bluuebunny/crossref_metadata_2025 huggingface dataset:
The Delirium Interview as a new reference standard in studies on delirium assessment tools
Authors: Ditzel Fienke L. , Slooter Arjen J. C. , van den Boogaard Mark , Boonstra Michel , van Nesselrooij Timotheus A. , Kromkamp Marjan , Pop‐Purceleanu Monica , Rood Paul J. T. , Osse Robert Jan , Chan Carol K. , MacLullich Alasdair M. J. , Tieges Zoë , Neufeld Karin J. , Hut Suzanne C. A.
Published: February 2023

Background

The reference standard in studies on delirium assessment tools is usually based on the clinical judgment of only one delirium expert and may be concise, unstandardized, or not specified at all. This multicenter study investigated the performance of the Delirium Interview, a new reference standard for studies on delirium assessment tools allowing classification of delirium based on written reports.

Methods

We tested the diagnostic accuracy of our standardized Delirium Interview by comparing delirium assessments of the reported results with live assessments. Our reference, the live assessment, was performed by two delirium experts and one well‐trained researcher who registered the results. Their delirium assessment was compared to the majority vote of three other independent delirium experts who judged the rapportage of the Delirium Interview. Our total pool consisted of 13 delirium experts with an average of 13 ± 8 years of experience.

Results

We included 98 patients (62% male, mean age 69 ± 12 years), of whom 56 (57%) intensive care units (ICUs) patients, 22 (39%) patients with a Richmond Agitation Sedation Scale (RASS) < 0 and 26 (27%) non‐verbal assessments. The overall prevalence of delirium was 28%. The Delirium Interview had a sensitivity of 89% (95% confidence interval [CI]: 71%–98%) and specificity of 82% (95% CI: 71%–90%), compared to the diagnosis of an independent panel of two delirium experts and one researcher who examined the patients themselves. Negative and positive predictive values were 95% (95% CI: 86%–0.99%), respectively, 66% (95% CI: 49%–80%). Stratification into ICU and non‐ICU patients yielded similar results.

Conclusion

The Delirium Interview is a feasible reference method for large study cohorts evaluating delirium assessment tools since experts could assess delirium with high accuracy without seeing the patient at the bedside.
Histone deacetylase OsHDA706 increases salt tolerance via H4K5/K8 deacetylation of OsPP2C49 in rice
Authors: Liu Kai , Chen Jijin , Sun Shang , Chen Xu , Zhao Xinru , Hu Yingying , Qi Guoxiao , Li Xiya , Xu Bo , Miao Jun , Xue Chao , Zhou Yong , Gong Zhiyun
Published: February 2023

High salt is a major environmental factor that threatens plant growth and development. Increasing evidence indicates that histone acetylation is involved in plant responses to various abiotic stress; however, the underlying epigenetic regulatory mechanisms remain poorly understood. In this study, we revealed that the histone deacetylase OsHDA706 epigenetically regulates the expression of salt stress response genes in rice (Oryza sativa L.). OsHDA706 localizes to the nucleus and cytoplasm and OsHDA706 expression is significantly induced under salt stress. Moreover, oshda706 mutants showed a higher sensitivity to salt stress than the wild‐type. In vivo and in vitro enzymatic activity assays demonstrated that OsHDA706 specifically regulates the deacetylation of lysines 5 and 8 on histone H4 (H4K5 and H4K8). By combining chromatin immunoprecipitation and mRNA sequencing, we identified the clade A protein phosphatase 2 C gene, OsPP2C49, which is involved in the salt response as a direct target of H4K5 and H4K8 acetylation. We found that the expression of OsPP2C49 is induced in the oshda706 mutant under salt stress. Furthermore, the knockout of OsPP2C49 enhances plant tolerance to salt stress, while its overexpression has the opposite effect. Taken together, our results indicate that OsHDA706, a histone H4 deacetylase, participates in the salt stress response by regulating the expression of OsPP2C49 via H4K5 and H4K8 deacetylation.
Global Banks and Synthetic Funding: The Benefits of Foreign Relatives
Authors: EGUREN‐MARTIN FERNANDO , OSSANDON BUSCH MATIAS , REINHARDT DENNIS
Published: February 2023

This paper examines the effect of dislocations in foreign currency (FX) swap markets (“CIP deviations”) on bank lending. Using data from UK banks we show that when the cost of obtaining swap‐based funds in a particular foreign currency increases, banks reduce the supply of cross‐border credit in that currency. This effect is increasing in the degree of banks' reliance on swap‐based FX funding. Access to foreign relatives matters as banks employ internal capital markets to shield their cross‐border FX lending supply from the described channel. Partial substitution occurs from banks outside the UK not affected by changes in synthetic funding costs.
Well‐differentiated chrondrosarcoma in a cynomolgus macaque (Macaca fascicularis)
Authors: Walz Sarah Ruth , Traslavina Ryan Patrick , Ruiz Byron Fredy
Published: February 2023

