bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating end‐to‐end continuous antibody manufacture with column‐free capture alternatives from economic, environmental, and robustness perspectives
Authors: Neves Catarina P. G. , Coffman Jonathan L. , Farid Suzanne S. 
Published: January 2024

AbstractProcess intensification efforts have renewed interest in the potential of end‐to‐end continuous manufacture with column‐free capture alternatives. This article describes a decisional tool that encompasses mass balance and design equations, process economics, stochastic simulation and multi‐criteria decision‐making and enables the evaluation of different batch, and continuous flowsheets for monoclonal antibody (mAb) manufacture. The traditional batch process was compared with end‐to‐end continuous bioprocesses with either protein A capture or column‐free capture employing aqueous two‐phase extraction or precipitation from economic, environmental, and robustness perspectives. The cost of goods analysis predicted that continuous flowsheets could offer substantial cost savings (~20%–40%) over the batch process at low and medium annual commercial demands (100–500 kg); however, at tonnage demands they resulted in either comparable or higher costs. Comparing the continuous options, the continuous flowsheets with protein A or precipitation yielded similar COG/g values, while aqueous two‐phase extraction presented higher costs. The analysis of overall process mass intensities accounting for water and consumables suggested that the continuous flowsheet with protein A would result in the lowest environmental burden. When the economic, environmental, and operational criteria were reconciled using multi‐criteria decision‐making analysis, the continuous protein A‐based flowsheet was found to be the most favorable. A target analysis highlighted the need for process improvements in the following parameters to reduce the manufacturing costs of the continuous column‐free capture options below that of protein A: the perfusion volumetric productivity, the harvested cell culture fluid percentage in column‐free operations, the column‐free step yields along with the implementation of buffer concentrates.
Multi‐omics kinetic analysis of recombinant adeno‐associated virus production by plasmid transfection of HEK293 cells
Authors: Lu Min , Lee Zion , Hu Wei‐Shou 
Published: January 2024

AbstractRecombinant adeno‐associated virus (rAAV) is among the most commonly used vectors for gene therapy. It is commonly produced by transfection of HEK293 cells with three plasmids each containing the vector genome including gene of interest (GOI), helper functions, and rep and cap genes for genome replication and capsid formation. To meet the potential clinical needs, the productivity of the production system needs to be enhanced. A better process characterization of the production system will further advance our insights into ways to enhance productivity. Here, we employed transcriptomic analysis to quantify the dynamics of different isoforms of viral transcripts and to assess the shift of cellular physiology, and deployed targeted proteomic analysis for absolute quantification of viral proteins and tandem mass tags (TMTs) for assessing cellular responses at the protein level. Functional analysis at transcriptome and proteome levels identified defense and immune response, unfolded protein response, p53 signaling as enriched. The small molecule additive intervention study based on functional analysis showed the potential of such omics‐guided productivity enhancement. Together, multi‐omics analysis advanced understanding of rAAV production and provided insight into enhancing rAAV production by plasmid transfection.
Predicting valuable missense variants with AlphaMissense in a multiple pulmonary infection patient
Authors: Wang Tianyuan , Ma Jindi , Shu Yuan , Hong Bao , Wang Zhouhan , Lu Yingfeng , Yu Xiaopeng , Huang Xi , Zhang Yimin 
Published: January 2024

Key Clinical MessageAlphaMissense is proficient in predicting the clinical classification of missense variants. we utilized AlphaMissense to find disease‐relevant variants within a polymicrobial pulmonary infection case. Exome sequencing was performed in this patient, and AlphaMissense and Phenolyzer were combined to investigate disease‐relevant variants screening from exome sequencing results.
Role of Ionic Solvents in the Electrocatalytic CO2 Conversion and H2 Evolution Suppression: From Ionic Liquids to Deep Eutectic Solvents
Authors: Leal‐Duaso Alejandro , Adjez Yanis , Sánchez‐Sánchez Carlos M. 
Published: January 2024

