bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative fatty acid signature analysis reveals a high level of dietary specialization in killer whales across the North Atlantic
Authors: Remili Anaïs , Dietz Rune , Sonne Christian , Samarra Filipa I. P. , Rikardsen Audun H. , Kettemer Lisa E. , Ferguson Steven H. , Watt Cortney A. , Matthews Cory J. D. , Kiszka Jeremy J. , Jourdain Eve , Borgå Katrine , Ruus Anders , Granquist Sandra M. , Rosing‐Asvid Aqqalu , McKinney Melissa A.
Published: April 2023

Quantifying the diet composition of apex marine predators such as killer whales (Orcinus orca) is critical to assessing their food web impacts. Yet, with few exceptions, the feeding ecology of these apex predators remains poorly understood.

Here, we use our newly validated quantitative fatty acid signature analysis (QFASA) approach on nearly 200 killer whales and over 900 potential prey to model their diets across the 5000 km span of the North Atlantic.

Diet estimates show that killer whales mainly consume other whales in the western North Atlantic (Canadian Arctic, Eastern Canada), seals in the mid‐North Atlantic (Greenland), and fish in the eastern North Atlantic (Iceland, Faroe Islands, Norway). Nonetheless, diet estimates also varied widely among individuals within most regions. This level of inter‐individual feeding variation should be considered for future ecological studies focusing on killer whales in the North Atlantic and other oceans.

These estimates reveal remarkable population‐ and individual‐level variation in the trophic ecology of these killer whales, which can help to assess how their predation impacts community and ecosystem dynamics in changing North Atlantic marine ecosystems.

This new approach provides researchers with an invaluable tool to study the feeding ecology of oceanic top predators.
Ordoliberalism: What We Know and What We Think We Know
Authors: Cole Matthew , Hartmann Sören
Published: April 2023

This article draws on direct archival evidence from the Committee responsible for drafting the Gesetz gegen Wettbewerbsbeschränkungen 1957 (GWB) to establish what the priorities and beliefs of the Ordoliberals (broadly construed) were during the mid‐ to late‐1950s. This is done primarily by analysing the views expressed by Franz Böhm, Finance Minister Ludwig Erhard and Alfred Müller‐Armack. This work is important as it challenges the current understanding of Ordoliberalism. It reveals that aspects of the current understanding of Ordoliberalism are either flawed or do not take into account the changes that occurred between the submission of the Josten Draft (1949) and the drafting of the GWB (enacted 1957). This evidence also challenges the argument that the influence of Ordoliberalism on EU competition law has been exaggerated.
The use of nomogram for detecting mild cognitive impairment in patients with type 2 diabetes mellitus
Authors: Maimaitituerxun Rehanguli , Chen Wenhang , Xiang Jingsha , Xie Yu , Kaminga Atipatsa C. , Wu Xin Yin , Chen Letao , Yang Jianzhou , Liu Aizhong , Dai Wenjie
Published: April 2023

Background

Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram‐based model to detect mild cognitive impairment (MCI) in T2DM patients.

Methods

Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well‐qualified investigators conducted face‐to‐face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM‐related information, and history of depression and anxiety. Cognitive function was assessed using the Mini‐Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively.

Results

A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%–38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815–0.883), and the threshold probability ranged from 35.0% to 85.0%.

Conclusions

Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.
Firm size‐specific trade effects of regional trade agreements: Estimating extensive and intensive margins of trade
Authors: Park Soonchan , Park Innwon
Published: April 2023

We estimate the impacts of Korean firms’ participation in regional trade agreements (RTAs) on the extensive and intensive export margins by identifying exporting firms based on their firm size—small and medium‐sized enterprises (SMEs) and large enterprises (LEs) at the 5 399 HS six‐digit commodity level—and specifying characteristics of RTAs from 2004 to 2015. We apply the EK Tobit estimation technique to control zero trade and the OLS estimation with importer‐product and time fixed effects to alleviate the endogeneity problem. We find that firm size, product type, and depth of RTA significantly matter. Specifically, we find that deeper RTAs with larger, developing, and closer members significantly enhance the export creation effects of SMEs and LEs. Regarding the firm size‐specific effects, we find that SMEs are less sensitive to exploiting RTA participation but more sensitive to the import market size, bilateral and relative trade costs, and the RTA characteristics. LEs’ export creation is mainly driven by the intensive margin, while SMEs’ export creation is driven by extensive and intensive margins (slightly more by the extensive margin). For the product‐specific effects, we find that Korea's major exportable products such as chemicals, basic metals, motor vehicles, and transport equipment generate significantly strong export creation effects for both LEs and SMEs through their participation in RTAs.
Comprehensive clinical pharmacology characterization of AZD4635 in healthy participants to support dosing considerations
Authors: Moorthy Ganesh , Pouliot Gayle Pageau , Graham Lorraine , Pilling Elizabeth , Jung Lindsey , Alcobi Rachael , Zhu Yali , Li Yan , Sidhu Sharan , Forte Pablo , Mugundu Ganesh
Published: April 2023

Aims

Two phase 1 studies characterized the oral bioavailability of AZD4635 (potential anticancer therapy) and factors that may influence its pharmacokinetics (PKs; food, smoking, proton‐pump inhibitors [PPIs] and CYP1A2 inhibitors) to support continued clinical development of AZD4635.

