bluuebunny/crossref_metadata_2025 huggingface dataset:
No card, no service: Challenges faced by vulnerable populations of a cashless society
Authors: Horne Dan , Collins M. Cary
Published: September 2023

How people pay is critically important to consumers and businesses alike. Many consumers are choosing to pay for goods and services from an increasing number of options. Tech‐savvy urbanites buy coffee by tapping their phone on a reader. Parents returning from a night out use peer‐to‐peer payment apps, such as Venmo, to pay the sitter. The recent explosion of financial innovations promises faster, more efficient, and cheaper transactions. These increasing digital payment options coincide with decreased number and volume of cash transactions. However, vulnerable populations face more constrained payment choices and often rely exclusively on cash. Without experience, devices, or acceptable credit histories, vulnerable populations may have little access to digital transactions. The advantages of falling digital costs and other benefits thus accrue to the digitally connected. At the same time, those who must transact in coins and paper money are likely to find their relative costs increasing. This paper highlights payment trends and the potential impact on vulnerable populations in the United States as we move toward a cashless society. This paper should stimulate discussions of public policy initiatives to mitigate digital payment issues for vulnerable people.
Effects of canopy connectivity on the arboreal ant community in coffee shade trees
Authors: Wildtruth fern , Perfecto Ivette
Published: September 2023

Canopy connectivity influences foraging, movement, and competition in arboreal ant communities. Understanding how canopy connectivity affects arboreal ant communities could inform the development of management practices that maximize services from known biocontrol agents. We experimentally manipulated connectivity between the crowns of large shade trees to investigate the effects of canopy connectivity on arboreal ant species richness and composition in a coffee agroecosystem. A linear mixed‐effects analysis showed that the number of species observed at baits set in tree crowns increased significantly after the crowns had been connected with nylon ropes. Crowns that were connected increased in similarity of ant species composition, particularly between adjacent connected crowns. Connectivity may increase the number of species present in tree crowns by allowing ants to move and forage in the canopy while bypassing trunks with more aggressive, territorial species such as Azteca sericeasur. Because twig‐nesting species in the upper canopy have been shown to act as biocontrol agents of herbivores, an increase in species richness in tree crowns could have positive implications for agricultural pest‐control services.

Abstract in Spanish is available with online material.
High levels of mercury contamination in a necrophage dung beetle of the Amazon rainforest (Scarabaeidae: Scarabaeinae)
Authors: Chaboteaux Elena , Lopera Toro Alejandro , Vega Claudia Maribel , Forsyth Adrian
Published: September 2023

This study represents the first evidence of mercury contamination in the family Scarabaeidae, with a close focus on Coprophanaeus lancifer, the largest copro‐necrophagous beetle in South America. This work shows the repartition of total mercury (THg) in the insect body and lays the groundwork for additional future studies.

Abstract in Spanish is available with online material.
Increased mitochondria are responsible for the acquisition of gemcitabine resistance in pancreatic cancer cell lines
Authors: Masuo Hitoshi , Kubota Koji , Shimizu Akira , Notake Tsuyoshi , Miyazaki Satoru , Yoshizawa Takahiro , Sakai Hiroki , Hayashi Hikaru , Soejima Yuji
Published: September 2023

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa‐2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine‐resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti‐apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1–heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis‐related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.
Design, synthesis, and evaluation of the in vitro activity of novel dual inhibitors of XOR and URAT1 containing a benzoic acid group
Authors: Zhu Xin Ying , Chen Hong Ming , Zhang Lei , Qin Yu Xiang , Li Jing
Published: September 2023

Xanthine oxidoreductase (XOR) and uric acid transporter 1 (URAT1) are involved in the production and reabsorption of uric acid, respectively. However, the currently available individual XOR‐ or URAT1‐targeted drugs have limited efficacy. Thus, strategies for combining XOR inhibitors with uricosuric drugs have been developed. Previous virtual screening identified Compounds 1–5 as hits for the potential dual inhibition of XOR/URAT1. Nevertheless, in vitro experiments yielded unsatisfactory results. The first round of optimization work on those hits was performed, and two series of compounds were designed and synthesized. Compounds of the A series exerted moderate inhibitory effects on URAT1, but extremely weak inhibitory effects on XOR. Compounds of the B series exerted strong inhibitory effects on both XOR and URAT1. B5 exhibited the greatest inhibitory activity, with similar inhibitory effects on XOR and URAT1. The half maximal inhibitory concentration (IC50) of XOR was 0.012 ± 0.001 μM, equivalent to that of febuxostat (IC50 = 0.010 ± 0.001 μM). The IC50 of URAT1 was 30.24 ± 3.46 μM, equivalent to that of benzbromarone (IC50 = 24.89 ± 7.53 μM). Through this optimization, the in vitro activity of most compounds of the A and B series against XOR and URAT1 was significantly improved versus that of the hits. Compound B5 should be further investigated.
Long term outcome and prognostic indicators in Posner Schlossman syndrome
Authors: Joseph Danica M. , Lim Lyndell L. , Samalia Priya D. , Wells Jane M. , McCluskey Peter J. , Paul Eldho , Hall Anthony J.
Published: September 2023

