bluuebunny/crossref_metadata_2025 huggingface dataset:
Flotillins in membrane trafficking and physiopathology
Authors: Bodin Stéphane , Elhabashy Hadeer , Macdonald Ewan , Winter Dominic , Gauthier‐Rouvière Cécile
Published: January 2025

Flotillin 1 and 2 are highly conserved and homologous members of the stomatin, prohibitin, flotillin, HflK/C (SPFH) family. These ubiquitous proteins assemble into hetero‐oligomers at the cytoplasmic membrane in sphingolipid‐enriched domains. Flotillins play crucial roles in various cellular processes, likely by concentrating sphingosine. They primarily act as scaffolding protein complexes within membrane microdomains (also called lipid rafts) and induce endocytosis and trafficking. Their diverse cargos in the upregulated flotillin–induced trafficking (UFIT) pathway, including tyrosine kinase receptors, adhesion molecules, and neurotransmitter receptors, link them to a wide range of cellular processes and diseases. Consequently, flotillin upregulation has been associated with various pathological conditions such as cancer, metabolic disorders, and neurodegenerative diseases. Flotillins may also be co‐opted by pathogens to facilitate their entry and growth within host cells.

In this review, we examined recent advancements in elucidating the structure and functions of the flotillin protein complex, including its implications in favoring the generation of sphingosine 1‐phosphate, an essential bioactive lipid. We emphasized how the recent cryo‐electron microscopy (cryo‐EM) structure of a truncated cone‐shaped cage composed of 22 copies of flotillin 1 and 2 subunits has enhanced our understanding of the flotillin complex organization within membrane microdomains and its role in membrane remodeling. We also explored how flotillin upregulation can perturb endosomal trafficking and contribute to various pathologies.

A comprehensive understanding of flotillin oligomer organization and function is crucial to developing targeted therapies for diseases associated with flotillin overexpression.
SGK3 promotes estrogen receptor‐positive breast cancer proliferation by activating STAT3/ZMIZ2 pathway to stabilise β‐catenin
Authors: Yuan Lie , Cai Yongqing , Wang Gang , Liu Xu , Chen Bo , Zhou Duanfang , Wu Yuanli , Qu Na , Li Xiaoli , Zhou Weiying
Published: January 2025

Background and Purpose

Breast cancer is a leading threat to women's health, with approximately 70% of cases being estrogen receptor‐positive. SGK3 is regulated by estrogen and is positively associated with estrogen receptor expression, although its molecular role remains unclear.

Experimental Approach

Proteomics was used to identify SGK3's downstream targets. Tissue microarray immunofluorescence evaluated SGK3 and ZMIZ2 expression in ER+ breast cancer. Lentiviral‐mediated knockdown and overexpression of SGK3 and/or ZMIZ2 assessed their effects on cell proliferation in vitro and in vivo. Chromatin immunoprecipitation (ChIP) analyzed p‐STAT3 binding to the ZMIZ2 promoter, and Co‐immunoprecipitation (Co‐IP) examined ZMIZ2‐β‐catenin interaction.

Key Results

SGK3 expression was elevated in breast tumour tissues correlating with reduced patient survival. Proteomic analysis identified ZMIZ2 as a downstream target of SGK3. Overexpression of SGK3 promoted the proliferation of estrogen receptor‐positive breast cancer in MCF‐7 and T47D cells. Inhibition had the opposite effects. ZMIZ2 overexpression rescued the proliferation deficit in SGK3 knockdown cells. ZMIZ2 was found to bind and stabilises β‐catenin. Knockdown of SGK3 led to β‐catenin degradation via polyubiquitination, a process reversed by ZMIZ2 overexpression. STAT3 was identified as a downstream effector of SGK3 and its knockdown reduced cytoplasmic and nuclear p‐STAT3 and STAT3, and inhibited ZMIZ2 and β‐catenin expression. Celastrol suppressed estrogen receptor‐positive breast cancer cell proliferation by inhibiting the SGK3/STAT3/ZMIZ2/β‐catenin pathway.

Conclusions and Implications

SGK3 expression is associated with poorer survival rates, thus SGK3 is a potential therapeutic target. As celastrol can inhibit SGK3 expression it could be an effective therapeutic agent.
Supervised Toothbrushing Programmes: Understanding Barriers and Facilitators to Implementation
Authors: Gray‐Burrows Kara A. , El‐Yousfi Sarab , Hudson Kristian , Watt Samantha , Lloyd Ellen , El Shuwihdi Hanin , Broomhead Tom , Day Peter F. , Marshman Zoe
Published: January 2025

Objectives

Supervised toothbrushing programmes (STPs), whereby children brush their teeth at nursery or school with a fluoride toothpaste under staff supervision, are a clinically and cost‐effective intervention to reduce dental caries. However, uptake is varied, and the reasons unknown. The aim was to use an implementation science approach to explore the perspectives of key stakeholders on the barriers and facilitators at each level of implementation of STPs.

