bluuebunny/crossref_metadata_2025 huggingface dataset:
Subacute cadmium exposure changes different metabolic functions, leading to type 1 and 2 diabetes mellitus features in female rats
Authors: da Costa Charles S. , de Oliveira Thiago F. , Dos Santos Flavia C. F. , Padilha Alessandra S. , Krause Maiara , Carneiro Maria Tereza W. D. , Miranda‐Alves Leandro , Graceli Jones B.
Published: May 2024

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd‐exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd‐exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.
Firewalls from wormholes in higher genus
Authors: Zolfi Hamed
Published: May 2024

Abstract

An old black hole can tunnel into a white hole/firewall by emitting large baby universes. This phenomenon was investigated in Jackiw-Teitelboim (JT) gravity for genus one. In this paper, the focus is on higher genus corresponding to emitting more than one baby universe (n > 1). The probability of encountering a firewall or tunneling into a white hole after emitting n baby universes is proportional to $$ {e}^{-2 nS(E)}{e}^{4\pi \sqrt{E}\left(n-1\right)}{E}^{2{n}^2-n-9/2}{t}^{4{n}^2-2n-5} $$

e

−
2
nS

E

e

4
π

E

n
−
1

E

2

n
2

−
n
−
9
/
2

t

4

n
2

−
2
n
−
5

, where t is the age of the black hole, and S and E represent the entropy and energy of the black hole, respectively.
Dark matter bound-state formation in the Sun
Authors: Chu Xiaoyong , Garani Raghuveer , García-Cely Camilo , Hambye Thomas
Published: May 2024

Abstract

The Sun may capture asymmetric dark matter (DM), which can subsequently form bound-states through the radiative emission of a sub-GeV scalar. This process enables generation of scalars without requiring DM annihilation. In addition to DM capture on nucleons, the DM-scalar coupling responsible for bound-state formation also induces capture from self-scatterings of ambient DM particles with DM particles already captured, as well as with DM bound-states formed in-situ within the Sun. This scenario is studied in detail by solving Boltzmann equations numerically and analytically. In particular, we take into consideration that the DM self-capture rates require a treatment beyond the conventional Born approximation. We show that, thanks to DM scatterings on bound-states, the number of DM particles captured increases exponentially, leading to enhanced emission of relativistic scalars through bound-state formation, whose final decay products could be observable. We explore phenomenological signatures with the example that the scalar mediator decays to neutrinos. We find that the neutrino flux emitted can be comparable to atmospheric neutrino fluxes within the range of energies below one hundred MeV. Future facilities like Hyper-K, and direct DM detection experiments can further test such scenario.
Differential association of dietary scores with the risk of type 2 diabetes by metabotype
Authors: Deng Zhongyi , Wawro Nina , Freuer Dennis , Peters Annette , Heier Margit , Meisinger Christine , Breuninger Taylor A. , Linseisen Jakob
Published: May 2024

Purpose

We aimed to examine the association between dietary patterns and type 2 diabetes mellitus (T2DM) while considering the potential effect modification by metabolic phenotypes (metabotypes). Additionally, we aimed to explore the association between dietary scores and prediabetes.

Methods

A total of 1460 participants (11.8% with T2DM) from the cross-sectional population-based KORA FF4 study were included. Participants, classified into three metabotype subgroups, had both their FSAm-NPS dietary index (underpinning the Nutri-Score) and ultra-processed foods (UPF) intake (using NOVA classification) calculated. Glucose tolerance status was assessed via oral glucose tolerance tests (OGTT) in non-diabetic participants and was classified according to the American Diabetes Association criteria. Logistic regression models were used for both the overall and metabotype-stratified analyses of dietary scores’ association with T2DM, and multinomial probit models for their association with prediabetes.

Results

Participants who had a diet with a higher FSAm-NPS dietary index (i.e., a lower diet quality) or a greater percentage of UPF consumption showed a positive association with T2DM. Stratified analyses demonstrated a strengthened association between UPF consumption and T2DM specifically in the metabolically most unfavorable metabotype (Odds Ratio, OR 1.92; 95% Confidence Interval, CI 1.35, 2.73). A diet with a higher FSAm-NPS dietary index was also positively associated with prediabetes (OR 1.19; 95% CI 1.04, 1.35).

Conclusion

Our study suggests different associations between poorer diet quality and T2DM across individuals exhibiting diverse metabotypes, pointing to the option for stratified dietary interventions in diabetes prevention.
Gene therapy: principles, challenges and use in clinical practice
Authors: Ay Cihan , Reinisch Andreas
Published: May 2024

Introduction

Gene therapy is an emerging topic in medicine. The first products have already been licensed in the European Union for the treatment of immune deficiency, spinal muscular atrophy, hemophilia, retinal dystrophy, a rare neurotransmitter disorder and some hematological cancers, while many more are being assessed in preclinical and clinical trials.

