bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A008: Epigenetic dynamics in KMT2A-amplified leukemia
Authors: Ogino Jayme , Liu Yang , Yang Wentao , Sukhanova Madina , Li Sheng , Dou Yali
Published: February 2025

The lysine methyltransferase KMT2A/MLL1 plays a crucial role in normal development and hematopoiesis. Rearrangement of KMT2A results in the formation of a KMT2A fusion protein with aberrant activity, which is a well-characterized driver of leukemogenesis and is therapeutically targetable. In contrast to the widely studied KMT2A translocation, the molecular consequences of other KMT2A alterations, including KMT2A amplification, remain unknown. KMT2A amplification is detected in highly aggressive and treatment-resistant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It strongly associates with TP53 mutations and complex karyotypes. Unlike KMT2A rearrangement, KMT2A amplification is reported mostly in patients older than 65 and treated with alkylating agents. Here, we conducted a comprehensive molecular analysis of KMT2A-amplified MDS/AML by long-read nanopore sequencing. We have revealed the unique epigenetic landscape, including DNA methylation, histone modification, and chromatin accessibility, associated with KMT2A amplification. We also explored the potential of targeting KMT2A or KMT2A-medicated pathways to block leukemogenesis. These results provide a foundation for targeting the KMT2A complex in KMT2A-amplified disease, representing a promising first step toward treating MDS/AML associated with KMT2A amplification.

Citation Format: Jayme Ogino, Yang Liu, Wentao Yang, Madina Sukhanova, Sheng Li, Yali Dou. Epigenetic dynamics in KMT2A-amplified leukemia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr A008.
Abstract B004: Promoter methylation gains in aging and cancer are independent of replication
Authors: Thursby Sara-Jayne , Jin Zhicheng , Patel Nibedita , Tao Yong , Bhandari Yuba , Petkovich Daniel , Lu Shangzhi , Yang Lijing , Wang Tza-Huei , Pisanic Thomas R. , Baylin Stephen B , Easwaran Hariharan
Published: February 2025

DNA methylation alterations are observed across multiple cancers, occurring early during tumor initiation. However, evolution and drivers of these changes remain poorly understood and difficult to assess at the clonal level. Consequently, we developed a method for profiling genome-wide DNA methylation from low DNA amounts and applied it to the organoid model of BRAFV600E oncogene-induced colon cancer (CC) tumorigenesis. Single organoid clones, derived from single stem cells, were profiled every month for 5 months to map nucleotide-level dynamic heterogeneity in methylation changes. Uninduced control organoids exhibit a pattern of epigenetic drift leading towards clonal convergence not until 5 months. Whereas BRAFV600E-induced organoids exhibit a step-wise divergence throughout the different time points, likely explained by progressive clonal takeovers. The methylation changes in BRAFV600E induced organoids are explained by the age-in-culture associated methylation changes; especially BRAFV600E did not induce epigenetic changes, as previously thought. The CpG sites affected in the control and BRAFV600E comparison were not shared but mapped to the same genomic elements, indicating common drivers of methylation changes regardless of oncogene. Investigation of promoter CpG-island methylation gains revealed that they are decoupled from replication. External validation in other pre-cancerous and CC datasets, and experimental cell line data sets, show that methylation gains at regulatory elements are a function of “biological aging” and independent of replication or cell division cycles. Our studies provide new insights into the early epigenetic changes involved in BRAFV600E driven carcinogenesis rooted in the age-dependent drivers of epigenetic alterations.

Citation Format: Sara-Jayne Thursby, Zhicheng Jin, Nibedita Patel, Yong Tao, Yuba Bhandari, Daniel Petkovich, Shangzhi Lu, Lijing Yang, Tza-Huei Wang, Thomas R. Pisanic II, Stephen B Baylin, Hariharan Easwaran. Promoter methylation gains in aging and cancer are independent of replication [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B004.
Abstract B005: The functional role of transposable element-oncogene chimeric transcript during cancer progression
Authors: Saintilnord Wesley N , Wu Yixin , Liang Yonghao , Wang Ting
Published: February 2025

Nearly half of the human genome is composed of transposable elements (TEs), which were once considered “junk” DNA due in part to their repetitive and non-coding characteristics. However, TEs are now emerging as important regulators of gene activity, especially when they escape typical epigenetic silencing mechanisms like DNA methylation and histone modifications. When activated, TEs can contribute sequences that are exploited as disruptors of genomic stability or novel gene regulatory elements, making them important factors in both development and disease, including cancer. In cancer, these previously silenced elements can act as alternative promoters of oncogenes, leading to the production of TE-chimeric transcripts in a process called “onco-exaptation”. While these oncoexaptation events are reported to be widespread across many cancers, only a few TE-chimeric transcripts have been validated as active contributors to cancer progression. Additionally, it remains unclear whether these TE-chimeric transcripts are merely a consequence of the inherent genomic instability in cancer or whether they can initiate cancer. To address these gaps, we designed a cDNA overexpression library incorporating our previously identified pan-cancer TE-chimeric transcript candidates. This library is used in early passage (EP) BJ fibroblast, a cell line known for its transformation potential in the well-established Weinberg transformation model, which allows us to systematically investigate these onco-exaptation events during cancer progression. Our initial analyses indicate that most TE-chimeric oncogenes are not expressed in EP fibroblast, but are activated in subsequent transformation stages following hTERT, SV40 and HRas induction, underscoring the model viability. We are currently using this model to distinguish TE-chimeric transcripts that act as drivers (TE-chimeric oncogenes) from those requiring previous vulnerabilities, such as telomere inactivation by hTERT or p53 and Rb inactivation by SV40. Ultimately, this work will identify novel biomarkers and therapeutic targets, enhance insights into gene regulation, and provide opportunities for early detection and intervention. These findings have the potential to improve cancer treatment and patient outcomes.