Methods

This qualitative study involved individual interviews and focus groups with a purposive sample of stakeholders involved at all levels of implementation of STPs: (1) policymakers; (2) providers of STPs; (3) nursery/school staff; (4) parents/carers; and (5) children (aged 2‐6 years old) across England. Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR).

Results

A total of 159 stakeholders were interviewed (40 individual interviews and 17 focus groups) across all levels of implementation. Barriers and facilitators to STP implementation were identified across 35 of the 39 CFIR constructs. Four themes were identified that determined STP implementation: (1) acceptability of STPs; (2) external ‘make or break’ conditions; (3) the importance of engagement across the system; and (4) desire for centralised support.

Conclusions

This is the first study to qualitatively explore the barriers and facilitators to STP at all levels of implementation underpinned by an implementation science framework. The findings have strong implications for policymakers who wish to implement STPs, highlighting the need for careful consideration of the adaptability of the programmes, the role of formal and informal engagement systems, and the need for centralised support. This work has facilitated the co‐design and piloting of a supervised toothbrushing implementation toolkit, which provides a central hub of resources and good practice to optimise implementation of STPs at scale.
Iron Overload, Oxidative Stress, and Somatic Mutations in MDS: What Is the Association?
Authors: Leitch Heather A.
Published: January 2025

Introduction

Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited.

Methods

The literature was reviewed on how IOL and oxidative stress interact with specific SM in MDS to influence cellular physiology. PubMed searches included keywords of each specific mutation combined with iron, oxidative stress, and reactive oxygens species (ROS). Papers relevant to hematopoietic stem/progenitor cells, the bone marrow microenvironment, MDS, AML or other myeloid disorders were preferred. Included were the most frequent SM in MDS, SM of the International Prognostic Scoring System‐Molecular (IPSS‐M), of familial predisposing conditions and the CMML PSS‐molecular.

Results

About 31 SM plus four familial conditions were searched. Discussed are the frequency of each SM, whether function is gained or lost, early or late SM status, a function of the unmutated gene, and function considering iron and oxidative stress.

Discussion

Given limited effective MDS therapies, considering how IOL and ROS interact with SM to influence cellular physiology in the hematopoietic system, increasing bone marrow failure progression or malignant transformation may be of benefit and support optimization of measures to reduce IOL or neutralize ROS.
Evaluation of the Effect of Aeration Tubes and Holes on Soil Gas Exchange Using a Simulation Model
Authors: Weltecke Katharina , Löwe Oliver , Gaertig Thorsten
Published: January 2025

A prevalent strategy to mitigate the negative impacts of soil compaction or sealing on urban trees involves installing aeration tubes, aeration holes or near surface aeration horizons to enhance gas exchange between the soil air and the atmosphere. Despite their widespread use, there is currently no scientific evidence confirming their effectiveness. In this study, gas exchange between the atmosphere and soils that were aerated using different methods was modelled and evaluated in the laboratory and in the field. Both the laboratory and field measurements could be modelled well with the simulation model. The research showed that the effectiveness of aeration tubes and holes is highly dependent on the air‐filled porosity of the soil. The more gas exchange can take place via the soil pores, the lesser the influence of the aeration equipment. Thus, the use of aeration tubes is not necessary when using tree substrates in unsealed tree pits but could mitigate disturbances in soil aeration in compacted and fine‐grained soils with low air capacity. However, modelling shows that the effect of aeration tubes and holes is less than expected and that near‐surface aeration layers are generally more effective than vertical aeration systems. With the help of the modelling of gas exchange as presented here, it is possible to optimise the level of aeration of the soil depending on the existing degree of compaction and/or the planned surface sealing.
Cysteine S‐conjugate sulfoxide β‐lyase activity for human ACCS
Authors: Gao Jinmin , Xu Yueqi , Yeh Christopher , Zou Yike , Hai Yang
Published: January 2025

1‐Aminocyclopropane‐1‐carboxylate synthase (ACCS) catalyzes the conversion of S‐adenosyl‐methionine to 1‐aminocyclopropane‐1‐carboxylate (ACC), a rate‐limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure. In this study, through a biochemical profiling approach, we demonstrate that human ACCS possesses cysteine conjugate sulfoxide β‐lyase activity. This function is unexpected but reasonable, as it somewhat parallels the activity of ACCS proteins found in non‐seed plants. Structure–function relationship study of human ACCS, guided by an AlphaFold2 model, allowed us to identify key active site residues that are important for its β‐lyase activity. Our biochemical study of human ACCS also provided insights into the function of other mammalian ACCS homologs.
Geographical Variation in Carbon and Nitrogen Stable Isotope Ratios and Feeding Habits of Japanese Jack Mackerel (Trachurus japonicus)
Authors: Enomoto Megumi , Ohshimo Seiji , Ito Shin‐ichi
Published: January 2025

