bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily uncertainty may overshadow the role of perceived manager effectiveness on daily performance via experienced daily positive affect: A multilevel study
Authors: Junça‐Silva Ana , Caetano António 
Published: January 2024

ObjectivesIn this study, we expand on the existing work on daily performance by focusing on (1) within‐person fluctuation in perceived manager effectiveness in relation to daily positive affective experiences and daily performance and (2) between‐person fluctuations in uncertainty as a relevant boundary condition of these relationships.MethodsMultilevel data from 101 managers (1,010 measurement occasions) were used to test the hypotheses.ResultsThe results showed that fluctuations in the perception of a manager's effectiveness related positively to daily positive affective experiences, and this relationship was moderated by the team member's uncertainty levels in such a way that perceived uncertainty buffered the positive effect of leadership effectiveness on positive affective experiences. Further, the findings evidenced a positive association between daily positive affective experiences and daily performance. Finally, results showed a significant indirect effect from perceived manager's effectiveness to daily fluctuations in performance via daily fluctuations in positive affective experiences.ConclusionsPerceived manager's effectiveness made employees feel more positive affective experiences, which contributed to their daily performance. However, uncertainty overshadows the influence of a manager's effectiveness on their workers' positive affective experiences. We discuss implications for theory and practice.
Truth commissions in the established democracies of the Global North: Theoretical and practical perspectives
Authors: Gawerc Michelle I. 
Published: January 2024

AbstractIn the wake of South Africa's truth‐telling experiment as part of its transition from apartheid to democracy, truth commissions have become one of the most utilized mechanisms for addressing past atrocities. While most truth commissions are established in countries undergoing “transition” to democratic governance or peace, increasingly, established democracies such as Canada, Norway, Sweden, and Finland have also undertaken such processes to address historical (and often, racial) injustices. The U.S. Department of State has denied the relevance of truth commissions to the United States for addressing its own history of racial injustice, however, the U.S. itself has been home to at least 13 official truth commissions (operating primarily at the state‐, county‐, and city‐level) and numerous unofficial truth‐telling processes emanating from civil society. In this article, I review literature on truth commissions with a focus on history and theorized importance, recent application to the more established democracies of the “Global North” and overall significance and limitations in terms of fostering racial justice and social transformation in what are primarily settler colonial states. I conclude by evaluating the state of this research area and by suggesting directions for future research.
Enhancing Part Quality Management Using a Holistic Data Fusion Framework in Metal Powder Bed Fusion Additive Manufacturing
Authors: Yang Zhuo , Kim Jaehyuk , Lu Yan , Jones Albert , Witherell Paul , Yeung Ho , Ko Hyunwoong 
Published: January 2024

Abstract
Metal powder bed fusion additive manufacturing (AM) processes have gained widespread adoption for the ability to produce complex geometries with high performance. However, a multitude of factors still affect the build process, which significantly impacts the adoption rate. This, in turn, leads to great challenges in achieving consistent and reliable part quality. To address this challenge, simulations and measurements have been progressively deployed to provide valuable insights into the quality of individual builds. This paper proposes an AM data fusion framework that combines data sources beyond a single-part, development cycle. Those sources include the aggregation of measurements from multiple builds and the outputs from their related models and simulations. Both can be used to support decision-makings that can improve part quality. The effectiveness of the holistic AM data fusion framework is illustrated through three use case scenarios: one that fuses process data from a single build, one that fusses data from a build and simulation, and one that fuses data from multiple builds. The case studies demonstrate that a data fusion framework can be applied to effectively detect over-melting scan strategies, monitor material melting conditions, and predict down-skin surface defects. Overall, the proposed method provides a practical solution for enhancing part quality management when individual data sources or models have intrinsic limitations.
Toward Polydisperse Flows With mfix-exa
Authors: Lattanzi Aaron M. , Fullmer William D. , Myers Andrew , Musser Jordan 
Published: January 2024

Abstract
In the presence of large size disparities, single-grid neighbor search algorithms lead to inflated neighbor lists that significantly degrade the performance of Lagrangian particle solvers. If Eulerian–Lagrangian (EL) frameworks are to remain performant when simulating realistic systems, improved neighbor detection approaches must be adopted. To this end, we consider the application of a multigrid neighbor search (MGNS) algorithm in the mfix-exa software package, an exascale EL solver built upon the AMReX library. Details regarding the implementation and verification of MGNS are provided along with speedup curves for a bidisperse mixing layer. MGNS is shown to yield up to 15× speedup on CPU and 6× speedup on GPU for the problems considered here. The mfix-exa software is then validated for a variety of polydisperse flows. Finally, a brief discussion is given for how dynamic MGNS may be completed, with application to spatially varying particle size distributions.
Exascale Computational Fluid Dynamics in Heterogeneous Systems
Authors: Trebotich David 
Published: January 2024