Methods

Study 1 (comparative PK study; nonsmokers) consists of Part A and Part B. Participants (fasted) in Part A were administered 50 mg of AZD4635 either as nanosuspension or capsule. In Part B, these participants were administered a 50‐mg capsule either following a high‐fat meal or with a PPI in the fasted state. In Study 2 (CYP1A2 mediated drug‐drug interaction study), a 25‐mg AZD4635 capsule was administered to smokers and nonsmokers (fasted) with or without 100 mg of fluvoxamine.

Results

In Study 1 (N = 21), AZD4635 exposure was comparable between the capsule and nanosuspension. The high‐fat meal produced a 12% decrease in AUCinf, a ≥50% reduction in Cmax and delayed absorption (Tmax: 4.0 h vs 1.5 h) for the capsule. The PPI did not affect the oral bioavailability of the AZD4635 capsule. In Study 2 (N = 28), AZD4635 + fluvoxamine (compared with AZD4635 alone) produced ~5‐fold increases in AUCinf, 2‐fold increases in Cmax and prolonged AZD4635 elimination half‐life in smokers (22.7 vs 9.0 h) and nonsmokers (22.4 vs 9.2 h). All treatment regimens were well tolerated. The most common adverse events included dizziness, nausea and headache.

Conclusions

The high‐fat meal reduced the rate but not the extent of AZD4635 absorption. The effect of gastric pH on AZD4635 was minimal. Smoking had no effect on the exposure (Cmax and AUCinf) of AZD4635, while fluvoxamine increased AZD4635 Cmax and total exposure. No new safety concerns were identified.
Ensovibep, a SARS‐CoV‐2 antiviral designed ankyrin repeat protein, is safe and well tolerated in healthy volunteers: Results of a first‐in‐human, ascending single‐dose Phase 1 study
Authors: Stojcheva Nina , Gladman Stacy , Soergel Marianne , Zitt Christof , Drake Roxana , Lockett Tony , Marchand Carine , Fustier Pierre , Stavropoulou Vaia , Fernandez Elena , Pettigiani Nathana Lopes , Watkins Kate , Puri Adeep , Watson Randall , Legenne Philippe , Stumpp Michael T. , Boyce Malcolm
Published: April 2023

Aims

This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID‐19 treatment, in healthy volunteers in a first‐in‐human ascending single‐dose study.

Methods

Subjects were dosed intravenously, in a randomized double‐blinded manner, with either ensovibep at 3, 9 or 20 mg/kg or with placebo, and followed until Day 100. PK and safety were assessed throughout the study duration. Immunogenicity and PD via viral neutralization in serum were also assessed.

Results

All adverse events were of mild to moderate severity, and no serious adverse events were observed. One subject who received the 20‐mg/kg dose presented with moderate hypersensitivity vasculitis 3 weeks after infusion, which fully resolved using standard procedures. In most subjects ensovibep showed expected mono‐exponential decline with a half‐life of around 2 weeks. Anti‐drug antibodies were detected in 15 of 17 subjects, with the earliest onset detected on Day 29. Viral neutralization assays on subject serum showed effective viral neutralization over the first 3 weeks following dosing with titre values in a dose dependent manner.

Conclusion

Ensovibep proved safe in this first‐in‐human safety study and exhibited PK and PD parameters consistent with the expected treatment period required for acute COVID‐19 infection.
Editorial: Evidence in the real world – the need for context and the gender gap
Authors: Dubicka Bernadka
Published: April 2023

We are in a competitive, burgeoning market for journals and currently in a transition to open access publications, with the aim of making research more widely accessible. Where is the place for practice‐based journals in this new and evolving world of publishing? The recent growth of CAMH in terms of Impact Factor, downloads and submissions suggests there is a need for such journals. Professionals are swamped with research findings, often contradictory, sometimes inflammatory, with little time to explore the meaning of these findings within the real world. This editorial reflects on the need for academics and practitioners to be able to debate the evidence base within the real world context (or to consider the lack of it) to inform practice and policy, and also on the importance of providing a platform for topics that are current and/or controversial. Recent contributions to CAMH are highlighted, namely the perceived gender gap in research on emotional disorders in women and girls, and the need for an ethical data sharing framework for academics to investigate the potential harms and benefits of technology. CAMH will continue to ask questions, and aim to remain relevant by focusing on both the evidence and real world context, in order to inform best practice and policy decisions.
Single‐cell RNA sequencing reveals new subtypes of lens superficial tissue in humans
Authors: Zhu Meng‐Chao , Hu Wei , Lin Lei , Yang Qing‐Wen , Zhang Lu , Xu Jia‐Lin , Xu Yi‐Tong , Liu Jia‐Sheng , Zhang Meng‐Di , Tong Xiao‐Yu , Zhu Kai‐Yi , Feng Ke , Feng Yi , Su Jian‐Zhong , Huang Xiu‐Feng , Li Jin
Published: April 2023

