bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study of parameters in micro-photochemical machining using maskless digital projection on flat surfaces of 100Cr6 steel
Authors: Samani Farshid Norouzi , Esfahani Ehsan Rouhani
Published: January 2025

Photochemical machining (PCM) is a chemical etching process, in which a photoresist agent is used to cover parts of the workpiece that need to be protected from etching. In this study, the main goal is to create a groove on the flat surface of a workpiece made of 100Cr6 steel using the PCM process and to investigate different variables on the dimensional and geometrical accuracy of the groove. The experiments were designed using the response surface method with a central composite methodology, involving 20 experiments and three repetitions. In this study, the effects of different variables such as time of etching, the concentration of ferric chloride (FeCl3) in the etchant solution, and the weight ratio of hydrochloric acid (HCl) to FeCl3 in the etchant solution were investigated on dimensional accuracy such as length and width error and also geometrical accuracy such as out of parallelism, out of squareness, and out of straightness. Results indicate that as the etching duration increases, the length, width, out of straightness, out of parallelism, and out of squareness also increase. This error becomes substantial with longer durations. Also, with an increase in FeCl3 concentration in etchant solution, errors in length and width, out of straightness, out of parallelism, and out of squareness reduce. The optimal variables resulting in the least possible errors were an etching duration of 10.72 minutes (10 minutes and 43 seconds), FeCl3 solution concentration of 599.64 g/L, and a weight ratio of HCl to FeCl3 in the etchant solution of 0.1. The following results on the flat surface were obtained: groove length: 3,056 µm, groove width: 625 µm, groove depth: 48 µm, and surface roughness (Ra): 1.285 µm.
Sleepiness, sleep time, and depression of caregivers are linked with sleep and behaviors of their paired partners with dementia
Authors: Manning Carol A , Youngkin Anna , Quigg Mark
Published: January 2025

Background

Sleep difficulties in people with Alzheimer's disease (AD) and their caregivers (CGs) have been documented. Additionally, sleep disturbances are a risk for AD indicating that poor sleep in CGs may place them at risk for AD. Little is known about the relationship between sleep in people with dementia (PWD) and their CGs.

Objective

This pilot study examines sleep in PWD and CGs dyads, and the relationship between PWD sleep and CG sleep, cognition, and burden. We explore whether disordered sleep, degree of dementia and PWD behaviors are related to CG sleep difficulties and burden.

Methods

We examined sleep using overnight polysomnography (PSG) and day/night activity using 14-day actigraphy in PWD/CG dyads form the Virginia Alzheimer's Disease Center Clinical Cohort. Dyad members received the Montreal Cognitive Assessment (MoCA), behavioral and mood assessments. CGs completed CG burden and preparedness assessments.

Results

Mean activity from actigraphy did not differ within dyad members. PSG measurement of total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SEff), and wake after sleep onset (WASO) revealed that CGs had significantly decreased TST compared to their PWD and experienced greater SOL. Lower PWD MoCA scores were unrelated to CG sleep. However, PWD neuropsychiatric symptoms and CG burden correlated with worse CG SOL.

Conclusions

Our findings suggest that chronic rest and activity are linked within dyad members and that when separated, CGs experience shorter TST, lower SEff, and longer SOL than their partners. Additionally neuropsychiatric symptoms and CG burden were associated with worse CG sleep.
Neuropsychological and clinical indicators of Lewy body and Alzheimer's pathology
Authors: Simpson Austin J , Wyman-Chick Kathryn A , Daniel Michael S
Published: January 2025

Background

Clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) poses significant challenges due to pathological comorbidity. Similar ages of onset and overlapping cognitive and psychiatric symptoms can lead to diagnostic inaccuracy and inappropriate treatment recommendations.

Objective

Identify the best combination of clinical and neuropsychological predictors of AD, DLB, and mixed DLB/AD neuropathology in dementia patients.

Methods

Using the National Alzheimer's Coordinating Center dataset, we selected either pure AD ( n = 189), DLB ( n = 21), or mixed DLB/AD ( n = 42) patients on autopsy. Neuropsychological and clinical predictors, including core clinical features of DLB, were entered into multivariable logistic regressions.

Results

Gait disturbances (odds ratio (OR) = 19.32; p = 0.01), visual-spatial complaints (OR = 6.06; p = 0.03), and visual hallucinations (OR = 31.06; p = 0.002) predicted DLB compared to AD, along with better memory (OR = 3.42; p = 0.003), naming (OR = 3.35; p = 0.002), and worse processing speed (OR = 0.51; p = 0.01). When comparing DLB to DLB/AD, gait disturbances (OR = 6.33; p = 0.01), increased depressive symptoms (OR = 1.44; p = 0.03), and better memory (OR = 3.01; p = 0.004) predicted DLB. Finally, rapid eye movement sleep behavior disorder (RBD) (OR = 6.44; p = 0.004), parkinsonism severity (OR = 1.07; p = 0.02), and lower depressive symptoms (OR = 0.70; p = 0.006) and memory impairment (OR = 0.57; p = 0.02) distinguished DLB/AD from AD.