Objective

The purpose of this review is to provide an overview of the core principles of gene therapy along with information on challenges and risks. Benefits, adverse effects and potential risks are illustrated based on the examples of hemophilia and spinal muscular atrophy.

Results

At present, in-vitro and in-vivo gene addition or gene augmentation is the most commonly established type of gene therapy. More recently, more sophisticated and precise approaches such as in situ gene editing have moved into focus. However, all types of gene therapy require long-term observation of treated patients to ensure safety, efficacy, predictability and durability. Important safety concerns include immune reactions to the vector, the foreign DNA or the new protein resulting from gene therapy, and a remaining low cancer risk based on insertional mutagenesis. Ethical and regulatory issues need to be addressed, and new reimbursement models are called for to ease the financial burden that this new treatment poses for the health care system.

Conclusion

Gene therapy holds great promise for considerable improvement or even cure of genetic diseases with serious clinical consequences. However, a number of questions and issues need to be clarified to ensure broad accessibility of safe and efficacious products.
Treatment of fecal incontinence—is there a light in the end of the tunnel?
Authors: Riss Stefan , Dawoud Christopher
Published: May 2024

Fecal incontinence (FI) is a common disease with higher incidence rates in the elderly population. Treatment of affected patients remains challenging and ranges from conservative management to surgical techniques. Despite all efforts patients often undergo several therapeutic measurements to achieve reasonable functional improvements.

Although sacral neuromodulation still remains a key therapy with success rates up to 80%, a significant number of patients do not respond sufficiently and require further treatment.

Several artificial bowel sphincter devices exist, which can lead to better functional control in selected patients. Notably, complications after these surgeries do occur frequently and the need for implant replacement is still considerable high.

A novel anal band, developed by Agency for Medical Innovations (A.M.I., Austria) is currently under evaluation. This device, composed of silicone and polyester, is placed around the anus outside the external sphincter muscle complex aiming to improve stool continence via mechanical pressure. Early results of this new operation are eagerly awaited.
Systematic review and meta-analysis comparing surgical site infection in abdominal surgery between triclosan-coated and uncoated sutures
Authors: Depuydt Martijn , Van Egmond Sarah , Petersen Stine Mette , Muysoms Filip , Henriksen Nadia , Deerenberg Eva
Published: May 2024

Purpose

Surgical site infection (SSI) is a frequent complication after abdominal surgery and impacts morbidity, mortality and medical costs. This systematic review evaluates whether the use of triclosan-coated sutures for closing the fascia during abdominal surgery reduces the rate of SSI compared to uncoated sutures.

Methods

A systematic review and meta-analysis were conducted using the PRISMA guidelines. On February 17, 2024, a literature search was performed in Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Embase. Randomized controlled trials (RCTs) on abdominal fascial closure in human adults, comparing triclosan-coated and uncoated sutures, were included. The risk of bias was assessed using the Cochrane RoB 2 tool. Pooled meta-analysis was performed using RevMan.

Results

Out of 1523 records, eleven RCTs were included, with a total of 10,234 patients: 5159 in the triclosan-coated group and 5075 in the uncoated group. The incidence of SSI was statistically significantly lower in the triclosan-coated group (14.8% vs. 17.3%) with an odds ratio (OR) of 0.84 (95% CI [0.75, 0.93], p = 0.001). When polydioxanone was evaluated separately (coated N = 3999, uncoated N = 3900), triclosan-coating reduced SSI; 17.5% vs. 20.1%, OR 0.86 (95% CI [0.77; 0.96], p = 0.008). When polyglactin 910 was evaluated (coated N = 1160, uncoated N = 1175), triclosan-coating reduced the incidence of SSI; 5.4% vs. 7.8%, OR 0.67 (95% CI [0.48; 0.94], p = 0.02).

Conclusion

According to the results of this meta-analysis the use of triclosan-coated sutures for fascial closure statistically significantly reduces the incidence of SSI after abdominal surgery with a risk difference of about 2%.
beta-Irradiation of pure 1-alkyl-3-methylimidazolium-based ionic liquids
Authors: Lehrhofer Anna F. , Hosoya Takashi , Hettegger Hubert , Potthast Antje , Rosenau Thomas
Published: May 2024

1-Alkyl-3-methylimidazolium ionic liquids are common cellulose solvents and biomass pretreatment agents, while beta-irradiation (“e-beaming”) is often used to decrease the recalcitrance of biomass towards hydrolysis or saccharification. Aiming at the general goal of elucidating the interaction between lignocellulosics, imidazolium-based ionic liquids, and beta-irradiation, we studied the effect of beta-irradiation on the pure ILs 1-ethyl-3-methylimidazolium and 1-butyl-3-methylimidazolium, both as chloride and acetate. Contrary to the expectation of inertness, irradiation caused degradation of the ILs, which was proportional to irradiation dosage, i.e., to irradiation time and intensity. At a dosage of 2400 kGy, 0.2% (2000 ppm) of the IL were chemically altered. The main degradation pathway is the formation of imidazole and N-methylimidazole with concomitant dealkylation. The cleaved-off alkyl groups, apparently in cationic form, react with the anions present, accounting for the formation of alkyl chlorides and alkyl acetates from the chloride ILs and acetate ILs, respectively. A second, minor pathway comprises the degradation of the imidazole ring under conversion of the C2-unit from the former C4-C5 moiety into ethylenediamine and reaction of the C1-unit from the former C2 with the IL anions. Because of the non-neglible byproduct formation, the degradation of the ILs upon beta-irradiation and possible side reactions of the resulting byproducts need to be kept in mind for all setups that involve beta-irradiation and imidazolium ILs simultaneously.