Japanese jack mackerel (Trachurus japonicus) is subject to substantial and escalating commercial harvesting activities, yet its habitat structure is poorly understood. We analyzed the carbon and nitrogen stable isotope ratios (δ13C and δ15N) of this species to evaluate geographical fluctuations in these ratios, allowing a delineation of the jack mackerel feeding habits. Fish specimens were collected across the East China Sea (ECS) and Sea of Japan (JS), and isotopic data were retrieved from two previous studies. Six subareas were considered: the southern, central, and northern ECS; Tsushima Strait; and eastern and western JS. The residuals of isotope ratios predicted from fork length showed significant geographical variation in the ratios (a lower δ13C in the JS than in the ECS and Tsushima Strait; a lower δ15N in the eastern JS and southern ECS than in other areas). Comparisons of stable isotope ratios between jack mackerel and prey candidates also revealed geographical differences in potential prey selection. The potential prey was identified as anchovy larvae and larger Copepoda in the western and eastern JS, respectively, whereas various prey species contributed to the diet in the other areas. Both δ13C and δ15N increased with fork length, suggesting ontogenetic changes in foraging habitat, associated with habit shifts into demersal layers of jack mackerel during their growth. Collectively, our results suggest that stable isotope ratio values—and consequently, the feeding habits—of jack mackerel differed between the ECS and JS but that they possess a limited migration range after an ontogenetic shift to demersal layers.
Interobserver agreement and practice patterns for grading of colorectal carcinoma: World Health Organization (WHO) classification of tumours 5th edition versus American Joint Committee on Cancer (AJCC) 8th edition staging manual
Authors: Karamchandani Dipti M , Gonzalez Raul S , Lee Hwajeong , Westerhoff Maria , Cox Brian , Pai Rish K
Published: January 2025

Aims

The current American Joint Committee on Cancer (AJCC) staging manual and the College of American Pathologists (CAP) colorectal carcinoma (CRC) protocol specify use of a four‐tiered grading system (i.e. grades 1–4; well‐differentiated–undifferentiated) for CRC, based on percentage of gland formation. The World Health Organization (WHO) 5th edition grades CRC into low‐grade (well‐ and moderately differentiated) and high‐grade (poorly and undifferentiated), based on the least differentiated component. We studied interobserver agreement and practice patterns among pathologists when grading CRC by these two grading systems.

Methods and results

Five gastrointestinal pathologists reviewed 100 scanned CRC slides and graded the tumour on each slide, per provided criteria in (a) WHO 5th edition book, (b) AJCC manual/CAP CRC protocol and (c) their clinical practice. A questionnaire for grading selected CRC subtypes was also provided. Statistical analysis was performed using Pearson's χ2 test and Fleiss multi‐rater kappa analyses. Overall, agreement among the five reviewers when grading via WHO and AJCC criteria for low‐grade and high‐grade CRC was moderate (κ = 0.568, P < 0.001) and good (κ = 0.611, P < 0.001), respectively. All reviewers graded significantly more tumours as high‐grade when using WHO (median = 46) versus AJCC/CAP criteria (median = 20).

Conclusions

Interobserver agreement was higher using the AJCC grading criteria as a two‐tiered system. Significantly more tumours were called high‐grade using the WHO criteria. This raises concerns regarding upgrading tumours, as well as potential differences in grading tumours among pathologists worldwide, based on regional preferred grading systems. Synchronisation of these two grading systems is necessary for uniform grading of CRCs throughout institutions.
Innate Immunity Never “NODs” Off: NLRs Regulate the Host Anti‐Viral Immune Response
Authors: Woolls Mackenzie K. , Mott Madeline D. , Poole Cassandra S. , Gregory Julia A. , Ivester Hannah M. , Allen Irving Coy
Published: January 2025

A robust innate immune response is essential in combating viral pathogens. However, it is equally critical to quell overzealous immune signaling to limit collateral damage and enable inflammation resolution. Pattern recognition receptors are critical regulators of these processes. The cytosolic nucleotide‐binding domain leucine‐rich repeat (NLR; NOD‐like receptor) family of pattern recognition receptors plays essential roles in the sensing of viral pathogen‐associated molecular patterns and is best characterized for itsr pro‐inflammatory biological functions. Specifically, these include the formation of multi‐protein complexes, defined as inflammasomes or NODosomes that regulate the production of IL‐1beta, IL‐18, and pyroptosis, or the induction of NF‐ΚB signaling. While these biological effects are inherently pro‐inflammatory, it is also important to recognize that other NLR family members conversely function to negatively regulate inflammation through modulating signaling initiated by other families of pattern recognition receptors. Mechanistically, these unique NLRs also form multiprotein complexes that act to attenuate a variety of biological signaling pathways, such as the inhibition of NF‐ΚB. This inhibition facilitates inflammation resolution and functions to restore cellular homeostasis. Despite extensive characterization of individual NLR family members, the mechanisms of immune system regulation are highly nuanced and remain enigmatic. This is especially true for non‐inflammasome‐forming, regulatory NLRs. Here, we discuss recent findings associated with NLR family members that play essential roles in the host immune response to viruses and mechanisms by which these pattern recognition receptors may function to regulate antiviral immunity.
Behavior of the dielectric and pyroelectric responses of ferroelectric fine‐grained ceramics
Authors: Pylypchuk Oleksandr S. , Ivanchenko Serhii E. , Yelisieiev Mykola Y. , Nikolenko Andrii S. , Styopkin Victor I. , Pokhylko Bohdan , Kushnir Vladyslav , Stetsenko Denis O. , Bereznykov Oleksii , Leschenko Oksana V. , Eliseev Eugene A. , Poroshin Vladimir N. , Morozovsky Nicholas V. , Vainberg Victor V. , Morozovska Anna N.
Published: January 2025