Citation Format: Wesley N Saintilnord, Yixin Wu, Yonghao Liang, Ting Wang. The functional role of transposable element-oncogene chimeric transcript during cancer progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B005.
Abstract B010: Concurrent analysis of multiple methylated CpG sites using multiplex MethyLight assay for epithelial ovarian cancer detection
Authors: Bisht Deepa , Sachan Manisha
Published: February 2025

Objective: Epithelial ovarian cancer (EOC), a heterogeneous and aggressive gynaecologic malignancy, remains a leading cause of cancer-related death due to the lack of reliable, sensitive, and specific early diagnostic biomarkers. Methods: This study employed a cost-effective, CpG site-specific Amplification Refractory Mutation System PCR (ARMS-PCR) to assess the methylation frequency of six diagnostically potent CpG sites (cg18878992, cg00480298, cg029572270, cg10636246, cg10061138, and cg12910797) in 45 EOC samples and 25 normal controls. Methylation patterns (methylated, unmethylated, partially methylated) were confirmed through image analysis and Combined Bisulfite Restriction Analysis (COBRA). Three top methylated CpG sites were chosen to form two biomarker panels, which were subsequently tested for diagnostic efficiency. Furthermore, a TaqMan-based quantitative PCR (MethyLight) assay was developed, integrating the three most hypermethylated CpG sites (cg02957270, cg00480298, and cg10061138) in a triplex format. Results: ARMS-PCR revealed the diagnostic potential of two hypermethylated CpG sites (cg02957270, cg10061138) and one hypomethylated site (cg10061138). The sensitivity of the singleplex and multiplex panels reached 80%, 73.3%, and 82.3%, respectively. The MethyLight assay demonstrated an enhanced sensitivity of 86% and specificity of 92% for the multiplex panel (cg02957270 and cg00480298) along with control col2A1. ROC curve analysis revealed AUC values of 0.96, 0.91, and 0.84 for the singleplex assays and 0.97 for the multiplex panel. While ARMS-PCR showed limited correlation with clinicopathological characteristics, significant associations were found in the MethyLight assay (p < 0.05). Conclusions: This discovery opens a new frontier in DNA methylation research, suggesting the potential to harness clinically relevant, independent CpG sites, in hypermethylated state for the development of novel biomarkers.

Citation Format: Deepa Bisht, Manisha Sachan. Concurrent analysis of multiple methylated CpG sites using multiplex MethyLight assay for epithelial ovarian cancer detection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B010.
Abstract B015: Collection and purification of microgram amounts of cfDNA from urine for methylation analysis
Authors: Taub Floyd , Ray Lindsey , Neff Charles Preston , Barstis Elijah , Henry Charles , Arnold Kirsten
Published: February 2025

Background: DNA methylation studies often require relatively large amounts of DNA, typically methods suggest hundreds of nanograms to a microgram per assay. While this is easy to obtain if genomic DNA (gDNA) is used, preforming similar studies on circulating cell free DNA (cfDNA) may be difficult. Plasma, especially that from normal individuals needed for comparison, may yield only 10 ng to 20 ng per ml. Thus, experimental designs involving multiple repeat analysis of the same specimen, or applying different complementary methylation methods to one specimen, may be limited by the amount of cfDNA in a blood sample. It is known that urine contains cfDNA, but reports on the amount vary from very low to being comparable to blood; the conflicting data may be due in part to the low yield some methods of isolation have reported to have when the DNA is small. Hypothesis: We postulated that a system which filtered hundreds of mls of urine and captured the DNA based on charge rather than absorption to silica, could capture adequate amounts of cfDNA from urine for repeat studies. Results: Initially, filtering large amounts of urine was problematic due to clogging. A system of stacked filters was devised. The method uses 200- 250 ml size syringes and 5 cm filter cartridges. It allows full voids, in fact up to 1 liter, to be filtered. The urine is first collected in a measuring cup containing preservatives, it is immediately filtered. This is simple enough to be done by a patient at home. The first of the stacked filters, collects urothelial and other cells that may be used to analyze gDNA; it also clarifies the urine sufficiently to pass through a second lower pore size filter modified to be highly positively charged. On average, a 150 ml void provides 2100 nanograms of cfDNA. The binding to the filter is sufficiently strong that DNases cannot bind or digest the DNA. Thus, the DNA is stable in the cartridge for four days and allows for shipping without special handling. The in-lab purification consists of separating the filters, then washing the cfDNA trapping filter, followed by elution of the DNA. It takes under 10 minutes and results in purified DNA that is suitable for downstream analysis. Conclusions: Microgram amounts of cfDNA can be easily extracted from urine to facilitate initial analyses sufficient for statistically robust studies and banking of specimens for future testing.