Conclusions

Our study converges with prior research suggesting specific neuropsychological and clinical features can help distinguish DLB from AD. Neuropsychological differentiation becomes more challenging among mixed pathologies and in advanced cognitive impairment, although the presence of RBD and parkinsonism distinguished DLB. Earlier clinical assessment and incorporation of in vivo and postmortem biomarkers should enhance diagnostic accuracy and understanding of disease characteristics, offering significant relevance for disease-modifying treatments.
Temporal modeling and AT profiles in the early phase of Alzheimer's disease
Authors: Platero Carlos
Published: January 2025

Background

Identifying markers that have predictive value for disease progression and clinical manifestations, such as mild cognitive impairment (MCI), is important to detect Alzheimer's disease (AD) early.

Objective

In this study, we combined biomarkers from amyloid and tau pathologies (AT profiles) with the prediction of diagnosis and the temporal evolution of clinical symptoms.

Methods

Multiple disease progression models were developed through supervised and unsupervised techniques via a two-stage data-driven approach. Models whose natural histories most closely resembled the diagnostic predictions were selected. Finally, various hypotheses regarding the progression of cognitive decline were tested using longitudinal patient data and AT profiles.

Results

At baseline, 22.5% of the cognitively unimpaired (CU) individuals and 46.2% of the CU converters (who progressed to MCI during the first four years) in the studied population had amyloid pathology (A+). Only a small subset of neuropsychological measures was used to predict cognitive decline and its timeline. The study revealed that amyloid pathology occurred approximately 5 years after cognitive decline in the population under investigation. Additionally, patients who were A+ at baseline experienced a more accelerated progression toward cognitive decline than those who were not (A−).

Conclusions

Based on the proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicate that only a single cerebrospinal fluid sample is necessary during the early phase of AD. The progression from CU to MCI and its timeline can be predicted exclusively through neuropsychological measures.
Heat shock protein 70 in Alzheimer's disease and other dementias: A possible alternative therapeutic
Authors: Valle-Medina Antonio , Calzada-Mendoza Claudia Camelia , Ocharan-Hernández María Esther , Jiménez-Zamarripa Carlos Alberto , Juárez-Cedillo Teresa
Published: January 2025

Alzheimer's disease (AD) is considered a global health issue with a high social burden due to the level of disability it causes in those who suffer from it. In the absence of a therapeutic alternative for this disease, we will follow one of the biochemical pathways involved in the development of AD, which is related to molecular chaperones. The molecules are responsible for eliminating toxins and misfolded proteins at the cerebral level. These chaperones are a set of proteins from the heat shock proteins (HSPs) family, which, among their functions, help maintain homeostasis and protect cells against stress. Various authors have described the activity of HSPs in different neurodegenerative diseases, highlighting the activity of heat shock protein 70 (HSP70) in the presence of aberrant proteins characteristic of neurodegeneration, such as amyloid-β (Aβ) and tau. The role of HSP70 in AD and other dementias lies in its mechanism, which, along with other proteins from the HSP family, has the capacity to eliminate Aβ aggregates by promoting catalytic pathways. In this review, we explore the biological role of the HSP70 protein in AD and other dementias and its potential therapeutic use
Alzheimer's disease classification by supervised and intelligent techniques
Authors: Mohamed Amine Jabli , Mourad Moussa ,   for the Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: January 2025

Background

Significant advancements in neuroimaging have emerged over the past decade, notably through positron emission tomography (PET) and magnetic resonance imaging (MRI) for diagnosing Alzheimer's disease (AD) and its precursor, mild cognitive impairment (MCI). Combining imaging modalities with machine learning (ML) techniques enhances diagnostic accuracy.

Objective

To develop predictive models using pre-treatment brain imaging data to distinguish between normal controls (NC), MCI, and AD stages, improving diagnostic precision.

Methods

We utilized the Alzheimer's Disease Neuroimaging Initiative database, processing 3D MRI, PET Florbetaben, and PET Flortaucipir images. Techniques included convolutional neural networks (CNN), fuzzy logic, and multi-layer perceptron (MLP). Feature extraction involved amyloid-β volume, tau protein levels, and empty space volumes.

Results

The fuzzy logic approach achieved a classification accuracy of 99.1%, outperforming CNN (90.67%) and MLP (94%). Integration of multimodal data significantly enhanced performance compared to single-modality approaches.

Conclusions

Our study demonstrates that integrating advanced ML techniques with multimodal neuroimaging can effectively classify AD stages. These findings address critical gaps in early detection and provide a foundation for future clinical applications.
The causal role of lipids in dementia: A Mendelian randomization study
Authors: Su Boyang , He Zhengqing , Mao Li , Huang Xusheng
Published: January 2025

Background

Increasing evidence suggests that abnormal lipid metabolism is one of the pathogeneses of dementia. It is necessary to reveal the relationship between lipids and dementia.

Objective

This study used bidirectional two-sample Mendelian randomization to explore the causal relationship between 179 lipid species and the risk of dementia.

