bluuebunny/crossref_metadata_2025_split huggingface dataset:
End‐to‐end continuous bioprocessing: Impact on facility design, cost of goods, and cost of development for monoclonal antibodies
Authors: Mahal Hanna , Branton Harvey , Farid Suzanne S. 
Published: April 2021

AbstractThis article presents a systematic approach to evaluate the business case for continuous processing that captures trade‐offs between manufacturing and development costs for monoclonal antibodies (mAbs). A decisional tool was built that integrated cost of goods (COG) with the cost of development models and new equipment sizing equations tailored to batch, hybrid, and end‐to‐end continuous processes. The COG analysis predicted that single‐use continuous facilities (sized using a dedicated downstream processing train per bioreactor) offer more significant commercial COG savings over stainless steel batch facilities at annual demands of 100–500 kg (~35%), compared to tonnage demands of 1–3 tons (~±10%) that required multiple parallel continuous trains. Single‐use batch facilities were found to compete with continuous options on COG only at 100 kg/year. For the scenarios where batch and continuous facilities offered similar COG, the analysis identified the windows of operation required to reach different COG savings with thresholds for the perfusion rate, volumetric productivity, and media cost. When considering the project lifecycle cost, the analysis indicated that while end‐to‐end continuous facilities may struggle to compete on development costs, they become more cost‐effective than stainless steel batch facilities when considering the total out‐of‐pocket cost across both drug development and commercial activities.
Efficient Synthesis of Monomeric Fe Species in Zeolite ZSM‐5 for the Low‐Temperature Oxidation of Methane
Authors: Yu Tao , Su Yang , Wang Aiqin , Weckhuysen Bert M. , Luo Wenhao 
Published: April 2021

AbstractDirect oxidation of methane into value‐added C1 oxygenated products, such as methanol, is essential and remains a significant challenge in the field of catalysis. In this work, we have prepared Fe/ZSM‐5 materials via three different methods and investigated the influence of various preparation methods on the composition and catalytic performance of Fe/ZSM‐5 for the low‐temperature oxidation of methane. Through a combination of scanning transmission electron microscopy, ultraviolet‐visible diffuse reflectance and 57Fe Mössbauer spectroscopy, we have found that the highest proportion of monomeric Fe species of 71 % could be achieved in the ZSM‐5 zeolite by the solid‐state ion‐exchange method, affording an excellent C1 oxygenates yield of 120 mol/molFe with a C1 oxygenates selectivity of 96 % at 50 °C for 30 min in the aqueous solution of H2O2.
Efficient Electroreduction of CO2 to CO on Porous ZnO Nanosheets with Hydroxyl Groups in Ionic Liquid‐based Electrolytes
Authors: Wang Hui , Yang Dexin , Yang Jie , Ma Xiaoxue , Li Hongping , Dong Weiwei , Zhang Renjie , Feng Chongyang 
Published: April 2021

AbstractElectrochemical reduction of CO2 is a very promising route to realize carbon cycle and alleviate energy shortage. Herein, the porous zinc oxide nanosheets with hydroxyl groups on carbon paper substrates (ZnO(OH)/CP‐x,×represents the deposition time) were proved to be excellent catalysts for CO2 electroreduction to CO. As far as we know, the hydroxyl groups were first introduced into ZnO catalysts for this reaction, which can enhance the surface areas and improve the capacity of binding CO2 by the formation of hydrogen bond. Especially, the total current density could reach 44.3 mA cm−2 with 97.8 % Faradaic efficiency (FE) of CO over ZnO(OH)/CP‐600 catalysts with moderate hydroxyl groups in 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([Bmim]PF6, 30 wt%)/acetonitrile/H2O (5 wt%) ternary electrolytes at −2.0 V versus Ag/Ag+, although the self‐reduction of the catalysts could be occurred simultaneously during electrolysis. Besides, the composition of the electrolytes also can significantly modulate the catalytic activity and selectivity of CO. The outstanding performance of ZnO(OH)/CP‐600 catalyst resulted mainly from the introduction of hydroxyl groups, high surface area, good contact with the substrate, and synergy effect between the catalyst and the electrolyte.
Controllable Multicomponent Co‐Assembly Approach to Ordered Mesoporous Zirconia Supported with Well‐Dispersed Tungsten Oxide Clusters as High‐Performance Catalysts
Authors: Li Jichun , Yang Xuanyu , Ma Junhao , Yuan Chenyi , Ren Yuan , Cheng Xiaowei , Deng Yonghui 
Published: April 2021