A cynomolgus macaque presented with an osteolytic lesion of the left femur. Histopathology was consistent with well‐differentiated chondrosarcoma. No metastasis was found in chest radiographs out to 12 months. This case suggests survival out to 1 year without metastasis following amputation may be possible in NHPs with this condition.
Mechanistic and therapeutic role of NLRP3 inflammasome in the pathogenesis of Alzheimer's disease
Authors: Jha Dhanshree , Bakker Erik N. T. P. , Kumar Rahul
Published: February 2023

Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Several pathological hallmarks have been identified, including neuroinflammation. A comprehensive insight into the underlying mechanisms that can fuel the development of novel therapeutic approaches is necessary because of the alarmingly rapid increase in the frequency of incidence. Recently, NLRP3 inflammasome was identified as a critical mediator of neuroinflammation. Activation of nucleotide‐binding domain (NOD)‐like receptor protein 3 (NLRP3) inflammasome by amyloid, neurofibrillary tangles, impaired autophagy and endoplasmic reticulum stress, triggers the release of pro‐inflammatory cytokines such as IL‐1β and IL‐18. Subsequently, these cytokines can promote neurodegeneration and cognitive impairment. It is well established that genetic or pharmacological ablation of NLRP3 alleviates AD‐related pathological features in in vitro and in vivo models. Therefore, several synthetic and natural compounds have been identified that exhibit the potential to inhibit NLRP3 inflammasome and alleviate AD‐associated pathology. The current review article will highlight the various mechanisms by which activation of NLRP3 inflammation occurs during Alzheimer's disease, and how it influences neuroinflammation, neurodegeneration and cognitive impairment. Moreover, we will summarise the different small molecules that possess the potential to inhibit NLRP3 and can pave the path for developing novel therapeutic interventions for AD.

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Diversity, taxonomy, and history of the tropical fern genus Didymoglossum Desv. (Hymenophyllaceae, Polypodiidae) in Africa
Authors: Dubuisson Jean‐Yves , Nivart Adèle , Bidault Ehoarn , Deblauwe Vincent , Droissart Vincent , Kamdem Narcisse G. , Rouhan Germinal , Ebihara Atsushi , le Péchon Timothée
Published: February 2023

The fern genus Didymoglossum (Hymenophyllaceae) is not so diverse in Africa with seven species at most. However, its local taxonomy is surprisingly still strongly debated, in particular within the Didymoglossum erosum complex interpreted either as a single polymorphic species or as a group of at least three distinct but morphologically very close taxa (D. erosum, Didymoglossum chamaedrys, and Didymoglossum benlii). Investigating these taxonomic issues and more generally the diversity of the genus in Africa and its origin, we conducted a complete anatomo–morphological analysis coupled with a molecular phylogenetic work based on rbcL. Our results support the recognition of all seven species, including Didymoglossum robinsonii that is likely distinct from the Neotropical Didymoglossum reptans to which the African populations were traditionally attributed. We here propose new characters and a novel key to distinguish the seven African species which also include Didymoglossum ballardianum, Didymoglossum lenormandii, and Didymoglossum liberiense. Once the taxonomy is clarified with respect to the distinct evolutionary lineages evidenced, the biogeographic history of the genus in Africa is discussed based on a divergence time estimation and the reconstruction of the ancestral geographic areas. These analyses reveal a Mesozoic (Cretaceous) vicariance event within Didymoglossum which is the second one hypothesized for the family Hymenophyllaceae.
Validation of the withdrawal assessment tool‐1 (WAT‐1) in pediatric cardiovascular patients on an inpatient unit
Authors: McAlister Sarah , Connor Jean A. , Engstrand Shannon , McLellan Mary C.
Published: February 2023

Purpose

Sedation and analgesia are administered to critically ill patients, which may result in physical dependence and subsequent iatrogenic withdrawal. The Withdrawal Assessment Tool‐1 (WAT‐1) was developed and validated as an objective measurement of pediatric iatrogenic withdrawal in intensive care units (ICUs), with a WAT‐1 score ≥ 3 indicative of withdrawal. This study's objectives were to test interrater reliability and validity of the WAT‐1 in pediatric cardiovascular patients in a non‐ICU setting.

Design and methods

This prospective observational cohort study was conducted on a pediatric cardiac inpatient unit. WAT‐1 assessments were performed by the patient's nurse and a blinded expert nurse rater. Intra‐class correlation coefficients were calculated, and Kappa statistics were estimated. A two‐sample, one‐sided test of proportions of weaning (n = 30) and nonweaning (n = 30) patients with a WAT‐1 ≥3 were compared.