Methods

We assessed the causal effects of 179 lipid species and four subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Inverse variance weighting, MR-Egger method, weighted median, simple mode, and weighted mode were used to analyze the relationship between lipids and dementia. Cochran's Q, MR-Egger intercept test, and MR-PRESSO test were used to test the heterogeneity and pleiotropy of the results. In addition, we performed an inverse MR analysis testing the causal effects of dementia on lipids.

Results

Our study revealed causal effects of glycerophospholipid, glycerolipid, and sterol on the risk of dementia. Phosphatidylcholine, phosphatidylinositol, and triglycerides play significant roles in AD. Notably, phosphatidylcholine played a protective role in both FTD and DLB. However, this study did not observe a significant effect of phosphatidylinositol on FTD. In the case of VaD, not only glycerophospholipid, but also glycerolipid, exerted an influence, but sterol was also a risk factor.

Conclusions

Our study provided new evidence supporting the causal role of genetically predicted lipid species in dementia. Future clinical trials are necessary to evaluate the potential role of lipid levels in dementia prevention.
Roadmap to advance therapeutics for SYNGAP1-related disorder: a patient organization perspective from SynGAP Research Fund
Authors: Graglia J. Michael , Harding Aaron J. , Helde Kathryn A.
Published: January 2025

SYNGAP1-related disorder (SRD) is a developmental and epileptic encephalopathy caused by a disruption of the SYNGAP1 gene. At the beginning of 2024, it is one of many rare monogenic brain disorders without disease-modifying treatments, but that is changing. This article chronicles the last 5 years, beginning when treatments for SRD were not publicly in development, to the start of 2024 when many SRD-specific treatments are advancing. We discuss the progress across many realms that have brought SRD to the forefront of drug development and highlight how Patient Advocacy Groups (PAGs) have had direct roles in accelerating the route to meaningful treatments for our children. We start with a summary of why SRD is an attractive pharmaceutical target. Second, we introduce the disease, the clinical features, and the number of patients. Next, we describe our PAG, our international partners and cite examples of the broad range of activities we believe are accelerating our pace toward treatments. We summarize the current SYNGAP1 pipeline and the status of each public project. Finally, we discuss two open questions that urgently need to be addressed in advance of clinical trials for SRD.
The start of a new journey: Decolonising the Global Mental Health curriculum
Authors: Sharp Laura , Foley Ailsa , Wilson Mia , Langan Martin Julie
Published: January 2025

Intellectual colonisation is defined as the imposition of Western knowledge systems onto non-Western cultures, resulting in the marginalisation and subordination of non-Western beliefs, practices, and technologies. Decolonisation aims to challenge this dominance. Higher Education Institutions play a crucial role in dismantling intellectual colonisation, and sustained efforts are needed to promote diverse perspectives. The authors adopt a critical pedagogy and cyclical improvement approach to develop inclusive and equitable learning environments. They have committed to the process of decolonising the curriculum, acknowledging it as ongoing and multifaceted. A range of staff-led developments have been initiated as understandings of decolonisation have deepened. Alumni have applied review tools related to decolonising the curriculum to identify potential improvement areas. A student workshop was facilitated to overview the initial project developments and gain insight on how to address the issues identified. Feedback from the diverse student cohort indicated this was highly valuable. The potential for student-staff partnerships in driving decolonising efforts has begun to be explored, but key challenges include resource constraints and the need for student upskilling. The project goal is to empower students and staff to acknowledge their positionality, critically engage, and adopt a decolonial lens in both educational and workplace arenas.
Linking changes in teacher discourse behaviors to changes in student learning outcomes in Hong Kong mathematics classrooms
Authors: Ng Oi-Lam , Ni Yujing , Shi Lian , Tam Winnie Wing Yi , Cheung Alan Chi-keung
Published: January 2025

This study investigated how changes in discourse behaviors of teachers receiving an intervention on dialogic classroom discourse might be associated with students’ mathematics learning outcomes. Thirty-two Hong Kong mathematics teachers and their 891 students (ages 9–10) participated in this study. The results of multilevel mediation analysis show an intervention effect on the amount of student talk in classroom discussions, students’ mathematical reasoning test scores, and their perceived interest in learning mathematics. However, the teacher discourse behaviors to evaluate students’ responses showed a negative mediation effect of the intervention on students’ perceived classroom participation. The results indicate that classroom discourse influences students in general and also culturally specific ways of student learning.
Optimal REIT Portfolio Selection Using Machine Learning
Authors: Zhang Wendi , Li Bin , Singh Tarlok , Liew Alan Wee-Chung , Roca Eduardo
Published: January 2025

Purpose

This study examines whether machine learning approaches can effectively solve the portfolio selection and optimization problems related to Real Estate Investment Trusts (REITs)-mixed portfolios. It also investigates the impact of different proportions of Equity-REIT (EREIT) and Mortgage-REIT (MREIT) on portfolio returns.

Study design

This research collects daily data from 157 EREITs and MREITs, totaling 1,283,800 observations, and construct 126 portfolios in the U.S. market, covering the period from January 1, 2000, to July 31, 2022. Using a genetic algorithm (GA), we optimize REITs combined with stocks, bonds, and gold, and compare GA’s performance with the classical mean-variance (MV) method. To assess robustness, authors also perform sub-period testing to examine portfolio performance under adverse economic conditions.