Abstract
Exascale computing has extended the reach of resolved flow simulations in complex, heterogeneous systems far beyond conventional computational fluid dynamics capabilities. As a result, unprecedented pore and microscale resolution have been achieved in domains that have been traditionally modeled by, and limited to, continuum, effective medium approaches. By making use of computational resources on the new exascale supercomputer, Frontier, at the Oak Ridge Leadership Computing Facility, we performed flow simulations that have pushed the limits of domain-to-resolution ratios by several orders of magnitude for heterogeneous media. Our approach is an incompressible, Navier–Stokes CFD solver based on adaptive, embedded boundary (EB) methods supported by the Chombo software framework for applied partial differential equations (PDEs). The computational workhorse in the CFD application code is an elliptic solver framework in Chombo for pressure-Poisson and viscous, Helmholtz terms that leverages a PETSc-hypre software interface tuned for accelerator-based platforms. We demonstrate scalability of the approach by replicating a unit cylinder packed with microspheres to achieve over 400 × 109 degrees-of-freedom simulated. These simulations model domain lengths of over 20 meters with channel volumes of over 400 cm3 and containing millions of packed spheres with 20 micron grid resolution, challenging current understanding of what it means to be a representative elementary volume (REV) of the continuum scale in heterogeneous media. We also simulate a range of Reynolds numbers to demonstrate wide applicability and robustness of the approach.
The mechanism of ceftazidime and cefiderocol hydrolysis by D179Y variants of KPC carbapenemases is similar and involves the formation of a long-lived covalent intermediate
Authors: Birgy Andre , Nnabuife Christina , Palzkill Timothy 
Published: January 2024

ABSTRACT

Klebsiella pneumoniae
carbapenemase (KPC) variants have been described that confer resistance to both ceftazidime–avibactam and cefiderocol. Of these, KPC-33 and KPC-31 are D179Y-containing variants derived from KPC-2 and KPC-3, respectively. To better understand this atypical phenotype, the catalytic mechanism of ceftazidime and cefiderocol hydrolysis by KPC-33 and KPC-31 as well as the ancestral KPC-2 and KPC-3 enzymes was studied. Steady-state kinetics showed that the D179Y substitution in either KPC-2 or KPC-3 is associated with a large decrease in both
k
cat
and
K
M
such that
k
cat
/
K
M
values were largely unchanged for both ceftazidime and cefiderocol substrates. A decrease in both
k
cat
and
K
M
is consistent with a decreased and rate-limiting deacylation step. We explored this hypothesis by performing pre-steady-state kinetics and showed that the acylation step is rate-limiting for KPC-2 and KPC-3 for both ceftazidime and cefiderocol hydrolysis. In contrast, we observed a burst of acyl-enzyme formation followed by a slow steady-state rate for the D179Y variants of KPC-2 and KPC-3 with either ceftazidime or cefiderocol, indicating that deacylation of the covalent intermediate is the rate-limiting step for catalysis. Finally, we show that the low
K
M
value for ceftazidime or cefiderocol hydrolysis of the D179Y variants is not an indication of tight binding affinity for the substrates but rather is a reflection of the deacylation reaction becoming rate-limiting. Thus, the hydrolysis mechanism of ceftazidime and cefiderocol by the D179Y variants is very similar and involves the formation of a long-lived covalent intermediate that is associated with resistance to the drugs.
Clofazimine as a substitute for rifampicin improves efficacy of
Mycobacterium avium
pulmonary disease treatment in the hollow-fiber model
Authors: Salillas Sandra , Raaijmakers Jelmer , Aarnoutse Rob E. , Svensson Elin M. , Asouit Khalid , van den Hombergh Erik , te Brake Lindsey , Stemkens Ralf , Wertheim Heiman F. L. , Hoefsloot Wouter , van Ingen Jakko 
Published: January 2024

ABSTRACT

Mycobacterium avium
complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model. THP-1 cells, which are monocytes isolated from peripheral blood from an acute monocytic leukemia patient, were infected with
M. avium
ATCC 700898 and exposed to a regimen of azithromycin and ethambutol with either rifampicin or clofazimine. Intrapulmonary pharmacokinetic profiles of azithromycin, ethambutol, and rifampicin were simulated. For clofazimine, a steady-state average concentration was targeted. Drug concentrations and bacterial densities were monitored over 21 days. Exposures to azithromycin and ethambutol were 20%–40% lower than targeted but within clinically observed ranges. Clofazimine exposures were 1.7 times higher than targeted. Until day 7, both regimens were able to maintain stasis. Thereafter, regrowth was observed for the rifampicin-containing regimen, while the clofazimine-containing regimen yielded a 2 Log
10
colony forming unit (CFU) per mL decrease in bacterial load. The clofazimine regimen also successfully suppressed the emergence of macrolide tolerance. In summary, substitution of rifampicin with clofazimine in the hollow-fiber model improved the antimycobacterial activity of the regimen. Clofazimine-containing regimens merit investigation in clinical trials.
Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection
Authors: Laksono Brigitta M. , Sooksawasdi Na Ayudhya Syriam , Aguilar-Bretones Muriel , Embregts Carmen W. E. , van Nierop Gijsbert P. , van Riel Debby 
Published: January 2024