Citation Format: Floyd Taub, Lindsey Ray, Charles Preston Neff, Elijah Barstis, Charles Henry, Kirsten Arnold. Collection and purification of microgram amounts of cfDNA from urine for methylation analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B015.
Abstract B026: NEBNext® enzymatic solutions for DNA methylation profiling at picogram scale
Authors: panchapakesa Vaishnavi , Ponnaluri Chaithanya , Evanich Daniel , Campbell Matthew , Blum Laura , Langhorst Bradley , Williams Louise
Published: February 2025

DNA methylation is an important epigenetic regulator of gene expression. 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) play distinct roles in epigenetic regulation, however the ability to distinguish between 5mC and 5hmC is often lost as they are frequently read as a combined signal in traditional sequencing approaches. NEBNext Enzymatic Methyl-seq v2 (EM-seq v2) and NEBNext Enzymatic 5hmC-seq (E5hmC-seq) are enzymatic approaches used to investigate cytosine methylation. EM-seq v2 detects both 5mC and 5hmC whereas E5hmC-seq detects only 5hmC. The first step for each method protects either 5mC and/or 5hmC from deamination by APOBEC enzyme. Cytosines are deaminated to uracil in EM-seq v2 whereas for E5hmC-seq, 5mC and cytosine bases are converted to thymine and uracil respectively. Using a subtractive data analysis approach, whereby E5hmC-seq data is subtracted from EM-seq data, the locations of 5mC and 5hmC can be decoupled at single base resolution. EM-seq v2 libraries and E5hmC-seq libraries were prepared using 0.1 ng to 200 ng of genomic DNA. Both methods leave DNA intact and result in superior sequencing libraries with longer insert sizes, lower duplication rates and minimal GC bias as well as accurately detecting methylation down to 0.1 ng DNA. These methods are streamlined due to reduced library preparation time as well as the removal of a cleanup step. Coverage of genomic features such as CpG islands and enhancers, for both methods were maintained to 1 ng but dropped as expected with the 0.1 ng inputs. EM-seq v2 and E5hmC-seq provides consistent methylation metrics for inputs ranging from 0.1 ng to 200 ng. EM-seq v2 and E5hmC-seq libraries provide accurate measurements across inputs from 0.1 ng – 200 ng with expected methylation, insert sizes and minimal GC bias. In addition, combining E5hmC-seq and EM-seq data to discriminate between 5mC and 5hmC will provide key insights into the role of these cytosine modifications in development and disease.

Citation Format: Vaishnavi panchapakesa, Chaithanya Ponnaluri, Daniel Evanich, Matthew Campbell, Laura Blum, Bradley Langhorst, Louise Williams. NEBNext® enzymatic solutions for DNA methylation profiling at picogram scale [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B026.
Abstract B028: Epigenetic landscape and gene regulations in embryonal brain tumors with multilayered rosettes (ETMR)
Authors: Wang Shanzheng , Lambo Sander , Mauermann Monika , Autry Robert J , Jäger Natalie , Pfister Stefan M , Kool Marcel
Published: February 2025

Embryonal Tumors with Multilayered Rosettes (ETMRs) are relatively rare but aggressive embryonal brain tumors that mainly affect children under the age of 4 and which have a poor outcome. Around 90% of ETMRs harbor amplification of the C19MC miRNA cluster, in most cases fused to the TTHY1 gene. The second most recurrent aberration, present in about half of the C19MC negative cases, are bi-allelic mutations in DICER1. ETMRs are also characterized by overall lower DNA methylation levels and high LIN28A gene expression as compared with other embryonal brain tumors like medulloblastomas (MB) and atypical teratoid rhabdoid tumors (ATRT). However, a more detailed description of the epigenetic landscape marked by DNA methylation and histone modifications, and how this affects the ETMR transcriptome is still lacking. To decode the epi-genome, we have collected whole genome bisulfite sequencing (WGBS) data, ChIP sequencing (ChIP-seq) data of various (active and repressive) histone marks and epigenetic modifiers (EZH2, BRD4, CTCF), and RNA sequencing (RNA-seq) data from a series of ETMR patient tumors, and similar data from a series of MBs and ATRTs covering all molecular subtypes for comparison reasons. Using all these data and performing bioinformatic analyses, we have depicted chromatin states and DNA-methylation-defined genomic segments of ETMR for the first time. ETMR genomes are generally hypomethylated, with wider distributions of un-methylated regions and DNA methylation valleys (DMVs) on its genome compared with MB and ATRT. By integrating these data with all other omics data, we found that BRD4-regulated overexpression of TET demethylases may cause global hypomethylation in ETMRs. Polycomb and TETs are recruited at DMVs to ensure DMVs are longer in ETMRs than MBs and ATRTs. Furthermore, genes involved in embryo development and cell proliferation are enriched in entity-shared DMVs and are highly expressed in ETMRs and other embryonal brain tumors. We also depicted that TET family members, BRD4, and Polycomb complex (EZH2) are potential therapeutic targets for ETMR patients. In conclusion, we have partially described the epi-genome and epigenetic regulations of ETMR, and are currently working on more detailed regulation axes and performing drug test experiments for these potential therapeutic targets to understand better the underlying biology of these tumors and how this may lead to alternative and more effective therapies.