Findings

The results show that the GA outperforms the MV method in optimizing REIT-mixed portfolios, especially during periods such as the pre-Global Financial Crisis (GFC) and COVID-19. Portfolios with higher allocations to REITs exhibit superior returns, with EREIT outperforming MREIT in enhancing returns and controlling risk. However, MV shows better results in some low-volatility periods, such as during the GFC.

Contributions

This study advances existing literature by applying machine learning techniques—specifically genetic algorithms—to the optimization of REIT-mixed portfolios. The contributions include demonstrating the effectiveness of GA in achieving better risk-adjusted returns compared to traditional methods, providing practical insights for investors on optimizing their portfolios in volatile markets. Additionally, it highlights opportunities for researchers to further explore the integration of heuristic methods in portfolio management, expanding the understanding of portfolio optimization in the context of REITs.

Implications

Our findings provide practical implications for investors and portfolio managers, demonstrating the benefits of GA-based optimization in the REIT sector, particularly in turbulent market conditions.
The intersection of autistic traits, ADHD traits, and gender diversity in disordered eating and drive for muscularity within the general population
Authors: Thomas Kai S , Cooper Kate , Jones Catherine RG
Published: January 2025

Neurodivergent and gender diverse people are overrepresented among individuals with eating disorders. There also appears to be an epidemiological overlap between autism, ADHD, and gender diversity, making it difficult to disentangle their possible contributions to eating behaviours and body image, including restrictive eating and muscle-building behaviours. We examined the unique associations between neurodivergent traits, dimensional gender diversity, disordered eating (DE), and drive for muscularity in a UK general population sample ( N = 492; 324 assigned female at birth; 98.6% cisgender; M age = 41.44 years), using correlations and hierarchical multiple regressions. We found higher levels of autistic traits, ADHD traits, and gender diversity were associated with elevated DE. Nonbinary gender diversity, when one's gender identity exists between or outside of the gender binary, was associated with higher levels of drive for muscularity in people assigned female at birth, but with elevated DE in people assigned male at birth. Notably, ADHD traits were the only independent predictor of DE and drive for muscularity when controlling for co-occurring internalising symptoms. The study highlights an association between ADHD traits and both DE and drive for muscularity, even after controlling for internalising symptoms. Additionally, it demonstrates the crucial role of internalising symptoms when examining the associations between autistic traits, gender diversity, and DE.
Affect and self-regulation at work: How do we take messy theories to the task?
Authors: Gabriel Allison S. , Zipay Kate P. , Shurman Matthew W.
Published: January 2025

Within this editorial, we highlight the importance of testing and extending our understanding of core theories associated with affect and self-regulation at work. Specifically, we center our initial discussion on two theories that have garnered substantial attention within the organizational literature—control theory and social cognitive theory—highlighting how these theories offer differential predictions for the benefits of positive and negative affect at work. We then shift our focus on providing three theoretical and/or empirical misses that have significant potential to advance our science forward: (1) arbitrary selection of self-regulation theories within research studies; (2) oversimplifying affective experiences into broad categories of positive and negative affect; and (3) forgetting the complexity of multi-emotion (or ambivalent) events. Overall, we highlight theoretical and empirical contributions, as well as limitations, in this literature, and provide paths forward to enhance both our understanding of affect and self-regulation at work.
What About Nights, Weekends, and Wait Times? Adding an On-Demand Facilitated Telemedicine Buprenorphine Component to a Community-Based Peer Support Outreach Program
Authors: Winograd Rachel P. , Brown Katherine C. , Newman Schyler T. , Banks Devin E. , Carpenter Ryan W. , Budesa Zach , Lunceford Jennifer , Siddiqui Saad T. , Jasdanwala Sarfaraz , Wing Bradley , Orson Wendy
Published: January 2025

Background:

In 2020, loosened federal regulations allowed for buprenorphine for opioid use disorder to be initiated via telemedicine. In response to these regulatory changes and growing racial inequities in overdose in St. Louis, MO, a local, peer-led outreach program incorporated a new rapid access (RA) to buprenorphine program. RA facilitated same-day buprenorphine access by conducting peer-facilitated telemedicine visits in community settings.

Methods:

This study used logistic regression to compare 1- and 3-month treatment and buprenorphine retention between clients in the RA and Traditional (ie, linkage to brick-and-mortar prescribers within 1-3 days) programmatic arms of a peer-led outreach program between December 2020 and June 2022. Propensity score matching allowed participants across groups to be matched on key factors (eg, sex, race, homelessness). Racial differences in program receipt/enrollment were also assessed through Chi-squared tests.

Results:

Total program participation (N = 4139) included 1% (n = 52) in the RA program. Those in RA were more likely to be in treatment at 1 and 3 months and more likely to be on buprenorphine at 3 months compared to those in the Traditional group. The RA program included more White and fewer Black clients than expected. Four of the 8 reasons for non-enrollment differed by race, with Black individuals more likely to already have treatment secured but also more likely to decline the program or be unable to be contacted.

