bluuebunny/crossref_metadata_2025 huggingface dataset:
Nivolumab receptor occupancy on effector regulatory T cells predicts clinical benefit
Authors: Hosonuma Masahiro , Hirasawa Yuya , Kuramasu Atsuo , Murayama Masakazu , Narikawa Yoichiro , Toyoda Hitoshi , Baba Yuta , Isobe Junya , Funayama Eiji , Tajima Kohei , Shida Midori , Hamada Kazuyuki , Tsurui Toshiaki , Ariizumi Hirotsugu , Ishiguro Tomoyuki , Suzuki Risako , Ohkuma Ryotaro , Kubota Yutaro , Horiike Atsushi , Sambe Takehiko , Tsuji Mayumi , Wada Satoshi , Kiuchi Yuji , Kobayashi Shinichi , Tsunoda Takuya , Yoshimura Kiyoshi
Published: January 2024

Immune checkpoint inhibitor discovery represents a turning point in cancer treatment. However, the response rates of solid tumors remain ~10%–30%; consequently, prognostic and immune‐related adverse event (irAE) predictors are being explored. The programmed cell death protein 1 (PD‐1) receptor occupancy (RO) of PD‐1 inhibitors depends on the number of peripheral blood lymphocytes and their PD‐1 expression levels, suggesting that the RO may be related to efficacy and adverse events. As PD‐1 inhibition affects each T‐cell subset differently, the RO of each cell population must be characterized. However, relevant data have not been reported, and the prognostic relevance of this parameter is not known. In this study, we aimed to clarify the association between the nivolumab RO in each T‐cell population and patient prognosis and reveal the development of irAEs in nivolumab‐treated patients. Thirty‐two patients were included in the study, and the mean follow‐up period was 364 days. The nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in the group that presented clinical benefits, and a significant negative association was observed between PD‐1 occupancy on eTregs and all‐cause mortality. The results suggest that the nivolumab RO on eTregs may be a prognostic factor in PD‐1 inhibitor therapy, implying that the inhibition of PD‐1/PD‐ligand 1 (PD‐L1) signaling on eTregs may attenuate antitumor effects.
Efficacy and safety of intragastric expandable oral capsules in adults with overweight or obesity: A randomized, double‐blind, placebo‐controlled trial
Authors: Lu Difei , Yuan Zhenfang , Guo Xiaohui , Zhu Liyong , Zhang Fan , Li Xuejun , Wang Wenbo , Lin Huandong , Luo Jingnan
Published: January 2024

Aim

This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity.

Methods

This double‐blind, placebo‐controlled study included adults with a body mass index of at least 24 kg/m2 and no more than 40 kg/m2. In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set.

Results

At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m2. The mean body weight change at week 24 was −4.9% with intragastric expandable capsules versus −1.9% with placebo [estimated treatment difference (ETD) −3.0%, 95% confidence interval (CI) −4.1 to −1.9; p < .001] using the full analysis set and −6.1% versus −2.5% (ETD −3.6%, 95% CI −5.0 to −2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7‐35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1‐42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: −5.6 ± 8.3 cm vs. −2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient.

Conclusions

In this 24‐week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo.
Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study
Authors: Nakamura Yuta , Horie Ichiro , Kitamura Tadahiro , Kusunoki Yoshiki , Nishida Kenro , Yamamoto Akane , Hirota Yushi , Fukui Tomoyasu , Maeda Yasutaka , Minami Masae , Matsui Takanori , Kawakami Atsushi , Abiru Norio
Published: January 2024

Aim

Clinical trials showed the efficacy of sodium‐glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat‐AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium‐glucose cotransporter 2 inhibitor, ipragliflozin.

Methods

Adults with T1D (n = 25) took 50‐mg open‐labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed‐meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C‐peptide, glucagon and β‐hydroxybutyrate.

Results

The area under the curve from fasting (0 min) to 120 min (AUC0‐120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial β‐hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0‐120min) from baseline to 12 weeks were significantly correlated with those in β‐hydroxybutyrate levels.

