bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trilobatin regulates glucose metabolism by ameliorating oxidative stress and insulin resistance in vivo and in vitro
Authors: He Ming , Zhang Yuqing , Zhai Yuhan , Li Yaping , Yang Guorui , Yu Shaoxuan , Xiao Haifang , Song Yuanda 
Published: April 2024

Abstract

Objectives
Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained.

Methods
In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated.

Key findings
Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 μM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1).

Conclusions
Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3β and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.
Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review
Authors: Pratima H , Shiraguppi Anita , Joojagar Priyadarshini , Shah Kamal , Cheeraladinni Sudharani S , Singh P Shivakumar , Mendem Suresh kumar , Chauhan Nagendra Singh 
Published: April 2024

Abstract
The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as ‘Bhumyamalaki’ (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.
A diagnostic dilemma—to operate or not to operate—a rare case report
Authors: Thirumurthy Sathish Kumar , Bapat Manjiri , Ahmed Ehsan 
Published: April 2024

Abstract
A 41-year-old male presented with a swelling in the right flank present since 2 years. Initially, it was small in size but increased in size for the past 6 months. Examination revealed a large swelling in the right flank that was soft in consistency and attached to the deeper muscle. CT scan revealed a heterogenous complex swelling with attachment to the underlying muscle. Core biopsy of the lesion was reported as undifferentiated sarcoma. After immunohistochemistry markers, the diagnosis was revised to a malignancy of a lymphomatous origin. Gene sequencing studies and extensive higher marker studies were done and a final diagnosis of plasmacytic infiltrate of uncertain clinical significance was reported. With no further diagnostic options available, the case still remains to be a diagnostic challenge as the choice of treatment between surgical resection and nonsurgical treatment with chemotherapy and/or radiation cannot be decided upon.
The ethico-religiousness of Atwood’s “God’s Gardeners” vis-à-vis Kierkegaard’s thought
Authors: Chou Christine Hsiu-Chin 
Published: April 2024

Abstract
This study aims to ascertain the ethico-religiousness of “God’s Gardeners” in Atwood’s The Year of the Flood, an eco-religious cult featured by the “self-rescue effort” rather than “God-relationship”. Through examining Atwood’s secularist imagination vis-à-vis Kierkegaard’s ideas about ethico-religiousness, the relationship between Atwood’s post-Christian speculation and Christianity will be re-estimated.
Starting with a comparative overview of the two writers’ situatedness in their own “post-Christian” milieu, the discussion then focuses on Kierkegaard’s thought to facilitate the investigation into the religiousness of Atwood’s ethical type. Ultimately, a certain “crossroads” is testified between the secularized vision and the Christian understanding of being ethical and religious.
The impact of a top-heavy IMF on the formation and evolution of dark star clusters
Authors: Shirazi Ali Rostami , Haghi Hosein , Zonoozi Akram Hasani , Farhani Asl Ahmad , Kroupa Pavel 
Published: April 2024

ABSTRACT
The Spitzer instability leads to the formation of a black hole subsystem (BHSub) at the centre of a star cluster providing energy to luminous stars (LSs) and increasing their rate of evaporation. When the self-depletion time of the BHSub exceeds the evaporation time of the LSs, a dark star cluster (DSC) will appear. Using the nbody7 code, we performed a comprehensive set of direct N-body simulations over a wide range of initial conditions to study the pure effect of the top-heaviness of the initial mass function (IMF) on the formation of the DSC phase. In the Galactic tidal field, top-heavy IMFs lead to the fast evaporation of LSs and the formation of DSCs. Therefore, DSCs can be present even in the outer region of the Milky Way (MW). To successfully transition to the DSC phase, the MW Globular Clusters (GCs) must possess an initial black hole (BH) mass fraction of $\widetilde {\mathit {M}}_\mathrm{BH}(0)\gt 0.05$. For star clusters with $\widetilde {\mathit {M}}_\mathrm{BH}(0)\gt 0.08$, the DSC phase will be created for any given initial density of the cluster and Galactocentric distance. The duration of the cluster’s lifetime spent in the DSC phase shows a negative (positive) correlation with the initial density, and Galactocentric distance of the star cluster if $\widetilde {\mathit {M}}_\mathrm{BH}(0)\le 0.12$ ($\widetilde {\mathit {M}}_\mathrm{BH}(0)\ge 0.15$). Considering the canonical IMF, it is unlikely for any MW GCs to enter the DSC phase. We discuss the BH retention fraction in view of the observed properties of the GCs of the MW.
The Impoverishing Effect of Tobacco Use in Indonesia
Authors: Swarnata Arya , Kamilah Fariza Zahra , Melinda Gea , Adrison Vid 
Published: April 2024