Results

Interrater reliability was low (K = 0.132). The WAT‐1 area under the receiver operating curve was 0.764 (95% confidence interval; ± 0.123). There was a significantly higher proportion (50%, p = 0.009) of weaning patients with WAT‐1 scores ≥3 compared to the nonweaning patients (10%). The WAT‐1 elements of moderate/severe uncoordinated/repetitive movement and loose, watery stools were significantly higher in the weaning population.

Practice Implications

Methods to improve interrater reliability warrant further examination. The WAT‐1 had good discrimination at identifying withdrawal in cardiovascular patients on an acute cardiac care unit. Frequent nurse re‐education may increase accurate tool use. The WAT‐1 tool may be used in the management of iatrogenic withdrawal in pediatric cardiovascular patients in a non‐ICU setting.
Chronotype influence on the effects of COVID‐19 lockdown on sleep and psychological status in France
Authors: Bessot Nicolas , Langeard Antoine , Dosseville Fabrice , Quarck Gaelle , Freret Thomas
Published: February 2023

The present study aims to assess the influence of chronotype on lockdown‐induced effects on sleep and psychological outcomes. A total of 1671 participants were recruited in France and filled out online questionnaires about their sleeping hours and sleep quality, their chronotype (morning, intermediate, evening type), and their depressive, anxiety and stress symptoms both retrospectively (before lockdown) and currently (during the lockdown). Statistical analyses estimated the chronotype effect on the impact of the lockdown on sleep and psychological outcomes. Results show that during the lockdown, sleep quality decreased, sleep duration increased, and sleep midpoint was delayed and, while fatigue perception decreased, anxiety and depression increased. The decrease in sleep quality varied according to the participants' chronotype. The evening type's sleep quality decreased the most. A similar chronotype effect was also observed on sleep duration and sleep midpoint. Evening‐type participants also increased their depressive symptoms. These results suggest that evening‐type individuals have lower resilience to lockdown effect on psychological status and sleep pattern.
Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies
Authors: Caffrey A. , Lamers Y. , Murphy M. M. , Letourneau N. , Irwin R. E. , Pentieva K. , Ward M. , Tan A. , Rojas‐Gómez A. , Santos‐Calderón L. A. , Canals‐Sans J. , Leung B. M. Y. , Bell R. , Giesbrecht G. F. , Dewey D. , Field C. J. , Kobor M. , Walsh C. P. , McNulty H.
Published: February 2023

Suboptimal status of folate and/or interrelated B vitamins (B12, B6and riboflavin) can perturb one‐carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate‐related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence‐based health improvement strategies. TheEpiBrainproject, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition–epigenome–brain relationship, particularly focussing on folate‐related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio‐banked samples from existing well‐characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition–epigenome–brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state‐of‐the‐art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.
Serum chemokine CC‐motif ligand 17 is a predictive marker of severe COVID‐19 in haemodialysis patients: A retrospective observational study
Authors: Beppu Hiroko , Fukuda Tatsuya , Otsubo Naoya , Kawanishi Tomoko , Ogawa Toshie , Abe Yasutomo , Endo Mariko , Hanawa Tomohide , Sugita Chise , Kikkawa Yoshiaki , Hatakeyama Shuji , Yamada Tetsuya , Wakai Sachiko
Published: February 2023

Background

Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID‐19). Because of a limited number of facilities that can provide inpatient treatment for COVID‐19 and HD, it is important to identify HD patients who are at high risk for severe COVID‐19. For mild to moderate COVID‐19 patients, chemokine CC‐motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID‐19; however, the validity of CCL17 among HD patients is unknown.

Methods

This retrospective observational study enrolled 107 HD patients with mild or moderate COVID‐19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID‐19.

Results

During hospitalization, 32 patients developed severe COVID‐19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C‐reactive protein for the prediction of severe COVID‐19. The optimal cut‐off value for CCL17 was 150.5 pg/mL. A multi‐variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID‐19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017–0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C‐reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID‐19 using the net reclassification (1.16, 95% CI: 0.82–1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09–0.26, p < .001) improvement.

Conclusion

CCL17 levels in HD patients with mild or moderate COVID‐19 predict risk of developing severe COVID‐19.
Transient dynamics in plant–pollinator networks: fewer but higher quality of pollinator visits determines plant invasion success
Authors: Valdovinos Fernanda S. , Dritz Sabine , Marsland Robert
Published: February 2023