ABSTRACT

Enterovirus D68 (EV-D68) is predominantly associated with mild respiratory infections, but can also cause severe respiratory disease and extra-respiratory complications, including acute flaccid myelitis. Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 spreads systemically (viremia). We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, in B cell-rich cultures, such as Epstein–Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, which better represent lymphoid B cells, were productively infected. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, could play an important role in the pathogenesis of EV-D68 infection. Infection of these cells may contribute to systemic dissemination of EV-D68, which is an essential step toward the development of extra-respiratory complications.

IMPORTANCE
Enterovirus D68 (EV-D68) is an emerging respiratory virus that has caused outbreaks worldwide since 2014. EV-D68 infects primarily respiratory epithelial cells resulting in mild respiratory diseases. However, EV-D68 infection is also associated with extra-respiratory complications, including polio-like paralysis. It is unclear how EV-D68 spreads systemically and infects other organs. We hypothesized that immune cells could play a role in the extra-respiratory spread of EV-D68. We showed that EV-D68 can infect and replicate in specific immune cells, that is, B cells and dendritic cells (DCs), and that virus could be transferred from DCs to B cells. Our data reveal a potential role of immune cells in the pathogenesis of EV-D68 infection. Intervention strategies that prevent EV-D68 infection of immune cells will therefore potentially prevent systemic spread of virus and thereby severe extra-respiratory complications.
Utilization of a
Histoplasma capsulatum
zinc reporter reveals the complexities of fungal sensing of metal deprivation
Authors: Blancett Logan T. , Evans Heather M. , Candor Kathleen , Buesing William R. , Figueroa Julio A. Landero , Deepe Jr George S. 
Published: January 2024

ABSTRACT

Histoplasma capsulatum
is a dimorphic fungal pathogen acquired via inhalation of soil-resident spores. Upon exposure to mammalian body temperatures, these fungal elements transform into yeasts that reside primarily within phagocytes. Macrophages (MΦ) provide a permissive environment for fungal replication until T cell-dependent immunity is engaged. MΦ activated by granulocyte macrophage colony stimulating factor (GM-CSF) induces metallothioneins (MTs) that bind zinc (Zn) and deprive yeast cells of labile Zn, thereby disabling fungal growth. Prior work demonstrated that the zinc transporter,
ZRT2
, was important for fungal survival
in vivo
. Hence, we constructed a yeast cell reporter strain that expresses green fluorescent protein (GFP) under control of the
ZRT2
zinc-regulated promoter. This reporter accurately responds to a medium devoid of Zn.
ZRT2
expression increased in GM-CSF, but not interferon-γ, stimulated MΦ. To examine the
in vivo
response, we infected mice with a reporter yeast strain and assessed
ZRT2
expression at 0, 3, 7, and 14 days post-infection (dpi).
ZRT2
expression minimally increased at 3 dpi and peaked at 7 dpi, corresponding with the onset of adaptive immunity. We discovered that the major MΦ populations that restrict Zn from the fungus are interstitial MΦ and exudate MΦ. Neutralizing GM-CSF blunted the control of infection but unexpectedly increased
ZRT2
expression. This increase was dependent on another cytokine that activates MΦ to control
H. capsulatum
replication, M-CSF. These findings illustrate the reporter’s ability to sense Zn
in vitro
and
in vivo
and correlate
ZRT2
expression with GM-CSF and M-CSF activation of MΦ.

IMPORTANCE

Phagocytes use an arsenal of defenses to control the replication of
Histoplasma
yeasts, one of which is the limitation of trace metals. On the other hand,
H. capsulatum
combats metal restriction by upregulating metal importers such as the Zn importer
ZRT2
. This transporter contributes to
H. capsulatum
pathogenesis upon activation of adaptive immunity. We constructed a fluorescent
ZRT2
transcriptional reporter to probe
H. capsulatum
Zn sensing during infection and exposed the role for M-CSF activation of macrophages when GM-CSF is absent. These data highlight the ways in which fungal pathogens sense metal deprivation
in vivo
and reveal the potential of metal-sensing reporters. The work adds a new dimension to study how intracellular pathogens sense and respond to the changing environments of the host.
Effects of the synergistic treatments of arbuscular mycorrhizal fungi and trehalose on adaptability to salt stress in tomato seedlings
Authors: Chen Gongshan , Yang Anna , Wang Jianzhong , Ke Lixia , Chen Shaoxing , Li Wentao 
Published: January 2024