We demonstrated the correlations between the specific temperature behavior of the colossal dielectric permittivity, unusual electro‐transport characteristics, and frequency dependences of the pyroelectric response of the fine‐grained ceramics prepared by the spark plasma sintering of the ferroelectric BaTiO3 nanoparticles. The temperature dependences of the electro‐resistivity indicate the frequency‐dependent transition in the electro‐transport mechanisms between the lower and higher conductivity states accompanied by the maximum in temperature dependence of the loss angle tangent. The pyroelectric thermal wave probing revealed the existence of the spatially inhomogeneous counter‐polarized ferroelectric states at the opposite surfaces of the ceramic sample. We described the temperature behavior of the colossal dielectric response and losses using the core−shell model for ceramic grains, effective medium approximation, and Maxwell−Wagner approach.
Association of Pulse Prssure Index With Mortality in Patients With Hypertension: Results From NHANES 1999–2018
Authors: Jin Hongjin , Fang Shusheng , An Shuo , Ding Yanchun
Published: January 2025

Vascular compliance is an important predictor of cardiovascular disease and mortality. Pulse pressure index (PPI) is a reliable indicator for evaluating vascular compliance. However, the association between PPI, all‐cause mortality (ACM), and cardiovascular mortality (CVM) in patients with hypertension is still unclear. In this study, we aimed to investigate the association of PPI with ACM and CVM in patients with hypertension. Kaplan–Meier survival curves, Cox proportional hazards regression models, restricted cubic splines, and subgroup and interaction analyses were used to investigate the association of PPI with ACM and CVM. U‐shaped associations were observed between PPI and both ACM and CVM, and the inflection points for ACM and CVM were at PPI values of 0.327 and 0.363, respectively. Time‐dependent receiver operating characteristic curves indicated that PPI showed good predictive value for both ACM and CVM occurrence at 1, 3, 5, and 10 years, and its predictive value was higher than PP for ACM and CVM at 5 and 10 years. These results showed that PPI can be used to identify patients with hypertension who are at a high risk of mortality and can guide more aggressive anti‐hypertensive treatment strategies. Moreover, these findings demonstrate that PPI is a superior vascular compliance indicator than PP.
AQP3 Influences Unexplained Recurrent Abortion by Regulating Trophoblast Cell Migration and Invasion via the METTL14/IGF2BP1/AQP3/PI3K/AKT Pathway
Authors: Nong Yingqi , Zhai Qiyi , Liu Wenjuan , Wei Jiahui , Wang Zhaoyi , Lv Xiaoyin , Li Zitao , Zhang Xiqian , Liu Fenghua
Published: January 2025

Reduced trophoblast migration and invasion contribute to unexplained recurrent spontaneous abortion (URSA). Aquaporin 3 (AQP3) plays a crucial role in facilitating trophoblast migration and invasion during early pregnancy through fetal‐maternal crosstalk. This study aimed to comprehensively investigate the mechanism involving AQP3 and its modulatory effects on human extravillous trophoblast (HTR‐8/SVneo cells) migration and invasion. AQP3 and IGF2BP1 expression was analysed using immunohistochemistry and quantitative real‐time polymerase chain reaction. The AQP3‐associated molecular mechanisms were explored using western blot, meRIP, RNA stability assays and RNA‐protein pull‐down experiments. Furthermore, the role of IGF2BP1 in HTR‐8/SVneo cells was assessed using transwell assays. AQP3 and IGF2BP1 expression was lower in the chorionic villi samples of the URSA group than in those of the control group. AQP3 was involved in regulating the activation of the PI3K/AKT signalling pathway. Additionally, METTL14 interacted with AQP3 mRNA, thereby influencing its stability. Furthermore, AQP3 mRNA bound to the IGF2BP1 protein, and IGF2BP1 knockdown resulted in reduced AQP3 mRNA stability and impaired trophoblast migration and invasion. METTL14 and IGF2BP1 stabilise AQP3 mRNA expression by mediating m6A, thereby facilitating HTR‐8/SVneo cell migration and invasion via the PI3K/AKT signalling pathway. Targeting AQP3 could potentially contribute to strategies aimed at mitigating URSA development.
How Can We Make Information on Equity in Clinical Guidelines More Usable for Clinicians? A Case Study Methodology of General Practitioners
Authors: MacPherson Naomi , Norman Kimberley , Gunatillaka Nilakshi , Yao Alexa , Nielsen Suzanne , Sturgiss Elizabeth
Published: January 2025

Background

Clinical practice guidelines (CPGs) are moving toward greater consideration of population‐level differences, like health inequities, when creating management recommendations. CPGs have the potential to reduce or perpetuate health inequities. The intrinsic design factors of electronic interfaces that contain CPGs are known barriers to guideline use. There is little existing guidance on supporting the uptake of equity‐specific recommendations within CPGs by end users.