Conclusions

Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.
Quantitative investigation on the deformation modes and cracking behavior during cyclic torsional loading of extruded pure Mg and Mg‐3Y alloy
Authors: He Liuyong , Wen Guilan , Zheng Jiang , Shi Rong , Xia Lihong , Li Tianjiao , Jiang Bin
Published: January 2024

This study explores the effect of adding 3 wt.% Y to pure magnesium (Mg) on its mechanical behavior under cyclic torsional loadings at room temperature. The research examines deformation and cracking modes in both pure Mg and Mg‐3Y samples. Deformation modes are monitored using quasi‐in‐situ EBSD observations coupled with slip trace analysis. The findings reveal that basal slip dominates the cyclic deformation throughout the fatigue life of the pure Mg sample, while both basal and pyramidal slip dominate the cyclic deformation in the Mg‐3Y sample. Intergranular cracking is the primary cracking mode for both samples under cyclic torsional loadings. Basal and pyramidal slip persistent slip band (PSB) cracking serves as a primary transgranular cracking mode in the pure Mg and Mg‐3Y samples, respectively. The study also investigates the underlying mechanism governing the activity of various deformation modes, cracking modes, and mechanical behavior.
Assessing the global vulnerability of dryland birds to heatwaves
Authors: Ding Chenchen , Newbold Tim , Ameca Eric I.
Published: January 2024

As global average surface temperature increases, extreme climatic events such as heatwaves are becoming more frequent and intense, which can drive biodiversity responses such as rapid population declines and/or shifts in species distributions and even local extirpations. However, the impacts of extreme climatic events are largely ignored in conservation plans. Birds are known to be susceptible to heatwaves, especially in dryland ecosystems. Understanding which birds are most vulnerable to heatwaves, and where these birds occur, can offer a scientific basis for adaptive management and conservation. We assessed the relative vulnerability of 1196 dryland bird species to heatwaves using a trait‐based approach. Among them, 888 bird species are estimated to be vulnerable to heatwaves (170 highly vulnerable, eight extremely vulnerable), of which ~91% are currently considered non‐threatened by the IUCN, which suggests that many species will likely become newly threatened with intensifying climate change. We identified the top three hotspot areas of heatwave‐vulnerable species in Australia (208 species), Southern Africa (125 species) and Eastern Africa (99 species). Populations of vulnerable species recorded in the Living Planet Database were found to be declining significantly faster than those of non‐vulnerable species (p = .048) after heatwaves occurred. In contrast, no significant difference in population trends between vulnerable and non‐vulnerable species was detected when no heatwave occurred (p = .34). This suggests that our vulnerability framework correctly identified vulnerable species and that heatwaves are already impacting the population trends of these species. Our findings will help prioritize heatwave‐vulnerable birds in dryland ecosystems in risk mitigation and adaptation management as the frequency of heatwaves accelerates in the coming decades.
Wildfire‐induced increases in photosynthesis in boreal forest ecosystems of North America
Authors: Kim Jinhyuk E. , Wang Jonathan A. , Li Yue , Czimczik Claudia I. , Randerson James T.
Published: January 2024

Observations of the annual cycle of atmospheric CO2 in high northern latitudes provide evidence for an increase in terrestrial metabolism in Arctic tundra and boreal forest ecosystems. However, the mechanisms driving these changes are not yet fully understood. One proposed hypothesis is that ecological change from disturbance, such as wildfire, could increase the magnitude and change the phase of net ecosystem exchange through shifts in plant community composition. Yet, little quantitative work has evaluated this potential mechanism at a regional scale. Here we investigate how fire disturbance influences landscape‐level patterns of photosynthesis across western boreal North America. We use Alaska and Canadian large fire databases to identify the perimeters of wildfires, a Landsat‐derived land cover time series to characterize plant functional types (PFTs), and solar‐induced fluorescence (SIF) from the Orbiting Carbon Observatory‐2 (OCO‐2) as a proxy for photosynthesis. We analyze these datasets to characterize post‐fire changes in plant succession and photosynthetic activity using a space‐for‐time approach. We find that increases in herbaceous and sparse vegetation, shrub, and deciduous broadleaf forest PFTs during mid‐succession yield enhancements in SIF by 8–40% during June and July for 2‐ to 59‐year stands relative to pre‐fire controls. From the analysis of post‐fire land cover changes within individual ecoregions and modeling, we identify two mechanisms by which fires contribute to long‐term trends in SIF. First, increases in annual burning are shifting the stand age distribution, leading to increases in the abundance of shrubs and deciduous broadleaf forests that have considerably higher SIF during early‐ and mid‐summer. Second, fire appears to facilitate a long‐term shift from evergreen conifer to broadleaf deciduous forest in the Boreal Plain ecoregion. These findings suggest that increasing fire can contribute substantially to positive trends in seasonal CO2 exchange without a close coupling to long‐term increases in carbon storage.
Herbivore exclusion stabilizes alpine grassland biomass production across spatial scales
Authors: Zhu Juntao , Zhang Yangjian , Wu Jianshuang , Zhang Xianzhou , Yu Guirui , Shen Zhenxi , Yang Xian , He Yunlong , Jiang Lin , Hautier Yann
Published: January 2024