Graphical abstract
Beta-irradiation of biomass in the presence of 1-alkyl-3-methyl-imidazolium ionic liquids. Identification of an unexpected product from a model compound reaction
Authors: Lehrhofer Anna F. , Bacher Markus , Hettegger Hubert , Böhmdorfer Stefan , Potthast Antje , Rosenau Thomas
Published: May 2024

A combination of swelling in imidazolium ionic liquids and beta-irradiation – both common pretreatments in biomass processing on their own – leads to unexpected effects, with beta-irradiation causing degradation of the pure ionic liquid and also modification of cellulose suspended in the ionic liquid. The underlying chemistry was investigated in a series of model compound experiments. Here, we report that beta-irradiation of the ionic liquid EMIM-OAc containing equimolar amounts of benzaldehyde and d-glucose affords an unexpected condensation product C17H20O7, of which the structure was elucidated as 5-[(1S,2R,3R)-1,2,3,4-tetrahydroxybutyl]-2-phenyl-3-furoic acid, applying a combination of analytical techniques, mainly NMR spectroscopy, after conversion into the ethyl ester derivative for purification. No reaction at all occurred without beta-irradiation under otherwise identical conditions. Intriguingly, the acetate – the IL´s anion – was incorporated into the condensation product, which can formally be regarded as the condensation product of benzoylacetic acid (from benzaldehyde and the IL´s acetate) and d-glucose. The reaction occurred only when all three components – acetate-type IL, glucose and PhCHO – were irradiated simultaneously. The structure elucidation of the compound is presented, along with a discussion of possible formation mechanisms. Future experiments need to address the generality of the reaction for conversion of other aldehydes and aldoses, and the question of whether a similar process occurs with the reducing end of celluloses or other polysaccharides.

Graphical Abstract
Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention
Authors: Pai Padmini , Vijeev Aradhika , Phadke Sharada , Shetty Manasa Gangadhar , Sundara Babitha Kampa
Published: May 2024

Autoimmune diseases hold significant importance in the realm of medical research, prompting a thorough exploration of potential therapeutic interventions. One crucial aspect of this exploration involves understanding the intricate processes of histone acetylation and deacetylation. Histone acetylation, facilitated by histone acetyl transferases (HATs), is instrumental in rendering DNA transcriptionally active. Conversely, histone deacetylases (HDACs) are responsible for the removal of acetyl groups, influencing gene expression regulation. The upregulation of HDACs, observed in various cancers, has steered attention towards histone deacetylase inhibitors (HDACi) as promising anti-cancer agents. Beyond cancer, HDACi has demonstrated anti-inflammatory properties, prompting interest in their potential therapeutic applications for inflammatory diseases such as rheumatoid arthritis (RA). RA, characterized by the immune system erroneously attacking healthy cells, leads to joint inflammation. Recent studies suggest that HDACi could offer a viable therapeutic strategy for RA, with potential mechanisms including the inhibition of synovial tissue growth and suppression of pro-inflammatory cytokines. Furthermore, HDACi may exert protective effects on bone and cartilage, common targets in RA pathology. In-depth investigations through in vivo and histopathology studies contribute to the ongoing discourse on the therapeutic benefits of HDACis in the context of RA treatment.

Graphical Abstract
The Significance of Duration Weighted Neighborhood Effects for Violent Behavior and Explanation of Ethnoracial Differences
Authors: Bellair Paul E. , McNulty Thomas L. , Carlson Daniel L.
Published: May 2024

Purpose

Two important issues constrain the neighborhood effects literature. First, most prior research examining neighborhood effects on aggression and self-reported violence uses a point in time (i.e., cross-sectional) estimate of neighborhood disadvantage even though the duration of exposure to neighborhood disadvantage varies between families. Second, neighborhood effects may be understated due to over-controlling for family socioeconomic conditions. Both limitations suggest that prior research may be underestimating neighborhood effects, which impacts research on the invariance thesis and explanation of ethnoracial differences.

Methods

The sample is drawn from the restricted use Future of Families and Child Well-being study. Data to measure youth’s exposure to neighborhood disadvantage is drawn from birth through age 9, with dependent variables measured at age 15. We estimate marginal structural models (MSM) with inverse probability of treatment weights (IPTW.