AbstractThe ionic solvents, including both ionic liquids (ILs) and deep eutectic solvents (DES), are deeply studied for their potential in the carbon dioxide (CO2) capture and its further electrochemical conversion using different electrocatalysts. The aim of this review is to present and critically compare the role of ILs and DES in the activation of the electrochemical CO2 reduction reaction (CO2RR) and suppression of the hydrogen evolution reaction (HER). Therefore, the most relevant advances in the use of these ionic solvents in CO2RR, either as neat reaction medium or as electrolyte in molecular solvents, have been summarized and discussed. A special focus has been made on comparing the current density, overpotential, faradaic efficiency and products selectivity of the CO2RR in the presence of the ionic solvents and relaying those results with their chemical composition. Herein, the most recent strategies reported in the literature based on the use of either DES or ILs for enhancing the electrocatalytic CO2 conversion are reviewed, and some new perspectives based on immobilized ILs at the electrode surface are discussed.
Polymer Backbone Chemistry Shapes the Alkaline Stability of Metallopolymer Anion‐Exchange Membranes
Authors: Aggarwal Kanika , Li Songlin , Nijem Sally , Dekel Dario R. , Diesendruck Charles E. 
Published: January 2024

AbstractAnion‐exchange membrane fuel cells and water electrolyzers have garnered significant attention in past years due to their potential role in sustainable and affordable energy conversion and storage. However, the chemical stability of the polymeric anion‐exchange membranes (AEMs), the key component in these devices, currently limits their lifespan. Recently, metallopolymers have been proposed as chemically stable alternatives to organic cations, using metal centers as ion transporters. In metallopolymer AEMs, various properties such as alkaline stability, water uptake, flexibility, and performance, are determined by both the metal complex and polymer backbone. Herein we present a systematic study investigating the influence of the polymer backbone chemistry on some of these properties, focusing on the alkaline stability of low‐oxophilicity gold metallopolymers. Despite the use of a common N‐heterocyclic carbene ligand, upon gold metalation using the same reaction conditions, different polymer backbones end up forming different gold complexes. These findings suggest that polymer chemistry affects the metalation reaction in addition to the other properties relevant to AEM performance.
Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients
Authors: Ranjan Surabhi , Leung Denise , Ghiaseddin Ashley P. , Taylor Jennie W. , Lobbous Mina , Dhawan Andrew , Budhu Joshua A. , Coffee Elizabeth , Melnick Kaitlyn , Chowdhary Sajeel A. , Lu‐Emerson Christine , Kurz Sylvia C. , Burke Joy E. , Lam Keng , Patel Mallika P. , Dunbar Erin M. , Mohile Nimish A. , Peters Katherine B. 
Published: January 2024

AbstractManagement of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low‐molecular‐weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.
Theoretical study of NH3, H2S, and HCN adsorption enhancement on defective graphene‐supported Cu19 clusters
Authors: Liu Naigui , Gao Delu , Wang Dunyou 
Published: January 2024

AbstractRecent studies have shown that graphene‐supported metal clusters can enhance catalytic reactivity compared with corresponding metal clusters. In this study, the adsorptions of NH3, H2S, and HCN on Cu19 and defective graphene‐supported Cu19 clusters are investigated using plane‐wave density functional theory. The results reveal the three gas molecules can be adsorbed on three types of top sites of Cu atoms, respectively. The adsorption energies of the corresponding adsorption sites on the defective graphene‐supported Cu19 clusters are all increased compared with those on the Cu19 clusters. The orbital‐resolved, crystal orbital Hamilton population analysis demonstrates that the larger the integrated crystal orbital Hamilton population, the stronger the adsorption between the gas molecule and the bonded Cu atom. The center of antibonding states on the defective graphene‐supported Cu19 is shifted upward relative to Fermi level compared to the corresponding one on pure Cu19, which explains the enhanced adsorption energy on defective graphene‐supported Cu19. In addition, the closer d‐band center to the Fermi level on the defective graphene‐supported Cu19 indicates a stronger adsorption capacity than on pure Cu19.
The effect of tooth loss on the temporomandibular joint space: A CBCT study
Authors: Tabatabaei Salma , Paknahad Maryam , Poostforoosh Mahdi 
Published: January 2024