There is growing evidence that land‐use management practices such as livestock grazing can strongly impact the local diversity, functioning, and stability of grassland communities. However, whether these impacts depend on environmental condition and propagate to larger spatial scales remains unclear. Using an 8‐year grassland exclosure experiment conducted at nine sites in the Tibetan Plateau covering a large precipitation gradient, we found that herbivore exclusion increased the temporal stability of alpine grassland biomass production at both the local and larger (site) spatial scales. Higher local community stability was attributed to greater stability of dominant species, whereas higher stability at the larger scale was linked to higher spatial asynchrony of productivity among local communities. Additionally, sites with higher mean annual precipitation had lower dominant species stability and lower grassland stability at both the spatial scales considered. Our study provides novel evidence that livestock grazing can impair grassland stability across spatial scales and climatic gradients.
Colour characteristics, phenolic content and antioxidant activity of Spirulina platensis soaked in basil (Ocimum basilicum) leaves extract
Authors: Wijayanti Ima , Agustini Tri Winarni , Benjakul Soottawat
Published: January 2024

Spirulina platensis has been known as a super food with a high nutrition and biological activity. The limited addition of S. platensis into the food is due to its unpleasant odour. S. platensis was soaked in basil (Ocimum basilicum) leaves extract (BLE) to decrease the unpleasant odour and its antioxidant activities after soaking were unknown. This study aimed to evaluate the effect of ratio S. platensis with BLE on colour and sensory characteristics and to determine the total phenolic content (TPC) and antioxidant capacity of extracted S. platensis without and with BLE using different solvents. Spirulina platensis was soaked in BLE at a ratio of S. platensis and BLE of 1:3, 1:4, and 1:5 (w/v) for 15 min and then dried at 40°C for 10 h. The resultant powder was analysed for colour and sensory characteristics. The selected S. platensis with the best sensory characteristic was further extracted in water and ethanol and was compared with the S. platensis control (unsoaked in BLE). The ratio of S. platensis and BLE had a significant effect on the colour characteristics (P < 0.05). Spirulina platensis soaked in BLE at a ratio 1:4 had higher L* (35.98), a* (−6.57) and b* values (5.95) than the control. The ratio of S. platensis and BLE at 1:4 had a higher overall sensory value (4.16) than the control (2.35). The water extract of S. platensis unsoaked and soaked in BLE showed a higher TPC (1.178 and 1.667 mg GAE g−1 extract, respectively), DPPH, ABTS and metal chelating, but lower in FRAP compared with the ethanol extract. Spirulina platensis soaked in BLE which were extracted in water and ethanol had higher ORAC (63.27 and 56.33 mmol Teq g−1 extract, respectively) than the control. Spirulina platensis soaked in BLE increased its sensory value while maintaining the antioxidant capacity. Therefore, it can potentially be added in more quantities to various foods as functional foods.
Just‐in‐time scheduling problem with due windows and release dates for precast bridge girders
Authors: Liu Gang , Wang Hongwei , Xie Yong
Published: January 2024