Results

The results support hypotheses, indicating that the duration weighted measure of neighborhood disadvantage is more strongly associated with aggression and self-reported violence than the point in time, and that it accounts for a larger share of the ethnoracial differences.

Conclusions

The findings provide a clear image of the consequences of long-term exposure to neighborhood disadvantage for aggression and violence. They suggest that criminologists addressing neighborhood effects should attempt, when feasible, to document and model the duration of exposure to neighborhood disadvantage. They are also consistent with and add to a growing literature addressing MSM modeling with IPTW weights.
Feedback Through Digital Application Affordances and Teacher Practice
Authors: Muslu Nilay , Siegel Marcelle A.
Published: May 2024

Assessment feedback is an essential way to promote student learning. Students and teachers may benefit from educational technologies during the feedback process. The purpose of this study was to identify the feedback dimensions that were fulfilled by iPad applications (apps) and to compare teacher practice to the affordances of apps. Typological data analysis was used to perform this qualitative case study. We analyzed seven apps (QR Code Reader, Schoology, Kahoot!, Nearpod,Socrative, ZipGrade, and The Physics Classroom) that a high school physics teacher used to provide feedback in a technology-enhanced classroom. Data sources included classroom video recordings and the websites of these apps. To facilitate the analysis of the data, we enhanced the feedback dimensions identified by Hatzipanagos and Warburton (2009). Our analysis highlighted the diverse capabilities of these apps with regard to supporting the following dimensions of effective feedback: dialogue, visibility, appropriateness, community, power, learning, timeliness, clearness, complexity, reflection, and action. We found that through additional discussion and interactions with students, the teacher could support dimensions that an app did not support. This study not only underscores the critical interplay between technological tools and teacher practices with regard to crafting effective feedback mechanisms but also offers practical recommendations for educators seeking to optimize technology-enhanced feedback in classroom settings. Future research is encouraged to explore the technology implementation experiences of less experienced teachers. Examining teachers working at various school levels and from various countries can offer valuable insights.
Securitization and risk appetite: empirical evidence from US banks
Authors: Filomeni Stefano
Published: May 2024

I investigate the impact of securitization on the risk-taking by bank holding companies (BHCs). For 2001 to 2017, I find a negative relationship between securitization and the risk appetite of BHCs. I find a negative relationship between securitization and the risk appetite of BHCs that is consistent with the recourse hypothesis of securitization. I also discover that the equilibrium in this relationship changes from the pre-crisis to the crisis period (crisis effect). This crisis effect hampers BHCs’ ability to engage in securitization that leads them to accumulate more risky assets on their books due to the deteriorated quality of their loan portfolios. This equilibrium then reverses after the crisis (post-crisis effect) due to policy makers’ response to the excessive risk-taking that manifested during the crisis. Moreover, I find that the securitization of residential mortgages not only boosts the recourse hypothesis but also triggers the crisis effect. My findings provide novel empirical insights into the different nexuses between the securitization and risk appetite of BHCs around the financial crisis.
Max Weber’s rationalization processes disenchantment, alienation, or anomie?
Authors: Etzrodt Christian
Published: May 2024

The aim of this paper is to analyze which concept describes the central theme in Max Weber’s works — the rationalization processes — best: disenchantment, alienation, or anomie. I first describe how Weber’s rationalization processes were understood in the past. Most scholars have interpreted these processes as disenchantment, although some have seen a stronger affinity to the Marxist concept of alienation. Since the majority have regarded disenchantment as the central theme of Weber’s legacy, I discuss Weber’s rare statements about the disenchantment process, most of which appear in a speech that was published later as Science as a Vocation. I then introduce definitions of key concepts (Hegelian alienation, Marxist alienation, Durkheimian anomie, and de-magification) to provide a more varied and precise vocabulary. This will aid in describing at least two different rationalization processes that can be derived from Weber’s theoretical framework (Economy and Society) and his historical studies. The first, in the economic and political sphere, can be characterized as Marxist alienation, whereas the second, in the religious sphere, can be interpreted as de-magification and Hegelian alienation. It is possible to regard Weber’s statement in Science as a Vocation as a third rationalization process, in the sphere of knowledge production, which would suggest the concepts of de-magification and anomie. However, such a reading would seem to contradict the greater body of Weber’s methodological writings. Finally, it is concluded that the term disenchantment is not a very useful concept for portraying Weber’s intended view.
Establishing an inverted U-shaped pattern of violence and war from prehistory to modernity: towards an interdisciplinary synthesis
Authors: Rutar Tibor
Published: May 2024