Invasive plants often use mutualisms to establish in their new habitats and tend to be visited by resident pollinators similarly or more frequently than native plants. The quality and resulting reproductive success of those visits, however, have rarely been studied in a network context. Here, we use a dynamic model to evaluate the invasion success and impacts on natives of various types of non‐native plant species introduced into thousands of plant–pollinator networks of varying structure. We found that network structure properties did not predict invasion success, but non‐native traits and interactions did. Specifically, non‐native plants producing high amounts of floral rewards but visited by few pollinators at the moment of their introduction were the only plant species able to invade the networks. This result is determined by the transient dynamics occurring right after the plant introduction. Successful invasions increased the abundance of pollinators that visited the invader, but the reallocation of the pollinators' foraging effort from native plants to the invader reduced the quantity and quality of visits received by native plants and made the networks slightly more modular and nested. The positive and negative effects of the invader on pollinator and plant abundance, respectively, were buffered by plant richness. Our results call for evaluating the impact of invasive plants not only on visitation rates and network structure, but also on processes beyond pollination including seed production and recruitment of native plants.
Morphological disparity and evolutionary rates of cranial and postcranial characters in sloths (Mammalia, Pilosa, Folivora)
Authors: Casali Daniel M. , Boscaini Alberto , Gaudin Timothy J. , Perini Fernando A.
Published: February 2023

Sloth morphological evolution has been widely studied qualitatively, with comparative anatomy and morpho‐functional approaches, or through quantitative assessments of morphological variation using morphometrics. Only recently, however, have folivoran morphological disparity and evolutionary rates begun to be evaluated using discrete character data. Nonetheless, patterns of morphological evolution in separate character partitions have not been investigated, neither the relative influence of, on the one hand, phylogeny, and on the other, dietary and locomotory adaptations of sloths. Here we evaluate those patterns using a phylomorphospace approach, quantifying morphological disparity and evolutionary rates, and investigating possible drivers of morphological evolution for cranial and postcranial characters in Folivora. The evolution of the morphology in those partitions is associated with distinct patterns of disparity among clades and ecological groups, even though the two partitions do not differ substantially in overall evolutionary tempo. Historical processes shaped the morphological evolution of sloths more consistently than ecological ones, although changes in postcranial characters also seem to be associated with locomotory adaptations, in which morphological convergences were much more common. We also discuss important methodological trade‐offs in investigations of partitioned datasets mostly composed of fossil taxa.
Adherence to COVID‐19 health protocols in an online news context in the Philippines: A manifest content analysis
Authors: Sundiam Tyrone Gabriel D. , Sy Julia Czarina A. , Berdida Daniel Joseph E. , Talampas Patricia Yssabel R. , Suillan Hazel Abigail A. , Sumangil Eloisa Andrea V. , Sunga Angela Mariz E. , Sy Juco Samantha Nicole T. , Talastas Kyle Catherine
Published: February 2023

Objectives

Globally, adherence to COVID‐19 health and safety protocols played a crucial role in preventing the spread of the virus. Thus, this study analyzed online news articles reporting adherence to COVID‐19 health and safety protocols in the Philippines.

Design

Manifest content analysis.

Sample

News articles (n = 192) from three major online news portals in the Philippines.

Measurement

Published online news articles were collected during the peak of the COVID‐19 pandemic (March 2020 to March 2021). Bengtsson's content analysis approach was used to analyze the data. Member‐checking and intercoder reliability validated the study's results.

Results

Three main themes emerged: (a) adherence, (b) non‐adherence, and (c) partial adherence. The subthemes were labeled who, what, when, where, and why. The same behavior, social distancing, was the most adhered to and non‐adhered COVID‐19 health protocol. This protocol has the highest occurrences in political protest, religious‐related activities, and self‐initiated quarantine. Leisure activities both showed non‐adherence and partial adherence.

Conclusions

Online news articles depicted Filipinos’ adherence to health and safety protocols. Their adherence was primarily determined by one's group or community, social norms, and values. The government and its public health agencies should strengthen current efforts and continuously re‐evaluate existing policies to modify ineffective and confusing safety health protocols.
The impact of information on transportation systems with strategic customers
Authors: Logothetis Dimitrios , Economou Antonis
Published: February 2023

Nowadays, a transportation station has the possibility to provide its potential passengers with information regarding the arrival times of the successively arriving facilities, the congestion in the station and the space availability of future facilities. Such information influences the behavior of the passengers who think strategically and consequently the throughput and the welfare that are generated by the system. In the present work, we consider a general model of a transportation station where strategic customers arrive according to a Poisson process, the arriving instants of the transportation facilities form a renewal process and the capacities of successively arriving facilities are finite. Customers decide whether to stay or balk based on their expected waiting costs and the probability of being served, conditioning on the information provided. The information may include the capacity of the next facility, the elapsed time from the previous visit of the facility and/or the number of waiting customers in the station. We derive the customer equilibrium strategies and compare the equilibrium throughput and social welfare, under various information structures. We then determine the ideal level of information that should be provided according to the operational and economic parameters of a given system. Providing the elapsed time from the previous visit of the facility is of utmost importance for infrequent transportation visits. On the other hand, revealing the number of waiting customers is the most advantageous piece of information in the case of frequent facility's visits and small mean capacity.
Will your insurance type influence clinical quality outcomes? An investigation of contributing factors, underlying mechanism, and consequences
Authors: Sharma Luv , Goradia Deepa
Published: February 2023