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single‐nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single‐cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single‐cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.
The effect of group status on children's hierarchy‐reinforcing beliefs
Authors: Rizzo Michael T. , Roberts Steven O. , Rhodes Marjorie
Published: April 2023

Members of advantaged groups are more likely than members of disadvantaged groups to think, feel, and behave in ways that reinforce their group's position within the hierarchy. This study examined how children's status within a group‐based hierarchy shapes their beliefs about the hierarchy and the groups that comprise it in ways that reinforce the hierarchy. To do this, we randomly assigned children (4–8 years; N = 123; 75 female, 48 male; 21 Asian, 9 Black, 21 Latino/a, 1 Middle‐Eastern/North‐African, 14 multiracial, 41 White, 16 not‐specified) to novel groups that differed in social status (advantaged, disadvantaged, neutral third‐party) and assessed their beliefs about the hierarchy. Across five separate assessments, advantaged‐group children were more likely to judge the hierarchy to be fair, generalizable, and wrong to challenge and were more likely to hold biased intergroup attitudes and exclude disadvantaged group members. In addition, with age, children in both the advantaged‐ and disadvantaged‐groups became more likely to see membership in their own group as inherited, while at the same time expecting group‐relevant behaviors to be determined more by the environment. With age, children also judged the hierarchy to be more unfair and expected the hierarchy to generalize across contexts. These findings provide novel insights into how children's position within hierarchies can contribute to the formation of hierarchy‐reinforcing beliefs.

Research Highlights

A total of 123 4–8‐year‐olds were assigned to advantaged, disadvantaged, and third‐party groups within a hierarchy and were assessed on seven hierarchy‐reinforcing beliefs about the hierarchy.

Advantaged children were more likely to say the hierarchy was fair, generalizable, and wrong to challenge and to hold intergroup biases favoring advantaged group members.

With age, advantaged‐ and disadvantaged‐group children held more essentialist beliefs about membership in their own group, but not the behaviors associated with their group.

Results suggest that advantaged group status can shape how children perceive and respond to the hierarchies they are embedded within.
The physical and mental health returns of Head Start 25 years after participation: Evidence from income eligibility cutoffs
Authors: Lacey Lindsey
Published: April 2023

Most studies that look at long‐term effects of Head Start, the largest early childhood intervention in the US, exploit its rollout in the 1960s, missing the effects of many changes to the program in the 1980s and 1990s. I study the effects of Head Start on long‐term physical and mental health for children who attend Head Start in the 1980s–1990s and are new labor market entrants. I find large improvements in health, resulting in a 0.15 standard deviation decrease in the incidence of poor health. Ultimately, Head Start improves health outcomes up to 25 years after participation in the program.
Colleagues or adversaries: Ministerial coordination across party lines
Authors: Klüser K. Jonathan , Schmuck David , Sieberer Ulrich
Published: April 2023

In multiparty governments, policymaking is a collaborative effort among the different incumbent parties. Often hidden by public debates about broader government policy, the necessary coordination routinely happens at the ministerial level, where ministries of different parties jointly devise viable and equitable policy solutions. However, since coordination involves substantial transaction costs, governments must carefully gauge the potential benefits. We study the political rationales that motivate governments to make this investment. We argue that coordination during the process of ministerial policy design hinges on both a conducive ministerial structure and sufficient authority. Once these conditions are met, cross‐party coordination is more likely in policy areas where the implementation of government policy cannot be taken for granted. We investigate these claims, drawing on two new datasets. The first contains information about ministerial collaborations on all legislative projects sponsored by German governments, while the second maps the distribution of policy responsibilities among German ministries from 1976 until 2013, based on data about the policy briefs of all individual working units within the top‐level federal executive. Given that ministries imprint their own perspective on legislation, our results are beyond administrative pedantries, but have substantial implications for the type and content of policies coalition governments formulate.
Estimating the effect of dialysis staffing ratio regulations on mortality and hospitalizations for Medicare hemodialysis patients
Authors: Jacob Allan , Norris Conor , Timmons Edward
Published: April 2023

Background and Objectives

Eight states and Washington, DC have implemented regulations mandating a minimum ratio between treatment staff and patients receiving hemodialysis in a facility in an effort to improve the quality of hemodialysis treatment. Our investigation examines the association between minimum staffing regulations and patient mortality for four states and hospitalizations for two states that implemented these rules during our sample period.