Background

Posner Schlossman syndrome is a well‐defined uveitis entity that is characterised by relapsing remitting unilateral anterior uveitis with markedly raised intraocular pressure. The aim of this study was to determine the risk factors for progression in patients with Posner Schlossman syndrome.

Methods

Ninety‐eight patients were enrolled in a retrospective case series. Progression was defined as a composite endpoint of any of development of permanent glaucoma (in patients with no evidence of glaucomatous loss on presentation), corneal failure, or chronic inflammation. Relapse was defined as a resolving episode of inflammation not meeting the criteria for progression.

Results

Seventy seven percent of patients relapsed on average each 2.2 years. Forty percent of patients progressed. On univariate analysis, increased age at enrolment, immunocompromise at enrolment, the presence of glaucomatous optic neuropathy at enrolment, the performance of an anterior chamber tap and a positive anterior chamber tap were all associated with increased risk of progression. On multivariate analysis, age at enrolment, immunocompromise at enrolment, the performance of an anterior chamber tap, and the presence of glaucomatous optic neuropathy at enrolment were independently associated with increased risk of disease progression.

Conclusions

Posner Schlossman syndrome is not a benign uveitis entity and risk of both relapse and progression are high. Older patients, immunocompromised patients, patients with glaucomatous optic neuropathy at enrolment and those with a positive anterior chamber tap are all at increased risk of progression.
Spectrum of variants in a large Chinese Gitelman syndrome cohort
Authors: Mou Lijun , Tang Mengyue , Zhu Lina , Lin Wanbing , Gu Ying
Published: September 2023

Gitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation‐dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant allele. LRGs were detected by MLPA in 20 out of 27 cases, including 15 cases with suspected LRGs by MPS. Among these 20 cases with LRGs, the results of MPS and MLPA were identical in only 8 cases. Additional LRGs in 6 cases were detected by MLPA alone. In 6 cases, E4_E6del was identified by MPS, while E4_E5del and Intron6del were identified by MLPA. Among the 102 distinct variants, 30 are novel. LRGs were found in 20 cases (12.1%). LRGs were found in 12.1% of our Chinese GS patients cohort. We show that MPS and MLPA are two complementary techniques with the ability to improve the diagnostic yield of GS.
CD100 boosts the inflammatory response in the challenge phase of allergic contact dermatitis in mice
Authors: Mraz Veronika , Funch Anders B. , Jee Mia H. , Gadsbøll Anne‐Sofie Ø. , Weber Julie F. , Yeung Kelvin , Lohmann Rebecca K. D. , Hawkes Alana , Ødum Niels , Woetmann Anders , McKay Dianne , Witherden Deborah , Geisler Carsten , Bonefeld Charlotte M.
Published: September 2023

Background

Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal‐resident memory CD8+ T (TRM) cells play a key role. The mechanisms involved in the activation of CD8+ TRM cells during allergic flare‐up responses are not understood.

Methods

The expression of CD100 and its ligand Plexin B2 on CD8+ TRM cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT‐qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild‐type mice.

Results

We show that CD8+ TRM cells express CD100 during homeostatic conditions and up‐regulate it following re‐exposure of allergen‐experienced skin to the experimental contact allergen 1‐fluoro‐2,4‐dinitrobenzene (DNFB). Furthermore, Plexin B2 is up‐regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL‐17A, CXCL1, CXCL2, CXCL5, and IL‐1β and decreased recruitment of neutrophils to the epidermis.

Conclusion

Our study demonstrates that CD100 is expressed on CD8+ TRM cells and is required for full activation of CD8+ TRM cells and the flare‐up response of ACD.
Trajectories and risk factors of fatigue following colorectal cancer diagnosis
Authors: Li Xiaoyin , Hoogland Aasha I. , Small Brent J. , Crowder Sylvia L. , Gonzalez Brian D. , Oswald Laura B. , Sleight Alix G. , Nguyen Nathalie , Lorona Nicole C. , Damerell Victoria , Komrokji Khaled R. , Mooney Kathi , Playdon Mary C. , Ulrich Cornelia M. , Li Christopher I. , Shibata David , Toriola Adetunji T. , Ose Jennifer , Peoples Anita R. , Siegel Erin M. , Bower Julienne E. , Schneider Martin , Gigic Biljana , Figueiredo Jane C. , Jim Heather S. L.
Published: September 2023

Aim

This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups.