AbstractObjectiveThe tooth loss has a significant impact on the positioning of the condyle in the glenoid fossa and joint spaces of the temporomandibular joint (TMJ). The aim of this study was to assess the association between tooth loss and TMJ spaces using cone beam computed tomography (CBCT) images.Materials and MethodsThis retrospective investigation involved the evaluation of CBCT images of the bilateral TMJs in a cohort of 111 individuals, comprising 68 males and 43 women. The dentition of the patients was categorized into three categories, including A (65.4%), B (19.1%), and C (16.4%), based on the Eichner index. Anterior, superior, and posterior joint spaces were then measured in sagittal views. The Kruskal–Wallis test and Mann–Whitney test were employed to identify significant differences among the three Eichner groups.ResultsThe findings of the present study suggested that there was no statistically significant variation in the anterior joint space among different Eichner groups within the general population (p = .781). Nevertheless, the superior and posterior joint spaces exhibited statistically significant alterations, as indicated by p‐values of .039 and .010, respectively. It was detected that condyles were positioned inferiorly and posteriorly in group C when compared to groups A and B.ConclusionThe present study indicated that greater loss of tooth‐supporting zones is associated with posterior and inferior displacement of condyles. Understanding these relationships helps emphasize how crucial it is to replace missing teeth to enhance occlusion support and, in turn, stop the progression and further deterioration of temporomandibular disorders.
N‐Substituted piperazine‐coupled imidazo[2,1‐b]thiazoles as inhibitors of Mycobacterium tuberculosis: Synthesis, evaluation, and docking studies
Authors: Chirra Nagaraju , Abburi Naga Pranathi , Rekha Estharla Madhu , Pedapati Ravi kumar , Bollikanda Rakesh Kumar , Murahari Manikanta , Sriram Dharmarajan , Sridhar Balasubramanian , Kantevari Srinivas 
Published: January 2024

AbstractAn innovative series of N‐substituted piperazine‐linked imidazothiazole derivatives 7(a–x) were synthesized, and their antitubercular effectiveness was evaluated. A three‐step reaction sequence involving the condensation of 1,3‐dichloroacetone and thiourea, coupling with substituted piperazines to give the intermediates 5(a–d) and cyclization with substituted α‐bromoacetophenones produced the desired imidazothiazole derivatives 7(a–x) in excellent yields. In vitro screening of new derivatives against Mycobacterium tuberculosis H37Rv resulted in 7k (minimum inhibitory concentration [MIC]: 0.78 μg/mL) and 7g and 7h (MIC: 1.56 μg/mL) as potent hit compounds. Further, the docking studies of the promising compounds 7k, 7g, and 7h revealed that the best molecular interactions are with the DprE1 in complex with sulfonyl PBTZ of M. tuberculosis as the target protein (PDB ID: 6G83).
Stabilizing effects of spatially heterogeneous disturbance via reduced spatial synchrony on a rocky shore community
Authors: Mintrone Caterina , Rindi Luca , Benedetti‐Cecchi Lisandro 
Published: January 2024

AbstractUnderstanding how synchronous species fluctuations affect community stability is a main research topic in ecology. Yet experimental studies evaluating how changes in disturbance regimes affect the synchrony and stability of populations and communities remain rare. We hypothesized that spatially heterogeneous disturbances of moderate intensity would promote metacommunity stability by decreasing the spatial synchrony of species fluctuations. To test this hypothesis, we exposed rocky shore communities of algae and invertebrates to homogeneous and gradient‐like spatial patterns of disturbance at two levels of intensity for 4 years and used synchrony networks to characterize community responses to these disturbances. The gradient‐like disturbance at low intensity enhanced spatial β diversity compared to the other treatments and produced the most heterogeneous and least synchronized network, which was also the most stable in terms of population and community fluctuations. In contrast, homogeneous disturbance destabilized the community, enhancing spatial synchronization. Intense disturbances always reduced spatial β diversity, indicating that strong perturbations could destabilize communities via biotic homogenization regardless of their spatial structure. Our findings corroborated theoretical predictions, emphasizing the importance of spatially heterogeneous disturbances in promoting stability by amplifying asynchronous spatial and temporal fluctuations in population and community abundance. In contrast to other networks, synchrony networks are vulnerable to the removal of most peripheral nodes, which are less synchronized, but may contribute more to stability than other nodes by dampening large fluctuations in species abundance. Our findings suggest that climate change and direct anthropogenic disturbance can compromise the stability of ecological communities through combined effects on diversity and synchrony, as well as further affecting ecosystems through habitat loss.
Too young for an acquired cardiomyopathy? Cobalt metallosis as a cardiac amyloidosis mimicker
Authors: Casian Mihnea , Bica Ramona , Ionescu Virgil , Predescu Vlad , Țincu Radu , Jurcuț Ruxandra 
Published: January 2024