Design, Setting, Participants, and Measurements

We utilized a synthetic difference in differences estimation to analyze the effect of minimum staffing ratios on hemodialysis treatment quality, measured by deaths and hospitalizations for end‐stage renal disease patients. We used data gathered by the US Renal Data System and aggregated at the state level.

Results

We are unable to find evidence that mandated dialysis staffing ratios area associated with a reduction in mortality or hospitalizations. We estimate a slight reduction in deaths per 1000 patient hours and a slight increase in hospitalizations, but neither are statistically significant.

Conclusions

We were unable to find evidence that minimum staffing ratios for hemodialysis facilities are associated with improved patient outcomes. Our findings highlight the need for future work, studying the impact of these regulations at the facility level.
Is Macroprudential Policy Instrument Blunt? Empirical Analysis Based on Japan's Experience from the 1970s to the 1990s
Authors: SONODA KATSURAKO , SUDO NAO
Published: April 2023

Macroprudential instruments, especially sectoral instruments, are considered to be precise tools that work only in areas of concern. However, it has not yet been fully tested in practice whether they affect only the targeted sectors and do not have undesirable spillover effects on nontargeted sectors. To fill this gap, we empirically study the impact of an instrument called Quantitative Restriction (QR), a policy tool used in Japan in the 1990s to curb excessive land price rises by requiring banks to contain real estate lending. We use narrative records to construct QR shocks and estimate their impact using a factor‐augmented vector autoregression (FAVAR). Our findings are summarized as follows. First, contractionary QR shocks reduced not only real estate lending and land prices, but also lending to other industries, putting downward pressure on the macroeconomy and lowering bank solvency. Second, industry groups and banks with balance sheets that were more exposed to changes in land prices and real estate transactions responded greater to these shocks, illustrating the role of balance sheet composition in spillovers and the importance of choosing the right timing for implementation following these shocks, suggesting that there may have been leakages through these institutions. Third, some nonbank financial institutions that were not required to report the loan results to the authorities did not reduce their lending following these shocks, which accords with the view that there were leakages through these institutions.
A qualitative exploration of the strategies used by patients and nurses when navigating a standardised care programme
Authors: Roche Dominic , Jones Aled
Published: April 2023

The main aim of this paper is to explore and discuss the interesting juxtaposition of patient involvement within a standardised Enhanced Recovery After Surgery care programme (ERAS). We address our aim by examining the work and strategies of nursing staff caring for patients during postoperative recovery from surgery, exploring how these two potentially competing priorities might effectively co‐exist within a hospital ward. This was a qualitative exploratory study, with data generated through 42 semi‐structured interviews with patients and nurses who had taken part in an ERAS programme in one of three hospital wards in the United Kingdom, adopting a reflexive thematic approach to data analysis. We shine a light on the work undertaken by patients and nurses during the navigation of postoperative recovery, identifying strategies of collaboration and negotiation during this journey. Furthermore, we also identify and consider patients engaged in peer‐peer support during postoperative recovery. This paper adds to the existing literature and current ways of thinking in relation to the quest for standardised, clinically effective care balanced with the aspirations for individualised, patient‐centred care. This paper also helps inform thinking about the use of care pathways in relation to service delivery, considering how best to initiate and deploy best practice aimed at safe and effective postoperative recovery.
The miR156b–GmSPL2b module mediates male fertility regulation of cytoplasmic male sterility‐based restorer line under high‐temperature stress in soybean
Authors: Ding Xianlong , Guo Jinfeng , Lv Menglin , Wang Hongjie , Sheng Ying , Liu Ying , Gai Junyi , Yang Shouping
Published: April 2023

High‐temperature (HT) stress at flowering stage causes significant damage to soybean, including pollen abortion and fertilization failure, but few genes involved in male fertility regulation under HT stress in soybean have been characterized. Here, we demonstrated that miR156b–GmSPL2b module involved in male fertility regulation of soybean cytoplasmic male sterility (CMS)‐based restorer line under HT stress. Overexpression of miR156b decreased male fertility in soybean CMS‐based restorer line and its hybrid F1 with CMS line under HT stress. RNA‐seq analysis found that miR156b mediated male fertility regulation in soybean under HT stress by regulating the expression of pollen development and HT response related genes. Metabolomic analysis of miR156bOE revealed reduction in flavonoid content under HT stress. Integrated transcriptomic and metabolomic analysis showed that the overexpression of miR156b caused flavonoid metabolism disorder in soybean flower bud under HT stress. Knockout of GmSPL2b also decreased the thermotolerance of soybean CMS‐based restorer line during flowering. Moreover, GmSPL2b turned out to be directly bounded to the promoter of GmHSFA6b. Further verification indicated that GmHSFA6b overexpression enhanced HT tolerance in Arabidopsis during flowering. Substance content and gene expression analysis revealed that miR156b–GmSPL2b may mediate reactive oxygen species clearance by regulating flavonoid metabolism, thus participating in the regulation of male fertility in soybean under HT stress. This study not only provided important progress for understanding the molecular mechanism of miR156b–GmSPL2b regulating the male fertility of soybean CMS‐based restorer line under HT stress, but also provided genetic resources and theoretical basis for creating HT‐tolerant strong restorer lines.
The tree peony nuclear factor Y transcription factor PrNF‐YC2 promotes seed oil accumulation
Authors: Yang Weizong , Xin Ziwei , Hu Jiayuan , Zhang Yanlong , Zhang Qingyu , Niu Lixin
Published: April 2023