Although past studies have found differences in clinical quality outcomes based on patients' insurance type, the extent of these discrepancies, the underlying mechanisms supporting this relationship, and factors that can moderate this effect have not yet been addressed. We seek to fill this gap by studying the relationship between insurance type and clinical quality outcomes using the level of care received, that is, treatment intensity, as a mediator. Using agency theory, we argue that underinsured patients (patients insured by Medicaid) will experience more adverse clinical quality outcomes due to lower treatment intensity compared to privately insured patients. We then explore whether two contextual factors—patient complexity and resource utilization—influence the relationship between insurance type and treatment intensity, and in turn clinical quality outcomes. We use 2010–2016 data from California to test these relationships. The insurance types used for comparison are private and Medi‐Cal (California's equivalent of Medicaid, representing underinsured patients). A patient's 30‐day readmission rate is used as a measure of clinical quality and the log of charges normalized by wage index and inflation (called treatment intensity) is used as a proxy for the level of care they received. We use within‐hospital coarsened exact score matching to create a comparable group of patients using private and Medi‐Cal insurance followed by a hospital fixed effects regression with errors clustered by hospital to test these relationships. Results indicate that treatment intensity mediates the relationship between insurance type and clinical quality outcomes. Further, the difference in treatment intensity based on insurance type is reduced as patient complexity increases, while higher utilization at a hospital lowers its incentive to provide equitable care to underinsured patients.
Immune globulin usage trends in commercially insured and Medicare populations, 2009–2019
Authors: Jiao Yixin , Moll Keran , Dores Graça M. , Tworkoski Ellen , Zhou Cindy Ke , Scott Dorothy , Wong Hui‐Lee , Fingar Kathryn , Burrell Timothy , McEvoy Rowan , Hobbi Shayan , Chillarige Yoganand , Obidi Joyce , MaCurdy Thomas , Kelman Jeffrey , Shoaibi Azadeh
Published: February 2023

Background

Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life‐saving/health‐preserving therapy. The study describes US IG utilization patterns from 2009 to 2019.

Study Design and Methods

Using IBM MarketScan commercial and Medicare claims data, we examined four metrics overall and by condition‐specific categories during 2009–2019: (1) IG administrations per 100,000 person‐years, (2) IG recipients per 100,000 enrollees, (3) average annual administrations per recipient, and (4) average annual dose per recipient.

Results

In the commercial and Medicare populations respectively: IG administrations per 100,000 person‐years increased by 120% (213–470) and 144% (692–1693); IG recipients per 100,000 enrollees grew by 71% (24–42) and 102% (89–179); average annual administrations per recipient rose by 28% (8–10) and 19% (8–9); and average annual dose (grams) per recipient increased by 29% (384–497) and 34% (317–426). IG administrations associated with immunodeficiency (per 100,000 person‐years) increased by 154% (from 127 to 321) and 176% (from 365 to 1007). Autoimmune and neurologic conditions were associated with higher annual average administrations and dose than other conditions.

Discussion

IG use increased, coinciding with a growth in the IG recipient population in the United States. Several conditions contributed to the trend, with the largest increase observed among immunodeficient individuals. Future investigations should assess changes in the demand for IVIG by disease state or indication and consider treatment effectiveness.
WHAT MAKES A QUANTUM PHYSICS BELIEF BELIEVABLE? MANY‐WORLDS AMONG SIX IMPOSSIBLE THINGS BEFORE BREAKFAST
Authors: Henson Shaun C.
Published: February 2023

An extraordinary, if circumscribed, positive shift has occurred since the mid‐twentieth century in the perceived status of Hugh Everett III's 1956 theory of the universal wave function of quantum mechanics, now widely called the Many‐Worlds Interpretation (MWI). Everett's starkly new interpretation denied the existence of a separate classical realm, contending that the experimental data can be seen as presenting a state vector for the whole universe. Since there is no state vector collapse, reality as a whole is strictly deterministic. Explained jointly by the dynamical variables and the state vector, “this reality is not the reality we customarily think of, but is a reality composed of many worlds,” wrote Everett's colleague Bryce DeWitt. In this essay, I account briefly for the change of status in conventional scientific terms, yet chiefly in extended terms of three sets of ideas that I argue can be understood to affect believability in both scientific and religious contexts, illuminating helpfully the MWI phenomenon, and its engagement with theology: orthodoxy and heresy, language and reference, and faith and agnosticism. One's orientation relative to the variable content of these dynamic, socially oriented categories helps to make belief in ideas as metaphysically challenging as Everettian Quantum Mechanics, or particular ideas about God, either more or less believable. The categories will have the same function in a theology engaging Everett's theory, and in any theology at all written in a society deeply marked by what I further argue is a subtle, powerful, and pervasive mode of quasi‐scientific thinking we can call societal constructive agnosticism, of which anyone doing theology today must be aware.
Zeolite Linde type A powder analyzed by x-ray photoelectron spectroscopy
Authors: David Gonzalez E. , Botero M. A. , Ospina R.
Published: February 2023