How have broad patterns of violence and war changed from the dawn of humanity up to present time? In answering this question, researchers have typically framed their arguments and evidence in terms of the polarized debate between Hobbes (or hawks) and Rousseau (or doves). This article moves beyond the stalemated debate and integrates the most robust existing theoretical developments and empirical findings that have emerged from various disciplines over the past 20 years – primarily sociology, political science, anthropology, and archaeology – to answer the question. Drawing on carefully curated violent lethality data for pre historically appropriate hunter-gatherers, as well as historical pre-state and state societies, it shows that simple narratives of violence and war decreasing through history from ostensibly high levels in the human state of nature, on the one hand, and the obverse insistence that the once mostly peaceful communities became highly belligerent with the transition to modernity, on the other, are both wrong. Instead, multiple lines of existing evidence and theoretical perspectives suggest a complex, non-linear, Kuznets-style relationship between violence and the passage of history.
Determination of ecological statuses of streams in the Ceyhan River Basin using composition and ecological characteristics of diatoms
Authors: Lekesiz Ömer , Çelekli Abuzer , Yavuzatmaca Mehmet , Dügel Muzaffer
Published: May 2024

The present study aimed to evaluate the interactions between diatoms and ecological factors in various streams and to test the suitability of diatom indices to evaluate the ecological status of 44 streams in the Ceyhan River Basin during the spring and autumn periods of 2021 and the summer of 2022. Canonical correspondence analysis indicated the significant effects of electrical conductivity (EC), dissolved oxygen, biological oxygen demand (BOD5), total phosphorus (TP), and total nitrogen (TN) on the distribution of diatom species of streams in the Ceyhan River Basin. Of the streams, Aksu and Erkenez streams were associated with high EC, BOD5, and TP and characterized by pollution-tolerant species. Pollution-sensitive species showed close integration with Aksu Spring Brook, Gözpınar Creek, Göksun Creek, and Yeşilgöz Spring Brook, which related to a high dissolved oxygen gradient. Different eco-regional diatom indices displayed different scores, representing from bad to high ecological status in the Ceyhan River basin. Among the diatom indices, Trophic Index Turkey (TIT) proved to be the more suitable metric to assess the ecological status of streams. TIT indicated deterioration of water quality in Karasu (S06), Erkenez (S07) streams, and downstream areas of the Ceyhan River and the least distributed sampling stations in the basin. Results suggested that eco-regionally developed diatom indices, like TIT, are required to more accurately assess the ecological status of streams in the Mediterranean region. The study provides a fundamental assessment of the ecological status of streams in the Ceyhan River Basin using an appropriate diatom index before the Pazarcık-centered earthquake on February 6, 2023. Findings allow someone to assess the impact of the earthquake on diatom communities and ecological factors in the region in the future studies.
Farming in the shadow of violent organizations: understanding farmers’ relational place-making in socio-ecological crises
Authors: Panico T. , Pascucci S. , Cicia G. , del Giudice T.
Published: May 2024

This study investigates how farmers develop place-based relations when subject to structural conditions of violence and environmental crime. We particularly focus on environmental crimes perpetrated by the Camorra, the Neapolitan Mafia, at the expense of farming communities in the metropolitan areas of Naples and Caserta, in Italy. Farmers located in this area have struggled to mobilize collectively, with only a group of farmers enable to re-act to land exploitation, illegal burning or dumping, and more in general to the waste crisis. Stimulated by this rather puzzling empirical evidence, our research team engaged in a deeper investigation of the waste crisis, exploring how farmers located in the Land of Fires reacted to conditions of violence and environmental crime by developing a differentiated set of place-based narratives and practices. Using the Land of Fires and the waste crisis as an empirical context, in this study we focus particularly on conceptualizing place-based processes emerging in the context of organized violence and environmental crime. In our approach, these are structural conditions produced by the Camorra and the state, to which local agencies, such as farmers, respond.
Potential treatment of squamous cell carcinoma by targeting heparin-binding protein 17/fibroblast growth factor-binding protein 1 with vitamin D3 or eldecalcitol
Authors: Shintani Tomoaki , Higaki Mirai , Rosli Siti Nur Zawani , Okamoto Tetsuji
Published: May 2024

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.
Intra-annual dynamics of stem circumference variation and water status of four coniferous tree species (Pinus sylvestris, Picea abies, Larix decidua and Abies alba) under warmer and water-limited conditions
Authors: Leštianska Adriana , Fleischer Peter , Merganičová Katarína , Fleischer Peter , Střelcová Katarína
Published: May 2024