Method

Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ‐C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups.

Results

Among 1615 participants (57% men, 86% non‐Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II−IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05).

Conclusion

A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.
Factors associated with higher alcohol concentrations in emergency department presentations: PACE study
Authors: Cameron Cate M. , Vuong Kim , McWhinney Brett , Zournazi Anna , Manzanero Silvia , Warren Jacelle , Mitchell Gary , Vallmuur Kirsten , Howell Tegwen , Ungerer Jacobus P. J.
Published: September 2023

Introduction

The health impact from alcohol is of recognised concern, from acute intoxication as well as increased risk of chronic health issues over time. Identifying factors associated with higher alcohol consumption when presenting to the emergency department (ED) will inform public health policy and enable more targeted health care and appropriate referrals.

Methods

Secondary testing of blood samples collected during routine clinical care of 1160 ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, for 10 days between 22 January and 1 February 2021. Alcohol was measured by blood ethanol (intake in recent hours) and phosphatidylethanol (PEth; intake over 2–4 weeks). Zero‐inflated negative binomial regression was used to identify demographic and clinical factors associated with higher alcohol concentrations.

Results

Males were found to have 83% higher blood ethanol and 32% higher PEth concentrations than females (adjusted rate ratio [ARR] 1.83, 95% confidence interval [CI] 1.37–2.45 and ARR 1.32, 95% CI 1.04–1.68, respectively). Blood ethanol concentrations were 3.4 times higher for those 18–44 years, compared to those aged 65+ (ARR 3.40, 95% CI 2.40–4.82) whereas PEth concentrations were found to be the highest in those aged 45–64 years, being 70% higher than those aged 65+ (ARR 1.70, 95% CI 1.19–2.44). Patients brought in involuntarily had eight‐times higher blood ethanol concentrations than those who self‐attended.

Discussion and Conclusions

This study used two alcohol markers to identify factors associated with higher alcohol concentrations in emergency presentations. The findings demonstrate how these biomarkers can provide informative data for public health responses and monitoring of alcohol use trends.
Perioperative Schmerztherapie bei dermatochirurgischen Eingriffen – aktuelle Praxis in Deutschland: Datenauswertung einer deutschlandweiten Online‐Umfrage unter Dermatochirurgen
Authors: Gschnell Martin , Volberg Christian , Eubel Verena , Pfützner Wolfgang
Published: September 2023

Hintergrund

Adäquate Schmerztherapie sollte bei operativen Eingriffen zum regelhaften Behandlungskonzept gehören. In der Dermatochirurgie gibt es hierzu jedoch kaum Daten, wie am besten vorgegangen werden sollte. In einer standardisierten Online‐Umfrage unter in Deutschland tätigen Dermatochirurgen wurde die gängige Praxis der perioperativen Schmerztherapie bei dermotochirurgischen Eingriffen erhoben.

Methodik

Mitglieder der Deutschen Gesellschaft für Dermatochirurgie (DGDC) sowie Leiter dermatochirurgischer Abteilungen wurden um Teilnahme gebeten. Fragen bezogen sich auf praktische Umsetzung des perioperativen Schmerzmanagements, Schmerzdokumentation und persönliche Informationsquellen zum Themenkomplex.

Ergebnisse

116 Fragebögen konnten ausgewertet werden. Während prophylaktische Analgesie kaum angewandt wird, berichtet die überwiegende Mehrzahl (86%), eine postoperative Bedarfsmedikation einzusetzen. Feste Therapieregime existieren mehrheitlich nicht. Zumeist werden NSAR und gelegentlich niedrigpotente Opioide verwendet. Schmerzen werden von der Mehrzahl (59,1%) als Freitext dokumentiert. Die größte Bedeutung beim schmerztherapeutischen Management besitzen persönliche Erfahrungswerte (69%) und hausinterne Standards (51%). Die Nutzung von Leitlinien (25%) spielt eine untergeordnete Rolle.