Zeolite Linde type A powder was characterized by x-ray photoelectron spectroscopy. Sample was fixed to a stainless-steel sample holder with a copper double-sided adhesive tape. The spectra of survey spectra, C 1s, O 1s, Na 1s, Al 2p, and Si 2p, core levels were acquired. Results showed the presence of carbon, oxygen, aluminum, and silicon, elements that constitute the aluminosilicate molecule.
Can Physical Activity Breaks Assist Mathematics Learning? A Domain Learning Theory Perspective
Authors: Wang Wen-Yi , Chen Ang
Published: February 2023

Purpose: Guided by the model of domain learning theory, this study was intended to determine the extent to which integrating a 10-min physical activity (PA) break in elementary school mathematics lessons would enhance the learning of mathematics content. Methods: A sample of 22 intact classes from a random sample of eight schools in Taiwan were randomly assigned to an experimental condition with PA breaks (n = 11) and a control condition (n = 11) for 12 weeks. Students’ (N = 420) mathematics knowledge was assessed using the standardized aptitude tests accompanying the curriculum, which encompassed five knowledge domains. Results: Analysis on class means showed that adding the PA breaks did not benefit mathematics learning, which lends support to the model of domain learning theory. Discussion/Conclusion: The findings seem to question the theoretical foundation for adding PA breaks to classroom-taught content, including mathematics. Although interdisciplinary or cross-disciplinary instruction and learning may be necessary to advance students’ knowledge, including PA in classroom-taught subjects needs extensive research.
Optogenetic decoding of Akt2-regulated metabolic signaling pathways in skeletal muscle cells using transomics analysis
Authors: Kawamura Genki , Kokaji Toshiya , Kawata Kentaro , Sekine Yuka , Suzuki Yutaka , Soga Tomoyoshi , Ueda Yoshibumi , Endo Mizuki , Kuroda Shinya , Ozawa Takeaki
Published: February 2023

Insulin regulates various cellular metabolic processes by activating specific isoforms of the Akt family of kinases. Here, we elucidated metabolic pathways that are regulated in an Akt2-dependent manner. We constructed a transomics network by quantifying phosphorylated Akt substrates, metabolites, and transcripts in C2C12 skeletal muscle cells with acute, optogenetically induced activation of Akt2. We found that Akt2-specific activation predominantly affected Akt substrate phosphorylation and metabolite regulation rather than transcript regulation. The transomics network revealed that Akt2 regulated the lower glycolysis pathway and nucleotide metabolism and cooperated with Akt2-independent signaling to promote the rate-limiting steps in these processes, such as the first step of glycolysis, glucose uptake, and the activation of the pyrimidine metabolic enzyme CAD. Together, our findings reveal the mechanism of Akt2-dependent metabolic pathway regulation, paving the way for Akt2-targeting therapeutics in diabetes and metabolic disorders.
Engineered Bacterial Outer Membrane Vesicles with Lipidated Heterologous Antigen as an Adjuvant-Free Vaccine Platform for Streptococcus suis
Authors: Li Quan , Zhou Guodong , Fei Xia , Tian Yichen , Wang Shifeng , Shi Huoying
Published: February 2023

Bacterial outer membrane vesicles (OMVs) have become a promising vaccine platform due to their excellent built-in adjuvanticity properties. However, the location and amount of the expression of the heterologous antigen in the OMVs delivered by the genetic engineering strategies should be optimized.
Metagenomic Next-Generation Sequencing of Plasma for Diagnosis of COVID-19-Associated Pulmonary Aspergillosis
Authors: Hoenigl Martin , Egger Matthias , Price Jessica , Krause Robert , Prattes Juergen , White P. Lewis
Published: February 2023

Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which in its early stages is characterized by tissue-invasive growth of the lungs with limited angioinvasion. Currently available mycological tests show limited sensitivity when testing blood specimens.
Genome-Scale CRISPR Screening Reveals Host Factors Required for Ribosome Formation and Viral Replication
Authors: Ohlson Maikke B. , Eitson Jennifer L. , Wells Alexandra I. , Kumar Ashwani , Jang Seoyeon , Ni Chunyang , Xing Chao , Buszczak Michael , Schoggins John W.
Published: February 2023

Viruses are well known for their ability to co-opt host ribosomes to synthesize viral proteins. The specific factors involved in translation of viral RNAs are not fully described.
Late Embryogenesis Abundant Proteins Contribute to the Resistance of Toxoplasma gondii Oocysts against Environmental Stresses
Authors: Arranz-Solís David , Warschkau David , Fabian Benedikt T. , Seeber Frank , Saeij Jeroen P. J.
Published: February 2023