AbstractMetallosis with subsequent cardiac involvement is a possible long‐term complication of hip arthroplasty. We report the case of a young female referred to our centre for the suspicion of cardiac amyloidosis presenting with low electrocardiogram voltage, left ventricular hypertrophy, pericardial effusion, and global and longitudinal systolic impairment with apical sparing pattern. Her medical history was remarkable for arthroplasty in the context of congenital hip dysplasia. Two years prior to presentation, she underwent revision surgery for prosthesis malfunction, and tissue metallosis was initially documented. At the current presentation, cobalt metallosis was confirmed, as the circulating cobalt and chromium levels were severely elevated. The accurate diagnosis prompted the removal of the cobalt source with extensive tissue debridement and the use of chelating agents. Reversal of the cardiac abnormalities occurred as the circulating cobalt levels returned to normal.
Ring‐Expansion Reactions of the Biomass Derivative Cyrene via Enamine Dihalocyclopropanation
Authors: Puschnig Johannes , Greatrex Ben W. 
Published: January 2024

AbstractA ring‐expansion process for the biomass derivative Cyrene obtained from levoglucosenone has been developed using gem‐dihalocyclopropanes as intermediates. The process involves conversion of Cyrene to an enamine, reaction with an in situ generated dihalocarbene, and then ring‐opening. Competition between endocyclic and exocyclic olefinic products was switchable using solvent and temperature, and ring‐expanded alkenyl halides were obtained in 50–64 % yield from Cyrene. Under extended heating, dehalogenation occurred giving homologated levoglucosenone in 25 % overall yield from Cyrene in 3 steps.
Exploring the facilitators and barriers in opioid deprescribing for non‐cancer pain treatment experienced by general practitioners: A qualitative study
Authors: de Kleijn Loes , Jansen‐Groot Koerkamp Elsemiek A. W. , van der Kooij Iris , Veen Mario , Rijkels‐Otters Hanneke J. B. M. , Koes Bart W. , Chiarotto Alessandro 
Published: January 2024

AbstractBackgroundGuidelines recommend opioid deprescribing in patients on long‐term opioid treatment for chronic non‐cancer pain. This study aims to explore facilitators and barriers in opioid deprescribing among general practitioners in the Netherlands. In addition, this study aims to identify possibilities for improvement regarding opioid deprescribing in primary care.MethodsFocus group discussions with Dutch General practitioners were held by two skilled moderators. The focus group discussions were transcribed verbatim and analysed using MAXQDA software. Three independent reviewers searched for overarching themes using thematic analysis with an inductive approach. Discussions were organized until data saturation was reached.ResultsTwenty‐two general practitioners participated in four focus group discussions. Five main themes emerged from the data: (1) patient‐centred care; (2) ensuring proper pain management (3) dilemmas and hardships in dealing with opioid use disorder; (4) the competency gap; (5) needs and possibilities to improve opioid deprescribing in primary care. The first theme addresses the main facilitators in opioid tapering. The following three themes emerged as main barriers in opioid deprescribing. The fifth theme identified possibilities for change.ConclusionsThis study indicates the importance of intrinsic motivation and a tailored approach to deprescribe opioids in patients with chronic pain on long‐term opioid treatment. Identified barriers include struggles in pain management, challenges caused by opioid use disorder, insufficient capacities such as time constraints and lack of skills. Recommendations for improvement involve enhanced collaboration with healthcare professionals in primary and secondary care, provision of practical tools and assurance of sufficient time.SignificanceThis focus group study among 22 Dutch general practitioners elucidates the complexities of opioid deprescribing and reveals pivotal themes such as patient‐centred care, pain management challenges, and competency gaps. The findings underscore the crucial role of intrinsic motivation and that of a tailored approach in opioid deprescribing, while demonstrating how a lack in effective pain treatments, practical capacities and challenges caused by opioid dependence, impede opioid deprescribing. By uncovering these complexities, this study aims to inform future deprescribing strategies.
Maximal fat oxidation rate across the adult lifespan of trained women
Authors: Dahlgaard Hansen I. M. , Wismann J. F. , Sahl R. E. , Frandsen J. , Hansen M. , Ingersen A. , Schmücker M. , Modvig J. L. , Dela F. , Larsen S. , Helge J. W. 
Published: January 2024