Schlussfolgerungen

Perioperatives Schmerzmanagement in der Dermatochirurgie ist stark von persönlichen Erfahrungswerten geprägt und kann je nach durchgeführtem Eingriff unterschiedlich ausfallen. Konsensbasierte standardisierte Empfehlungen hierfür fehlen. Für eine suffiziente perioperative Analgesie ist die Entwicklung bedarfsorientierter Schmerzkonzepte wünschenswert. Dafür bedarf es prospektiver Studien, die das spezielle Patientenklientel und operative Vorgehen in der Dermatologie berücksichtigen.
A guide to between‐community functional dissimilarity measures
Authors: Lengyel Attila , Botta‐Dukát Zoltán
Published: September 2023

One of the effective tools to study the variation between communities is the use of pairwise dissimilarity indices. Besides species as variables, the involvement of trait information provides valuable insight into the functioning of ecosystems. In recent years, a variety of indices have been proposed to quantify functional dissimilarity between communities. These indices follow different approaches to account for between‐species similarities in calculating community dissimilarity, yet they all have been proposed as straightforward tools. In this paper, we review the trait‐based dissimilarity indices available in the literature and identify the most important conceptual and technical properties that differentiate among them, and that must be considered before their application. We identify two primary aspects that need to be considered before choosing a functional dissimilarity index. The first one is the way communities are represented in the trait space. The three main types of representations are the typical values, the discrete sets using the combination of species × sites and species × traits matrices, and the hypervolumes. The second decision is the concept of dissimilarity to follow, including two options: distances and disagreements. We use the above scheme to discuss the available functional dissimilarity indices and evaluate their relations to each other, their capabilities, and accessibility.
Assessment of local officials and government‐initiated CSR: Evidence from targeted poverty alleviation in China
Authors: Huang Yujing , Li Xiujuan , Yu Minggui
Published: September 2023

This paper explores whether the assessment of local government officials affects firm participation in targeted poverty alleviation. Using a sample of Chinese A‐share listed companies in the Midwest from 2016 to 2019, the results show that the greater the importance of officials' poverty alleviation assessment, the higher the participation of firms in precise poverty alleviation. State‐owned enterprises (SOEs) contribute more to the reduction of destitution than private enterprises. We further find that local SOEs' participation in precision poverty alleviation enhances the likelihood of executive promotion, while private enterprises' participation in precision poverty alleviation increases government subsidies and reduces the cost of debt financing. These findings imply that the evaluation mechanisms of Chinese officials can effectively promote enterprises fulfilling social responsibilities.
Piece‐wise constant cluster modelling of dynamics of upwelling patterns
Authors: Nascimento Susana , Martins Alexandre , Relvas Paulo , Luís Joaquim F. , Mirkin Boris
Published: September 2023

A comprehensive approach is presented to analyse season's coastal upwelling represented by weekly sea surface temperature (SST) image grids. Our three‐stage data recovery clustering method assumes that the season's upwelling can be divided into shorter periods of stability, ranges, each to be represented by a constant core and variable shell parts. Corresponding clustering algorithms parameters are automatically derived by using the least‐squares clustering criterion. The approach has been successfully applied to real‐world SST data covering two distinct regions: Portuguese coast and Morocco coast, for 16 years each.
Multiscale Continuous and Discrete Spatial Heterogeneity Analysis: The Development of a Local Model Combining Eigenvector Spatial Filters and Generalized Lasso Penalties
Authors: Peng Zhan , Inoue Ryo
Published: September 2023

Two types of spatial heterogeneity can exist simultaneously: continuous variations across an entire space and significant changes that occur only in specific spatial units. Moreover, each of these can act across multiple spatial scales. To effectively detect both continuous and discrete spatial heterogeneity across different scales, this study proposes a novel approach that combines the random effects eigenvector spatially filtering‐based spatially varying coefficient (RE‐ESF‐SVC) model and the generalized lasso (GL) technique. Additionally, a restricted maximum likelihood estimation (REML)‐based two‐step iterative algorithm is developed for parameter estimation. Simulation experiments and an empirical application using rental price data confirm the ability of the proposed model to identify multiscale continuous and discrete spatial heterogeneity.
Enhanced microwave absorption performance of geopolymer composites by incorporating hollow Fe3O4 nanospheres
Authors: Ding Enjie , Bai Ben , Wang Xue , Zhang Wenting , Liu Wanshuang , Zhang Liying
Published: September 2023

Hollow Fe3O4 nanospheres (h‐Fe3O4) with tunable sizes were synthesized and proposed as fillers to prepare microwave absorbing geopolymer (GP) composites. We studied the effect of different sizes of h‐Fe3O4 on microwave absorption (MA). The MA performance was enhanced as the size of h‐Fe3O4 in GP decreased. Furthermore, the GP composites containing h‐Fe3O4 achieved better MA capability than their counterparts containing solid Fe3O4 nanospheres (s‐Fe3O4) of the same size. The GP composites with a small size of h‐Fe3O4 exhibited the best minimum reflection loss (RLmin) of −39.3 dB at 14.0 GHz and an effective absorption bandwidth (EAB) of 4.8 GHz at 2.2 mm. The outstanding MA capability, possibly as a result of improved dielectric loss and magnetic loss together with well‐matched impedance, demonstrated that GP composites are competitive construction materials when MA is critical. The radar cross section (RCS) simulation was conducted to assess the MA performance of composite materials in practical environments.
Physical activity, screen time and body composition in 13‐year‐old adolescents: The Generation R Study
Authors: Wu Tong , Yang‐Huang Junwen , Vernooij Meike W. , Rodriguez‐Ayllon María , Jaddoe Vincent W. V. , Raat Hein , Klein Stefan , Oei Edwin H. G.
Published: September 2023

Background

Body composition between prepubertal children and adolescents varies, and it is unclear how physical activity and sedentary behaviour affect adolescent body composition.