Objective

To investigate (1) How do General Practitioners (GPs) use Therapeutic Guidelines to adapt their clinical management for disadvantaged populations and do they support equity recommendations in this CPG? (2) How could Therapeutic Guidelines embed health equity information into their guidelines?

Methods

The Therapeutic Guidelines was used as a case study as it is the most frequently used CPG in Australian healthcare settings. We employed descriptive qualitative methods, focused on semistructured interviews with 17 eligible GPs. Interviews were structured around four case studies that initially explored the management of a patient from the general population, with their details then changed so they belonged to a disadvantaged population. We used a ‘think aloud’ interview technique to explore the clinician's application of CPGs.

Results

Three themes were developed relating to: (1) GPs agree that health equity information needs to be intentionally included in guidelines and should focus on disadvantaged subgroups to support their clinical decision‐making, (2) GPs want CPGs to include equity information which is relevant to the purpose and use of each guideline, acknowledging that other clinical aids could provide additional information when needed, (3) GPs want clearer signposting of information within guidelines to help navigation of key sections, highlighting the utility of symbols, colours and dropdown functions.

Conclusion

This research extends existing literature by showing that including equity information tailored to the articulated purpose of each CPG, as perceived by end users, may maximise uptake. Our outlined strategies could be used by CPG developers to make equity‐focused management recommendations more accessible. This may increase the implementation of equity‐focused recommendations by clinicians, supporting current primary care strategies in achieving more equitable outcomes.
Interdisciplinary Approach to Retreatment of a Full‐Mouth Rehabilitation: Horizontal Preparations, Vertical Dimension of Occlusion Increase, and Mucogingival Surgery in a Tetracycline‐Stained Dentition
Authors: Gil Alfonso , Morón‐Conejo Belén , Bonfanti Mónica , Martínez‐Rus Francisco , Pradies Guillermo
Published: January 2025

Objective

This case report presents the interdisciplinary retreatment of a patient with a worn full‐mouth rehabilitation using defect‐oriented restorations, horizontal preparations, and vertical dimension of occlusion (VDO) increase.

Clinical Considerations

A 58‐year‐old woman with a previous full‐mouth rehabilitation presented with worn dentition, loss of VDO, and reduced posterior support. Examination revealed signs of parafunctional habits, tetracycline‐stained teeth, and compromised aesthetics with exposed discolored teeth and open embrasure spaces. Additionally, the veneers showed wear and ceramic chipping. The retreatment started with a diagnostic phase, including a wax‐up and mock‐up to guide the treatment plan. Mucogingival surgery was performed to correct gingival recession according to the restorative margins established by the mock‐up. The full‐mouth rehabilitation involved increasing the VDO through anterior crowns and veneers, posterior overlays, and dental implant restoration. Horizontal chamfer preparations ensured sufficient thickness for the ceramic material, allowing for durable adhesive restorations.

Conclusions

The interdisciplinary approach, combining diagnostic, surgical, and prosthetic phases, enabled the successful retreatment of this complex case, restoring function and aesthetics. A 2‐year follow‐up confirmed the stability and positive outcomes of the rehabilitated dentition.

Clinical Significance

This interdisciplinary approach provides an effective strategy for managing complex full‐mouth rehabilitations, integrating aesthetics, function, and periodontal health through defect‐oriented preparation techniques.
Dopamine genetic risk scores and psychiatric symptoms: Interacting risk factors for impulse control behaviours in de novo Parkinson's disease
Authors: Whooley Emma , Koppelmans Vincent , MacDonald Hayley J. , Hall Alison , Ruitenberg Marit F. L.
Published: January 2025

Up to 45% of patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by a loss of voluntary control over impulses, drives or temptations. This study aimed to investigate whether previously identified genetic and psychiatric risk factors interact towards the development of ICDs in PD. A total of 278 de novo PD patients (ICD‐free at enrollment) were selected from the Parkinson's Progression Markers Initiative database. ICD presence at baseline and yearly follow‐up assessments were evaluated via the Questionnaire for Impulsive‐Compulsive Disorders. Symptoms of anxiety and depression at baseline were measured via the State–Trait‐Anxiety Inventory and Geriatric Depression Scale, respectively. Furthermore, an individual dopamine genetic risk score was calculated according to polymorphisms in genes coding for dopamine (D1, D2 and D3 receptors and catechol‐O‐methyltransferase), with higher scores reflecting higher central dopamine neurotransmission. In total, 146 participants (47.5%) developed an ICD with an average onset time of 36 months (range 3–96) from baseline. Results from a Cox proportional hazards model showed a trait anxiety × genetics interaction, suggesting that individuals with both higher baseline trait anxiety scores and higher dopamine genetic risk scores were at increased risk of ICD development. This interaction remained significant after controlling for age, sex and motor symptom severity. Our findings suggest that genetic and psychiatric predictors of impulsivity in PD interact and jointly yield increased ICD risk during the course of the disorder. This implies that early screening of anxiety symptoms in combination with genotyping can be useful to identify those at risk for ICD.
Decoding Green Bonds for Sustainable Development: A Hybrid Review and Research Agenda
Authors: Joshipura Mayank , Mathur Sachin , Joshipura Nehal , Castelino Reema
Published: January 2025