Abstract

Introduction
Smoking households in Indonesia diverted a significant share of their budget to tobacco. Tobacco expenditure is deemed unproductive, as it crowds out resources from essential commodities and increases health care expenditure driven by tobacco-induced diseases. Therefore, despite having adequate resources, some smoking families in Indonesia may spend less on basic needs, which inadvertently puts their standard of living below the poverty line.

Aims and Methods
Employing data from 2021 (March) Indonesia’s Socioeconomic Survey (SUSENAS), this research aims to quantify the impoverishing effect of tobacco consumption in Indonesia, considering spending on tobacco and tobacco-attributable health care costs as unproductive expenditure. The de facto headcount poverty rate and poverty gap index are calculated by removing tobacco expenditures and tobacco-attributable health care expenditures from the household’s total spending.

Results
Accounting for unproductive spending related to tobacco use, Indonesia’s headcount poverty ratio in March 2021 would rise by 3.22 percentage points, equivalent to an additional 8.75 million people living below the poverty line. In addition, the poverty gap index would increase by 0.77 percentage points. The impoverishment effect of tobacco is larger among rural populations than their urban counterparts. Moreover, the impoverishment is mainly driven by direct tobacco spending rather than tobacco-attributable health care expenditure.

Conclusions
Significant portions of Indonesia’s population are exposed to secondary poverty because of tobacco use. A high level of cigarette spending among smoking households is the major source of the impoverishing effect of tobacco use.

Implications
The study provides quantitative evidence of the true cost of smoking in Indonesia, where the de facto number of the poor population after accounting for tobacco-related spending is higher than what is published in the official statistics. The findings of this study support tobacco control policies in Indonesia, particularly to effectively reduce tobacco use and mitigate the impoverishing impact of tobacco use on low-income households.
A Qualitative Analysis of How Underage Adolescents Access Nicotine Vaping Products in Aotearoa New Zealand
Authors: Frost Katie , Graham-DeMello Anna , Ball Jude , Pettie (Ngāti Pūkenga) Michaela , Hoek Janet 
Published: April 2024

Abstract

Introduction
Despite policies setting a minimum legal sales age, youth continue to access electronic cigarettes (ECs). Evidence of rising youth vaping prevalence in many countries suggests existing measures have serious loopholes and raise important questions about how youth source vaping products.

Aims and Methods
We explored how youth source ECs using in-depth interviews with 30 adolescents aged 16–17 who vaped at least once a month and lived in Aotearoa New Zealand. Our semistructured interview guide probed participants’ vaping experiences and how they developed and used social, quasi-commercial, and commercial supply routes to access ECs. We used an inductive reflexive thematic analysis approach to interpret the data.

Results
Nearly all participants shared ECs with peers and sharing was the sole access route for some. Many used proxies, often older relatives or people they knew socially, to purchase ECs on their behalf; however, others recruited proxies by approaching previously unknown people they identified on social media. Participants also sourced ECs via quasi-commercial networks that existed within schools and on social media, and some purchased in their own right, usually from smaller retail outlets that did not ask for ID.

Conclusions
Disrupting social supply will be challenging, though reducing ECs’ availability, appeal, and affordability could make social supply, including sharing and proxy purchasing, more difficult. Reports that youth purchase ECs from commercial retailers known to waive age verification suggest stronger monitoring and enforcement, along with escalating retailer penalties, are required.