Objectives

This study aimed to examine the associations of physical activity and screen time with overall and specific fat depots in the general adolescent population.

Methods

In a population‐based prospective cohort study, among 3258 adolescents aged 13 years, physical activity and screen time were assessed via self‐report questionnaires. Body mass index, dual‐energy X‐ray absorptiometry‐based measures (i.e. fat mass and lean body mass) and magnetic resonance imaging–based measures (i.e. abdominal subcutaneous and visceral fat mass) were obtained.

Results

After adjusting for social‐demographic and growth‐related factors, each additional hour of daily physical activity was associated with lower fat mass, abdominal visceral fat mass and higher lean body mass (all p < 0.05). However, these associations were not observed in the longitudinal analyses. Each additional hour of daily screen time was associated with higher body mass index, fat mass, abdominal subcutaneous and visceral fat mass (all p < 0.05), which were consistent with the longitudinal analyses.

Conclusion

Adolescents with higher physical activity and lower screen time had lower levels of adiposity both at the general and visceral levels.
Les syndicats et les inégalités de revenus: témoignages d'un panel de pays européens
Authors: MONTEBELLO Roberta , SPITERI Jonathan , VON BROCKDORFF Philip
Published: September 2023

Cet article examine la relation entre les syndicats et la hausse des inégalités de revenus observée dans les économies avancées au cours des dernières décennies. Le rôle des syndicats dans la lutte contre l'inégalité croissante des revenus a été négligé dans les études empiriques, malgré son ambiguïté théorique. Le modèle empirique de référence, estimé pour 26 pays européens de 2005 à 2018, spécifie l'inégalité des revenus en fonction du taux de syndicalisation, de sa valeur au carré et d'un ensemble de variables de contrôle. Les institutions du marché du travail, autres que les syndicats, sont incorporées dans le modèle pour évaluer les effets distributifs de la densité syndicale dans l'ensemble du cadre institutionnel. Les auteurs constatent que la densité syndicale a une relation en forme de U inversé statistiquement significative et persistante avec l'inégalité des revenus.
The diapausing mosquito Culex pipiens exhibits reduced levels of H3K27me2 in the fat body
Authors: Wei Xueyan , Dhungana Prabin , Sim Cheolho
Published: September 2023

Culex pipiens, the northern house mosquito, is a major vector of West Nile virus. To survive the severe winter, adult mosquitoes enter a diapause programme. Extended lifespan and an increase in lipid storage are key indicators of diapause. Post‐translational modifications to histone proteins impact the expression of genes and have been linked to the lifespan and energy utilisation of numerous insects. Here, we investigated the potential contribution of epigenetic alterations in initiating diapause in this mosquito species. Multiple sequence alignment of H3 sequences from other insect species demonstrates a high conservation of the H3 histone in Cx. pipiens throughout evolution. We then compared the levels of histone methylation in the ovaries and fat body tissues of diapausing and non‐diapausing Cx. pipiens using western blots. Our data indicate that histone methylation levels in the ovaries of Cx. pipiens do not change during diapause. In contrast, H3K27me2 levels decrease more than twofold in the fat body of diapausing mosquitoes relative to non‐diapausing counterparts. H3K27 methylation plays a crucial role in chromosome activation and inactivation during development in many insect species. This is predominantly governed by polycomb repressor complex 2. Intriguingly, a previous ChIP‐seq study demonstrated that the transcription factor FOXO (Forkhead box O) targets the genes that comprise this complex. In addition, H3K27me2 exhibits dynamic abundance throughout the diapause programme in Cx. pipiens, suggesting its potential role in the initial activation of the diapause programme. This study expands our understanding of the relationship between alterations in epigenetic regulation and diapause.
Ecdysone‐induced microRNA miR‐276a‐3p controls developmental growth by targeting the insulin‐like receptor in Drosophila
Authors: Lee Sojeong , Kim Nayeon , Jang Daegyu , Kim Hee Kyung , Kim Jongin , Jeon Ji Won , Lim Do‐Hwan
Published: September 2023