The green bond market and related scholarly research have grown exponentially recently. However, the literature remains scattered. This study addresses the gap by analyzing 744 Scopus‐indexed journal articles using a mix of bibliometric and content analyses to unveil trends, current dynamics, and knowledge structures. The bibliometric analysis shows dynamic transformation and differential development among clusters. It indicates the following three prominent research themes: (a) reducing carbon emissions, (b) premium and financing, and (c) connectedness and portfolio risk effects. From policymakers' perspective, the content analysis reveals positive linkages and channels between green bonds and the environment. Pertinent to issuers and investors, estimates of green bond premiums vary by time, context, and methodology. Future scholarly research should focus on causality, regional variations, and the role of policy design in the impact of green finance. Researchers must further investigate the motives of green bond investors and issuers.
Fresh frozen plasma, fibrinogen concentrate, and antithrombin concentrate administration for obstetrical disseminated intravascular coagulation by the Japanese previous and new criteria
Authors: Morikawa Mamoru , Matsunaga Shigetaka , Makino Shintaro , Takeda Yoshiharu , Hyodo Hironobu , Nii Masafumi , Serizawa Mariko , Eto Eriko , Takeda Jun , Adachi Tomoko , Kobayashi Takao , Itakura Atsuo
Published: January 2025

Aim

The purpose of this study is to clarify the frequencies of fresh frozen plasma (FFP) ± fibrinogen concentrate administration (fibrinogen concentrate [FC] therapy) and antithrombin (AT) concentrate administration (AT therapy) for the women with obstetrical disseminated intravascular coagulation (DIC).

Methods

Two retrospective multicenter case–control studies as Study‐1 (January–December 2018) and Study‐2 (July 2022–June 2023) were conducted. Study‐1 was the historical control of Study‐2. All participants experienced a blood loss of ≥1000 mL during vaginal delivery or ≥2000 mL during cesarean section. All participants were subsequently assigned to the DIC group or non‐DIC group.

Results

Study‐1 comprised 175 women (obstetrical DIC, 27; control, 148; by the previous criteria) and Study‐2 comprised 175 women (obstetrical DIC, 9; control, 166; by the new criteria). The frequencies of FFP (±FC therapy) or FC therapy in DIC group were significantly higher than non‐DIC group in Study‐1 (88.9% vs. 25.0%, 44.4% vs. 4.0%) and Study‐2 (100% vs. 24.7%, 77.8% vs. 5.4%); however, the frequencies of AT therapy were similar. Furthermore, in the DIC group, all women with fibrinogen <150 mg/dL received FFP ± FC therapy in Study‐1 (n = 19) and Study‐2 (n = 8); however, those with AT activity <70% received AT therapy (16.7% [4/24] and 12.5% [1/8], respectively).

Conclusion

We revealed an association between the high frequency of FFP ± FC therapy and lower fibrinogen levels, but a low frequency of AT therapy regardless of AT activity, in obstetrical DIC regardless of diagnosis criteria.
Baseline Alpha‐Fetoprotein Elevation and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B: A Multicentre Cohort Study
Authors: Park ChulHyoung , Hwang Gyubeom , Choi Won‐Mook , Han Ji Eun , Kim Chungsoo , Lee Dong Yun , Heo Subin , Park Rae Woong
Published: January 2025

Alpha‐fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver‐related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high‐AFP (≥ 10 ng/mL) and normal‐AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver‐related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high‐AFP and 3731 normal‐AFP patients were analysed. The high‐AFP group had a significantly higher 2‐year incidence of HCC (HR: 4.29; 95% CI: 3.31–5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high‐AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow‐up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver‐related laboratory values can help in risk stratification.
Labial Melanotic Macules in Two Pediatric Patients of Chinese Descent With Atopic Dermatitis
Authors: Katsiaunis Apostolos , Petrillo Madalyn , Robinson Sarah N.
Published: January 2025

We report two pediatric patients of Chinese descent with atopic dermatitis (AD) who developed labial melanotic macules in the absence of previous topical calcineurin inhibitor (TCI) usage. Both patients presented with multiple hyperpigmented macules on the upper and lower vermilion lips with a negative genetic workup for Peutz–Jeghers. These findings suggest labial melanotic macules may be a cutaneous manifestation of chronic eczematous dermatitis in pediatric patients, particularly those of Asian descent. Increased recognition of this phenomenon may help clinicians as they are making treatment decisions and avoid unnecessary genetic testing, thus optimizing patient care and reducing costs.
Piecing together the jigsaw: Forests in the EU's Fit for 55 Package
Authors: Sasso Caterina , Savaresi Annalisa , Vesa Seita
Published: January 2025