Toxoplasma gondii
oocysts are highly infectious and may survive in the environment for years.
The Entomopathogenic Fungus Beauveria bassiana Employs Autophagy as a Persistence and Recovery Mechanism during Conidial Dormancy
Authors: Ding Jin-Li , Lin Hai-Yan , Hou Jia , Feng Ming-Guang , Ying Sheng-Hua
Published: February 2023

Conidial environmental persistence is essential for fungal dispersal in ecosystems while also serving as a determinant for the biocontrol efficacy of entomopathogenic fungi during integrated pest management. This study identified autophagy as a mechanism to safeguard conidial lifespans and vitality postmaturation.
Ent2 Governs Morphogenesis and Virulence in Part through Regulation of the Cdc42 Signaling Cascade in the Fungal Pathogen Candida albicans
Authors: Lash Emma , Prudent Victoria , Stogios Peter J. , Savchenko Alexei , Noble Suzanne M. , Robbins Nicole , Cowen Leah E.
Published: February 2023

Candida albicans
is a leading human fungal pathogen that can cause life-threatening infections in immunocompromised individuals, with mortality rates of ~40%. The ability of this organism to grow in both yeast and filamentous forms is critical for the establishment of systemic infection.
Novel
In Situ
Hybridization Assay for Chromogenic Single-Molecule Detection of Human Papillomavirus E6/E7 mRNA
Authors: Rao Xuelian , Zheng Liangkai , Wei Kaipeng , Li Meiqing , Jiang Meng , Qiu Jianlong , Zhou Yulin , Ke Rongqin , Lin Chen
Published: February 2023

In situ
detection of viral mRNA expression in tissue samples is of great value for pathological diagnosis to access viral infection status. Unfortunately, conventional RNA
in situ
hybridization assays lack sensitivity and specificity for clinical diagnostic purposes.
Synergistic Activity of Colistin in Combination with Clofoctol against Colistin Resistant Gram-Negative Pathogens
Authors: Collalto Diletta , Fortuna Alessandra , Visca Paolo , Imperi Francesco , Rampioni Giordano , Leoni Livia
Published: February 2023

Colistin is used as a last-resort antibiotic against extensively drug-resistant Gram-negative pathogens. However, colistin resistance is on the rise.
Analysis of the pachychoroid phenotype in an Asian population: methodology and baseline study population characteristics
Authors: Wong Wendy Meihua , Sun Wu , Vyas Chinmayi , Fong Angie Hon Chi , Chee Caroline K , Su Xin Yi , Teo Kelvin YC , Cheung Chui Ming Gemmy
Published: February 2023

Aim

To describe the clinical characteristics in a cohort of patients with the pachychoroid phenotype and to evaluate the association of ocular and systemic factors with type of complications observed.

Methods

We report baseline findings from a prospective observational study which recruited subjects with subfoveal choroidal thickness (SFCT) of ≥300 µm on spectral-domain optical coherence tomography (OCT). Multimodal imaging was used to classify eyes as uncomplicated pachychoroid (UP) or pachychoroid disease with pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC) or pachychoroid neovasculopathy (PNV) subtypes.

Results

Among 181 eyes of 109 participants (mean age 60.6 years, 33 (30.3%) female, 95 (7.2%) Chinese), 38 eyes (21.0%) had UP. Of 143 eyes (79.0%) with pachychoroid disease, 82 (45.3%), 41 (22.7%) and 20 (11.0%) had PPE, CSC and PNV, respectively. Addition of autofluorescence and OCT angiography to structural OCT led to reclassification of 31 eyes to a more severe category. Systemic and ocular factors evaluated, including SFCT, were not associated with disease severity. Comparison of PPE, CSC and PNV eyes showed no significant difference in OCT features of retinal pigment epithelial (RPE) dysfunction, but disruption of the ellipsoid zone (PPE 30.5% vs CSC 70.7% vs PNV 60%, p<0.001) and thinning of inner nuclear/inner plexiform layers (PPE 7.3% vs CSC 36.6% vs PNV 35%, p<0.001) were more frequent in CSC and PNV eyes.

Conclusions

These cross-sectional associations suggest pachychoroid disease manifestations may reflect progressive decompensation from the choroid to the RPE then retinal layers. Planned follow-up of this cohort will be beneficial in clarifying the natural history of the pachychoroid phenotype.
Cost of hepatocellular carcinoma to the national health service in England: a registry-based analysis
Authors: Cullen Katherine , Jones Mari , Pockett Rhys D. , Burton Anya , Cross Timothy J.S. , Rowe Ian A. , Paley Lizz , Tataru Daniela , Alexander Graeme , Marshall Aileen , Fitzsimmons Deborah
Published: February 2023

Objective

Hepatocellular carcinoma (HCC) incidence in the UK trebled between 1997 and 2017. With increasing numbers requiring treatment, understanding the likely impact on healthcare budgets can inform service planning and commissioning. The aim of this analysis was to use existing registry data to describe the direct healthcare costs of current treatments for HCC and estimate the impact on National Health Service (NHS) budgets.