Animal growth is controlled by a variety of external and internal factors during development. The steroid hormone ecdysone plays a critical role in insect development by regulating the expression of various genes. In this study, we found that fat body‐specific expression of miR‐276a, an ecdysone‐responsive microRNA (miRNA), led to a decrease in the total mass of the larval fat body, resulting in significant growth reduction in Drosophila. Changes in miR‐276a expression also affected the proliferation of Drosophila S2 cells. Furthermore, we found that the insulin‐like receptor (InR) is a biologically relevant target gene regulated by miR‐276a‐3p. In addition, we found that miR‐276a‐3p is upregulated by the canonical ecdysone signalling pathway involving the ecdysone receptor and broad complex. A reduction in cell proliferation caused by ecdysone was compromised by blocking miR‐276a‐3p activity. Thus, our results suggest that miR‐276a‐3p is involved in ecdysone‐mediated growth reduction by controlling InR expression in the insulin signalling pathway.
Peroxisome proliferator‐activated receptors as therapeutic target for cancer
Authors: Wang Yuqing , Lei Feifei , Lin Yiyun , Han Yuru , Yang Lei , Tan Huabing
Published: September 2023

Peroxisome proliferator‐activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR‐α, PPAR‐β/δ and PPAR‐γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and tumour immune response, and are essential components in tumour progression and metastasis. As such, they have become a target for cancer therapy research. In this review, we discussed the current state of knowledge on the involvement of PPARs in cancer, including their role in tumourigenesis, the impact of PPARs in tumour microenvironment and the potential of using PPARs combinational therapy to treat cancer by targeting essential signal pathways, or as adjuvants to boost the effects of current chemo and immunotherapies. Our review highlights the complexity of PPARs in cancer and the need for a better understanding of the mechanism in order to design effective cancer therapies.
Systemic anti‐inflammatory treatment of atopic dermatitis during conception, pregnancy and breastfeeding: Interdisciplinary expert consensus in Northern Europe
Authors: Deleuran M. , Dézfoulian B. , Elberling J. , Knutar I. , Lapeere H. , Lossius A. H. , Schuttelaar M. L. A. , Stockman A. , Wikström E. , Bradley M. , de Bruin‐Weller M. , Gutermuth J. , Mandelin J. M. , Schmidt M. C. , Thyssen J. P. , Vestergaard C.
Published: September 2023

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision‐making on systemic anti‐inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti‐inflammatory treatment in men and women of reproductive age. Twenty‐one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two‐round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first‐choice long‐term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short‐course prednisolone for flare management. No consensus was reached on second‐choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication‐specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3‐month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared‐care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.
The disperser dilemma in cooperatively breeding birds
Authors: Heifetz Aviad
Published: September 2023

In most cooperatively breeding birds, individuals do not breed with their natal group members. In order to breed, they have either to disperse into another group or wait for an opposite-sex individual to join their group. In most of these species, females disperse more than males. We develop a dynamic game-theoretic model to account for this asymmetry. When males are physically larger/heavier than females, this allows them to effectively welcome female immigrants into their natal group and overcome the local females' opposition more than vice versa. The model further assumes that the dispersal decision is not confined to a restricted time window, but is rather based on acquired information and responsive to opportunities. The model predicts that (i) females disperse more than males, and (ii) females are willing to tolerate more risks in dispersal than do males. The latter prediction is supported inter alia by the fact that in many cooperatively breeding birds, females disperse at a younger age, and further away from their natal group as compared to dispersing males.

Abstract

In cooperatively breeding birds, the optimal upper bound of dispersal-failure risk tolerated by females (yellow-green) and males (red-blue) as a function of the other sex's upper bound, with the ESS at their intersection. The parameter a is the maximal dispersal-failure probability for females, which decreases when males are stronger and better able to welcome emigrating females into their natal group despite local females' opposition.
Cryptic community structure and metabolic interactions among the heritable facultative symbionts of the pea aphid
Authors: Peng Linyao , Hoban Jessica , Joffe Jonah , Smith Andrew H. , Carpenter Melissa , Marcelis Tracy , Patel Vilas , Lynn-Bell Nicole , Oliver Kerry M. , Russell Jacob A.
Published: September 2023