This article considers the intricate regulatory jigsaw of forest governance that has emerged from the Fit for 55 Package. It focuses on the 2023 revision of the Land Use, Land‐use Change and Forestry Regulation, the treatment of forest biomass in the 2023 Renewables Directive, and Regulation on carbon removals and carbon farming. The article explores the interconnections between these instruments, their relationship with other relevant EU Law instrument, and their projected impacts. Recognising the evolving nature of law and policy in this area, we offer an initial assessment of this regulatory jigsaw, highlighting the challenges of balancing the cultural, economic, social, political, and scientific considerations intersecting in EU forest governance.
Technical Measures, Environmental Protection, and Trade
Authors: Santeramo Fabio Gaetano , Lamonaca Emilia , Emlinger Charlotte
Published: January 2025

Technical regulations are increasingly numerous, complex, and often less transparent than traditional price‐based measures. Widely employed to achieve nontrade policy objectives, these measures are frequently adopted for environmental protection purposes. However, the trade effects of environmental measures remain underexplored. Using a unique and original dataset of technical measures notified for environmental reasons, we provide robust evidence that such measures significantly reduce both trade values and volumes. Our analysis further reveals substantial variation in the trade impacts of environmental technical measures across sectors and countries, highlighting notable differences. These findings are critical for assessing whether these measures function as trade barriers and underscore the importance of further research into their trade‐offs and spillover effects. Such research is essential for understanding the broader implications of environmental technical measures on global trade dynamics.
Assessing the Moist and Dry Static Energies in the Atmosphere as a Van Der Waals Gas in 2015 and 2017 over the Metropolitan Region of Natal-RN, Brazil
Authors: Medeiros Deusdedit Monteiro , De Mendonça Silva Isamara , Mendes David
Published: January 2025

This study evaluated the monthly average of the enthalpy, geopotential, latent heat content, moist static energy, and dry static energy at several levels of the atmosphere as a Van Der Waals gas from radiosonde data at 00:00 UTC and 12:00 UTC over the metropolitan region of Natal-RN-Brazil. The years 2015 and 2017 were considered because they presented more than 70% of complete data, with days coinciding at both times. To construct the vertical profiles of the variables, the density, specific humidity, and geopotential were calculated at each level through a mathematical approximation based on the Calculus. The Van der Waals-like atmosphere results showed that the latent heat content compensated for any change in enthalpy and potential energy from the surface to the mid-troposphere. Energy was exchanged among enthalpy, geopotential, and latent heat content, showing a roughly constant moist static energy. The moist static energy was a conserved quantity under adiabatic and hydrostatic transformations, although the dry static energy was not conserved. The results of the atmosphere as a Van Der Waals gas and the atmosphere as an ideal gas were compared, proving to be similar.
A Vision for the Formal Documentation and Digitalization of Sports Commentators’ Commentaries
Authors: Teixeira da Silva Jaime A. , Scelles Nicolas
Published: January 2025

One of the aspects that can fortify the engagement of a viewer or listener of a sport competition is the nature of the sports commentator’s commentary. By providing their thoughts on the actions and performance that viewers are viewing (or listeners are listening to) in real time, sports commentators can enliven a game with their wit, knowledge, and personal and professional expertise. In other cases, comments might be irritating, off-putting, excessive, or ill-timed. Independent of the quality of a sports commentator’s comments, we advocate for the formal documentation and digitalization of past, present, and future comments as textual and audio-visual files for use in academic sport communication studies. Although this might be achieved using artificial intelligence, its limitations need to be considered. Provided that issues related to commentaries’ rights can be resolved, as well as issues related to data access and use, and digital ethics, our proposal would allow for decades-old historical records to be developed and digitized, allowing commentaries to be appreciated, scrutinized, studied, and applied by all stakeholders. Lessons are drawn from the digitization of political commentary. These commentaries would serve not only as a learning training set for students and would-be sports commentators but also as an audio aid for those with visual impairment. Finally, they could be used for business purposes by broadcasters who would be able to better understand commentaries that increase fan viewership and therefore optimize their return on investment.
Dog skull shape challenges assumptions of performance specialization from selective breeding
Authors: Hebdon Nicholas , Ortega Alexa , Orlove Alexander , Wheeler Nichole , Pham Mia , Nguyen Vivian , Gladman Justin , Waldrop Lindsay D.
Published: January 2025

Through selective breeding, humans have driven exceptional morphological diversity in domestic dogs, creating more than 200 recognized breeds developed for specialized functional tasks such as herding, protection, and hunting. Here, we use three-dimensional reconstructions of dog skulls to ask whether these function-oriented kennel-club groups reflect differences in morphology that correspond to those functions. We analyzed 117 canid skulls, representing 40 domestic dog breeds and 18 wild subspecies, using geometric morphometric techniques and
k
-means clustering. Results show near-full overlap in kennel-club groups and with natural species, except for companion dogs having extreme snout shape. When categorized by task-specific historic function (i.e., bite work and scent work), this morphology overlap remains. These results indicate that, despite producing extreme morphological diversity, humans have not produced breeds specialized for functional tasks.
Variable vertical land motion and its impacts on sea level rise projections
Authors: Govorcin Marin , Bekaert David P. S. , Hamlington Benjamin D. , Sangha Simran S. , Sweet William
Published: January 2025