Conclusions:

This study is the first to demonstrate sustained benefits in treatment and medication engagement following same-day access to buprenorphine via community-based, peer-facilitated telemedicine. Lower-than-expected enrollment of Black individuals indicates a need for more culturally responsive implementation strategies for peer- and telemedicine-facilitated programs.
An assessment of current policy scenarios over the 21st century and the reduced plausibility of high-emissions pathways
Authors: Hausfather Zeke
Published: January 2025

The literature on current policy scenarios has become increasingly robust in recent years, with a growing consensus that the central estimate of 21st century warming is now likely below 3 °C. This reflects progress on both clean energy technologies and climate policies that has reduced the plausibility of high-emissions pathways, as well as a recognition that the higher end of emissions scenarios was never intended to represent the most likely no policy baseline outcome. However, it is difficult to fully preclude warming of 4 °C or more under a current policy world if there are continued positive emissions after 2100 or if carbon cycle feedbacks and climate sensitivity are on the high end of current estimates in the literature. Current policy scenarios are a useful benchmark for assessing climate impacts and the effects of further mitigation, but should not be seen as either a ceiling or a floor on future warming outcomes.
A frequency-domain beamforming procedure for extracting Rayleigh wave attenuation coefficients and small-strain damping ratio from 2D ambient noise array measurements
Authors: Abbas Aser , Aimar Mauro , Cox Brady R , Foti Sebastiano
Published: January 2025

The small-strain damping ratio plays a crucial role in assessing the response of soil deposits to earthquake-induced ground motions and general dynamic loading. The damping ratio can theoretically be inverted for after extracting frequency-dependent Rayleigh wave attenuation coefficients from wavefields collected during surface wave testing. However, determining reliable estimates of in situ attenuation coefficients is much more challenging than achieving robust phase velocity dispersion data, which are commonly measured using both active-source and ambient-wavefield surface wave methods. This article introduces a new methodology for estimating frequency-dependent attenuation coefficients through the analysis of ambient noise wavefield data recorded by two-dimensional (2D) arrays of surface seismic sensors for the subsequent evaluation of the small-strain damping ratio. The approach relies on the application of an attenuation-specific wavefield conversion and frequency-domain beamforming. Numerical simulations are employed to verify the proposed approach and inform best practices for its application. Finally, the practical efficacy of the proposed approach is showcased through its application to field data collected at a deep, soft soil site in Logan, Utah, USA, where phase velocity and attenuation coefficients are extracted from surface wave data and then simultaneously inverted to develop deep shear wave velocity and damping ratio profiles.
The world’s most venomous spider is a species complex: systematics of the Sydney funnel-web spider (Atracidae: Atrax robustus)
Authors: Loria Stephanie F. , Frank Svea-Celina , Dupérré Nadine , Smith Helen M. , Jones Braxton , Buzatto Bruno A. , Harms Danilo
Published: January 2025

The Sydney funnel-web spider Atrax robustus O. Pickard-Cambridge, 1877 is an iconic Australian species and considered among the most dangerously venomous spiders for humans. Originally described in 1877 from a single specimen collected in “New Holland”, this spider has a complex taxonomic history. The most recent morphological revision of funnel-web spiders (Atracidae) lists this species as both widespread and common in the Sydney Basin bioregion and beyond, roughly 250 km from the Newcastle area south to the Illawarra, and extending inland across the Blue Mountains. Morphological variability and venom diversity in this species appear to be unusually high, raising questions about species concepts and diversity in these spiders. In this study, we use a combination of molecular phylogenetics, divergence time analyses and morphology to establish the Sydney funnel-web spider as a complex of three species. The “real” Sydney funnel-web spider Atrax robustus is relatively widespread in the Sydney metropolitan region. A second species, Atrax montanus (Rainbow, 1914), which is revalidated here, overlaps but mainly occurs further south and west, and a third larger species, Atrax christenseni sp. nov., is found in a small area surrounding Newcastle to the north. The revised taxonomy for funnel-web spiders may have practical implications for antivenom production and biochemical studies on spider venoms. Although no human fatalities have occurred since the development of antivenom in the 1980s, antivenom for Sydney funnel-web spiders might be optimized by considering biological differentiation at the species level.
N6-methyladenosine RNA modification regulates the transcription of SLC7A11 through KDM6B and GATA3 to modulate ferroptosis
Authors: Zhang Haisheng , Yi Cheng , Li Jianing , Lu Yunqing , Wang Haoran , Tao Lijun , Zhou Jiawang , Tan Yonghuang , Li Jiexin , Chen Zhuojia , Asadikaram Gholamreza , Cao Jie , Peng Jianxin , Li Wanglin , He Junming , Wang Hongsheng
Published: January 2025

Background

Recent studies indicate that N6-methyladenosine (m6A) RNA modification may regulate ferroptosis in cancer cells, while its molecular mechanisms require further investigation.

