bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary
Authors: Florian Jeffry , Sun Qin , Schrieber Sarah J. , White Richard , Shubow Sophie , Johnson‐Williams Bernadette E. , Sheikhy Morasa , Harrison Nicholas R. , Parker Valerie J. , Wang Yow‐Ming , Strauss David G. 
Published: November 2022

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA‐approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke‐Margolis Center for Health Policy collaborated with the FDA to host a two‐day virtual public workshop entitled “Pharmacodynamic Biomarkers for Biosimilar Development and Approval” on September 20–21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii) summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two‐day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.
Evaluating the Clinical and Immune Responses to Spotted Fever Rickettsioses in the Guinea Pig‐Tick‐Rickettsia System
Authors: Stokes John V. , Levin Michael L. , Cross Claire E. , Ross Anne‐Marie L. , Snellgrove Alyssa N. , Willeford Bridget V. , Alugubelly Navatha , Varela‐Stokes Andrea S. 
Published: November 2022

AbstractThe guinea pig was the original animal model developed for investigating spotted fever rickettsiosis (SFR). This model system has persisted on account of the guinea pig's conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig‐tick‐Rickettsia model for monitoring the course of infection and immune response to an infection by spotted fever group Rickettsia (SFGR) that can be studied at biosafety level 2 (BSL‐2) and arthropod containment level 2 (ACL‐2); adaptations must be made for BSL‐3 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of Rickettsia to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick‐borne pathogens. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Tick transmission of SFGR to guinea pigsSupport Protocol 1: Laboratory infection of ticks by injectionAlternate Protocol 1: Needle inoculation of SFGR to guinea pigsBasic Protocol 2: Monitoring the course of guinea pig rickettsial infection: clinical signsBasic Protocol 3: Monitoring the course of guinea pig rickettsial infection: collection of biological specimensSupport Protocol 2: Guinea pig anesthesiaBasic Protocol 4: Monitoring rickettsial burden in guinea pigs by multiplex qPCRBasic Protocol 5: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometryBasic Protocol 6: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometryBasic Protocol 7: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISASupport Protocol 4: Coating ELISA PlatesAlternate Protocol 2: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay
Bacteriophage Isolation, Purification, and Characterization Techniques Against Ubiquitous Opportunistic Pathogens
Authors: Peters Danielle L. , Harris Greg , Davis Carly M. , Dennis Jonathan J. , Chen Wangxue 
Published: November 2022

AbstractHealthcare‐associated infection with “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) is a global health crisis due to their extensive intrinsic antibiotic resistance and the ability to quickly acquire resistance determinants. Alternative treatment options are required to combat this crisis, and one possibility is the use of bacteriophages, or viruses that strictly infect the pathogenic bacteria. Currently, there is a renaissance in research and development into the use of phages to target multi‐, extensively, and pan‐resistant bacterial infections in humans, known as phage therapy. Using A. baumannii as an example, this article describes the isolation and purification of bacteriophages from sewage and soil samples, as well as general methods used in phage research such as precipitation of phages using polyethylene glycol, host range analysis, single‐cell burst size determination, DNA extraction, and restriction fragment length polymorphism analysis. © 2022 National Research Council Canada. Current Protocols © 2022 Wiley Periodicals LLC. Reproduced with the permission of the Minister of Innovation, Science, and Industry.Basic Protocol 1: Isolation of bacteriophages against A. baumannii from sewage samplesAlternate Protocol 1: Isolation of bacteriophages against A. baumannii from soil samplesSupport Protocol 1: Titering a bacteriophage stockBasic Protocol 2: Purification of phage to an axenic working stockSupport Protocol 2: Liquid propagation of bacteriophageBasic Protocol 3: Host range analysis using the spot plate methodBasic Protocol 4: Single burst size analysisAlternate Protocol 2: One‐step growth curveBasic Protocol 5: Precipitation of bacteriophage using PEG 6000Basic Protocol 6: DNA extraction from dsDNA bacteriophagesBasic Protocol 7: Restriction fragment length polymorphism analysis of novel phage genomes
Enhancing iPSC‐CM Maturation Using a Matrigel‐Coated Micropatterned PDMS Substrate
Authors: Jimenez‐Vazquez Eric N. , Jain Abhilasha , Jones David K. 
Published: November 2022