AbstractThe fat oxidation capacity is higher in young compared to elderly subjects and higher in premenopausal compared to postmenopausal women, but the influence of age on maximal fat oxidation (MFO) is not clear. Therefore, this study aimed to evaluate MFO (g/min) across the lifespan of trained adult women. In total, 36 healthy trained women were recruited into three groups: (n = 12), young (27 ± 3 years, mean ± SD) premenopausal, middle‐aged (57 ± 3 years), and older (71 ± 2 years) postmenopausal women and all had a body mass index <25 kg/m2. After an overnight fast, body composition was determined by dual‐energy X‐ray absorptiometry, and blood samples were obtained. A FATmax‐test was performed on a cycle ergometer, and MFO was calculated from the pulmonary V̇O2 and V̇CO2 measured by indirect calorimetry. The absolute MFO was significantly higher in young (0.40 ± 0.07 g/min) compared to both middle‐aged (0.33 ± 0.07 g/min) (p = 0.035) and old (0.25 ± 0.05 g/min) women (p < 0.001). Absolute MFO was higher in middle‐aged compared to old women (p = 0.018). Relative MFO (MFO/LBM, mg/min/LBM) was higher in young (8.39 ± 1.62 mg/min/LBM) compared to old (6.16 ± 1.14 mg/min/LBM) women (p = 0.004). A significant linear relationship was observed between absolute MFO and age (R2 = 0.41; p < 0.001), V̇O2max (R2 = 0.40; p < 0.001), and LBM (R2 = 0.13; p = 0.033), respectively, and between relative MFO and fat mass (R2 = 0.12; p = 0.04). In conclusion, the maximal capacity to oxidize fat is attenuated with age in trained women. Furthermore, postmenopausal middle‐aged women have higher absolute MFO compared to older women, and this implies that it is age per se and not a change in estrogen availability that leads to lower absolute MFO.
Effect of different periodization models of combined training on the perception of barriers to physical activity in adults with obesity: A randomized clinical trial
Authors: Rosa Fernanda , Tozetto Willen Remon , Benedet Jucemar , Del Duca Giovani Firpo 
Published: January 2024

AbstractThis study aimed to analyze the effect of combined training with linear and non‐periodized periodization and a control group on the perception of barriers to physical activity in adults with obesity. A randomized, controlled, and blinded clinical trial was conducted, comprising the control (CG), non‐periodized (NG), and linear periodization (PG) groups. Combined training was prescribed for 16 weeks. The NG kept the relative training intensity fixed (50%–59% of the heart rate reserve [HRres] and 10 to 12 repetition maximums [RMs]), while the PG linearly progressed (40%–49% HRres to 60%–69% HRres and 12 to 14 RMs to 8 to 10 RMs). The 19 barriers were obtained through a questionnaire. Generalized estimating equations (GEE) were used, adopting p ≤ 0.05 as a significant result, and individual responsiveness analyses. The CG significantly increased the score of lack of space (Δ = 0.6) and lack of equipment (Δ = 1.1) barriers. The NG (Δ = −0.4 and −0.6, respectively) and PG (Δ = −0.1 and −0.2, respectively) reduced their scores, showing a group*time interaction (p = 0.019 and 0.011, respectively). Through the individual responses, we verified a reduction in the number of barriers, notably in the groups with combined training (CG: 4 of 14; NG: 12 of 18; and PG: 10 of 17 individuals). Regardless of the form of periodization, the training groups reduced the score of some analyzed barriers. From a clinical point of view, individuals submitted to different forms of combined training periodization showed more expressive reductions in their total scores, when compared to the CG.