Methods

Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS/MS) was used to detect changes in m6A levels in cells. Transmission electron microscopy and flow cytometry were used to detect mitochondrial reactive oxygen species (ROS). RNA sequencing (RNA-seq) was employed to analyze the factors regulating ferroptosis. Chromatin immunoprecipitation (ChIP) was used to assess the binding of regulatory factors to the SLC7A11 promoter, and a Dual-Luciferase reporter assay measured promoter activity of SLC7A11. The dm6ACRISPR system was utilized for the demethylation of specific transcripts. The Cancer Genome Atlas Program (TCGA) database and immunohistochemistry validated the role of the METTL3/SLC7A11 axis in cancer progression.

Results

The m6A methyltransferase METTL3 was upregulated during cancer cell ferroptosis and facilitated erastin-induced ferroptosis by enhancing mitochondrial ROS. Mechanistic studies showed that METTL3 negatively regulated the transcription and promoter activity of SLC7A11. Specifically, METTL3 induced H3K27 trimethylation of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases KDM6B. Furthermore, METTL3 suppressed the expression of GATA3, which regulated SLC7A11 transcription by binding to the putative site at − 597 to − 590 of the SLC7A11 promoter. METTL3 decreased the precursor mRNA stability of GATA3 through m6A/YTHDF2-dependent recruitment of the 3′-5′ exoribonuclease Dis3L2. Targeted demethylation of KDM6B and GATA3 m6A using the dm6ACRISPR system significantly increased the expression of SLC7A11. Moreover, the transcription factor YY1 was responsible for erastin-induced upregulation of METTL3 by binding to its promoter-proximal site. In vivo and clinical data supported the positive roles of the METTL3/SLC7A11 axis in tumor growth and progression.

Conclusions

METTL3 regulated the transcription of SLC7A11 through GATA3 and KDM6B to modulate ferroptosis in an m6A-dependent manner. This study provides a novel potential strategy and experimental support for the future treatment of cancer.
H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts
Authors: Bouchereau Wilhelm , Pham Hong-Thu , Samruan Worawalan , Vu Van-Hong , Joly Thierry , Afanassieff Marielle , Savatier Pierre , Parnpai Rangsun , Beaujean Nathalie
Published: January 2025

Post-translational modifications of histone H3 on lysine 9, specifically acetylation (H3K9ac) and tri-methylation (H3K9me3), play a critical role in regulating chromatin accessibility. However, the role of these modifications in lineage segregation in the mammalian blastocyst remains poorly understood. We demonstrate that di- and tri-methylation marks, H3K9me2 and H3K9me3, decrease during cavitation and expansion of the rabbit blastocyst. Notably, H3K9me3 levels are particularly low in inner cell mass cells at the onset of blastocyst formation but increase again just before gastrulation. Conversely, H3K9ac is abundant in early blastocyst stages but decreases during the transition from the inner cell mass to the epiblast. These distinct distribution patterns correlate with high expression levels of methyltransferases (EHMT1, EHMT2, SETDB1) and deacetylases (HDAC1, HDAC2, HDAC5) in expanding blastocysts. Functionally, inhibiting H3K9me2/3 through an EHMT1/2 inhibitor disrupts primitive endoderm segregation, whereas enhancing histone acetylation (including H3K9ac) using a class I HDAC inhibitor promotes epiblast expansion at the expense of the primitive endoderm. These modifications impact the expression of genes associated with pluripotency and lineage determination, underscoring the importance of H3K9 modifications in embryonic cell fate decisions.
Genomic analysis and replication kinetics of the closely related EHV-1 neuropathogenic 21P40 and abortigenic 97P70 strains
Authors: Mohamed Eslam , Zarak Ines , Vereecke Nick , Theuns Sebastiaan , Laval Kathlyn , Nauwynck Hans
Published: January 2025

Varicellovirus equidalpha 1, formerly known as Equid alphaherpesvirus 1 (EHV-1), is highly prevalent and can lead to various problems, such as respiratory problems, abortion, neonatal foal death, and neurological disorders. The latter is known as equine herpes myeloencephalopathy (EHM). Cases of EHM have significantly increased since the beginning of the twenty-first century. The genomic sequences of five isolates associated with the fatal neurological outbreak in Valencia, Spain, in 2021 were analyzed and documented. The genome and replication kinetics of the Belgian EHM isolate 21P40, associated with the Valencia outbreak, and the well-characterized abortigenic strain 97P70 were compared. Both strains exhibited a nucleotide identity of 99.96%, with only seven genetic mutations in ORFs 13, 24, 30, 32, 40, 65, and 71. Isoleucine and asparagine at loci 291 and 207 of ORF30 (DNA polymerase) and ORF65 (ICP22), respectively, were unique to isolates from the Valencia outbreak. The replication kinetics of these two genetically closely related strains were determined in rabbit kidney (RK-13), equine respiratory, and vaginal mucosal explant cells, as well as equine blood monocytes (CD172a+). Both strains replicated equally well in RK-13 cells. The neuropathogenic isolate 21P40 exhibited a more extensive infection in respiratory explants and blood monocytes, as demonstrated by more plaques and single infected leukocytes, and a higher percentage of infected monocytes. In contrast, vaginal explants infected with the abortigenic strain 97P70 demonstrated more plaques and single infected leukocytes. In conclusion, 21P40 replicated significantly different compared to 97P70 but shared similarities with the Belgian well-studied neuropathogenic EHV-1 strain 03P37.
Supervised machine learning statistical models for visual outcome prediction in macular hole surgery: a single-surgeon, standardized surgery study
Authors: Godani Kanika , Prabhu Vishma , Gandhi Priyanka , Choudhary Ayushi , Darade Shubham , Kathare Rupal , Hande Prathiba , Venkatesh Ramesh
Published: January 2025

Purpose

To evaluate the predictive accuracy of various machine learning (ML) statistical models in forecasting postoperative visual acuity (VA) outcomes following macular hole (MH) surgery using preoperative optical coherence tomography (OCT) parameters.