AbstractCardiac myocytes isolated from adult heart tissue have a rod‐like shape with highly organized intracellular structures. Cardiomyocytes derived from human pluripotent stem cells (iPSC‐CMs), on the other hand, exhibit disorganized structure and contractile mechanics, reflecting their pronounced immaturity. These characteristics hamper research using iPSC‐CMs. The protocol described here enhances iPSC‐CM maturity and function by controlling the cellular shape and environment of the cultured cells. Microstructured silicone membranes function as a cell culture substrate that promotes cellular alignment. iPSC‐CMs cultured on micropatterned membranes display an in‐vivo‐like rod‐shaped morphology. This physiological cellular morphology along with the soft biocompatible silicone substrate, which has similar stiffness to the native cardiac matrix, promotes maturation of contractile function, calcium handling, and electrophysiology. Incorporating this technique for enhanced iPSC‐CM maturation will help bridge the gap between animal models and clinical care, and ultimately improve personalized medicine for cardiovascular diseases. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Cardiomyocyte differentiation of iPSCsBasic Protocol 2: Purification of differentiated iPSC‐CMs using MACS negative selectionBasic Protocol 3: Micropatterning on PDMS
How do introductory field biology students feel? Journal reflections provide insight into student affect
Authors: Treibergs Kira A. , Esparza David , Yamazaki Jeannie A. , Goebel Marc , Smith Michelle K. 
Published: November 2022

AbstractAn understanding of both cognitive and affective domains of learning is critical to promoting undergraduate student success in biology. Field courses—which support student learning, observation, and experimentation in the outdoors—have been shown to be effective in supporting cognitive student outcomes. However, less is known about students' affective responses during field instruction. To better understand the affective domain in this course type, we asked students enrolled in a campus‐based introductory field biology course to engage in weekly reflective journaling over the course of a semester. We employed inductive and deductive coding of over 700 field journal reflections using the Model of the Affective Domain for the Geosciences as a conceptual basis. Informed by our results, we present a theoretically‐driven, five‐part Framework of Student Affect in Field Biology and in‐depth and novel insights into what students feel, believe, and value as they participate in an undergraduate field course. Our framework and coding results can be used by field course instructors to understand how to better design experiences that leave students feeling confident in their abilities, interested to learn more about nature, and empowered to persist in the discipline.
Assessing the importance of interspecific interactions in the evolution of microbial communities
Authors: Raynaud Tiffany , Blouin Manuel , Devers‐Lamrani Marion , Garmyn Dominique , Spor Aymé 
Published: November 2022

AbstractInterspecific interactions play an important role in the establishment of a community phenotype. Furthermore, the evolution of a community can both occur through an independent evolution of the species composing the community and the interactions among them. In this study, we investigated how important the evolution of interspecific interactions was in the evolutionary response of eight two‐bacterial species communities regarding productivity. We found evidence for an evolution of the interactions in half of the studied communities, which gave rise to a mean change of 15% in community productivity as compared to what was expected from the individual responses. Even when the interactions did not evolve themselves, they influenced the evolutionary responses of the bacterial strains within the communities, which further affected community response. We found that evolution within a community often promoted the adaptation of the bacterial strains to the abiotic environment, especially for the dominant strain in a community. Overall, this study suggested that the evolution of the interspecific interactions was frequent and that it could increase community response to evolution.
Functional traits and phylogeny explain snake distribution in the world's largest dry forest ecoregion, the Gran Chaco
Authors: Cabral Hugo , Guedes Thaís B. , Santana Diego J. 
Published: November 2022

AbstractMacroecological studies describe large‐scale diversity patterns through analyses of species distribution patterns and allows us to elucidate how species differing in ecology, physical requirements, and life histories are distributed in a multidimensional space. These patterns of distributions can be explained by vegetation, and climatic factors, and are determined by historical and current factors. The continuous accumulation of information on the distribution patterns of species is essential to understand the history and evolution of the biota. In this study, we aimed to identify functional and evolutionary drivers that explain the geographic patterns of vertical stratification. We compiled morphological, ecological, and distribution data of 140 species of Chacoan snakes and constructed null models to map their geographic pattern. We used a range of environmental variables to assess which drivers are influencing these biogeographic patterns. Lastly, we used evolutionary data to build the first map of the phylogenetic regions of Chacoan snakes. We found a latitudinal pattern, with a marked verticality in the snake assemblies in the Chaco. Verticality and long‐tailed species richness increased in areas with high stratified habitats and stable temperature. Fossoriality is driven mainly by soil conditions, especially soils with fewer sand particles and less stratified habitat. Phylogenetic regions in the Chaco showed a marked latitudinal pattern, like that observed in the geographic pattern of verticality. The distribution pattern of Chacoan snakes also reflects their evolutionary history, with a marked phylogenetic regionalization.
Data transmission reduction techniques for improving network lifetime in wireless sensor networks: An up‐to‐date survey from 2017 to 2022
Authors: Jain Khushboo , Kumar Anoop , Singh Akansha 
Published: November 2022