Implications
Vaping access routes sit on a continuum from informal, spontaneous sharing to carefully planned commercial purchases. While supply via friends, siblings and other social contacts is an important means of access, nicotine dependence drives some to use riskier access routes, including approaching unknown people to act as proxy purchasers. Evidence young people identify noncompliant retailers suggests policy makers should monitor and enforce existing measures more stringently and consider additional penalties for recidivist underage suppliers. A more comprehensive response that reduces the appeal, addictiveness, affordability, and availability of vaping products would address factors fostering and maintaining youth vaping.
Administrative Justice in the Modern Mixed Administrative State: Moving Beyond Taxonomies
Authors: Boughey Janina 
Published: April 2024

Abstract
The challenges that government outsourcing presents for administrative law were the topic of considerable scholarly discussion in the 1990s and early 2000s, with broad agreement amongst public lawyers that outsourcing should not result in a loss of the particular kind of accountability with which administrative justice is concerned. Yet, over the past two decades, while government outsourcing has continued and evolved, very little has been done to address these challenges. This article explores the question of when non-court-based administrative justice accountability mechanisms ought to extend to outsourced government functions. I argue that much of the focus of administrative lawyers to date has been on the approaches that courts should take, which has led governments and legislatures to adopt tests and taxonomies largely developed in or for the courts, which distinguish between ‘public’ and ‘private’ functions. I show that these taxonomies are not well adapted to administrative justice mechanisms outside of the courts, are not fit for purpose in many modern government outsourcing arrangements and have resulted in significant accountability gaps. I propose a different starting point for thinking about administrative justice in the modern mixed administrative state, based on normative principles as opposed to categories.
Delays in presentation, diagnosis, and treatment in Sudanese women with breast cancer: a cross-sectional study
Authors: Alfadul Esraa S A , Tebaig Badria , Alrawa Salma S , Elgadi Ammar Tarig , Margani Ensaf E M A , Adam Maab E B , Mohamoud Mawaheb Sh Adem , Elhassan Safa A M , Elhassan Moawia Mohammed Ali 
Published: April 2024

Abstract

Background
The poor prognosis of breast cancer in Sudan could be due to delayed treatment and diagnosis at an advanced stage. Our study aimed to assess the extent of delays from onset of symptoms to treatment in Sudanese women with breast cancer, as well as identify factors contributing to these delays.

Materials and Methods
We conducted a multi-center cross sectional study between March and April 2023. Data were collected from the medical records and interviews with women with breast cancer in the two main oncology centers in Sudan. Linear regression was used to identify the predictors of delayed presentation.

Results
We interviewed 601 women with breast cancer. The majority of women (50.1%) were diagnosed at locally advanced or metastatic disease. The median interval from the onset of symptoms to receiving oncologic treatment was 221 days (IQR = 92, 496). The longest delay was the presentation delay 61 (31 244) days. The median duration for diagnosis delay and treatment delay was 21 (10.57) days and 27 (10.64) days, respectively. Predictors of early presentation included, being young (β = −5.3; 95% CI = 0.06 to 10), married (β = −264; 95% CI = −427 to −101), divorced (β = −306; 95% CI = −549 to −63), or widowed (β = −320; 95% CI = −-543 to −97), urban residence (β = −107; 95% CI = −213 to −2.3), and seeking traditional healer (β = −204; 95% CI = −383 to −26).

Conclusion
Most Sudanese women with breast cancer experience significant patient delays, often presenting at advanced stages. Factors like being single, older, and living in rural areas contribute to these delays. Increasing breast cancer education, improving healthcare access and addressing sociodemographic barriers can potentially expedite diagnosis and improve outcomes.
On Möbius Functions from Automorphic Forms and a Generalized Sarnak’s Conjecture
Authors: Wei Zhining , Zhao Shifan 
Published: April 2024

Abstract
In this paper, we consider generalized Möbius functions associated with two types of L-functions: Rankin–Selberg L-functions of symmetric powers of distinct holomorphic cusp forms and L-functions derived from Maass cusp forms. We show that these generalized Möbius functions are weakly orthogonal to bounded sequences. As a direct corollary, a generalized Sarnak’s conjecture holds for these two types of Möbius functions.
Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus
Authors: Yuan Zixin , Liu Mengdi , Zhang Lei , Jia Li , Hao Siao , Su Danhua , Tang Longhai , Wang Chunhong , Wang Mingyuan , Wen Zhenke 
Published: April 2024

Abstract

Objectives
Patients with SLE display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain.