As the prefabrication construction method plays an increasingly important role in the construction of cross‐sea bridges, coordinating the schedule between off‐site prefabrication and on‐site assembly becomes crucial and challenging. This paper studies a just‐in‐time single‐machine scheduling problem with due windows and release dates, which originates from the production and supply process of large segments of precast steel box girders in bridge construction. To solve this problem, we equivalently decompose it into the independent and same type of subproblems and formulate a mixed‐integer linear mathematical programming model. Furthermore, we propose a branch‐and‐bound algorithm with the initialization of a novel linear early and tardy dispatching rule with due windows to solve the problem exactly. The dispatching rule, based on the local dominance criteria with due windows, is designed and used to improve the upper bound. Moreover, a lower bound is obtained by further decomposing and relaxing the subproblems. Finally, the parameter of the dispatching rule is calibrated, and the best search strategy of the branch‐and‐bound algorithm is determined. The comprehensive computational experiments carried out show the efficiency and effectiveness of the proposed branch‐and‐bound algorithm.
Psychological effects of the COVID‐19 pandemic on primary healthcare professionals in Turkey: One year into the pandemic
Authors: Yücel Ummahan , Erkal Aksoy Yasemin , Yaşar Yetişmiş Habibe , Gök Çiğdem
Published: January 2024

Aim and Objectives

This study aimed to determine the psychological effects of the COVID‐19 pandemic on healthcare professionals working in primary care settings in the first year of the pandemic.

Background

The healthcare industry has faced an unprecedented burden in the COVID‐19 pandemic. Primary care professionals experienced the high level of psychological problems.

Design and Methods

A total of 793 healthcare professionals from different regions of Turkey participated in this cross‐sectional study. The STROBE (Strengthening the reporting of observational studies in epidemiology) checklist was used in the study. Data were collected online.

Results

It has been found that more than half of healthcare professionals experienced severe depression, three‐quarters experienced anxiety, and almost half experienced stress. It was also found that about half of the participants experienced a high degree of acute and chronic fatigue, and one‐fifth experienced low inter‐shift recovery.

Conclusion

The effects of the COVID‐19 pandemic on the mental health of primary care professionals, especially nurses and midwives, are alarming. The problems that arise from the flawed healthcare delivery models and gender inequality, which worsen the usual psychological effects of the pandemic on primary care professionals, should be addressed urgently.

Relevance to Clinical Practice

Psychological support and rehabilitative services should be expanded to eliminate the short‐ and long‐term psychological effects of the pandemic on healthcare professionals.
Development and psychometric testing of the actualisation of evidence‐based nursing instrument
Authors: Parisod Heidi , Stolt Minna , Holopainen Arja , Siltanen Hannele , Pasanen Miko , Suhonen Riitta
Published: January 2024

Aim

To describe the development of the Actualisation of Evidence‐Based Nursing instrument targeted at nurses working in clinical practice (ActEBN‐nurses), meant for evaluating the actualisation of individual and organisational‐level support structures for evidence‐based nursing within social and healthcare organisations, and to test its validity and reliability.

Design

Cross‐sectional survey.

Methods

The FinYHKÄ model was used as the theoretical background of the instrument development and supplemented with the JBI Model of Evidence‐Based Healthcare, previous literature and items from a previous instrument, the Evidence‐Based Practice Process Assessment Scale, with permission of the copyright holders. After two rounds of expert panel and piloting, a national survey was conducted with the instrument in 2021. The target group consisted of nurses working in clinical practice. Psychometric testing included internal consistency (Omega, item analysis) confirmatory factor analysis and t‐test for comparison of two groups' differences (sensitivity).

Results

A new instrument, ActEBN‐nurses was developed, comprising two parts: Individual‐level (32 items, 5‐point Likert‐scale) and Organisational‐level support structures for evidence‐based nursing (37 items, 5‐point Likert‐scale). In total, 1289 nurses participated in the survey. The ActEBN‐nurses proved to have good internal consistency in both parts (Omega ω .931 and .966), structural validity and sensitivity based on the two educational levels within the sample. The structure of both parts was slightly modified, based on the CFA modification indices, considering the impact of the reverse worded items in part Individual and redundant items within both parts.

Conclusion

The ActEBN‐nurses has promising psychometrics, and it can be used for evaluating individual and organisational‐level support structures for evidence‐based nursing within social and healthcare organisations.

Implications for the profession and/or patient care

Evaluation of the support structures within social and healthcare organisations is needed to recognise shortcomings in current structures and advance evidence‐based nursing across different contexts.

Reporting Method

The authors state that they have adhered to relevant EQUATOR guidelines: STROBE statement for cross‐sectional studies.