Seed oil not only provides energy for seed postgermination development but also provides essential nutrients and raw materials for human products. However, the transcriptional regulatory mechanism controlling seed oil accumulation remains largely unknown. Tree peony (Paeonia rockii) is an emerging woody oilseed crop in China that is known for its high‐quality seed oil. Here, we revealed that a tree peony nuclear factor Y transcription factor, PrNF‐YC2, is expressed predominantly in developing seeds and functions as an essential positive regulator of seed oil accumulation. PrNF‐YC2 promoted oil accumulation in both transient ectopic overexpression Nicotiana benthamiana leaves and stable transgenic Arabidopsis thaliana seeds, globally upregulating the expression of genes involved in oil accumulation. In contrast, PrNF‐YC2‐silenced tree peony leaves using a virus‐induced gene silencing system showed reduced oil content and expression of oil synthesis‐related genes, including four master positive regulators contributing to oil accumulation, namely, LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and WRINKLED1 (WRI1). We demonstrated that PrNF‐YC2 directly activates PrLEC1 and PrABI3 alone and indirectly activates PrFUS3 and PrWRI1 by interacting with PrLEC1. Moreover, interaction with PrLEC1 also enhances the activation capacity of PrNF‐YC2. The activation of these four master positive regulators by PrNF‐YC2 triggered the upregulation of numerous oil synthesis‐related genes, thus promoting oil accumulation. These findings provide new insights into the regulatory mechanism of seed oil accumulation and manipulation of PrNF‐YC2 may be beneficial for enhancing oil yield in tree peony and other oilseed crops.
The Kℵ0$K^{\aleph _0}$ game: Vertex colouring
Authors: Bowler Nathan , Emde Marit , Gut Florian
Published: April 2023

We investigate games played between Maker and Breaker on an infinite complete graph whose vertices are coloured with colours from a given set, each colour appearing infinitely often. The players alternately claim edges, Maker's aim being to claim all edges of a sufficiently colourful infinite complete subgraph and Breaker's aim being to prevent this. We show that if there are only finitely many colours, then Maker can obtain a complete subgraph in which all colours appear infinitely often, but that Breaker can prevent this if there are infinitely many colours. Even when there are infinitely many colours, we show that Maker can obtain a complete subgraph in which infinitely many of the colours each appear infinitely often.
A new larval species of Nothrotrombidium (Acari: Trombellidae) from Iran, with new host records
Authors: Kohansal Mahnaz , Ramroodi Sara , Noei Javad , Saboori Alireza
Published: April 2023

Nothrotrombidium sadeghii Noei and Kohansal sp. nov. (Acari: Trombidiformes: Trombellidae) ectoparasitic on Erebidae, Noctuidae, Geometridae, Plutellidae (Lepidoptera) and Tettigoniidae (Orthoptera) in Hotel Kouhestan and Band-e dareh regions, Chahardeh, Chahkand, Chahkandan, Esfahrood, Giuk, Noferest, Rach and Razg villages, Birjand city, South Khorasan province, Iran, is described and illustrated. A key to world larval species of Nothrotrombidium is provided.
Association Between Moderate Physical Activity Level and Subsequent Frailty Incidence Among Community-Dwelling Older Adults: A Population-Based Cohort Study
Authors: Zhao Wenjing , Ukawa Shigekazu , Sasaki Sachiko , Okada Emiko , Kishi Tomoko , Kondo Kastunori , Tamakoshi Akiko
Published: April 2023

Our study aimed to demonstrate the association between physical activity (PA) and frailty incidence among Japanese community-dwelling older adults with a narrow age range of 70–74 years. This study included 485 participants from the Japan Gerontological Evaluation Study. Frailty was assessed at baseline and 3 years later by using the Kaigo-Yobo Checklist. PA was assessed using the short-term International PA Questionnaire at baseline. Logistic regression was performed to calculate the odds ratio with 95% confidence intervals after adjusting for potential confounders. The associations of frailty scores with both PA volume and daily walking time presented a U-shaped curve, albeit only the latter was statistically significant. After adjusting for potential confounders, walking for 0.5–1 hr/day displayed a greater association with decreased frailty risk than higher levels of daily walking time. Further study is needed to cumulate the evidence that moderate PA levels may delay frailty incidence and improve the aging process.
Blockade of VEGFR3 signaling leads to functional impairment of dural lymphatic vessels without affecting autoimmune neuroinflammation
Authors: Li Zhilin , Antila Salli , Nurmi Harri , Chilov Dmitri , Korhonen Emilia A. , Fang Shentong , Karaman Sinem , Engelhardt Britta , Alitalo Kari
Published: April 2023