Citation Format: Shanzheng Wang, Sander Lambo, Monika Mauermann, Robert J Autry, Natalie Jäger, Stefan M Pfister, Marcel Kool. Epigenetic landscape and gene regulations in embryonal brain tumors with multilayered rosettes (ETMR) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B028.
Abstract IA022: Harnessing epigenetic profiles in MDS for the development of predictive biomarkers
Authors: Figueroa Maria E
Published: February 2025

While significant progress has been made in understanding the genetic landscape of MDS, less is known about the epigenetic makeup of this disease and how this may impact biology and response to azacitidine (AZA). To address this, we performed genomic, epigenomic, and transcriptomic analyses on CD34+ cells from a multicenter cohort of 94 intermediate or higher-risk MDS patients treated with AZA who had documented responses. DNA methylation (DNAme) by ERRBS, gene expression (GE) by RNA-seq, mutational profiling, and detailed clinical, cytogenetic, and laboratory data were documented. Supervised and unsupervised analyses revealed that aberrant DNAme in MDS is not distributed randomly but rather is highly correlated with disease phenotypes, capturing clinically relevant heterogeneity, beyond what is identified by methodologies used in the past that focused solely on promoter regions. Moreover, this epigenetic information can be harnessed for the development of robust biomarkers predictive of AZA response and integrative approaches combining clinical, mutation, GE and DNAme data can further improve the predictive performance of these biomarkers, with an AUC score=0.94.

Citation Format: Maria E Figueroa. Harnessing epigenetic profiles in MDS for the development of predictive biomarkers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA022
Improving Outcomes in Hepatocellular Carcinoma through Integration of Machine Learning: Development of a Tumor-Associated Macrophage Signature
Authors: Zhou Zicheng , Ge Sijia , Gu Chiyu , Chen Jing , Lu Cuihua , Liu Yanhua , Jiang Sutian
Published: February 2025

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally. Macrophages, as essential components of the immune system, play crucial roles in immune regulation, inflammation modulation, and antitumor activity. However, it remains unclear whether tumor-associated macrophages can serve as prognostic markers for HCC.
Methods: First, we identified tumor-associated macrophages based on single-cell data from GSE140228. Then, using a machine learning approach with a combination of 101 module genes, we constructed an optimal prognostic model. Subsequently, we compared our constructed model with other published prognostic models for HCC. Finally, we utilized the generated model score to predict the response to chemotherapy and immune therapy.
Results: First, we identified clusters of tumor-associated macrophages using single-cell data. Subsequently, we calculated the tumor-associated macrophage score based on module genes from the previous step. Compared to traditional clinical indicators, tumor-associated macrophage signature (TAMS) exhibits significant advantages. The TAMS C-index not only predicts overall survival, but also recurrence-free survival in HCC patients. Additionally, there was a higher prevalence of TP53 mutations in HCC patients with high TAMS. Furthermore, patients with low TAMS showed greater sensitivity to immunotherapy compared to those with high TAMS. Notably, the number and intensity of interactions between TAM and other T lymphocytes were significantly higher than those involving other cell populations. Interestingly, the high TAMS group exhibited significantly elevated levels of immune checkpoint markers and M2 macrophage markers.
Conclusion: TAMS can serve as a novel and potent tool, offering improved treatment options and prognostic assessment for patients with HCC.
The Riddles of Nerses Shnorhali in the Yaysmawurk Collections
Authors: Khachatryan Ovsanna
Published: February 2025

The article is dedicated to the riddles by St. Nerses Shnorhali that are included in the Yaysmawurk (hereafter Synaxarium) collections. We have attempted to show that the inclusion of riddles in these collections is not a result of chance but has a specific purpose. All of the Synaxarium collections examined within the scope of this article were edited by Grigor Khlatetsi. This fact, along with several other key pieces of evidence, indicates that the inclusion of riddles into the Synaxarium collections was carried out by Khlatetsi, and that this occurred at the beginning of the 15th century. By incorporating riddles, Khlatetsi aimed to make the Synaxarium more accessible to the general public and to facilitate the understanding of the Lives of the Saints, given that the Synaxarium collections served as pedagogical tool for a period. Thus, by incorporating riddles into the Synaxarium collections, Khlatetsi established a distinctive genre juxtaposition that is unique within the Armenian medieval literature.
Do Unwanted Births Affect the Educational Well-Being of Indian Children? Evidence from a Panel Study
Authors: Paul Ronak , Rashmi Rashmi
Published: February 2025