Patient or Public Contribution

No patient or public contribution.
Survey of flea infestation in cats and dogs in Western Andalusia, Spain: Seasonality and other risk factors for flea infestation
Authors: Zurita Antonio , Trujillo Ignacio , García‐Sánchez Ángela María , Cutillas Cristina
Published: January 2024

This epidemiological survey aims to provide an update on the main flea species that parasitize domestic animals in the Western Andalusia assessing several ecological features that could be considered as possible risk factors for flea infestation. Over a 19‐month period (June 2021 to January 2023), we obtained a total of 802 flea samples from 182 dogs (Canis lupus familiaris, Carnivora: Canidae, Linnaeus, 1758) and 78 cats (Felis silvestris catus, Carnivora: Felidae, Schreber, 1775). For each parasitized host, an epidemiological survey was completed, including the following information: geographical origin, age, sex, rural or urban habitat, type of animal's lifestyle (domestic or non‐domestic), health status, cohabiting or not with other animals and the total number of collected fleas. The most common species was Ctenocephalides felis (Siphonaptera: Pulicidae) (Bouché, 1835) with a total of 713 specimens, which accounted for 89% of the total fleas. The second most abundant species was Pulex irritans (Siphonaptera: Pulicidae) (Linnaeus, 1758) with a total of 46 collected fleas (6% of the total). The remaining species identified were Archaeopsylla erinacei (Siphonaptera: Pulicidae) (Bouché, 1835) (25 specimens), Spilopsyllus cuniculi (Siphonaptera: Pulicidae) (Dale, 1878) (12 specimens) and Ctenocephalides canis (Siphonaptera: Pulicidae) (Curtis, 1826) (6 specimens), which accounted for 3%, 1% and 1%, respectively, of the total fleas collected. The months with the highest number of collected fleas were, in ascending order, May 2022, September 2021 and July 2021. Dogs had a greater diversity of flea species, and flea sex ratios were female biased in all identified species and among all studied hosts. Finally, we identified some potential host risk factors that promoted higher flea intensities, such as living in rural areas, or presenting other pathologies.
CsHLS1‐CsSCL28 module regulates compact plant architecture in cucumber
Authors: Wang Chunhua , Li Jie , Fang Kai , Yao Hongxin , Chai Xingwen , Du Yalin , Wang Junwei , Hao Ning , Cao Jiajian , Li Baohai , Wu Tao
Published: January 2024

Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in cucurbits remain unclear. In this study, we identified a cucumber (Cucumis sativus) compact plant architecture (cpa1) mutant from an ethyl methane sulfonate (EMS)‐mutagenized library that exhibited distinctive phenotypic traits, including reduced leaf petiole angle and leaf size. The candidate mutation causes a premature stop codon in CsaV3_1G036420, which shares similarity to Arabidopsis HOOKLESS 1 (HLS1) encoding putative histone N‐acetyltransferase (HAT) protein and was named CsHLS1. Consistent with the mutant phenotype, CsHLS1 was predominantly expressed in leaf petiole bases and leaves. Constitutive overexpressing CsHLS1 in cpa1 restored the wild‐type plant architecture. Knockout of CsHLS1 resulted in reduces leaf petiole angle and leaf size and as well as decreased acetylation levels. Furthermore, CsHLS1 directly interacted with CsSCL28 and negatively regulated compact plant architecture in cucumber. Importantly, CsHLS1 knockout increased the photosynthesis rate and leaf nitrogen in cucumbers, thereby maintaining cucumber yield at normal density. Overall, our research provides valuable genetic breeding resource and gene target for creating a compact plant architecture for dense cucumber planting.
Parents’ use of digital technology for social connection during the COVID‐19 pandemic: A mixed‐methods study
Authors: Nowland Rebecca , McNally Lara , Gregory Peggy
Published: January 2024

Introduction

The COVID‐19 pandemic (2020–2021) resulted in isolation due to social distancing rules and lockdowns, during which technology was used to enable families and friends to maintain contact. Despite loneliness being high in parents, little is known about which parents are more likely to experience loneliness and strategies to support them.