Methods

This retrospective study included 158 eyes (151 patients) with full-thickness MHs treated between 2017 and 2023 by the same surgeon and using the same intraoperative surgical technique. Data from electronic medical records and OCT scans were extracted, with OCT-derived qualitative and quantitative MH characteristics recorded. Six supervised ML models—ANCOVA, Random Forest (RF) regression, K-Nearest Neighbor, Support Vector Machine, Extreme Gradient Boosting, and Lasso regression—were trained using an 80:20 training-to-testing split. Model performance was evaluated on an independent testing dataset using the XLSTAT software. In total, the ML statistical models were trained and tested on 14,652 OCT data points from 1332 OCT images.

Results

Overall, 91% achieved MH closure post-surgery, with a median VA gain of -0.3 logMAR units. The RF regression model outperformed other ML models, achieving the lowest mean square error (MSE = 0.038) on internal validation. The most significant predictors of VA were postoperative MH closure status (variable importance = 43.078) and MH area index (21.328). The model accurately predicted the post-operative VA within 0.1, 0.2 and 0.3 logMAR units in 61%, 78%, and 87% of OCT images, respectively.

Conclusion

The RF regression model demonstrated superior predictive accuracy for forecasting postoperative VA, suggesting ML-driven approaches may improve surgical planning and patient counselling by providing reliable insights into expected visual outcomes based on pre-operative OCT features.

Clinical trial registration number

Not applicable.
Comparison of anterior versus posterior approach for the treatment of cervical compressive myelopathy due to ossification of the posterior longitudinal ligament
Authors: Gaber Amr A. A , Habib Mohamad Alaa El-Din , AbdelFatah Mohamed AR , Ghobashy Mostafa K.
Published: January 2025

Background

Cervical myelopathy refers to an impairment of the spinal cord. It frequently occurs due to constriction of the cervical spinal canal. Cervical spondylotic myelopathy is the primary reason for spinal cord impairment in older individuals. Ossification of the posterior longitudinal ligament (OPLL) is rare although potentially significant factor contributing to degenerative cervical myelopathy. The etiology of OPLL is inadequately understood.

Materials and methods

This research aims to perform a comprehensive review and meta-analysis to assess the clinical outcomes of both anterior and posterior techniques in treating cervical compressive myelopathy caused by cervical OPLL. A comparative study examining the surgical findings of anterior and posterior approaches for cervical myelopathy owing to OPLL was conducted between January 2006 and October 2021. We reviewed online databases such as PubMed, EMBASE, and the Cochrane Library. This systematic review and meta-analysis (MA) covered 12 research articles including 1070 participants.

Results

Showed no statistically significant variations among the anterior group and posterior group regarding preoperative modified Japanese Orthopedic Association Score (mJOA score) (P = 0.23, SMD = 0.9; heterogeneity: P = 0.85; I
2 = 18%). However, the postoperative mJOA score was significantly greater in the anterior group contrasted to the posterior group (P = 0.004, SMD = 0.67; heterogeneity: P < 0.001; I
2 = 82%). The anterior surgery group had a substantially greater overall recovery rate than the posterior surgery group, also the recovery rate was significantly greater with the anterior technique contrasted to the posterior technique in individuals with a COR ≥ 50% (P value < 0.01). The study also found that the incidence of postoperative consequences in the anterior group was significantly greater (P < 0.01, OR = 1.88). Additionally, the duration of surgery in the anterior group was significantly longer (P < 0.01, SMD = 1.52), and there was a larger amount of intraoperative blood loss (P = 0.04, SMD = 0.74).

Conclusion

The findings of this MA indicate that anterior approach surgery is linked to superior postoperative neurological outcomes compared to the posterior method in managing cervical compressive myelopathy resulting from OPLL. We considered the anterior technique to be particularly advantageous for those with a canal-occupying ratio (COR) greater than 50%-60%, even though it results in more surgical trauma and an increased incidence of complications associated with the procedure. The posterior approach surgery demonstrated a higher level of safety with less surgical trauma and a decreased incidence of complications. We recommend the posterior approach to individuals whose COR is below 50% to 60.
Applications of ultrafast nano-spectroscopy and nano-imaging with tip-based microscopy
Authors: Zhao Zhichen , Kravtsov Vasily , Wang Zerui , Zhou Zhou , Dou Linyuan , Huang Di , Wang Zhanshan , Cheng Xinbin , Raschke Markus B. , Jiang Tao
Published: January 2025