In the paper, the intra-annual growth patterns and tree water balance of four different tree species (Pinus sylvestris, Picea abies, Larix decidua and Abies alba) were examined. Seasonal radial increment, tree water deficit (ΔW) and maximum daily shrinkage (MDS) were derived from the records obtained using high-resolution digital band dendrometers. The study area was located in Arboretum Borová hora (350 m a. s. l., Zvolen valley, Central Slovakia) characterised by a warmer climate (Picea abies) and warmer and drier climate (Abies alba, Larix decidua, Pinus sylvestris) compared to the sites of tree origins. Monitored species exhibited remarkably distinct growth and water balance patterns over the 2015 growing season characterised with the highly above normal temperature and uneven precipitation distribution. A. alba exhibited smooth continuous growth least affected by varying environmental conditions. Of all analysed species, only A. alba showed significant positive correlations of radial growth and ΔW with temperature and global radiation, despite environmental water limitations. The lowest cumulative growth, lower negative values of ΔW and greater MDS of L. decidua indicate a higher water limitation of this species. The results showed more pronounced sensitivity of P. sylvestris to increased temperature and drought. All monitored variables of environmental conditions, except precipitation, significantly influenced MDS values of all studied tree species. Based on 30 variables describing radial stem growth patterns and water status we identified large inter-species variability and discrete species-specific groups, while the indicators of growth and water status of L. decidua and P. sylvestris were similar and the most different patterns were observed between A. alba and L. decidua. The behaviour of P. abies was closer to A. alba than to the other two species.
Genetic variability of three common NK and γδ T cell receptor genes (FCγ3R, NCR3, and DNAM-1) and their role in Polish patients with rheumatoid arthritis and ankylosing spondylitis
Authors: Biały Sylwia , Iwaszko Milena , Świerkot Jerzy , Kolossa Katarzyna , Wielińska Joanna , Jeka Sławomir , Bogunia-Kubik Katarzyna
Published: May 2024

Various lymphocyte subpopulations, including NK cells as well as γδ T cells, have been considered an important element in the pathogenesis of autoimmune, inflammatory, rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The aim of this study was to assess the potential role of polymorphic variations in the genes coding for three NK and γδ T cell receptors: NCR3, FCγR3A, and DNAM-1 (rs1052248, rs396991, and rs763361, respectively) in the disease susceptibility and the efficacy of treatment with TNF inhibitors. The study included 461 patients with RA, 168 patients with AS, and 235 voluntary blood donors as controls. The NCR3 rs1052248 AA homozygosity prevailed in RA in patients lacking rheumatoid factor (p = 0.044) as well as in those who manifested the disease at a younger age (p = 0.005) and had higher CRP levels after 12 weeks of anti-TNF therapy (p = 0.021). The FCγR3A rs396991 polymorphism was associated with pain visual analogue scale (VAS) values before the initiation of anti-TNF treatment. Lower VAS values were observed in the GG homozygous RA patients (p = 0.024) and in AS patients with the TT genotype (p = 0.012). Moreover, AS heterozygous patients with the TG genotype presented higher CRP levels in the 12th week of anti-TNF treatment (p = 0.021). The findings suggest that the NCR3 rs1052248 AA homozygosity may have an adverse effect on RA, while the T allele potentially plays a protective role in the development of AS. Moreover, the rs1052248 T allele and TT genotype appear to have a favorable impact on the response to anti-TNF therapy in RA patients.
Combination of an aurora kinase inhibitor and the ABL tyrosine kinase inhibitor asciminib against ABL inhibitor-resistant CML cells
Authors: Okabe Seiichi , Moriyama Mitsuru , Gotoh Akihiko
Published: May 2024

The development of BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myeloid leukemia (CML). However, resistance to ABL TKIs can develop in CML patients due to BCR::ABL1 point mutations and CML leukemia stem cell (LSC). Aurora kinases are essential kinases for cell division and regulate mitosis, especially the process of chromosomal segregation. Aurora kinase members also promote cancer cell survival and proliferation. This study analyzed whether aurora kinases were regulated in the progression of CML. It also evaluated the efficacy of the ABL TKI asciminib and the aurora kinase inhibitor LY3295668. The expressions of AURKA and AURKB were higher in the CML cells compared with normal cells using a public database (GSE100026). Asciminib or LY3295668 alone inhibited CML cells after 72 h, and cellular cytotoxicity was increased. The combined use of Asciminib and LY3295668 increased superior efficacy compared with either drug alone. Colony formation was reduced by cotreatment with asciminib and LY3295668. In the cell-cycle analyses, LY3295668 induced G2/M arrest. Cell populations in the sub-G1 phase were observed when cotreating with asciminib and LY3295668. The combination treatment also changed the mitochondrial membrane potential. In addition, AURKA shRNA transfectant cells had increased asciminib sensitivity. Combining asciminib and aurora kinase inhibition enhanced the efficacy and is proposed as a new therapeutic option for patients with CML. These findings have clinical implications for a potential novel therapeutic strategy for CML patients.
Assessment of the Entomopathogenic Potential of Fungal and Bacterial Isolates from Fall Armyworm Cadavers Against Spodoptera frugiperda Caterpillars and the Adult Boll Weevil, Anthonomus grandis
Authors: Dos Santos Moreira Lidiane Maria , Marinho Luciene Silva , Neves Robério Carlos Santos , Harakava Ricardo , Bessa Layara Alexandre , Vitorino Luciana Cristina
Published: May 2024