The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its significance in mediating dural lymphatic function in CNS autoimmunity is unclear. We show that inhibition of the VEGF-C/VEGFR3 signaling pathway using a monoclonal VEGFR3-blocking antibody, a soluble VEGF-C/D trap, or deletion of the
Vegfr3
gene in adult lymphatic endothelium causes notable regression and functional impairment of dural LVs but has no effect on the development of CNS autoimmunity in mice. During autoimmune neuroinflammation, the dura mater was only minimally affected, and neuroinflammation-induced helper T (T
H
) cell recruitment, activation, and polarization were significantly less pronounced in the dura mater than in the CNS. In support of this notion, during autoimmune neuroinflammation, blood vascular endothelial cells in the cranial and spinal dura expressed lower levels of cell adhesion molecules and chemokines, and antigen-presenting cells (i.e., macrophages and dendritic cells) had lower expression of chemokines, MHC class II–associated molecules, and costimulatory molecules than their counterparts in the brain and spinal cord, respectively. The significantly weaker T
H
cell responses in the dura mater may explain why dural LVs do not contribute directly to CNS autoimmunity.
Approximate solutions of the transcendental equation for the square quantum wells by finding the real root of the cubic equation
Authors: Noël Jean-Marc , Lévesque Luc
Published: April 2023

The energy eigenvalues E n in finite square quantum wells (SQW) cannot be found using an analytic expression. As a result, numerical methods are normally used to find the eigenvalues from a transcendental equation. In this report, it will be shown that the eigenvalue solution for a given state consists in finding the only real positive root of a depressed trinomial polynomial of third order, which is as easy to solve as a quadratic equation. The method proposed can also be applied for semi-infinite, finite, and asymmetric SQW, which are often presented in quantum mechanics textbooks at the undergraduate level. The proposed method can be applied during an exam when programmable calculators are not allowed as the real root of the trinomial polynomial can be found using the formula for the cubic equation found nearly 500 years ago.
Numerical modeling of the brain poromechanics by high-order discontinuous Galerkin methods
Authors: Corti Mattia , Antonietti Paola F. , Dede’ Luca , Quarteroni Alfio M.
Published: April 2023

We introduce and analyze a discontinuous Galerkin method for the numerical modeling of the equations of Multiple-Network Poroelastic Theory (MPET) in the dynamic formulation. The MPET model can comprehensively describe functional changes in the brain considering multiple scales of fluids. Concerning the spatial discretization, we employ a high-order discontinuous Galerkin method on polygonal and polyhedral grids and we derive stability and a priori error estimates. The temporal discretization is based on a coupling between a Newmark [Formula: see text]-method for the momentum equation and a [Formula: see text]-method for the pressure equations. After the presentation of some verification numerical tests, we perform a convergence analysis using an agglomerated mesh of a geometry of a brain slice. Finally, we present a simulation in a three-dimensional patient-specific brain reconstructed from magnetic resonance images. The model presented in this paper can be regarded as a preliminary attempt to model the perfusion in the brain.
Variational multiscale method stabilization parameter calculated from the strain-rate tensor
Authors: Takizawa Kenji , Otoguro Yuto , Tezduyar Tayfun E.
Published: April 2023

The stabilization parameters of the methods like the Streamline-Upwind/Petrov–Galerkin, Pressure-Stabilizing/Petrov–Galerkin, and the Variational Multiscale method typically involve two local length scales. They are the advection and diffusion length scales, appearing in the expressions for the advective and diffusive limits of the stabilization parameter. The advection length scale has always been in the flow direction. The diffusion length scales in use have mostly been just element-geometry-dependent, but there is good justification for also making that direction-dependent, so that the spatial variation of the solution is taken into account somehow. The length scale in the solution-gradient direction, which was introduced in 2001, was intended for making sure that near solid surfaces, the element length in the surface-normal direction is selected even if that is not the minimum element length. It was also intended for making sure that in a 2D computation with a 3D mesh, there would be no dependence on the element length in the third direction. With the same objectives, and with better invariance properties, we are now introducing the direction-dependent diffusion length scale calculated from the strain-rate tensor. We accomplish those objectives, get invariance with respect to switching to a different inertial reference frame, and the element length in the surface-normal direction, even when the surface is undergoing rotation, is selected as the diffusion length scale.
Singular patterns in Keller–Segel-type models
Authors: Campos Juan , Pulido Carlos , Soler Juan , Veruete Mario
Published: April 2023