In India, the occurrence of unwanted births is linked to the growing preference for smaller family sizes, revealing a gap between family planning goals and effective contraception. While previous studies have acknowledged the adverse health outcomes of unwanted births, there is limited literature on their impact on educational well-being. This study examines the effect of unwanted births on the educational well-being of Indian children, using data from the India Human Development Survey panel of 6,575 children aged 1–4 in 2005, followed up in 2012. Using the principal component factor analysis and propensity score matching, we found that unwanted births significantly reduce both objective and subjective educational well-being scores. Additionally, improved sanitation, higher socioeconomic status, and greater educational attainment among adults, especially females, in households were associated with better educational outcomes. The findings highlight the importance of effective family planning programmes to reduce unwanted births and enhance child development in India.

JEL Codes: C31, C38, C52, I24, J13, Y8
Dynamics of Adult Child-Mother Relationships in Emerging Adulthood by Gender and Race
Authors: Thomeer Mieke Beth , Reczek Rin , Cao Rui , Ferguson Dee
Published: February 2025

Despite the turbulence of emerging adulthood, past research has mostly overlooked within-person heterogeneity in adult children’s levels of contact and closeness with their mothers during this period. Research further obscures how such temporal relationship patterns may vary across sociodemographic categories. We identify unique trajectories of the adult child-mother relationship using sequence analysis on the National Longitudinal Survey of Youth 1979-Young Adult data set (N = 2,299). About one-third of mother-adult child dyads are characterized by consistently high levels of contact and closeness. The other two-thirds shift considerably over this life course stage, with differences in trajectory distributions by gender and race. For example, White sons are the least likely to be in the only socially positive group, whereas Black sons are the least likely to be in the low closeness group. We provide a social-psychological-informed perspective on intergenerational relationships during emerging adulthood, which highlights how social location shapes intergenerational dynamic ties during children’s emerging adult life course stage.
The global market and the war: Origins, development, and effectiveness of marginalist irenicism
Authors: Giachetti Fulvia
Published: February 2025

The current crisis of the liberal world order manifested, primarily in the outbreak of new wars of global significance, can be read and diagnosed in many ways. One is identifying it by radically questioning the view that the globalized market can produce international order and peace. The article reconstructs and investigates the main theoretical assumptions of this view, tracing them, especially to the marginalist tradition, whose historical-conceptual trajectory and main effects it analyzes, from the scientific disputes of Eugen Böhm-Bawerk’s Privatseminar to the theoretical and militant activity of Friedrich August von Hayek. Finally, the article turns to the main effects of marginalism on global history, arriving at the thesis of its, at least momentary, historic failure.
The efficacy of vortioxetine in the acute treatment of major depressive disorder: A systematic review and meta-analysis
Authors: Berardelli Isabella , Rogante Elena , Formica Federico , Iannazzo Riccardo , Mammoliti Attilio Valerio , Riccioni Raffaele , Veizi Skender , McIntyre Roger S , Pompili Maurizio
Published: February 2025

Background:

Among the available pharmacological treatments for acute major depressive disorder (MDD), vortioxetine, a serotonin transporter inhibitor (SERT), has been widely used for its multimodal action on serotonin neurotransmission, which produces essential changes also on glutamate, gamma amino butyric acid (GABA), norepinephrine, acetylcholine, and dopamine.

Aim:

This systematic review and meta-analysis aimed to evaluate the acute efficacy of vortioxetine across multiple dosing and to evaluate whether there is a dose–response effect and as well there is a dose–response issue with respect to side effects in acute depression.

Methods:

According to PRISMA guidelines, we systematically searched three major electronic databases (PubMed/MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials) for Randomized Controlled Trial (RCT) studies published between January 2013 and April 2024. Twenty-four studies were included in the review and two meta-analyses were conducted to determine whether the mean Montgomery–Asberg Depression Rating Scale (MADRS) scale values in the placebo groups differ significantly from the mean MADRS scale values in the group receiving vortioxetine 10 mg or vortioxetine 20 mg.

Results:

Vortioxetine significantly improved acute depression severity, anxiety symptoms, and cognitive function, with high response and remission rates in acute MDD. It was also well tolerated with a relatively low occurrence of severe or serious treatment-emergent adverse events (TEAEs). Observing the results of the meta-analysis, the effect was significant for both vortioxetine 10 and 20 mg, with a greater effect size for vortioxetine 20 mg.