Increased attention is being focused on the biological control of agricultural pests using microorganisms, owing to their potential as a viable substitute for chemical control methods. Insect cadavers constitute a potential source of entomopathogenic microorganisms. We tested whether bacteria and fungi isolated from Spodoptera frugiperda (JE Smith) cadavers could affect its survival, development, egg-laying pattern, and hatchability, as well as induce mortality in Anthonomus grandis Boheman adults. We isolated the bacteria Enterobacter hormaechei and Serratia marcescens and the fungi Scopulariopsis sp. and Aspergillus nomiae from fall armyworm cadavers and the pest insects were subjected to an artificial diet enriched with bacteria cells or fungal spores to be tested, in the case of S. frugiperda, and only fungal spores in the case of A. grandis. Enterobacter hormaechei and A. nomiae were pathogenic to S. frugiperda, affecting the survival of adults and pupae. The fungus Scopulariopsis sp. does not affect the survival of S. frugiperda caterpillars and pupae; however, due to late action, moths and eggs may be affected. Aspergillus nomiae also increased mortality of A. grandis adults, as well as the development of S. frugiperda in the early stages of exposure to the diet, as indicated by the vertical spore transfer to offspring and low hatchability. Enterobacter hormaechei and A. nomiae are potential biocontrol agents for these pests, and warrant further investigation from a toxicological point of view and subsequently in field tests involving formulations that could improve agricultural sustainability practices.
Decay of correlations in stochastic quantization: the exponential Euclidean field in two dimensions
Authors: Gubinelli Massimiliano , Hofmanová Martina , Rana Nimit
Published: May 2024

We present two approaches to establish the exponential decay of correlation functions of Euclidean quantum field theories (EQFTs) via stochastic quantization (SQ). In particular we consider the elliptic stochastic quantization of the Høegh–Krohn (or $$\exp (\alpha \phi )_2$$

exp

(
α
ϕ
)

2

) EQFT in two dimensions. The first method is based on a path-wise coupling argument and PDE apriori estimates, while the second on estimates of the Malliavin derivative of the solution to the SQ equation.
Anisotropic tribology and electrification properties of sliding-mode triboelectric nanogenerator with groove textures
Authors: Yang Weixu , Wang Jieyang , Wang Xiaoli , Chen Ping
Published: May 2024

Sliding-mode triboelectric nanogenerator (S-TENG) is based on the coupling of triboelectrification and electrostatic induction, converting electrical energy from sliding motion. Introducing micro-textures into the sliding surface, and adjusting the angle between the texture and sliding direction (direction angle) may achieve performance anisotropy, which provides novel ideas for optimizing the tribology and electrification performance of S-TENG. To guide the performance optimization based on the anisotropy, in this paper, groove micro-textures were fabricated on the surface of S-TENG, and anisotropic tribology and electrification performance were obtained through changing the direction angle. Based on the surface analysis and after-cleaning tests, the mechanism of the anisotropy was explained. It is shown that the anisotropy of friction coefficient can be attributed to the changes of texture edge induced resistance and groove captured wear debris, while the voltage anisotropy is due to the variations of debris accumulated on the sliding interface and the resulting charge neutralization. Among the selected 0°–90° direction angles, S-TENG at angle of 90° exhibits relatively small stable friction coefficient and high open-circuit voltage, and thus it is recommended for the performance optimization. The open-circuit voltage is not directly associated with the friction coefficient, but closely related to the wear debris accumulated on the sliding interface. This study presents a simple and convenient method to optimize the performance of S-TENG, and help understand the correlation between its tribology and electrical performance.
Erwartungen der Generation Z an Lehr- und Prüfungsmethoden im österreichischen Medizinstudium
Authors: Schöfl Rainer , Weilguny-Schöfl Gerlinde , Ziachehabi Alexander , Mandorfer Mattias , Fickert Peter
Published: May 2024

Im Rahmen einer „Summer School“ der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) wurden Medizinstudierende, die meisten im letzten Studienjahr, zu Lehr‑, Lern- und Prüfungsmethoden sowie zu Berufsbildern befragt. Österreichische Medizinstudierende, die meisten gehören der Generation Z (geboren zwischen 1995 und 2009) an, bevorzugen Präsenz- gegenüber Onlineunterricht, wollen ergänzend elektronische Lernunterlagen, Vorbereitungsvideos und Falldiskussionen in Seminaren und POL-Gruppen (problemorientiertes Lernen). Mündliche Prüfungen werden gegenüber schriftlichen Prüfungsformaten bevorzugt. Die von Studierenden favorisierten Lehrveranstaltungen und Lehrmethoden sowie Prüfungstypen unterliegen einem generationsbedingten Wandel. Akademische Lehrpersonen im Allgemeinen und Curriculums-Verantwortliche im Besonderen sollten diese Präferenzen kennen.
Developing Together
Authors: Garte Rebecca R.
Published: May 2024