Design

A retrospective data analysis based on the National Cancer Registration and Analysis Service cancer registry informed a decision-analytic model for England comparing patients by cirrhosis compensation status and those on palliative or curative treatment pathways. Potential cost drivers were investigated by undertaking a series of one-way sensitivity analyses.

Results

Between 1 January 2010 and 31 December 2016, 15 684 patients were diagnosed with HCC. The median cost per patient over 2 years was £9065 (IQR: £1965 to £20 491), 66% did not receive active therapy. The cost of HCC treatment for England over 5 years was estimated to be £245 million.

Conclusion

The National Cancer Registration Dataset and linked data sets have enabled a comprehensive analysis of the resource use and costs of secondary and tertiary healthcare for HCC, providing an overview of the economic impact to the NHS England of treating HCC.
Aspirations and realities of intergovernmental collaboration in national- level interventions: insights from maternal, neonatal and child health policy processes in Nigeria, 2009–2019
Authors: Etiaba Enyi , Eboreime Ejemai Amaize , Dalglish Sarah L , Lehmann Uta
Published: February 2023

In Nigeria’s federal government system, national policies assign concurrent healthcare responsibilities across constitutionally arranged government levels. Hence, national policies, formulated for adoption by states for implementation, require collaboration. This study examines collaboration across government levels, tracing implementation of three maternal, neonatal and child health (MNCH) programmes, developed from a parent integrated MNCH strategy, with intergovernmental collaborative designs, to identify transferable principles to other multilevel governance contexts, especially low-income countries.

National-level setting was Abuja, where policymaking is domiciled, while two subnational implementation settings (Anambra and Ebonyi states) were selected based on their MNCH contexts. A qualitative case study triangulated information from 69 documents and 44 in-depth interviews with national and subnational policymakers, technocrats, academics and implementers. Emerson’s integrated collaborative governance framework was applied thematically to examine how governance arrangements across the national and subnational levels impacted policy processes.

The results showed that misaligned governance structures constrained implementation. Specific governance characteristics (subnational executive powers, fiscal centralisation, nationally designed policies, among others) did not adequately generate collaboration dynamics for collaborative actions. Collaborative signing of memoranda of understanding happened passively, but the contents were not implemented. Neither state adhered to programme goals, despite contextual variations, because of an underlying disconnect in the national governance structure.

Collaboration across government levels could be better facilitated via full devolution of responsibilities by national authorities to subnational governments, with the national level providing independent evaluation and guidance only. Given the existing fiscal structure, innovative reforms which hold government levels accountable should be linked to fiscal transfers. Sustained advocacy and context-specific models of achieving distributed leadership across government levels are required across similar resource-limited countries. Stakeholders should be aware of what drivers are available to them for collaboration and what needs to be built within the system context.
Development and validation of nomograms to predict survival in patients with invasive micropapillary carcinoma of the breast
Authors: Cheng Yixin , Zhang Pengkun , Huang Yulin , Zhang Zhihui , Tang Ru , Chi Feng , Sun Jia-Yuan , He Zhenyu
Published: February 2023

Objectives

The present study aimed to develop and validate nomograms to predict the survival of patients with breast invasive micropapillary carcinoma (IMPC) to aid objective decision-making.

Design

Prognostic factors were identified using Cox proportional hazards regression analyses and used to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) at 3 and 5 years. Kaplan-Meier analysis, calibration curves, the area under the curve (AUC) and the concordance index (C-index) evaluated the nomograms’ performance. Decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system.

Setting

Patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. This database holds data related to the incidence of cancer acquired from 18 population-based cancer registries in the US.

Participants

We ruled out 1893 patients and allowed the incorporation of 1340 patients into the present study.

Results

The C-index of the AJCC8 stage was lower than that of the OS nomogram (0.670 vs 0.766) and the OS nomograms had higher AUCs than the AJCC8 stage (3 years: 0.839 vs 0.735, 5 years: 0.787 vs 0.658). On calibration plots, the predicted and actual outcomes agreed well, and DCA revealed that the nomograms had better clinical utility compared with the conventional prognosis tool. In the training cohort, the NRI for OS was 0.227, and for BCSS was 0.182, while the IDI for OS was 0.070, and for BCSS was 0.078 (both p<0.001), confirming its accuracy. The Kaplan-Meier curves for nomogram-based risk stratification showed significant differences (p<0.001).

Conclusions

The nomograms showed excellent discrimination and clinical utility to predict OS and BCSS at 3 and 5 years, and could identify high-risk patients, thus providing IMPC patients with personalised treatment strategies.