AbstractZirconia supported WOx clusters with high acid strength and good stability are important solid acid catalysts in many reactions. However, conventional synthetic methods such as incipient‐wetness impregnation and co‐precipitation usually result in the products with low catalytic activity due to low surface area, uncontrollable and non‐homogeneous distribution of tungsten species. In this study, a facile multicomponent co‐assembly approach was utilized to straightforwardly synthesize ordered mesoporous WOx/ZrO2 composites (OMWZr) with mesopore size over 17 nm, pore volume of 0.13–0.18 cm3/g and surface area of 27.3–41.7 m2/g. The materials were composed of robust crystalline ZrO2 skeleton and well‐dispersed WOx clusters (polytungstates) in framework under the optimized conditions. The tungsten species were well stablized by the crystallized skeletons of mesoporous ZrO2, which can inhibit the growth of tetragonal ZrO2 but facilitate crystallization of monoclinic ZrO2. The states of tungsten species (monotungstates, polytungstates and crystalline WO3) can be precisely adjusted by their doping amount in framework and calcination temperature as well, which can further tune the surface acidity of OMWZr composites. Owing to the existence of numerous active surface WOx clusters generated over exposed surface of mesoporous ZrO2, the OMWZr catalysts not only show great spatial homogeneity of accessible Brønsted acid sites and feasible mass diffusion during catalytic reactions, but also display outstanding acid‐catalytic performance over hydrolysis reactions of benzaldehyde dimethyl acetal. The catalyst can be reused for more than 10 cycles, without reduction of catalytic activity and selectivity to benzaldehyde.
Sequential Tether‐Directed Synthesis of New [3 : 2 : 1] Hexakis‐Adducts of C60 with a Mixed Octahedral Addition Pattern
Authors: Wachter Michael , Jurkiewicz Lisa , Hirsch Andreas 
Published: April 2021

AbstractA new concept for the regioselective synthesis of [3 : 2 : 1] hexakis‐adducts of fullerene C60 was developed. Based on sequential tether‐directed remote functionalizations, chiral [3 : 2] pentakis‐adducts with an incomplete octahedral addition pattern were synthesized via stepwise cyclopropanation of C60 with suitable macrocyclic tri‐ and bifunctional cyclomalonate tethers. The four resulting stereoisomers were isolated using chiral HPLC. The corresponding pairs of enantiomers show mirror image behavior in their CD‐spectra. The pentakis‐adducts served as suitable building blocks for the spatially controlled synthesis of mixed hexakis‐adducts. Implementation of functional group‐bearing monomalonates afforded octahedral [3 : 2 : 1] hexakis‐adducts suitable for the construction of larger molecular and supramolecular fullerene architectures in excellent yield.
Click and Release Chemistry for Activity‐Based Purification of β‐Lactam Targets
Authors: Saidjalolov Saidbakhrom , Braud Emmanuelle , Edoo Zainab , Iannazzo Laura , Rusconi Filippo , Riomet Margaux , Sallustrau Antoine , Taran Frédéric , Arthur Michel , Fonvielle Matthieu , Etheve‐Quelquejeu Mélanie 
Published: April 2021