ABSTRACT

Arbuscular mycorrhizal fungi (AMF) could establish symbiosis with plant roots, which enhances plant resistance to various stresses, including drought stress and salt stress. Besides AMF, chemical stimulants such as trehalose (Tre) can also play an important role in helping plants alleviate damage of adversity. However, the mechanism of the effect of AMF combined with chemicals on plant stress resistance is unclear. The objective of this study was to explore the synergistic effects of
Claroideoglomus etunicatum
AMF and exogenous Tre on the antioxidant system, osmoregulation, and resistance-protective substance in plants in response to salt stress. Tomato seedlings were inoculated with
Claroideoglomus etunicatum
and combined with exogenous Tre in a greenhouse aseptic soil cultivation experiment. We measured the arbuscular mycorrhizal symbiont development, organic matter content, and antioxidant enzyme activity in tomato seedlings. Both AMF and Tre improved the synthesis of chlorophyll content in tomato seedlings; regulated the osmotic substance including soluble sugars, soluble protein, and proline of plants; and increased the activity of superoxide dismutase, peroxidase, and catalase. The combination of AMF and Tre also reduced the accumulation of malondialdehyde and alleviated the damage of harmful substances to plant cells in tomato seedlings. We studied the effects of AMF combined with extraneous Tre on salt tolerance in tomato seedlings, and the results showed that the synergistic treatment of AMF and Tre was more efficient than the effects of AMF inoculation or Tre spraying separately by regulating host substance synthesis, osmosis, and antioxidant enzymes. Our results indicated that the synergistic effects of AMF and Tre increased the plant adaptability against salt damage by enhancing cell osmotic protection and cell antioxidant capacity.

IMPORTANCE
AMF improve the plant adaptability to salt resistance by increasing mineral absorption and reducing the damage of saline soil. Trehalose plays an important role in plant response to salt damage by regulating osmotic pressure. Together, the use of AMF and trehalose in tomato seedlings proved efficient in regulating host substance synthesis, osmosis, and antioxidant enzymes. These synergistic effects significantly improved seedling adaptability to salt stress by enhancing cell osmotic protection and cell antioxidant capacity, ultimately reducing losses to crops grown on land where salinization has occurred.
Experiences and perspectives on chimeric antigen receptor (CAR) T-cell therapy among recipients, carers and referrers (RE-TELL): a qualitative study to inform CAR T-cell service design
Authors: Fyfe Robert , Anstis Olivia , Kapadia Kushant , Jordan Mallory , Sword Danielle Oriwa , Weinkove Robert 
Published: January 2024

ObjectivesRE-TELL is a qualitative study, which aims to understand patient, support person, clinician and coordinator experiences and perspectives of chimeric antigen receptor (CAR) T-cell therapy, to inform design of a clinical CAR T-cell service in Aotearoa New Zealand.DesignSemistructured qualitative interviews focused on domains of: experience through treatment, elements that work well and those that could be improved on. Interviews used thematic analysis to identify key themes. A workshop was held to obtain participants’ reflections on interim analysis and proposed improvements.ParticipantsNew Zealanders with experience of CAR T-cell therapy, including recipients, support persons, clinicians and coordinators.ResultsWe interviewed 19 participants comprising 5 CAR T-cell recipients, 3 support persons, 6 clinicians and 5 coordinators. Four participants identified as Māori. Thematic analysis identified three global themes. The first, ‘sociocultural factors impact CAR T access’, identified potential sources of inequity including geographic, financial and informed consent barriers. The second, ‘varying emotions, roles and enablers’, identified an easier treatment experience compared with alternatives; an underwhelming cell administration process; frustration with inpatient monitoring; burden on support persons and importance of ‘bridge’ organisations such as charities and patient support groups. Lastly, ‘golden opportunities: reimagining CAR T service delivery’, suggested: improved geographical access to CAR T-cell therapy, while retaining consolidated clinician experience; a ‘dashboard’ with information on CAR T-cell treatment, time frames and manufacture; a health navigator to co-ordinate non-medical aspects of treatment and signpost care; embedding of indigenous data sovereignty and ownership of cells; a cell infusion ceremony, incorporating family involvement and Māori cultural elements and outpatient administration and monitoring where possible.ConclusionThis study documented the current experience of New Zealanders receiving CAR T-cell therapy and identified opportunities for future service development. These insights are relevant to service design within Aotearoa New Zealand, and other countries developing equitable CAR T-cell services.