bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous delivery of several antimicrobial drugs from multi‐compartment glycerol‐silicone membranes
Authors: Mazurek Piotr , Yuusuf Nuura A. , Silau Harald , Mordhorst Hanne , Pamp Sünje J. , Brook Michael A. , Skov Anne L. 
Published: March 2021

AbstractCombining drugs is an efficient tool in fighting bacterial infections. It has been proven to enable an increased antimicrobial activity compared to mono‐drug therapies. Current commercial dressings for treatment of infected wounds provide delivery of one drug only. Therefore, there is an obvious need to develop a technology enabling incorporation and release of two and more actives. Ideally, such technology should prevent potential cross‐reactions between the drugs during long‐term storage. Here, a concept of drug compartmentalization within distinct glycerol domains of glycerol‐silicone elastomer membranes is presented. Multiple drugs are encapsulated within different types of glycerol domains hampering any cross‐reactions. The drugs are simultaneously released upon contact with aqueous media and the release kinetics can be precisely adjusted by tuning various material parameters, such as glycerol content and membrane thickness. Ultimately, the drug release capabilities and the antimicrobial potential are evaluated against a variety of bacteria in an agar diffusion assay. The membranes are proven effective against different bacterial species, which confirms the efficiency of release even at minimum moisture levels. The glycerol‐silicone platform technology enables delivery of virtually unlimited combinations of drugs from different drug families (e.g., antimicrobial, anti‐inflammatory, and pain relief agents) facilitating new ways of treating wound disorders.
The evolution and shift of research topics and methods in library and information science
Authors: Ma Jinxuan , Lund Brady 
Published: March 2021

AbstractEmploying approaches adopted from studies of library and information science (LIS) research trends performed by Järvelin et al., this content analysis systematically examines the evolution and distribution of LIS research topics and data collection methods at 6‐year increments from 2006 to 2018. Bibliographic data were collected for 3,422 articles published in LIS journals in the years 2006, 2012, and 2018. While the classification schemes provided in the Järvelin studies do not indicate much change, an analysis of subtopics, data sources, and keywords indicates a substantial impact of social media and data science on the discipline, which emerged at some point between the years of 2012 and 2018. These findings suggest a type of shift in the focus of LIS research, with social media and data science topics playing a role in well over one‐third of articles published in 2018, compared with approximately 5% in 2012 and virtually none in 2006. The shift in LIS research foci based on these two technologies/approaches appears similar in extent to those produced by the introduction of information systems in library science in the 1960s, or the Internet in the 1990s, suggesting that these recent advancements are fundamental to the identity of LIS as a discipline.
Improving an intensified and integrated continuous bioprocess platform for biologics manufacturing
Authors: Zhou Hang , Fang Mingyue , Zheng Xiang , Zhou Weichang 
Published: March 2021

AbstractThe WuXi Biologics' Ultra‐high Productivity platform (WuXiUP) technology is an innovative and integrated platform of continuous biomanufacturing. Through process intensification, the platform enables continuous manufacturing of almost any type of biologics and delivers processes with ultra‐high productivity. In this paper, a new case study producing a monoclonal antibody (mAb) via the WuXiUP process was further optimized. Key process parameters like culture temperature, basal media, and perfusion rate were evaluated to ensure an enhanced and robust process. To improve process efficiency for downstream processing, a continuous dual‐pore size hollow fiber cell separation and product harvest system were also designed to complement the increased harvest volume from upstream production. In this case study, a significant protein concentration increase and harvest volume reduction were achieved by the application of the new WuXiUP platform.
Theoretical Simulations of Thermochromic and Aggregation‐Induced Emission Behaviors of a Series of Red‐Light Anthracene‐o‐carborane Derivatives
Authors: Duan Ying‐Chen , Pan Qing‐Qing , Zhao Zhi‐Wen , Gao Ying , Wu Yong , Zhao Liang , Geng Yun , Zhang Min , Su Zhong‐Min 
Published: March 2021

AbstractQuantum mechanical and molecular dynamics simulations have been carried out on a series of anthracene‐o‐carborane derivatives (ANT‐H, ANT‐Ph, ANT‐Me and ANT‐TMS) with rare red‐light emission in the solid state. The simulation of the heating process of the crystals and further comparison of the molecular structures and excited‐state properties before and after heating help us to disclose the thermochromic behavior, that is, the red‐shift emission is caused by elongation of the C1−C2 bond in the carborane moiety after heating. Thus, we believe that the molecular structure in the crystal is severely affected by heating. Transformation of the molecular conformation appears in the ANT‐H crystal with increasing temperature. More specifically, the anthracene moiety moves from nearly parallel to the C1−C2 bond to nearly perpendicular, causing the short‐wavelength emission to disappear after heating. As for the aggregation‐induced emission phenomenon, the structures and photophysical properties were investigated comparatively in both the isolated and crystal states; the results suggested that the energy dissipation in crystal surroundings was greatly reduced through hindering structure relaxation from the excited to the ground state. We expect that discussion of the thermochromic behavior will provide a new analysis perspective for the molecular design of o‐carborane derivatives.
IL‐19 induced by IL‐13/IL‐17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP‐9 expression via ERK/NF‐κB signaling pathway
Authors: Li Xia , Huang Jiancong , Chen Xiaohong , Lai Xiaoping , Huang Zizhen , Li Yue , Li Shuaixiang , Chang Lihong , Zhang Gehua 
Published: March 2021

AbstractBackgroundTissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)‐19 or MMP‐9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL‐19 in mediating MMP‐9 expression in CRS.MethodsNasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were investigated using RT‐qPCR and Immunofluorescence (IF). Human nasal epithelial cells (HNECs) were stimulated by IL‐19; ERK phosphorylation, nuclear factor‐κB (NF‐κB) pathway activation, and MMP‐9 level were detected by RT‐qPCR, enzyme‐linked immunosorbent assay, western blot, and IF. We also explored the effect of type1/2/3 cytokines on IL‐19 production by RT‐qPCR, and western blot.ResultsExpression levels of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL‐19 significantly elevated the production of MMP‐9 in HNECs. Furthermore, IL‐19 could activate the ERK and NF‐κB pathways, accompanied by increased MMP‐9 production in HNECs. Conversely, both ERK and NF‐κB inhibitors significantly attenuated the role of IL‐19 in MMP‐9 production. siRNA knockdown of IL‐20R1 suppressed ERK and NF‐κB pathway activation, thereby decreasing MMP‐9 expression. IL‐13 and IL‐17A were found to stimulate IL‐19 production in HNECs.ConclusionIL‐19, promoted by IL‐13 and IL‐17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP‐9 in patients with CRS.
Results of a Dose‐Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non–Small Cell Lung Cancer
Authors: Felip Enriqueta , Burotto Mauricio , Zvirbule Zanete , Herraez‐Baranda Luis A. , Chanu Pascal , Kshirsagar Smita , Maiya Vidya , Chan Phyllis , Pozzi Emanuela , Marchand Mathilde , Monchalin Marion , Tanaka Kunihiko , Tosti Nadia , Wang Bei , Restuccia Eleonora 
Published: March 2021

AbstractIntravenous (IV) atezolizumab is approved for non–small cell lung and other cancers. Subcutaneous (SC) atezolizumab coformulated with recombinant human hyaluronidase, a permeation enhancer for SC dispersion and absorption, is being developed to improve treatment options, reduce burden, and increase efficiency for patients and practitioners. IMscin001 (NCT03735121), a 2‐part, open‐label, global, multicenter, phase 1b/3 study, is evaluating the pharmacokinetics (PK), safety, and efficacy of SC atezolizumab. The part 1 (phase 1b) objective was determination of an SC atezolizumab dose yielding a serum trough concentration (Ctrough) comparable with IV. Patients enrolled in 3 cohorts received SC atezolizumab 1800 mg (thigh) once (cohort 1), 1200 mg (thigh) every 2 weeks for 3 cycles (cohort 2), or 1800 mg (abdomen) every 3 weeks cycle 1, then cycles 2 and 3 (thigh) every 3 weeks (cohort 3). In subsequent cycles, IV atezolizumab 1200 mg every 3 weeks was administered until loss of clinical benefit. SC atezolizumab 1800 mg every 3 weeks and 1200 mg every 2 weeks provided similar Ctrough and area under the curve values in cycle 1 to the corresponding IV atezolizumab reference, was well tolerated, and exhibited a safety profile consistent with the established IV formulation. Exposure following SC injection in the abdomen was lower (20%, 28%, and 27% for Ctrough, maximum concentration, and area under the concentration‐time curve from time 0 to day 21, respectively) than in the thigh. Part 1 SC and IV PK data were analyzed using a population PK modeling approach, followed by simulations. Part 2 (phase 3) will now be initiated to demonstrate that SC atezolizumab PK exposure is not lower than that of IV.
A De Novo‐Designed Artificial Metallopeptide Hydrogenase: Insights into Photochemical Processes and the Role of Protonated Cys
Authors: Malayam Parambath Sreya , Williams Ashley E. , Hunt Leigh Anna , Selvan Dhanashree , Hammer Nathan I. , Chakraborty Saumen 
Published: March 2021