AbstractWireless sensor networks (WSNs) have now become a substantial part of our life as it provides an incredible setup for monitoring environmental conditions such as glaciers melting, earthquakes, climate change, volcanic eruption, agriculture, and other natural calamities. One of the most important challenges in data gathering and examining accurate data is “energy consumption.” However, continuously changing environmental conditions, mobility in devices and extreme resource usage, such as battery capacity in WSNs collectively contribute to a high possibility of redundant data transmission thus making it tremendously hard to achieve a satisfactory network lifetime. Additionally, these environmental monitoring applications periodically senses and aggregate data which usually exhibits high temporal and spatial redundancies. As a result, exploiting these redundancies is essential for both resource utilization, as well as accurate data transmission. Since a huge amount of energy is exhausted in transmitting the redundant data, which has become a bottleneck in scaling such applications. In this context, this article provides a thorough examination of existing energy‐efficient redundant data transmission reduction techniques, as well as their strengths and drawbacks. The idea of redundant data transmission reduction concept is divided into three stages: the sensor nodes (SN) at the first stage, the cluster heads (CHs) at the second stage, and the base station (BS) at the third stage. Furthermore, this survey focuses on the current issues and challenges, as well as the future directions in reducing redundant data transmission for future investigation.
Sex-dependent effects of parental age on offspring fitness in a cooperatively breeding bird
Authors: Sparks Alexandra M. , Hammers Martijn , Komdeur Jan , Burke Terry , Richardson David S. , Dugdale Hannah L. 
Published: November 2022

AbstractParental age can have considerable effects on offspring phenotypes and health. However, intergenerational effects may also have longer term effects on offspring fitness. Few studies have investigated parental age effects on offspring fitness in natural populations while also testing for sex- and environment-specific effects. Further, longitudinal parental age effects may be masked by population-level processes such as the selective disappearance of poor-quality individuals. Here, we used multigenerational data collected on individually marked Seychelles warblers (Acrocephalus sechellensis) to investigate the impact of maternal and paternal age on offspring life span and lifetime reproductive success. We found negative effects of maternal age on female offspring life span and lifetime reproductive success, which were driven by within-mother effects. There was no difference in annual reproductive output of females born to older versus younger mothers, suggesting that the differences in offspring lifetime reproductive success were driven by effects on offspring life span. In contrast, there was no association between paternal age and female offspring life span or either maternal or paternal age and male offspring life span. Lifetime reproductive success, but not annual reproductive success, of male offspring increased with maternal age, but this was driven by between-mother effects. No paternal age effects were found on female offspring lifetime reproductive success but there was a positive between-father effect on male offspring lifetime reproductive success. We did not find strong evidence for environment-dependent parental age effects. Our study provides evidence for parental age effects on the lifetime fitness of offspring and shows that such effects can be sex dependent. These results add to the growing literature indicating the importance of intergenerational effects on long-term offspring performance and highlight that these effects can be an important driver of variation in longevity and fitness in the wild.
hnRNP A1 dysfunction in oligodendrocytes contributes to the pathogenesis of multiple sclerosis
Authors: Jahanbazi Jahan‐Abad Ali , Salapa Hannah E. , Libner Cole D. , Thibault Patricia A. , Levin Michael C. 
Published: November 2022

AbstractOligodendrocyte (OL) damage and death are prominent features of multiple sclerosis (MS) pathology, yet mechanisms contributing to OL loss are incompletely understood. Dysfunctional RNA binding proteins (RBPs), hallmarked by nucleocytoplasmic mislocalization and altered expression, have been shown to result in cell loss in neurologic diseases, including in MS. Since we previously observed that the RBP heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was dysfunctional in neurons in MS, we hypothesized that it might also contribute to OL pathology in MS and relevant models. We discovered that hnRNP A1 dysfunction is characteristic of OLs in MS brains. These findings were recapitulated in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, where hnRNP A1 dysfunction was characteristic of OLs, including oligodendrocyte precursor cells and mature OLs in which hnRNP A1 dysfunction correlated with demyelination. We also found that hnRNP A1 dysfunction was induced by IFNγ, indicating that inflammation influences hnRNP A1 function. To fully understand the effects of hnRNP A1 dysfunction on OLs, we performed siRNA knockdown of hnRNP A1, followed by RNA sequencing. RNA sequencing detected over 4000 differentially expressed transcripts revealing alterations to RNA metabolism, cell morphology, and programmed cell death pathways. We confirmed that hnRNP A1 knockdown was detrimental to OLs and induced apoptosis and necroptosis. Together, these data demonstrate a critical role for hnRNP A1 in proper OL functioning and survival and suggest a potential mechanism of OL damage and death in MS that involves hnRNP A1 dysfunction.
Sustainable human resource management practices, employee resilience, and employee outcomes: Toward common good values
Authors: Lu Ying , Zhang Mingqiong Mike , Yang Miles M. , Wang Yue 
Published: November 2022