Method

This mixed‐methods study examines which parents were lonely during the pandemic and how digital technologies were used to reduce loneliness and social isolation. Data were collected during the first UK lockdown from May to July 2020 via an online survey (N = 145) and follow‐up interviews (n = 13).

Results

Loneliness reported during lockdown was greater than retrospective reporting of loneliness for all respondents, but it was higher in single parents, those caring for children with specific needs, and those with lower household incomes before and during lockdown. Parents rapidly adapted to and experimented with using technology for social connection during the lockdown, which helped to reduce feelings of isolation and loneliness. Video calling was found to be useful for making connections and enhancing social presence, but parents also experienced anxieties and difficulties with its use. There were mixed views about technology use; some were keen to continue using technology for socializing after the lockdown ended, but for others, it was only a temporary measure.

Conclusion

Although technology was invaluable during the pandemic, it was not a panacea, and the way parents used it was influenced by their approach to technology and existing social behaviors and networks.
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

Objectives

In 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.

Methods

Multilevel data from 101 managers (1,010 measurement occasions) were used to test the hypotheses.

Results

The 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.

Conclusions

Perceived 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

In 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.
Neutronic Activation of Amazon Technogenic Deposit Soil Used as Raw Material in Brick Manufacture
Authors: Passos de Oliveira Antonio Carlos Santos do Nascimento , Macêdo Alcebíades Negrão , Souza José Antonio da Silva , Oliveira Dênio Ramam Carvalho
Published: January 2024

Considering the extraction of soil from Technogenic Deposits, may result in the risk, this article investigated whether in the brick making process, there is a possibility that chemical elements, considered linked to human illness, may have evidence of release to the environment. The adopted strategy was to subject both the soil, as well as the brick manufactured with this soil, to the Neutronic Activation test, later, through the mass balance, to verify the variations in the global concentrations of chemical elements. The results show that of the 27 elements analyzed, 25 showed a reduction in their concentrations after the burning of the soil. As the systematic literature review points out, the release of these chemical elements to the environment, is intrinsically linked to the decrease in the environmental quality of the built environment, therefore, it is an indication of possible risks for human health.
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

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

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

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.
Electron emission properties of titanium nitride coated volcano-structured silicon emitters
Authors: Murata Hiromasa , Murakami Katsuhisa , Nagao Masayoshi
Published: January 2024

Volcano-structured field emitter arrays (FEAs) have achieved high-beam focusing and have been applied in electron beam lithography and image sensors. However, high current operation on the order of milliamperes is necessary for applications such as x-ray sources and traveling wave tubes. Thus, this study applied a TiN coating to a volcano-structured Si-FEA, which has a high melting point favorable for high-current operation. Transmission electron microscopy and x-ray photoelectron spectroscopy revealed that TiN was uniformly deposited on the Si tip by DC magnetron sputtering with the atomic ratio of Ti to N being 1:1. The TiN-coated volcano-structured FEA exhibited excellent electron emission property (7.7 mA/1027 tips) and an electron emission stability of >6 mA for 60 min in pulse operation. These results are expected to aid in the development of next-generation electron sources that can realize high-current operations under high-beam-focusing conditions.
A Mixed Methods Feasibility Study of Machine-Based Resistance Training With Prefrail Older Adults in Residential Care: The Keeping Active in Residential Elderly Trial II
Authors: Swales Bridgitte , Ryde Gemma C. , Whittaker Anna C.
Published: January 2024

Physical activity is an effective, proactive intervention to reduce or reverse frailty and functional decline. However, uncertainty exists about the feasibility and impact of resistance training on multidimensional health in prefrail older adults in residential care. This mixed methods feasibility study assessed practicability with limited efficacy testing on health and functional outcomes. Eleven prefrail older adults participated in a 6-week progressive resistance training protocol three times per week. The intervention and measures were found to be appropriate and acceptable by those who completed the trial, with participants self-reporting improved well-being, mood, and function. Analysis identified several barriers to recruitment, including prior commitments, seasonal impact, and session timing, and offered potential solutions with further recommendations for program refinement prior to a definitive randomized controlled trial. These findings add to our understanding of prefrail older adults’ preferences regarding participation in physical activity research and the perceived benefits of resistance training. This trial was registered with ClinicalTrials.gov: NCT03141879.
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

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

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

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

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.