AbstractHydrogenase enzymes produce H2 gas, which can be a potential source of alternative energy. Inspired by the [NiFe] hydrogenases, we report the construction of a de novo‐designed artificial hydrogenase (ArH). The ArH is a dimeric coiled coil where two cysteine (Cys) residues are introduced at tandem a/d positions of a heptad to create a tetrathiolato Ni binding site. Spectroscopic studies show that Ni binding significantly stabilizes the peptide producing electronic transitions characteristic of Ni‐thiolate proteins. The ArH produces H2 photocatalytically, demonstrating a bell‐shaped pH‐dependence on activity. Fluorescence lifetimes and transient absorption spectroscopic studies are undertaken to elucidate the nature of pH‐dependence, and to monitor the reaction kinetics of the photochemical processes. pH titrations are employed to determine the role of protonated Cys on reactivity. Through combining these results, a fine balance is found between solution acidity and the electron transfer steps. This balance is critical to maximize the production of NiI‐peptide and protonation of the NiII−H− intermediate (Ni−R) by a Cys (pKa≈6.4) to produce H2.
Challenges toward development of rear‐earth free FeCo based permanent magnet
Authors: Hasegawa Takashi 
Published: March 2021

AbstractAmong the various permanent magnets reported to date, FeNdB exhibits the highest magnetic performance, but reducing the use of the rare‐earth elements is necessary to avoid exhaustion of rare‐earth elements. The key to improve the performance of permanent magnets is to increase magnetization and coercivity. FeCo has a very large magnetization, but has a very small coercivity caused by the extremely small magnetic anisotropy due to the cubic crystal structure, so that FeCo has long been unsuitable for permanent magnets. However, recent reports have revealed that the transformation of the crystal structure from cubic to tetragonal causes large magnetic anisotropy. In 2017, the author reported that a large coercivity can be obtained by fabricating tetragonal FeCo nanodots. This article reviews recent progress of rear‐earth free permanent magnets especially for the tetragonal FeCo based alloys.
Scanning the human genome for “signatures” of positive selection: Transformative opportunities and ethical obligations
Authors: Hernandez Margarita , Perry George H. 
Published: March 2021

AbstractThe relationship history of evolutionary anthropology and genetics is complex. At best, genetics is a beautifully integrative part of the discipline. Yet this integration has also been fraught, with punctuated, disruptive challenges to dogma, periodic reluctance by some members of the field to embrace results from analyses of genetic data, and occasional over‐assertions of genetic definitiveness by geneticists. At worst, evolutionary genetics has been a tool for reinforcing racism and colonialism. While a number of genetics/genomics papers have disproportionately impacted evolutionary anthropology, here we highlight the 2002 presentation of an elegantly powerful approach for identifying “signatures” of past positive selection from haplotype‐based patterns of genetic variation. Together with technological advances in genotyping methods, this article transformed our field by facilitating genome‐wide “scans” for signatures of past positive selection in human populations. This approach helped researchers test longstanding evolutionary anthropology hypotheses while simultaneously providing opportunities to develop entirely new ones. Genome‐wide scans for signatures of positive selection have since been conducted in diverse worldwide populations, with striking findings of local adaptation and convergent evolution. Yet there are ethical considerations with respect to the ubiquity of these studies and the cross‐application of the genome‐wide scan approach to existing datasets, which we also discuss.
Methodological approaches for estimating regional emission values using national greenhouse gas inventory: A case study of the Republic of Korea
Authors: Yoo Jong‐Ik , Lee Do‐Hyung , Cheong Yu‐Kyong , Kim So‐Hee , Jeong Yu‐Sik , Lee Dae‐Han , Park Sung‐Kwon , Kim Moon‐Jung 
Published: March 2021

AbstractSince the Paris Agreement in 2015, the greenhouse gas (GHG) inventory has been considered as an indicator in the evaluation of national GHG reduction. Despite the importance of achieving and evaluating the national GHG reduction targets by the local government, GHG information availed to local governments is very limited, thus necessitating the use of additional resources to create a GHG inventory for each region. This study established and introduced procedures for the selection and distribution of activity data using a national inventory to allow for the estimation of emission values according to region and used them to calculate emissions in Korea. Statistics that were not based on regional data or those based on different data collection systems were identified, and in such cases, data required improvement to achieve consistency. Emission estimation showed that the applied activity data was consistent with the sum of the regional and national values for 12% of GHG emissions. We expect the improvement of certain statistical data to improve data consistency to 82% within a ± 5% variance. With this method, the consistency between the emission data at the national and local or regional levels can be ensured, and ultimately used to establish or evaluate the implementation of a GHG reduction plan. The proposed method can be particularly useful when capacity enhancement of local governments in developing countries is required for GHG inventory management. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Digital health and management of chronic disease: A multimodal technologies typology
Authors: Vansimaeys Camille , Benamar Lamya , Balagué Christine 
Published: March 2021