Abstractβ‐Lactams, the cornerstone of antibiotherapy, inhibit multiple and partially redundant targets referred to as transpeptidases or penicillin‐binding proteins. These enzymes catalyze the essential cross‐linking step of the polymerization of cell wall peptidoglycan. The understanding of the mechanisms of action of β‐lactams and of resistance to these drugs requires the development of reliable methods to characterize their targets. Here, we describe an activity‐based purification method of β‐lactam targets based on click and release chemistry. We synthesized alkyne‐carbapenems with suitable properties with respect to the kinetics of acylation of a model target, the Ldtfm L,D‐transpeptidase, the stability of the resulting acylenzyme, and the reactivity of the alkyne for the cycloaddition of an azido probe containing a biotin moiety for affinity purification and a bioorthogonal cleavable linker. The probe provided access to the fluorescent target in a single click and release step.
Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia
Authors: Rausch Caitlin R. , DiNardo Courtney D. , Maiti Abhishek , Jammal Nadya J. , Kadia Tapan M. , Marx Kayleigh R. , Borthakur Gautam , Savoy J. Michael , Pemmaraju Naveen , DiPippo Adam J. , Daver Naval G. , Chew Serena M. , Sasaki Koji , Issa Ghayas C. , Short Nicholas J. , Takahashi Koichi , Ohanian Maro N. , Ning Jing , Xiao Lianchun , Alvarado Yesid , Kontoyiannis Dimitrios P. , Ravandi Farhad , Kantarjian Hagop M. , Konopleva Marina Y. 
Published: April 2021

BackgroundVenetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients aged ≥75 years with newly diagnosed acute myeloid leukemia (AML). VEN and HMA treatment can result in prolonged and often profound neutropenia, and this warrants antifungal prophylaxis. Azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism; this results in VEN dose reductions for each concomitant antifungal. Limited clinical data exist on outcomes for patients treated with VEN, an HMA, and various azoles.MethodsThe time to neutrophil recovery (absolute neutrophil count [ANC] > 1000 cells/mm3) and platelet (PLT) recovery (PLT count > 100,000 cells/mm3) in 64 patients with newly diagnosed AML who achieved a response after course 1 of VEN plus an HMA were evaluated. HMA therapy included azacitidine (75 mg/m2 intravenously/subcutaneously for 7 days) or decitabine (20 mg/m2 intravenously for 5 or 10 days).ResultsForty‐seven patients (73%) received an azole: posaconazole (n = 17; 27%), voriconazole (n = 9; 14%), isavuconazole (n = 20; 31%), or fluconazole (n = 1; 2%). The median time to ANC recovery were similar for patients who did receive an azole (37 days; 95% confidence interval [CI], 34‐38 days) and patients who did not receive an azole (39 days; 95% CI, 30 days to not estimable; P = .8). The median time to PLT recovery was significantly longer for patients receiving azoles (28 vs 22 days; P = .01). The median times to ANC recovery (35 vs 38 days) and PLT recovery (26 vs 32 days) were similar with posaconazole and voriconazole.ConclusionsVEN plus an HMA resulted in neutropenia and thrombocytopenia, with the latter prolonged in patients receiving concomitant azoles. Concomitant posaconazole or voriconazole and VEN (100 mg) resulted in similar ANC and PLT recovery times, suggesting the safety of these dosage combinations during course 1.
Comorbidities and the risk of cardiovascular disease mortality among racially diverse patients with breast cancer
Authors: Connor Avonne E. , Schmaltz Chester L. , Jackson‐Thompson Jeannette , Visvanathan Kala 
Published: April 2021