Developing Together challenges systematic biases that have long plagued research with marginalized populations of children. It traces the unexamined assumptions guiding such research to definitions of subjectivity and the psyche based in Western cultural norms. The book provides alternative paradigms, applying a comprehensive methodology to two unique schooling contexts. Through this new approach children's development can be seen as an interactive, collaborative process. The chapters highlight how theoretical assumptions directly influence research methods and, in turn, affect educational practices. Unique in its provision of a detailed alternative method for conducting research with children, the book explains how the study of collaborative competence would influence education and applied fields. It is an essential resource for researchers in developmental psychology, educators, and policymakers alike.
Evaluating precision medicine tools in cystic fibrosis for racial and ethnic fairness
Authors: Colegate Stephen P. , Palipana Anushka , Gecili Emrah , Szczesniak Rhonda D. , Brokamp Cole
Published: May 2024

Introduction:

Patients with cystic fibrosis (CF) experience frequent episodes of acute decline in lung function called pulmonary exacerbations (PEx). An existing clinical and place-based precision medicine algorithm that accurately predicts PEx could include racial and ethnic biases in clinical and geospatial training data, leading to unintentional exacerbation of health inequities.

Methods:

We estimated receiver operating characteristic curves based on predictions from a nonstationary Gaussian stochastic process model for PEx within 3, 6, and 12 months among 26,392 individuals aged 6 years and above (2003–2017) from the US CF Foundation Patient Registry. We screened predictors to identify reasons for discriminatory model performance.

Results:

The precision medicine algorithm performed worse predicting a PEx among Black patients when compared with White patients or to patients of another race for all three prediction horizons. There was little to no difference in prediction accuracies among Hispanic and non-Hispanic patients for the same prediction horizons. Differences in F508del, smoking households, secondhand smoke exposure, primary and secondary road densities, distance and drive time to the CF center, and average number of clinical evaluations were key factors associated with race.

Conclusions:

Racial differences in prediction accuracies from our PEx precision medicine algorithm exist. Misclassification of future PEx was attributable to several underlying factors that correspond to race: CF mutation, location where the patient lives, and clinical awareness. Associations of our proxies with race for CF-related health outcomes can lead to systemic racism in data collection and in prediction accuracies from precision medicine algorithms constructed from it.
Inventing traditional authority: Lhomwe chiefs in Malawi
Authors: Robinson Amanda Lea
Published: May 2024

Chiefs in Malawi exercise significant authority based on legitimacy derived from the position's purportedly deep historical origins. But, does such legitimacy confer when a new chieftaincy is created from scratch? I address this question within the context of an ongoing cultural revival of the Lhomwe ethnic group in Malawi, which has included the appointment of many new Lhomwe chiefs and the creation of a Lhomwe paramount chieftaincy. Using a combination of in-depth interviews and original survey data, I explore the political drivers, mechanisms and implications of the this newly created Lhomwe chieftaincy. I find that its creation was driven by top-down, elite-led action rather than citizen demands, and that the newly appointed chiefs enjoy the most support among urban-based backers of the political party responsible for their appointments. This research contributes to historical work on the colonial-era creation of chieftaincies, but does so using a contemporary case of cultural engineering.
Supporting companies to reform nutrition policies and practices (REFORM): a multi-centre cluster randomised controlled trial
Authors: Ni Mhurchu C. , Sacks G. , Chan J. , Schultz S. , Shen S. , Marshall J. , Grey J. , Haliburton C. , Jiang Y. , Eyles H. , Young L.
Published: May 2024

Unhealthy food environments are major drivers of obesity and diet-related diseases(1). Improving the healthiness of food environments requires a widespread organised response from governments, civil society, and industry(2). However, current actions often rely on voluntary participation by industry, such as opt-in nutrition labelling schemes, school/workplace food guidelines, and food reformulation programmes. The aim of the REFORM study is to determine the effects of the provision of tailored support to companies on their nutrition-related policies and practices, compared to food companies that are not offered the programme (the control). REFORM is a two-country, parallel cluster randomised controlled trial. 150 food companies were randomly assigned (2:1 ratio) to receive either a tailored support intervention programme or no intervention. Randomisation was stratified by country (Australia, New Zealand), industry sector (fast food, other packaged food/beverage companies), and company size. The primary outcome is the nutrient profile (measured using Health Star Rating [HSR]) of foods and drinks produced by participating companies at 24 months post-baseline. Secondary outcomes include company nutrition policies and commitments, the nutrient content (sodium, sugar, saturated fat) of products produced by participating companies, display of HSR labels, and engagement with the intervention. Eighty-three eligible intervention companies were invited to take part in the REFORM programme and 21 (25%) accepted and were enrolled. Over 100 meetings were held with company representatives between September 2021 and December 2022. Resources and tailored reports were developed for 6 touchpoints covering product composition and benchmarking, nutrition labelling, consumer insights, nutrition policies, and incentives for companies to act on nutrition. Detailed information on programme resources and preliminary 12-month findings will be presented at the conference. The REFORM programme will assess if provision of tailored support to companies on their nutrition-related policies and practices incentivises the food industry to improve their nutrition policies and actions.