Conclusion:

Vortioxetine should be considered efficacious as a first- and second-line therapy.
Circulating cell-free DNA as a potential biomarker for prediction of disease activity and prognosis among Egyptian rheumatoid arthritis patients
Authors: Taha Sara I , Samaan Sara F , Hawash Sally Saber , El-Sehsah Eman M , Shamloul Sara , Elsheikh Dalia Hussein Helmy , Othman Basim , Albanghali Mohammad A , Aljadani Saeedah H , Elmanna Abdalla , Ghorab Rasha Ahmed
Published: February 2025

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls ( P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels ( P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores ( P-values <0.05) but did not correlate significantly with tenosynovitis scores ( P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients ( P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.
Everyday Acts of Resistance in Teachers’ Work: Leaders Making Distinctions Between Responsibility and Accountability
Authors: Talbot Debra
Published: February 2025

International studies mark a shift in the language of teachers from professional autonomy to safety induced by compliance measures. What is not well-documented is how teachers resist the pervasive, negative effects of accountability regimes. This paper contrasts teachers’ most creative classroom practice and professional learning with the effect of externally imposed accountability requirements. School leader research conversations support an argument that leaders who remained future-focused on responsibility initiated a culture in which resistance, to being governed by retrospective practices associated with accountability, was possible. Everyday acts of resistance, however, are vulnerable to institutional capture when regimes of accountability become normalised.
The perception and use of generative AI for science-related information search: Insights from a cross-national study
Authors: Greussing Esther , Guenther Lars , Baram-Tsabari Ayelet , Dabran-Zivan Shakked , Jonas Evelyn , Klein-Avraham Inbal , Taddicken Monika , Agergaard Torben Esbo , Beets Becca , Brossard Dominique , Chakraborty Anwesha , Fage-Butler Antoinette , Huang Chun-Ju , Kankaria Siddharth , Lo Yin-Yueh , Nielsen Kristian H. , Riedlinger Michelle , Song Hyunjin
Published: February 2025

Publicly accessible large language models like ChatGPT are emerging as novel information intermediaries, enabling easy access to a wide range of science-related information. This study presents survey data from seven countries ( N = 4320) obtained in July and August 2023, focusing on the perception and use of GenAI for science-related information search. Despite the novelty of ChatGPT, a sizable proportion of respondents already reported using it to access science-related information. In addition, the study explores how these users perceive ChatGPT compared with traditional types of information intermediaries (e.g. Google Search), their knowledge of, and trust in GenAI, compared with nonusers as well as compared with those who use ChatGPT for other purposes. Overall, this study provides insights into the perception and use of GenAI at an early stage of adoption, advancing our understanding of how this emerging technology shapes public understanding of science issues as an information intermediary.
Bleed and Blood: An Indian Anathema
Authors: Rao Ratna , Patil Surekha , Haritha Guduru
Published: February 2025

The current study, titled “Bleed and Blood—An Indian Anathema,” gives an Indian perspective on the stigma faced by women in the feminist geography of India. It discusses menstrual activism, menstruation, and periods’ religious and cultural significance. The history of why and when menstruation became a stigma and why it is shunned in India is also discussed. It also focuses on the theory of shame and isolation and menstrual equity from a menstruation point of view. The research amalgamates within its fold a survey covering educated professionals, both women and men of their changed perspectives. The survey for men indicates that though they do not think of menstruation as a taboo but as a mere biological process, they still believe in some practices. The survey conducted for women includes 21 questions based on the three principles of stigma proposed by Erving Goffman, namely the interpersonal, sociocultural, and individual stigma. The survey gives a direction that though the women are coming out of their trauma and now talk more freely about menstruation, stereotypes and taboos related to menstruation are prevalent. It is observed that menstrual equity is gradually emerging among Indian women. The survey responses emphasize the need for social media to be more proactive in helping women fight against taboos and trauma.
Authoring a Muslim Feminist “Self” Through Travel Writing: Reclaiming Agency Through Islam
Authors: Langah Nukhbah Taj , Shah Waqar Ali
Published: February 2025

This article aims to analyze nineteenth and twentieth-century travel writing by a Muslim woman writer, Nur Begum, who embarked on a 3-month journey to perform Hajj (pilgrimage). We aim to unravel her deliberate choice of poetic form as travel writing, which we argue consciously manifests her resistance against the prevailing patriarchal norms set by the Muslim culture. The study draws on Bakhtin’s dialogic framework of the human “self” as an agent engaged in constant negotiation of meanings as he emphasizes the link between human struggle for voice and their activity and growth. Within this theoretical framework, we decipher how Nur Begum authors her “feminist self” in a struggle to articulate her voice against patriarchy that denies her individuality. Moreover, we use insights from Muslim feminist scholarship (e.g. post-patriarchal reading of Islam and feminist theology) to explain how selected verses from Nur Begum’s travel writing deconstruct the myths emerging from the patriarchal interpretation of Islam and social practices in Muslim societies.
Effect of Green Human Resource Management on Green Creativity and Organizational Citizenship Behaviour Towards Environment: The Mediating Role of Green Work Engagement
Authors: Ishaque Sadia , Akmal Muhammad , Masood Samra , Ansari Nabeel Younas
Published: February 2025