BACKGROUNDWomen who have coexisting comorbidities at the time of breast cancer diagnosis have an increased risk of breast cancer and overall mortality. However, the associations between newly diagnosed comorbidities and the risk of cardiovascular disease (CVD) mortality among these patients have not been examined.METHODSThe authors compared the associations between coexisting and newly diagnosed CVD, type 2 diabetes, and hypertension and the risk of CVD mortality among patients with breast cancer identified in the Missouri Cancer Registry. In total, 33,099 women who had incident invasive breast cancer with inpatient and outpatient hospital discharge data within 2 years after breast cancer diagnosis were included: 9.3% were Black. Subdistribution hazard ratios (sdHRs) and 95% CIs were calculated for the risk of CVD‐related mortality using adjusted Cox proportional hazards regression models, accounting for a competing risk of breast cancer deaths.RESULTSWithin the first 2 years after breast cancer, the most reported newly diagnosed comorbidity was hypertension (9%), followed by CVD (4%), and type 2 diabetes (2%). CVD mortality was increased in women who had newly diagnosed CVD (sdHR, 2.49; 95% CI, 2.09‐2.99), diabetes (sdHR, 2.16; 95% CI, 1.68‐2.77), or hypertension (sdHR, 2.06; 95% CI, 1.71‐2.48) compared with women who did not have these conditions. Associations were similar by race. The strongest association was among women who received chemotherapy and then developed CVD (sdHR, 3.82; 95% CI, 2.69‐5.43).CONCLUSIONSMonitoring for diabetes, hypertension, and CVD from the time of breast diagnosis may reduce CVD mortality.
Effect of the Additional Carboxyl Group in Half‐Sandwich Organometallic 2,4‐Dipicolinate Complexes on Solution Speciation and Structure
Authors: Mészáros János P. , Németi Gábor , Poljarevic Jelena M. , Holczbauer Tamás , May Nóra V. , Enyedy Éva A. 
Published: April 2021

AbstractSolution speciation of Rh(η5‐C5Me5), Ru(η6‐p‐cymene) and Ru(η6‐toluene) complexes of 2,4‐pyridinedicarboxylic acid (2,4‐dipicH2) was studied and compared to that of 2‐picolinic acid (picH) in addition to their reactivity towards chloride and bromide ions, 1‐methylimidazole and guanosine. Structures of [Rh(η5‐C5Me5)(2,4‐dipicH)Cl] ⋅ 3H2O (1), 2[Ru(η6‐toluene)(2,4‐dipicH)Cl] ⋅ 3H2O (2) and [Ru(η6‐toluene)(2,4‐dipic)]3 ⋅ 7H2O (3) were analyzed by X‐ray diffraction. 1 and 2 show typical piano stool geometry, while 3 is a triangular complex stabilized via the monodentate coordination of the second carboxylate group to the neighboring Ru(II) center. High stability [M(arene)L(H2O/Cl)] species predominate at pH 7.4. 2,4‐Dipic forms more stable complexes with Ru(η6‐arene) than pic, with this difference being minor in the case of the Rh(η5‐C5Me5) complexes. A lower affinity of 2,4‐dipic complexes to halide ions was found compared to the corresponding pic complexes due to the additional COO− moiety.
A brief review of influenza virus infection
Authors: Javanian Mostafa , Barary Mohammad , Ghebrehewet Sam , Koppolu Veerendra , Vasigala VeneelaKrishnaRekha , Ebrahimpour Soheil 
Published: April 2021

AbstractInfluenza is an acute viral respiratory infection that affects all age groups and is associated with high mortality during pandemics, epidemics, and sporadic outbreaks. Nearly 10% of the world's population is affected by influenza annually, with about half a million deaths each year. Influenza vaccination is the most effective method for preventing influenza infection and its complications. The influenza vaccine's efficacy varies each season based on the circulating influenza strains and vaccine uptake rates. Currently, three antiviral drugs targeting the influenza virus surface glycoprotein neuraminidase are available for treatment and prophylaxis of disease. Given the significant burden of influenza infection globally, this review is focused on the latest findings in the etiology, epidemiology, transmission, clinical manifestation, diagnosis, prevention, and treatment of influenza.
Effect of rainfall and altitude on the 2‐acetyl‐1‐pyrroline and volatile compounds profile of black glutinous rice (Thai upland rice)
Authors: Sansenya Sompong , Wechakorn Kanokorn 
Published: April 2021