Innovation in microscopy has often been critical in advancing both fundamental science and technological progress. Notably, the evolution of ultrafast near-field optical nano-spectroscopy and nano-imaging has unlocked the ability to image at spatial scales from nanometers to ångströms and temporal scales from nanoseconds to femtoseconds. This approach revealed a plethora of fascinating light-matter states and quantum phenomena, including various species of polaritons, quantum phases, and complex many-body effects. This review focuses on the working principles and state-of-the-art development of ultrafast tip-enhanced and near-field microscopy, integrating diverse optical pump-probe methods across the terahertz (THz) to ultraviolet (UV) spectral ranges. It highlights their utility in examining a broad range of materials, including two-dimensional (2D), organic molecular, and hybrid materials. The review concludes with a spatio-spectral-temporal comparison of ultrafast nano-imaging techniques, both within already well-defined domains, and offering an outlook on future developments of ultrafast tip-based microscopy and their potential to address a wider range of materials.
An intersectional examination of the relationship between racial/ethnic discrimination and psychotic-like experiences: the role of other psychiatric symptoms
Authors: Ered Arielle , Lipner Emily , O’Brien Kathleen J. , Huque Zeeshan M. , Anglin Deidre M. , Ellman Lauren M.
Published: January 2025

Background

Racial and ethnic experiences of discrimination (EODs) are associated with numerous psychiatric symptoms, including outcomes along the psychosis spectrum; however, less is known about mechanisms by which EODs confer risk for psychotic-like experiences (PLEs; common subthreshold psychotic symptoms). Furthermore, work on gendered racism asserts that the intersection of race and gender impacts the nature of EODs experienced and, in turn, may impact the relationship between EODs and PLEs.

Aims

To utilize an intersectional lens (race and gender) to examine whether psychological correlates of EODs (post-traumatic stress, anxiety, depression, and dissociation) mediate the EOD–PLE relationship.

Methods

Undergraduates at a diverse, semipublic university (N = 1,759) completed self-report questionnaires (Experiences of Discrimination Scale, Prodromal Questionnaire, Center for Epidemiologic Studies Depression Scale, State–Trait Anxiety Inventory, Dissociative Experiences Scale, and Post-Traumatic Stress Disorder Checklist – Civilian Version). Analyses stratified the sample by race (non-Hispanic White, Black, and Asian) and examined three multiple mediation models, moderated by gender, examining the pathway from EODs to PLEs, through other psychiatric symptoms.

Results

In the full sample, all psychiatric symptoms significantly mediated the relationship between EODs and PLEs. Only depression varied by gender, such that the indirect effect was only significant in female participants (β = 0.09; 95% CI [0.02, 0.16]). Across race-stratified groups, significant mediators varied by both race and gender.

Conclusions

These findings underscore the importance of accounting for intersectionality and multiple psychological symptoms in understanding the EOD–PLE associations, which differ by race and ethnicity as well as gender, and should be considered in clinical treatment of individuals with PLEs and history of EODs.
Early career psychiatrists’ perceptions of and training experience in electroconvulsive therapy: A cross-sectional survey across Europe
Authors: Țăpoi Cristiana , Alexander Laith , de Filippis Renato , Agorastos Agorastos , Almeida Diogo , Bhatia Gautam , Erzin Gamze , Gołębiewska Martyna Ewa , Metaj Enita , Medved Sara , Mieze Krista , Milutinović Miloš , Noël Camille , Pushko Antonina , Gurrea Salas David , Compaired Sanchez Alejandro , Wilkowska Alina , Wolthusen Rick P. F. , Pinto da Costa Mariana
Published: January 2025

Background

Electroconvulsive therapy (ECT) is a safe and effective treatment for several major psychiatric conditions, including treatment-resistant depression, mania, and schizophrenia; nevertheless, its use remains controversial. Despite its availability in some European countries, ECT is still rarely used in others. This study aims to investigate the experiences and attitudes of early career psychiatrists (ECPs) across Europe towards ECT and to examine how their exposure to ECT influences their perceptions.

Methods

In Europe, a cross-sectional survey was conducted among ECPs, including psychiatric trainees and recently fully qualified psychiatrists.

Results

A total of 573 participants from 30 European countries were included in the study, of whom more than half (N = 312; 54.5%) received ECT training. Overall, ECPs had a positive attitude towards ECT, with the vast majority agreeing or strongly agreeing that ECT is an effective (N = 509; 88.8%) and safe (N = 464; 81.0%) treatment and disagreeing or strongly disagreeing that ECT was used as a form of control or punishment (N = 545; 95.1%). Those who had received ECT training during their psychiatry training were more likely to recommend ECT to their patients (p < 0.001, r = 0.34), and held more positive views on its safety (p < 0.001, r = 0.31) and effectiveness (p < 0.001, r = 0.33). Interest in further education about ECT was moderately high (modal rating on Likert scale: 4, agree), irrespective of prior training exposure.

Conclusions

ECT training is associated with more favorable perceptions of its safety and effectiveness among ECPs. There is a general willingness among ECPs to expand their knowledge and training on ECT, which could enhance patients’ access to this treatment.