Green human resource management is a vital organizational strategy that fosters growth. Despite the rising scholarly interest in studying green human resource management (GHRM), few studies have examined its impact on pro-environment employees’ behaviour and attitudes in mitigating environmental footprint and enhancing business sustainability. Hence, to address this research gap, this study extended the scope of green research by examining the impact of GHRM on green creativity (GC) and organizational citizenship behaviour towards environment (OCBE), focusing on the mediating role of GWE. Three hundred and ten employees working in the Brazilian manufacturing industry were surveyed. The statistical evaluation was performed by using structural equation modelling. The results suggest that the mediating effect of GWE improves the employee’s GC and OCBE. The current research findings are essential for developing HR strategies to achieve results and promote environmental protection and sustainability.
Acute Kidney Injury and Mortality Predictors of Systemic Autoimmune Diseases and Coronavirus Disease 2019: A Single Centre Observational Study from India
Authors: Nasar Ariba , Aslam Mohd. , Ansari Ahmad Ghayas
Published: February 2025

Introduction:

Systemic autoimmune diseases are known to have a significant impact on renal function, with varying degrees of severity that can influence overall patient outcomes. This study aims to assess the impact of Coronavirus Disease-2019 (COVID-19) on the renal outcomes associated with the spectrum of systemic autoimmune diseases.

Material and Methods:

This observational study was conducted in Jawaharlal Nehru Medical College, Aligarh, from 1 November 2020 to 31 October 2021, to evaluate outcomes in patients with systemic autoimmune diseases and COVID-19 who developed acute kidney injury (AKI).

Results:

A total of 129 patients with systemic autoimmune diseases were admitted, out of which 51 patients with AKI were included in the study. Of those, 18 patients were COVID-19 RT-PCR positive. The most common systemic autoimmune disorder observed was systemic lupus nephritis (35.3%) followed by rheumatoid arthritis (RA) (19.6%) and seronegative spondyloarthropathy (SpA) (17.6%). The most common renal manifestation observed was drug-induced kidney injury (37.2%) followed by lupus nephritis (29.4%), thrombotic microangiopathy (7.8%) and renal artery stenosis (7.8%). Patients who were COVID-19 RT-PCR positive ( P <.01), those who required inotropic support ( P <.01), ventilatory support ( P <.01), Intensive Care Unit admission ( P <.01), haemodialysis ( P <.01) and with peripheral oxygen saturation <94% at presentation ( P <.01), were significantly associated with mortality. The need for ventilatory support was observed as an independent predictor of mortality in patients with renal involvement and COVID-19 ( P <.01).

Conclusion:

The present study sheds light on the outcome of AKI in systemic autoimmune diseases and COVID-19, with the use of ventilatory support significantly contributing to mortality.
Can Herding Be Adaptive? Evidence from Markets Sentiment, News Sentiment and Happiness in Global Energy Markets
Authors: Loang Ooi Kok
Published: February 2025

This study investigates the adaptive nature of herding behaviour in global energy markets, focusing on the USA, Europe and Asia, from January 2013 to December 2023. Utilizing advanced sentiment analysis tools, including Thomson Reuters MarketPsych Indices, Bloomberg Sentiment Analysis and the Hedonometer, this study captures real-time fluctuations in market mood. By employing Cross-Sectional Absolute Deviation models, static regression, rolling regression and quantile-on-quantile regression, this study examines the impact of investor sentiment, news sentiment and happiness on herding behaviour under varying market conditions. The findings revealed significant regional variations and underscored the dynamic and context-dependent aspects of herding behaviour. In the USA, higher levels of investor happiness and positive market sentiment are linked to increased herding behaviour, whereas negative news sentiment is linked to reduced herding behaviour. Similar but less pronounced patterns are observed in Europe, whereas Asian markets show weaker correlations, highlighting the critical role of market volatility and trading volume. These insights offer valuable implications for portfolio management, regulatory frameworks and investment strategies, thus enhancing the understanding of herding behaviour in volatile and sentiment-driven markets.
Anesthetic Management for Proximal Aortic Repair
Authors: Powell Thomas R. , Shah Emily B. , Khalifa Ali , Orozco-Sevilla Vicente , Tolpin Daniel A.
Published: February 2025

Surgical repair of the proximal aorta is a complex endeavor, requiring cardiopulmonary bypass (CPB) and often the use of hypothermic circulatory arrest (HCA). In addition to the normal considerations for patients undergoing cardiopulmonary bypass, additional challenges include cerebral and end-organ protection during periods of circulatory arrest. This review aims to provide an up-to-date, evidence-based review on anesthetic management for proximal aortic repair.
The discursive function of Meta’s Newsroom: How Meta frames the problem of problematic online content
Authors: Hurcombe Edward , Dehghan Ehsan , Vodden Laura , Angus Daniel
Published: February 2025