AbstractBACKGROUNDThe aroma intensity of rice is mixed of more than 100 volatile compounds. Fragrant rice is famous in Thailand due to specific aroma. One important volatile compound that contributes to aromatic intensity and represents a characteristic compound for fragrant rice is 2‐acetyl‐1‐pyrroline (2AP). The production of volatile compounds and 2AP in rice is affected by various environmental factors, such as cultivation area, water content and temperature.RESULTSOur research employed 29 samples of fragrant colored rice (Luempua black glutinous rice cultivar) from Phetchabun province, Thailand from three harvested rice seasons (2015–2017). The cultivation areas of rice samples exhibited differences in rainfall (976.6–1260.5 mm y r−1) and altitude (26.26–1033.41 m). All volatile compounds and 2AP were identified by gas chromatography–mass spectrometry (GC–MS). In 29 rice samples, 2AP levels decreased with increasing of rainfall. The increase in altitude seems to increase 2AP levels, but some high‐altitude cultivation areas resulted in low 2AP content. A variety of volatile compounds was observed in 29 rice samples from different cultivation areas. The results showed that differences in altitude and rainfall affected the production of volatile compounds in fragrant colored rice. Moreover, our results indicated that different environmental conditions in cultivation areas potentially affect volatile compound production during rice growth.CONCLUSIONThe increase in 2AP levels under low rainfall conditions and the assortment of volatile compound varieties produced in colored rice grown in different cultivation areas may be useful information for rice cultivation management striving to produce rice with high aromatic intensities. © 2021 Society of Chemical Industry.
Effects of Pulsed‐Wave Photobiomodulation Therapy on Human Spermatozoa
Authors: Espey Burkhard T. , Kielwein Karin , van der Ven Hans , Steger Klaus , Allam Jean‐Pierre , Paradowska‐Dogan Agnieszka , van der Ven Katrin 
Published: April 2021

Background and ObjectivesPrevious studies reported that photobiomodulation (PBM) positively affects the mitochondrial respiratory chain in sperm, resulting in improved motility and velocity. As laser settings are not yet fully established, the present study aimed at optimizing PBM on human sperm. In addition, possible side‐effects of PBM on sperm DNA fragmentation level and acrosomal integrity have been analyzed.Study Design/Materials and MethodsA pulsed laser‐probe (wavelength 655 nm, output power 25 mW/cm², impulse duration 200 nanoseconds) was used. Native fresh liquefied semen samples underwent radiation with energy doses of 0 (control), 4, 6, and 10 J/cm². Sperm parameters were assessed at 0, 30, 60, 90, and 120 minutes after radiation using a computer‐assisted sperm analysis system. Motility and velocity of sperm from asthenozoospermic patients (n = 42) and normozoospermic controls (n = 22) were measured. The amount of DNA strand breaks was analyzed using ligation‐mediated quantitative polymerase chain reaction in patients with asthenozoospermia (n = 18) and normozoospermia (n = 13). Post‐irradiance acrosomal integrity was investigated using flow cytometry based on CD46 protein expression (n = 7).ResultsExposure to laser energy‐doses of 4 and 6 J/cm² improved sperm motility and velocity in asthenozoospermic patients. PBM exhibited no significant effect on DNA fragmentation level and expression of CD46 serving as a biomarker for acrosome integrity.ConclusionPBM improves sperm motility parameters by maintaining DNA and acrosome integrity and, therefore, represents a promising new tool for assisted reproductive therapy. In particular, improving sperm motility in asthenozoospermic patients by PBM in future may contribute to increasing the chance for successful intrauterine insemination. The present trial has no clinical registration number, as only in vitro studies were performed. The study was approved by the local ethics committee and performed according to the Declaration of Helsinki. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.
Let's play: Me and my AI‐powered avatar as one team
Authors: Butt Asad H. , Ahmad Hassan , Goraya Muhammad A. S. , Akram Muhammad S. , Shafique Muhammad N. 
Published: April 2021

