequent HF readmissions and all‐cause mortality.
The ADUC Prizes: Early Recognition at a Crucial Stage of an Academic Career
Authors: Gade Lutz H. 
Published: February 2021

AbstractProfessor Lutz H. Gade, Chairman of the Editorial Board of the European Journal of Inorganic Chemistry (EurJIC), introduces the Special Collection showcasing contributions by recipients of the ADUC Prizes awarded annually to junior independent researchers in the field of inorganic chemistry.
Eu2CuSe3 Revisited by Means of Experimental and Quantum‐Chemical Techniques
Authors: Gladisch Fabian C. , Maier Stefan , Steinberg Simon 
Published: February 2021

AbstractThe bonding nature between chalcogenides and rare‐earth‐elements is typically described as ionic in the spirit of the Zintl‐Klemm formalism; yet, recent efforts showed that lanthanides also act as d‐metals in transition‐metal‐post‐transition‐metal‐element bonding. Hence, how can we describe the bonding nature between chalcogen and europium atoms, which have frequently acted as electron‐donors like group‐I/II‐elements? To answer this question, we prototypically explored the electronic structure of Eu2CuSe3, which was obtained in considerable yields from solid‐state reactions of the pure elements at 600 °C. The crystal structure of Eu2CuSe3 was determined based on X‐ray diffraction experiments and it is composed of diverse types of linear chains of selenium polyhedra enclosing the copper and europium atoms. These chains are condensed into
[EuCuSe3] layers, which are separated by additional europium atoms. From analyses of the crystal structure and electronic structure of Eu2CuSe3, it is clear that there are two different europium valence states, whose nature controls if europium acts as an electron‐donor like a group‐I/II‐element or as a d‐metal.
Copper‐Catalyzed Cross‐Dehydrogenative Coupling Reactions
Authors: Afsina C. M. A. , Aneeja Thaipparambil , Neetha Mohan , Anilkumar Gopinathan 
Published: February 2021

AbstractCopper‐catalyzed organic reactions have received wide attention due to the high relative abundance of copper, its cheap price, low toxicity, eco‐friendliness, sustainable nature, and versatility as a catalyst. Copper catalysts are widely used in cross‐dehydrogenative coupling and have found wide applications in heterocyclic chemistry. This review focuses on the recent advances in the synthesis of biologically important compounds such as nitrogen heterocycles, amines, amides, imines, and alkynes using copper‐catalyzed cross‐dehydrogenative coupling and covers literature from 2018 to 2020.
Functionalized 2‐Hydroxybenzaldehyde‐PEG Modules as Portable Tags for the Engagement of Protein Lysine ϵ‐Amino Groups
Authors: Sacco Giovanni , Stammwitz Simon , Belvisi Laura , Pignataro Luca , Dal Corso Alberto , Gennari Cesare 
Published: February 2021

AbstractThe formation of reversible‐covalent interactions between a small‐molecule ligand and its protein target is emerging as a general strategy to design binders with increased affinity. In this context, 2‐hydroxybenzaldehyde (2HB) has been recently proposed as suitable electrophilic tag to engage primary amines, such as the ϵ‐amino group of lysine residues, in remarkably stable imines. Lys residues are often expressed in high amounts on protein surfaces and in the proximity of ligand binding sites, and a fine‐tuning of the chemical connection between the ligand and 2HB is fundamental for the affinity gain. Herein we report the synthesis of four 2HB tags functionalized with a short polyethylene glycol (PEG) spacer and a suitable reactive ‘handle’ (alkyne, azide, carboxylic acid and amine, respectively) for their conjugation to virtually any type of small molecule ligand.