The aim of this paper is to elucidate the existence of patterns for Keller–Segel-type models that are solutions of the traveling pulse form. The idea is to search for transport mechanisms that describe this type of waves with compact support, which we find in the so-called nonlinear diffusion through saturated flux mechanisms for the movement cell. At the same time, we analyze various transport operators for the chemoattractant. The techniques used combine the analysis of the phase diagram in dynamic systems together with its counterpart in the system of partial differential equations through the concept of entropic solution and the admissible jump conditions of the Rankine–Hugoniot type. We found traveling pulse waves of two types that correspond to those found experimentally.
On the triple point number of surface-links in Yoshikawa’s table
Authors: Cazet Nicholas
Published: April 2023

Yoshikawa made a table of knotted surfaces in [Formula: see text] with ch-index 10 or less. This remarkable table is the first to enumerate knotted surfaces analogous to the classical prime knot table. A broken sheet diagram of a surface-link is a generic projection of the surface in [Formula: see text] with crossing information along its singular set. The minimal number of triple points among all broken sheet diagrams representing a given surface-link is its triple point number. This paper compiles the known triple point numbers of the surface-links represented in Yoshikawa’s table and calculates or provides bounds on the triple point number of the remaining surface-links.
The Multi-User Constrained Pseudorandom Function Security of Generalized GGM Trees for MPC and Hierarchical Wallets
Authors: Guo Chun , Wang Xiao , Xie Xiang , Yu Yu
Published: April 2023

Multi-user (mu) security considers large-scale attackers that, given access to a number of cryptosystem instances, attempt to compromise at least one of them. We initiate the study of mu security of the so-called GGM tree that stems from the pseudorandom generator to pseudorandom function transformation of Goldreich, Goldwasser, and Micali, with a goal to provide references for its recently popularized use in applied cryptography. We propose a generalized model for GGM trees and analyze its
mu prefix-constrained pseudorandom function
security in the random oracle model. Our model allows to derive concrete bounds and improvements for various protocols, and we showcase on the Bitcoin-Improvement-Proposal standard
Bip32
hierarchical wallets and function secret sharing protocols. In both scenarios, we propose improvements with better performance and concrete security bounds at the same time. Compared with the state-of-the-art designs, our
SHACAL3
- and
Keccak
-p-based
Bip32
variants reduce the communication cost of MPC-based implementations by 73.3% to 93.8%, whereas our
AES
-based function secret sharing substantially improves mu security while reducing computations by 50%.
High Energy Density PVDF-Based Composites with Efficient Stripping of Boron Nitride Nanosheets
Authors: Liu Hui , Li Shuangcui , Ma Lili , Xin Meng , Wen Xin
Published: April 2023

Bronnitride nanosheets (BNNS) have attracted considerable interest in preparing high energy density (Ue) polymer nanocomposites due to its intrinsic high breakdown strength and thermal conductivity. However, efficient fabrication of BNNSs remains a challenge due to the low yield and complex fabrication process, which limits their further wide applications in polymer-based dielectrics. In this study, effectively stripped thin layer BNNS were prepared with high yield by urea-assisted ball milling combined with ultrasonic thermal stripping. The results showed that BNNS not only achieved efficient stripping and good dispersion in liquid solutions, but also effectively increased the energy storage capacity of the PVDF-based composites, with the highest Ue (7.5 J cm−3 at 450 MV m−1) achieved in 8 wt% BNNS/PVDF composites.
Interleukin-37b Suppressed ILC2s in Children with Allergic Rhinitis
Authors: Zeng Qingxiang , Zeng Yinhui , Xiao Haiqing , Li Jinyuan , Yang Chao , Luo Renzhong , Liu Wenlong , Wen Yanhui
Published: April 2023

Background. Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods. We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results. We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years’ SLIT, especially in the good response group. Conclusion. Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.
A Comparative Analysis among Quenched, Tempered, and Stepped Cooled TIG Welded SS-304 Plates Based on Tensile Strength, Hardness, and Microstructural Appearance
Authors: Dewangan Saurabh , Saksham Saksham , Chandra Paul Adhir , Burja Jaka
Published: April 2023

The present experimental work critically analyses the changes in microstructural orientation and mechanical properties of TIG (tungsten inert gas) welded AISI-304 (SS) plates which have undergone through various heat treatments. The characteristics of heat-treated samples have been compared with those of untreated samples which is denoted by the original sample in this study. Five SS-304 plates were welded by the TIG method. Out of five, four plates were heat treated and one plate was put in the original condition. Four heat treatment includes quenching, stepped heat treating (sand + water), tempering-1 (quick quench then sand cooling), and tempering-2 (quick quench then air cooling). In all the five plates, the tensile test and microhardness test have been performed. In addition, microscopic observation of cross-sectional surfaces has also been carried out. The base metal (BM) zone of all five plates mainly consists of equiaxed γ-grains, although twin can be observed only in the original sample. The heat-affected zone (HAZ) imparts both lathy and dendritic type δ-ferrite at the transition of the BM and welded zone (WZ). At the welded zone, the γ-matrix has become coarse with numerous spots and dendrites of δ-ferrite could be seen. Sample 3, tempered by means by water sprinkling for a very short time and then cooling in sand, has shown satisfactory results among all. The sample has achieved the 23% higher extension value and 10% higher hardness at WZ than these of the original sample, although a negligible loss (0.2%) of ultimate tensile strength (UTS) is also reported in sample 3.
Effects of Orthodontic Treatment on Pulp Stone Formation: A Retrospective Study
Authors: Babanouri Neda , Sahmeddini Sarina , Khoshmakani Marziye Rahimi
Published: April 2023