AbstractThis cross‐sectional descriptive study aims to (1) describe the current digital technology (DT) use of people with chronic diseases (CD) by identifying different user profiles and (2) determine whether those profiles have specific characteristics regarding health‐related variables and patient–doctor relationship quality (RQ). An online questionnaire assessing the uses of multiple types of DT (the Internet, mobile applications and connected devices) and several dimensions related to health and patient–doctor RQ was completed by 954 individuals living with CD. DT user groups were obtained by k‐means cluster analysis and then compared using Mann–Whitney tests. The results show three profiles of DT users: (1) hyperconnected (8.9%, regular users of all DTs), (2) biconnected (19.1%, regular users of the Internet and mobile apps) and (3) hypoconnected (72%, casual users of the Internet only). The hyperconnected and biconnected groups are more empowered, more knowledgeable about their treatment and more committed to their doctors than the hypoconnected group. Nonadherence to treatment, health motivations, self‐efficacy for health management and the trust dimension of the patient–doctor RQ did not differ between groups. We conclude by discussing the low use of the most recent technologies in the CD population, although these technologies seem to provide access to health information that empowers patients and leads to a better relationship with their doctors.
HDAC inhibition prevents hypobaric hypoxia‐induced spatial memory impairment through PΙ3K/GSK3β/CREB pathway
Authors: Kumar Rahul , Jain Vishal , Kushwah Neetu , Dheer Aastha , Mishra Kamla Prasad , Prasad Dipti , Singh Shashi Bala 
Published: March 2021

AbstractHypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of histone acetyltransferases and histone deacetylases (HDACs) gene expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3 and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat's hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2 g/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia‐exposed rats. Moreover, histone acetylation increased at the promoter regions of brain‐derived neurotrophic factor (BDNF); thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP‐response element binding protein (CREB) phosphorylation by stimulation of PI3K/GSK3β/CREB axis, which counteracts hypobaric hypoxia‐induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition.
Pursuing germline genome sequencing to reduce illness uncertainty may involve additional uncertainties for cancer patients: A mixed‐methods study
Authors: Bartley Nicci , Best Megan , Butow Phyllis 
Published: March 2021

AbstractCancer‐related illness uncertainty has been associated with poorer psychological outcomes for patients. While some cancer patients believe obtaining genomic information will reduce their illness uncertainty, the complexity of genomics has the potential to compound illness uncertainty. The aim of this mixed‐methods study was to investigate uncertainty in patients with a cancer of likely heritable origin immediately following their decision to have germline genome sequencing. Participant (N = 348) negative attitudes toward uncertainty were associated with higher satisfaction with decision to have germline genome sequencing and greater fear of cancer recurrence. Thematic analysis of semi‐structured interviews with a subset of participant (N = 20) revealed the following four themes: (a) germline genome sequencing to reduce illness uncertainty; (b) germline genome sequencing to reduce uncertainty related to relatives’ risk; (c) uncertainty generated by germline genome sequencing; and (d) resilience and coping with uncertainty. This study demonstrated the complexity of uncertainty in germline genome sequencing in cancer patients. These results provide genomic healthcare professionals with important information about cancer patient's motivation to pursue germline genome sequencing, the specific uncertainties generated by germline genome sequencing, and how cancer patients cope with uncertainty.
Men with an FMR1 premutation and their health education needs
Authors: Walsh Matthew B. , Charen Krista , Shubeck Lisa , McConkie‐Rosell Allyn , Ali Nadia , Bellcross Cecelia , Sherman Stephanie L. 
Published: March 2021

AbstractMen who carry an FMR1 premutation are at‐risk to develop a late‐onset neurodegenerative disorder called fragile X‐Associated Ataxia/Tremor syndrome (FXTAS). However, little is known about their health informational needs. This qualitative study is the first to describe diagnostic experiences and identify specific health information needs of male premutation carriers. In‐depth qualitative interviews were conducted by phone with ten men who carry an FMR1 premutation. Interviews were analyzed using direct content analysis. Saturation was assessed through use of the Comparative Method for Themes Saturation in qualitative interviews (CoMeTS). Five themes were identified: diagnosis experience, sources of health information, desired health information, barriers to obtaining health information, and facilitators to desired health information. Participants desired information about inheritance, symptoms, expectations for disease, and actions available to slow progression. Facilitators to obtaining health information included healthcare provider knowledge, positive experiences with providers, beneficial family dynamics, participating in research, and access to experts. Barriers to obtaining health information included lack of personal knowledge, lack of healthcare provider knowledge, negative experiences with providers, and uncertainty. Addressing the educational needs of men with/at‐risk for FXTAS could improve the quality of life of men who carry a fragile X premutation.