Methods
SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimaeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients.

Results
We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimaeras.

Conclusion
Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for the clinical management of SLE.
Psychiatry, Modernity and the Politics of the Individual: The Historical Contours of Mental Hygiene
Authors: Dufaud Grégory , Henckes Nicolas , Scarfone Marianna 
Published: April 2024

Summary
This introduction to this special issue devoted to mental hygiene movements in Europe examines the issues and problems facing their historical study. While the definition of mental hygiene was obvious to contemporaries, it referred to highly divergent projects in different socio-political contexts. As a result, historians have struggled to come up with a unified definition of mental hygiene as a category for analysis. After outlining historiographical responses to this question, this essay suggests that mental hygiene can best be understood as a specific way of articulating four dimensions of the psychiatric discipline, namely its organization and its relationship to the state, individuals and science. The final section provides an overview of the themes developed by the articles in this special issue.
My voyage in the enchanted world of sleep
Authors: Lavie Peretz 
Published: April 2024

Abstract
In this paper, I describe my 45-year career in sleep research. I started my undergraduate studies at Tel Aviv University, where I was first introduced to the enchanted world of sleep, continued to my graduate studies with Wilse B. Webb at the University of Florida, and then to post-doctoral training with Dan Kripke at the University of California at San Diego. Then, I describe the evolution of my academic career at the Technion-Israel Institute of Technology, where I started in 1975 as an Assistant Professor and retired in 2019 as the President of the Institute. I describe the areas of research that I pursued and how the research developed, emphasizing unexpected results that guided me and my lab team in new directions. This includes my early studies on ultradian rhythms, inspired by Nathaniel Kleitman’s Basic Rest Activity Cyle hypothesis, utilizing the ultrashort sleep–wake paradigm to chart the 24-hour sleep propensity function, and how these studies led us to explore the role of melatonin in sleep regulation. I also explain why we directed our attention to sleep apnea, and how clinical observations led to the provocative hypothesis that sleep apnea—typically seen as a disorder—may also play a protective role. Under the leadership of my research partner and wife, Lena, we confirmed this hypothesis. Also in this article, I describe my enthusiasm for the history of our field and, as derived from my experience as a Dean of Medicine and President of a university, I share my philosophy about the role of members of academia in society. I emphasize that none of my achievements could have been accomplished without the hard work and motivation of my students and research partners, who shared my enthusiasm and passion for the enchanted world of sleep.
This paper is part of the Living Legends in Sleep Research series, which is sponsored by Idorsia Pharmaceuticals and Jazz Pharmaceuticals.
Incorporating diverse values of nature in decision-making—theory and practice
Authors: Vatn A. , Pascual U. , Chaplin-Kramer R. , Termansen M. , Arias-Arévalo P. , Balvanera P. , Athayde S. , Hahn T. , Lazos E. 
Published: April 2024

Values play a significant role in decision-making, especially regarding nature. Decisions impact people and nature in complex ways and understanding which values are prioritised, and which are left out is an important task for improving the equity and effectiveness of decision-making. Based on work done for the IPBES Values Assessment, this paper develops a framework to support analyses of how decision-making influences nature as well as whose values get prioritised. The framework is used to analyse key areas of environmental policy: a) the present model for nature protection in market economies, b) the role of valuation in bringing nature values into decisions, and c) values embedded in environmental policy instruments, exemplified by protected areas for nature conservation and payments for ecosystem services. The analyses show that environmental policies have been established as mere additions to decision-making structures that foster economic expansion, which undermines a wide range of nature's values. Moreover, environmental policies themselves are also focused on a limited set of nature's diverse values.
This article is part of the theme issue ‘Bringing nature into decision-making’.