Most insects harbour influential, yet non-essential heritable microbes in their hemocoel. Communities of these symbionts exhibit low diversity. But their frequent multi-species nature raises intriguing questions on roles for symbiont–symbiont synergies in host adaptation, and on the stability of the symbiont communities, themselves. In this study, we build on knowledge of species-defined symbiont community structure across US populations of the pea aphid, Acyrthosiphon pisum. Through extensive symbiont genotyping, we show that pea aphids' microbiomes can be more precisely defined at the symbiont strain level, with strain variability shaping five out of nine previously reported co-infection trends. Field data provide a mixture of evidence for synergistic fitness effects and symbiont hitchhiking, revealing causes and consequences of these co-infection trends. To test whether within-host metabolic interactions predict common versus rare strain-defined communities, we leveraged the high relatedness of our dominant, community-defined symbiont strains vs. 12 pea aphid-derived Gammaproteobacteria with sequenced genomes. Genomic inference, using metabolic complementarity indices, revealed high potential for cooperation among one pair of symbionts—Serratia symbiotica and Rickettsiella viridis. Applying the expansion network algorithm, through additional use of pea aphid and obligate Buchnera symbiont genomes, Serratia and Rickettsiella emerged as the only symbiont community requiring both parties to expand holobiont metabolism. Through their joint expansion of the biotin biosynthesis pathway, these symbionts may span missing gaps, creating a multi-party mutualism within their nutrient-limited, phloem-feeding hosts. Recent, complementary gene inactivation, within the biotin pathways of Serratia and Rickettsiella, raises further questions on the origins of mutualisms and host–symbiont interdependencies.

Abstract

We genotyped seven bacterial species across protein-coding gene loci, to define common vs. rare ‘symbiont’ communities among pea aphids from the United States. Leveraging prior genome sequences from the identified strains, we tested the hypothesis that metabolic interactions among symbionts drive this ‘community structure’. We found support for this hypothesis for the symbiont pairing between the most abundant strains of Serratia symbiotica and Rickettsiella viridis. Specifically, genome-wide analyses revealed that these two commonly partnered symbionts exhibit high, reciprocal complementarity across the metabolic pathways encoded by their genomes. Together, the two symbionts enable the pea aphid ‘holobiont’ to synthesize biotin (vitamin B7), an important vitamin found at low levels in the pea aphid diet.
The Ecology of Father‐Child Relationships: An Expanded Model
Authors: Cabrera Natasha J. , Fitzgerald Hiram E. , Bradley Robert H. , Roggman Lori
Published: September 2023

We expand our 2007 heuristic model of father involvement using recent research on the dynamic and reciprocal processes by which fathers influence children's development over time. Based on new evidence, our expanded model incorporates more dynamic reciprocity, temporal factors, and nuanced considerations of context in which fathers parent. We identify aspects of context as well as fathers' personality and behavior that are central to the next generation of studies on fathers. We highlight studies related to fathering versus mothering, discuss ecological theory and how it has been used to understand fathering, and present an expanded version of our model.
Comment on: 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults
Authors: Burnett Allison E. , Barnes Geoffrey D. , Allen Arthur L. , Ansell Jack , Blumenstein Marilyn , Connors Jean M. , Dager William E. , Kaatz Scott , May Jori E. , Nemeth Ronni , O'Connor Carlee , Ragheb Bishoy , Rajasekhar Anita , Sardo Laurie , Siegal Deborah M. , Van Beek Andrea ,   The Anticoagulation Forum Board of Directors
Published: September 2023

See the Reply by Semla and Steinman in this issue.
What drives firms' commitment to fighting corruption? Evidence from the UK
Authors: Sarhan Ahmed A. , Al‐Najjar Basil
Published: September 2023

The recent leak of the FinCEN files has highlighted the widespread presence of corruption in developing and developed economies, including the UK. Accordingly, this study aims to investigate the factors that drive companies to implement measures for preventing corruption in developed countries using FTSE 350 nonfinancial firms. Specifically, the research examines the influence of corporate social responsibility (CSR) commitments, board structure, and shareholding structure on adopting strategies, policies, and procedures aimed at countering corruption. Drawing upon agency, stakeholder, and legitimacy theories, our empirical evidence supports that CSR commitments and board independence positively influence firms' engagement in anticorruption measures. Conversely, institutional and managerial shareholdings are found to have a negative association with firms' efforts to combat corruption. In addition, the study shows that the effect of board characteristics became more pronounced following the enactment of the UK Bribery Act 2010, indicating risk‐averse behavior. Various models, including cross‐sectional and two‐stage least squares (2SLS), are employed to analyze the data. Our findings have significant implications for understanding the complex relationship between CSR, corporate governance, and the ethical infrastructure of organizations. Ultimately, our results provide valuable insights for policymakers, companies, and other stakeholders in developing effective strategies, policies, and procedures to combat corruption activities.
Functional effects of haemoglobin can be rescued by haptoglobin in an in vitro model of subarachnoid haemorrhage
Authors: Warming Hannah , Deinhardt Katrin , Garland Patrick , More John , Bulters Diederik , Galea Ian , Vargas‐Caballero Mariana
Published: September 2023