AbstractArtificial intelligence (AI) tools have altered the gaming industry, thanks to their newly incepted functionalities, which have enhanced the consumer experience. Building on innovation diffusion theory, technology acceptance model, and flow theory, this study highlights an AI‐powered avatar concept. This study explores the roles of perceived easiness, usefulness, advantage, compatibility, enjoyment, customization, and interactivity in forming the gamers' intention to play with AI‐powered avatars. A survey data of 500 respondents from China having experience playing online video games is used to test the proposed hypotheses. The results offer significant support to the proposed relationships related to adopting an AI‐powered avatar and the consumers' psychological association with its adoption. Consequently, the results imply that AI‐powered avatars should allow gamers to customize, interact, and take assistance to move up levels with an enjoyable experience. Moreover, this study also suggests that digital technologies such as AI could be integrated into the gaming environment for a more pleasing and immersive experience.
Most men with artificial urinary sphincter cuff erosion have low serum testosterone levels
Authors: Wolfe Avery R. , Ortiz Nicolas M. , Baumgarten Adam S. , VanDyke Maia E. , West Mary L. , Dropkin Benjamin M. , Joice Gregory A. , Sanders Sarah C. , Hudak Steven J. , Morey Allen F. 
Published: April 2021

AbstractAimsTo evaluate the relationship between serum testosterone (T) levels and artificial urinary sphincter (AUS) cuff erosion in a population of incontinent men who underwent AUS placement.MethodsA retrospective analysis of our single‐surgeon AUS database was performed to identify men with T levels within 24 months of AUS placement. Men were stratified into two groups based on serum testosterone: low serum testosterone (LT) (<280 ng/dl) and normal serum testosterone (NT) (>280 ng/dl). Multivariable analysis was performed to control for risk factors. The outcome of interest was the incidence of and time to spontaneous urethral cuff erosion; other risk factors for cuff erosion were also evaluated.ResultsAmong 161 AUS patients with serum testosterone levels, 84 (52.2%) had LT (mean: 136.8 ng/dl, SD: 150.4 ng/dl) and 77 (47.8%) had NT (mean: 455.8 ng/dl, SD: 197.3 ng/dl). Cuff erosion was identified in 42 men (26.1%) at a median of 7.1 months postoperatively (interquartile range: 3.6–13.4 months), most of whom (30/42, 71.4%) were testosterone deficient. LT levels were less common (54/119, 45.4%) in the non‐erosion cohort (p = 0.004). Men with low T were nearly three times as likely to suffer AUS erosion than men with normal T (odds ratio = 2.519, p = 0.021). LT level was the only factor associated with AUS erosion on multivariable analysis.ConclusionsLT is an independent risk factor for AUS cuff erosion. Men with LT are more likely to present with cuff erosion, but there is no difference in time to erosion.
A Quantitative Molecular Orbital Perspective of the Chalcogen Bond
Authors: de Azevedo Santos Lucas , van der Lubbe Stephanie C. C. , Hamlin Trevor A. , Ramalho Teodorico C. , Matthias Bickelhaupt F. 
Published: April 2021

AbstractInvited for this month's cover are the groups of Prof. Dr. Teodorico C. Ramalho (Federal University of Lavras and University Hradec Kralove) and Prof. Dr. F. Matthias Bickelhaupt (Vrije Universiteit Amsterdam and Radboud University). The cover picture shows the key message of their work, that is, the covalency of the chalcogen bonds, in an elegantly simple and attractive manner. To that end, the chalcogen bonds are represented by schematic 3D structures of the bond donor D2Ch and the bond acceptor A–, and their attractive interaction in green. Then, a colorful molecular orbital (MO) diagram where the HOMO–LUMO mixing is represented by the mixing of red (HOMO) and blue (LUMO) into purple (MO) is presented. Read the full text of their Full Paper at 10.1002/open.202000323.