This article examines the social technology company Meta’s public communication on problematic content, via their official ‘Meta Newsroom’, within the context of growing regulatory scrutiny. For nearly a decade, the Meta Newsroom has been a major outlet for Meta company announcements, and since 2016, the Newsroom has increasingly become a key source for company responses to concerns regarding mis/disinformation and other kinds of problematic content on Meta’s platforms. Using a mixed-methods approach informed by discourse analysis, this article critically examines Newsrooms posts from 2016 to early 2021. It asks: how is Meta framing ‘problems’ on its platforms? How is Meta identifying ‘solutions’ to those problems? And is Meta ‘nudging’ policymakers in specific conceptual directions? Overall, we find that Meta is framing content moderation issues through four key frames – ‘authenticity’, ‘political advertising’, ‘technological solutions’, and ‘enforcement’ – that benefit Meta, as they shift responsibility while also demonstrating that Meta is an active and capable problem-solver.
Psychological well-being factors and the likelihood of transitioning from overweight and obesity to normal weight at population level: Evidence from two cohort studies of UK adults
Authors: Putra I Gusti Ngurah Edi , Daly Michael , Robinson Eric
Published: February 2025

We examined the prospective associations between psychological well-being related factors (depressive symptoms, life satisfaction, self-efficacy) and transitioning from overweight and obesity to normal body weight (vs persistence of overweight and obesity) and change in body mass index (BMI). We used multiple baselines and follow-ups from the National Child and Development Study (NCDS; 8513 observations) and the British Cohort Study (BCS; 11,113 observations). A proportion (8%–9%) of participants with overweight and obesity (BMI ≥25) at baseline transitioned into normal weight (BMI 18.5–<25) by follow-ups. There was no evidence of better psychological well-being related factors (e.g. lower depressive symptoms) being significantly associated with a transition from overweight and obesity to normal weight or reduced BMI in each cohort and pooled cohort analyses. However, age and gender were associated with transition. At population level, better psychological well-being may not be associated with likelihood of weight loss once obesity is developed in adulthood.
Unraveling the causal role of sleep traits in development of diabetic retinopathy: A UK Biobank observational study and Mendelian randomization
Authors: Huang Yikeng , Xu Xiaoyin , Zhang Xinyu , Zhu Xinyu , Li Bo , Ma Mingming , Zhou Chuandi , Gu Chufeng , Jiang Yujin , Wu Yanlin , Zheng Zhi , Zhao Shuzhi
Published: February 2025

Aims

To evaluate the potential causal role of sleep traits (STs) on diabetic retinopathy (DR).

Methods

The cross-sectional study included 23,851 patients with type 2 diabetes from the UK Biobank and used multivariate logistic models to investigate the observational association between STs and DR. Genetic correlation analysis and two-sample Mendelian randomization (MR) were conducted using ST data from the UK Biobank and DR data from the FinnGen consortium to investigate the genetic and causal associations between STs and DR.

Results

Patients who experienced daytime sleepiness often/all of the time had a higher risk for DR (OR: 1.40; 95% CI, 1.09–1.79; p = .008) compared with those who sometimes/never/rarely experienced daytime sleepiness. Genetic correlations between several STs and DR were detected by cross-trait linkage disequilibrium score regression. MR suggested a causal effect of self-reported daytime sleepiness (OR: 4.08; 95% CI, 1.44–11.61; p = .008), and accelerator-derived sleep duration (OR: 0.73; 95% CI, 0.54–0.98; p = .036) and sleep efficiency (OR: 0.54; 95% CI, 0.36–0.80; p = .002) on DR.

Conclusions

STs may have a potential causal role for DR. Attention should be paid to the STs of patients for better prevention and treatment of DR.
Incidence of Surgery for Pediatric Wrist Ganglion Cysts
Authors: Rancu Albert L. , Kammien Alexander J. , Katsnelson Beatrice M. , Diatta Fortunay H. , Lewis Katelyn , Grauer Jonathan N. , Colen David L.
Published: February 2025

Background:

While diagnosis of ganglion cysts of the wrist in the pediatric population is common, data on management are limited. This study describes a nationwide analysis of the incidence and treatment of pediatric ganglion cysts.

Methods:

Patients who were diagnosed with a wrist ganglion cyst were identified from the PearlDiver database. Exclusion criteria included age over 18 years, incidence of different cyst diagnosis codes, fewer than 6 months of records prior to first diagnosis, and fewer than 2 years of follow-up. The use of imaging and common treatments for ganglion cysts including bracing, aspiration/injection, and surgery were noted. Patients were followed for 2 years, and factors associated with undergoing surgery were analyzed. Trends in the diagnosis and surgical management of ganglion cysts by age were observed.

Results:

A total of 33 884 patients with a ganglion cyst on the wrist were identified. Diagnoses increased exponentially with age, while the percentage of patients who underwent surgery increased linearly with age. Those who underwent surgery tended to be older and were more likely to be female. These patients were also more likely to have undergone ultrasound or magnetic resonance imaging. There was a statistically significant difference in prior use of nonoperative management between patients that did and did not undergo surgery.

Conclusion:

This study offers a nationwide analysis of pediatric ganglion cysts. These findings are important to consider during longitudinal patient counseling and surgical planning.