Coastal vertical land motion (VLM), including uplift and subsidence, can greatly alter relative sea level projections and flood mitigations plans. Yet, current projection frameworks, such as the IPCC Sixth Assessment Report, often underestimate VLM by relying on regional linear estimates. Using high-resolution (90-meter) satellite data from 2015 to 2023, we provide local VLM estimates for California and assess their contribution to sea level rise both now and in future. Our findings reveal that regional estimates substantially understate sea level rise in parts of San Francisco and Los Angeles, projecting more than double the expected rise by 2050. Additionally, temporally variable (nonlinear) VLM, driven by factors such as hydrocarbon and groundwater extraction, can increase uncertainties in 2050 projections by up to 0.4 meters in certain areas of Los Angeles and San Diego. This study highlights the critical need to include local VLM and its uncertainties in sea level rise assessments to improve coastal management and ensure effective adaptation efforts.
PD-L1-CD80 interactions are required for intracellular signaling necessary for dendritic cell migration
Authors: Kantheti Uma , Forward Tadg S. , Lucas Erin D. , Schafer Johnathon B. , Tamburini Pierce J. , Burchill Matthew A. , Tamburini Beth Ann Jirón
Published: January 2025

Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration. We show that cis interactions between PD-L1 and CD80 are critical for promoting migration and define specific regions within these proteins necessary for migration. Furthermore, we demonstrate that αPD-L1 significantly impedes DC migration in a B16 melanoma tumor model. Last, we outline how blocking cis PD-L1:CD80 interactions or mutation of the intracellular domain of PD-L1, in an imiquimod-induced murine model of psoriasis, limits DC migration to the lymph node, decreases interleukin-17 production by CD4
+
T cells in the lymph node, and reduces epidermal thickening. Therefore, PD-L1 and CD80 interactions are important regulators of DC migration to the draining lymph node.
Light-emitting, self-healing robotic fibers
Authors: Yashinski Melisa
Published: January 2025

Optical and mechanical self-healing compatibility was achieved in a multilayered electroluminescent robotic soft fiber.
Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models
Authors: Guillot Simon J. , Lang Christina , Simonot Marie , Beckett Daniel , Lulé Dorothée , Balz Luisa T. , Knehr Antje , Stuart-Lopez Geoffrey , Vercruysse Pauline , Dieterlé Stéphane , Weydt Patrick , Dorst Johannes , Kandler Katharina , Kassubek Jan , Wassermann Laura , Rouaux Caroline , Arthaud Sébastien , Da Cruz Sandrine , Luppi Pierre-Hervé , Roselli Francesco , Ludolph Albert C. , Dupuis Luc , Bolborea Matei
Published: January 2025

Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic
C9ORF72
and
SOD1
mutation carriers exhibited increased wakefulness and reduced non–rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (

Sod1
G86R

,
Fus

Δ
NLS/+

, and

TDP43
Q331K

). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of

Sod1
G86R

mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.
Correcting a pathogenic mitochondrial DNA mutation by base editing in mice
Authors: Barrera-Paez Jose D. , Bacman Sandra R. , Balla Till , Van Booven Derek , Gannamedi Durga P. , Stewart James B. , Mok Beverly , Liu David R. , Lombard David B. , Griswold Anthony J. , Nedialkova Danny D. , Moraes Carlos T.
Published: January 2025

Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA
Ala
) gene. Because the original m.5024C→T mutation (G→A in the mt-tRNA
Ala
) destabilizes the mt-tRNA
Ala
aminoacyl stem, we designed a compensatory m.5081G→A edit (C→T in the mt-tRNA
Ala
) that could restore the secondary structure of the tRNA
Ala
aminoacyl stem. For this, the DdCBE gene construct was initially tested in an m.5024C→T mutant cell line. The reduced mt-tRNA
Ala
amounts in these cells were increased after editing up to 78% of the mtDNA. Then, DdCBE was packaged in recombinant adeno-associated virus 9 (AAV9) and intravenously administered by retro-orbital injections into mice. Expression of the transduced DdCBE was observed in the heart and skeletal muscle. Total mt-tRNA
Ala
amounts were restored in heart and muscle by the m.5081G→A edit in a dose-dependent manner. Lactate amounts, which were increased in the heart, were also decreased in treated mice. However, the highest dose tested of AAV9-DdCBE also induced severe adverse effects in vivo because of the extensive mtDNA off-target editing that it generated. These results show that although DdCBE is a promising gene therapy tool for mitochondrial disorders, the doses of the therapeutic constructs must be carefully monitored to avoid deleterious off-target editing.