Objective. This retrospective study was aimed at determining the incidence of dental pulp stone formation during fixed orthodontic treatment. Materials and Methods. A total of 100 patients who received fixed orthodontic treatment were included in this study. Pre‐ and posttreatment panoramic radiographs of the patients were examined to identify pulp stones. The data were analyzed using McNemar’s and Pearson’s chi‐square tests to investigate the correlations between having a dental pulp stone and gender, age, treatment type, and duration. Results. Dental pulp stones were detected in 17% of patients on pretreatment panoramic radiographs and 35% of patients on posttreatment panoramic radiographs. The incidence of pulp stones sharply increased in the pre‐ and posttreatment radiographs (38%) (P < 0.001). In addition, there were associations between age, treatment duration, and the incidence of pulp stones (P < 0.05). Nevertheless, no associations were found between treatment type, gender, and the presence of pulp stones. Dental pulp stones were most frequently observed in first molars (62%), followed by second molars (36%). Conclusion. Fixed orthodontic treatment may trigger pulp irritation and calcification, resulting in the formation of pulp stones. Although pulp stones have no serious consequences, an orthodontist must consider the probability of pulp stone formation because it can cause difficulties in endodontic treatment.
Power Load Prediction Based on IGWO‐BILSTM Network
Authors: Wang Fenqin , Liu Zhaosu
Published: April 2023

Recently, neural networks based on intelligent algorithms have been widely used in short‐term power load prediction. However, these algorithms have poor reproducibility in the case of repetition. Aiming at the shortcomings of the gray wolf optimizer (GWO) algorithm, such as slow convergence speed and easy to fall into local optimum, an improved gray wolf optimizer (IGWO) was proposed. In order to better extract features from time series data, the improved grey wolf optimizer‐bidirectional long short‐term memory (IGWO‐BILSTM) power load prediction model is established by bidirectional long short‐term memory (BILSTM). Pearson correlation analysis uses the actual power load data set of a certain region and selects the highly correlated factors as the input of the network. The BILSTM model was used to train the preprocessed data, the IGWO algorithm was used to find the optimal solution parameters during the training, and finally, the optimal prediction results were output to the test set. The experimental results show that compared with the prediction model established by the traditional optimization algorithm, the mean absolute percentage error (MAPE) value of the IGWO‐BILSTM model is 1.63, the root mean square error (RMSE) value is 1.47, and the mean absolute error (MAE) value is 1.17. The convergence speed is faster and the prediction result is more accurate. The accuracy of multidimension load forecasting is greatly improved.
Data from Fructose metabolism in tumor endothelial cells promotes angiogenesis by activating AMPK signaling and mitochondrial respiration
Authors: Fang Jian-Hong , Chen Jie-Ying , Zheng Jia-Lin , Zeng Hui-Xian , Chen Jun-Guang , Wu Chen-Hui , Cai Jia-Li , Wang Zhi-Yong , Zhuang Shi-Mei
Published: April 2023

Abstract
Angiogenesis is vital for tumor growth and metastasis. Emerging evidence suggests that metabolic reprogramming in endothelial cells (ECs) may affect angiogenesis. Here, we showed that multiple regulators in the fructose metabolism pathway, especially fructose transporter SLC2A5 and fructose-metabolizing enzyme ketohexokinase (KHK), were upregulated in tumor endothelial cells from hepatocellular carcinoma (HCC). In mouse models with hepatoma xenografts or with Myc/sgp53-induced liver cancer, dietary fructose enhanced tumor angiogenesis, tumor growth, and metastasis, which could be attenuated by treatment with an inhibitor of SLC2A5. Furthermore, vessel growth was substantially increased in fructose-containing matrigel compared to PBS-matrigel. Inhibiting fructose metabolism in EC cells in vivo using EC-targeted nanoparticles loaded with siRNA against KHK significantly abolished fructose-induced tumor angiogenesis. Fructose treatment promoted the proliferation, migration and tube formation of ECs and stimulated mitochondrial respiration and ATP production. Elevated fructose metabolism activated AMPK to fuel mitochondrial respiration, resulting in enhanced EC migration. Fructose metabolism was increased under hypoxic conditions as a result of HIF1α-mediated upregulation of multiple genes in the fructose metabolism pathway. These findings highlight the significance of fructose metabolism in ECs for promoting tumor angiogenesis. Restricting fructose intake or targeting fructose metabolism is a potential strategy to reduce angiogenesis and suppress tumor growth.