During subarachnoid haemorrhage, a blood clot forms in the subarachnoid space releasing extracellular haemoglobin (Hb), which causes oxidative damage and cell death in surrounding tissues. High rates of disability and cognitive decline in SAH survivors are attributed to loss of neurons and functional connections during secondary brain injury. Haptoglobin sequesters Hb for clearance, but this scavenging system is overwhelmed after a haemorrhage. Whilst exogenous haptoglobin application can attenuate cytotoxicity of Hb in vitro and in vivo, the functional effects of sub‐lethal Hb concentrations on surviving neurons and whether cellular function can be protected with haptoglobin treatment remain unclear. Here we use cultured neurons to investigate neuronal health and function across a range of Hb concentrations to establish the thresholds for cellular damage and investigate synaptic function. Hb impairs ATP concentrations and cytoskeletal structure. At clinically relevant but sub‐lethal Hb concentrations, we find that synaptic AMPAR‐driven currents are reduced, accompanied by a reduction in GluA1 subunit expression. Haptoglobin co‐application can prevent these deficits by scavenging free Hb to reduce it to sub‐threshold concentrations and does not need to be present at stoichiometric amounts to achieve efficacy. Haptoglobin itself does not impair measures of neuronal health and function at any concentration tested. Our data highlight a role for Hb in modifying synaptic function in surviving neurons, which may link to impaired cognition or plasticity after SAH and support the development of haptoglobin as a therapy for subarachnoid haemorrhage.

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Operating Hedge and Gross Profitability Premium
Authors: KOGAN LEONID , LI JUN , ZHANG HAROLD H.
Published: September 2023

We show theoretically that variable production costs reduce systematic risk of firms' cash flows if capital and variable inputs are complementary in firms' production and input prices are procyclical. In our dynamic model, this operating hedge effect is weaker for more profitable firms, giving rise to a gross profitability premium. Moreover, gross profitability and value factors are distinct and negatively correlated, and their premia are not captured by the capital asset pricing model (CAPM). We estimate the model by simulated method of moments, and find that its main implications for stock returns and cash flow dynamics are quantitatively consistent with the data.
Interest Rate Skewness and Biased Beliefs
Authors: BAUER MICHAEL , CHERNOV MIKHAIL
Published: September 2023

Conditional skewness of Treasury yields is an important indicator of the risks to the macroeconomic outlook. Positive skewness signals upside risk to interest rates during periods of accommodative monetary policy and an upward‐sloping yield curve, and vice versa. Skewness has substantial predictive power for future bond excess returns, high‐frequency interest rate changes around Federal Open Market Committee announcements, and survey forecast errors for interest rates. The estimated expectational errors, or biases in beliefs, are quantitatively important for statistical bond risk premia. These findings are consistent with a heterogeneous‐beliefs model in which one of the agents is wrong about consumption growth.
Prognostic significance of cyclin D1 expression pattern in HPV‐negative oral and oropharyngeal carcinoma: A deep‐learning approach
Authors: Yang Ke , Zhu Guixin , Sun Yanan , Hu Yaying , Lv Yinan , Li Yiwei , Pan Juncheng , Chen Fu , Zhou Yi , Zhang Jiali
Published: September 2023

Background

We aimed to establish image recognition and survival prediction models using a novel scoring system of cyclin D1 expression pattern in patients with human papillomavirus‐negative oral or oropharyngeal squamous cell carcinoma.

Methods

The clinicopathological data of 610 patients with human papillomavirus‐negative oral/oropharyngeal squamous cell carcinoma were analyzed retrospectively. Cox univariate and multivariate risk regression analyses were performed to compare cyclin D1 expression pattern scoring with the traditional scoring method—cyclin D1 expression level scoring—in relation to patients' overall and progression‐free survival. An image recognition model employing the cyclin D1 expression pattern scoring system was established by YOLOv5 algorithms. From this model, two independent survival prediction models were established using the DeepHit and DeepSurv algorithms.

Results

Cyclin D1 had three expression patterns in oral and oropharyngeal squamous cell carcinoma cancer nests. Superior to cyclin D1 expression level scoring, cyclin D1 expression pattern scoring was significantly correlated with the prognosis of patients with oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). Moreover, it was an independent prognostic risk factor in both oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). The cyclin D1 expression pattern‐derived image recognition model showed an average test set accuracy of 78.48% ± 4.31%. In the overall survival prediction models, the average concordance indices of the test sets established by DeepSurv and DeepHit were 0.71 ± 0.02 and 0.70 ± 0.01, respectively.

Conclusion

Combined with the image recognition model of the cyclin D1 expression pattern, the survival prediction model had a relatively good prediction effect on the overall survival prognosis of patients with human papillomavirus‐negative oral or oropharyngeal squamous cell carcinoma.