AbstractExtant literature has generated limited understanding of whether and how sustainable human resource management (HRM) will lead to better and more sustainable outcomes, such as enhanced employee well‐being and improved employee performance. Moving toward common good values and drawing on the job demands‐resources model, this study theorizes and tests the relationships among sustainable HRM practices, employee resilience, work engagement, and employee performance. The empirical results of a multilevel and multisource study in the Chinese context provide supporting evidence for our theoretical model. The findings demonstrate that sustainable HRM practices positively affect employee resilience, and lead to a high level of work engagement among employees. Employee resilience also has an indirect effect on employee performance through work engagement. This study, with its theoretical and practical implications, reveals a serial mediation mechanism through which sustainable HRM practices contribute to both employee well‐being and employee performance.
Resin‐modified glass ionomer enriched with BIOGLASS: Ion‐release, bioactivity and antibacterial effect
Authors: de Oliveira Roma Fábia Regina Vieira , de Oliveira Tarcisio Jorge Leitão , Bauer José , Firoozmand Leily Macedo 
Published: November 2022

AbstractDeveloping dental materials for the prevention of remineralization or demineralization is important for high‐risk caries patients. This study aimed to evaluate the physicochemical and microbiological effects of adding 45S5 bioglass to resin‐modified glass ionomer cement (RMGIC). Samples belonged to the following groups: GIC: conventional glass ionomer cement (Vitro Fil), RMGIC: resin‐modified GIC (Vitro Fil LC), and RMGIC/45S5: RMGIC with 10% (wt %) of 45S5. Changes in pH and release of fluoride, calcium, and phosphorus ions under acidic (pH 4) and neutral (pH 7) pH conditions were evaluated. Antibacterial activity was verified based on colony‐forming units. Material sorption and solubility were analyzed after bacterial exposure. After 28 days, the bioactivity of the materials was evaluated using scanning electron microscopy/energy dispersive X‐ray spectroscopy (SEM/EDS). Analysis of variance, post hoc Scheffe, and Tukey (α = 0.05) tests were employed for statistical analysis. RMGIC/45S5 showed higher alkalization activity, calcium release at pH 4 and 7, and sorption than GIC and RMGIC (p < .05). Release of phosphorus and fluoride at pH 4 and 7 was higher for GIC than that for RMGIC and RMGIC/45S5 (p < .05). RMGIC/45S5 showed higher values than RMGIC (p < .05). However, antibacterial activity did not differ among the groups. Precipitates of calcium and phosphorus were visualized in RMGIC/45S5 samples via SEM/EDS. These results indicate that the RMGIC/45S5 promotes alkalization and increases the release of calcium, phosphorus, and fluoride ions, resulting in precipitate deposition rich in calcium and phosphorus, thereby being a promising option to improve the bioactivity of RMGIC.
Adaptive regularized Gaussian process regression for application in the context of hydrogen adsorption on graphene sheets
Authors: Schmitz Gunnar , Schnieder Bastian 
Published: November 2022

AbstractWe present a Gaussian process regression (GPR) scheme with an adaptive regularization scheme applied to the QM7 and QM9 test set, several protonated water clusters and specifically to the problem of atomic hydrogen adsorption on graphene sheets. For the last system our goal is to achieve good predictive accuracy with only a few training points. Therefore, we assess for these systems a self‐correcting multilayer GPR model, in which the prediction is corrected by a chain of additional GPR models. In our adaptive regularization scheme, we impose no noise on the training data, but use an approach based on the data itself to account for its impurity. The strength of this strategy is that the data points are treated differently based on their importance and that the regularization can still be controlled by a single parameter. We assess how the accuracy of the prediction depends on this parameter. We can show that the new regularization scheme as well as the multilayer approach results in more robust predictors. Furthermore, we demonstrate that the predictor can be in good agreement with the density‐functional theory results.