bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. ,   for the COLUMBUS Consortium, Fejerman Laura 
Published: December 2024

Abstract

Background:
A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women.

Methods:
PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve.

Results:
Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry.

Conclusions:
A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice.

Impact:
The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.
The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application
Authors: Monette Anne , Aguilar-Mahecha Adriana , Altinmakas Emre , Angelos Mathew G. , Assad Nima , Batist Gerald , Bommareddy Praveen K. , Bonilla Diana L. , Borchers Christoph H. , Church Sarah E. , Ciliberto Gennaro , Cogdill Alexandria P. , Fattore Luigi , Hacohen Nir , Haris Mohammad , Lacasse Vincent , Lie Wen-Rong , Mehta Arnav , Ruella Marco , Sater Houssein Abdul , Spatz Alan , Taouli Bachir , Tarhoni Imad , Gonzalez-Kozlova Edgar , Tirosh Itay , Wang Xiaodong , Gnjatic Sacha 
Published: December 2024

Abstract
With immuno-oncology becoming the standard of care for a variety of cancers, identifying biomarkers that reliably classify patient response, resistance, or toxicity becomes the next critical barrier toward improving care. Multiparametric, multi-omics, and computational platforms generating an unprecedented depth of data are poised to usher in the discovery of increasingly robust biomarkers for enhanced patient selection and personalized treatment approaches. Deciding which developing technologies to implement in clinical settings ultimately, applied either alone or in combination, relies on weighing pros and cons, from minimizing patient sampling to maximizing data outputs, and assessing the reproducibility and representativeness of findings, while lessening data fragmentation toward harmonization. These factors are all assessed while taking into consideration the shortest turnaround time. The Society for Immunotherapy of Cancer Biomarkers Committee convened to identify important advances in biomarker technologies and to address advances in biomarker discovery using multiplexed IHC and immunofluorescence, their coupling to single-cell transcriptomics, along with mass spectrometry–based quantitative and spatially resolved proteomics imaging technologies. We summarize key metrics obtained, ease of interpretation, limitations and dependencies, technical improvements, and outward comparisons of these technologies. By highlighting the most interesting recent data contributed by these technologies and by providing ways to improve their outputs, we hope to guide correlative research directions and assist in their evolution toward becoming clinically useful in immuno-oncology.
METTL3-Mediated m6A Modification Regulates the Polycomb Repressive Complex 1 Components BMI1 and RNF2 in Hepatocellular Carcinoma Cells
Authors: Chen Weina , Zhang Jinqiang , Ma Wenbo , Liu Nianli , Wu Tong 
Published: December 2024

Abstract
Methyltransferase-like 3 (METTL3) is a primary RNA methyltransferase that catalyzes N6-methyladenosine (m6A) modification. The current study aims to further delineate the effect and mechanism of METTL3 in hepatocellular carcinoma (HCC). By using a murine model of hepatocellular cancer development induced via hydrodynamic tail vein injection, we showed that METTL3 enhanced HCC development. In cultured human HCC cell lines (Huh7 and PLC/PRF/5), we observed that stable knockdown of METTL3 by short hairpin RNA significantly decreased tumor cell proliferation, colony formation, and invasion, in vitro. When Huh7 and PLC/PRF/5 cells with short hairpin RNA knockdown of METTL3 were inoculated into the livers of SCID mice, we found that METTL3 knockdown significantly inhibited the growth of HCC xenograft tumors. These findings establish METTL3 as an important oncogene in HCC. Through m6A sequencing, RNA sequencing, and subsequent validation studies, we identified BMI1 and RNF2, two key components of the polycomb repressive complex 1, as direct downstream targets of METTL3-mediated m6A modification in HCC cells. Our data indicated that METTL3 catalyzed m6A modification of BMI1 and RNF2 mRNAs which led to increased mRNA stability via the m6A reader proteins IGF2BP1/2/3. Furthermore, we showed that the METTL3 inhibitor, STM2457, significantly inhibited HCC cell growth in vitro and in mice. Collectively, this study provides novel evidence that METTL3 promotes HCC development and progression through m6A modification of BMI1 and RNF2. Our findings suggest that the METTL3–m6A–BMI1/RNF2 signaling axis may represent a new therapeutic target for the treatment of HCC.
Implications: The METTL3–m6A–BMI1/RNF2 signaling axis promotes HCC development and progression.
Claudin-4 Stabilizes the Genome via Nuclear and Cell-Cycle Remodeling to Support Ovarian Cancer Cell Survival
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia G. , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G. 
Published: December 2024

Abstract
Alterations in the interplay between the nucleus and the cell cycle during cancer development lead to a state of genomic instability, often accompanied by observable morphologic aberrations. Tumor cells can regulate these aberrations to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer, overexpression of claudin-4 significantly contributes to therapy resistance through mechanisms associated with genomic instability regulation. However, the molecular mechanisms underlying claudin-4 overexpression in epithelial ovarian cancer remain poorly understood. In this study, we modified claudin-4 expression and employed a unique claudin mimic peptide to investigate claudin-4’s function. Our findings show that claudin-4 supports ovarian cancer cell survival by stabilizing the genome through nuclear and cell-cycle remodeling. Specifically, claudin-4 induced nuclear constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, thereby altering nuclear structure and dynamics. Similarly, cell-cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability in tumors. Importantly, disrupting claudin-4’s biological effects using claudin mimic peptide and forskolin increased the efficacy of PARP inhibitor treatment, correlating with alterations in the oxidative stress response. Our data indicate that claudin-4 protects tumor genome integrity by modulating the crosstalk between the nucleus and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability–inducing agents.

Significance:
High-grade serous ovarian carcinoma is marked by chromosomal instability, which can serve to promote disease progression and allow cancer to evade therapeutic insults. The report highlights the role of claudin-4 in regulating genomic instability and proposes a novel therapeutic approach to exploit claudin-4–mediated regulation.
The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain
Authors: Gomez Daniel E.P. , Polimeni Jonathan R. , Lewis Laura D. 
Published: December 2024

Abstract
The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter which blurs rapid changes. However, the shape and timing of hemodynamic responses are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of functional MRI (fMRI) signals, or the ability of fMRI to preserve fast information, could also vary substantially across the cortex. In this work we investigated how local differences in hemodynamic response timing affect the temporal specificity of fMRI. We used ultra-high-field (7T) fMRI at high spatiotemporal resolution, studying the primary visual cortex (V1) as a model area for investigation. We used visual stimuli oscillating at slow and fast frequencies to probe the temporal specificity of individual voxels. As expected, we identified substantial variability in temporal specificity, with some voxels preserving their responses to fast neural activity more effectively than others. We investigated which voxels had the highest temporal specificity, and tested whether voxel timing was related to anatomical and vascular features. We found that low temporal specificity is only weakly explained by the presence of large veins or cerebral cortical depth. Notably, however, temporal specificity depended strongly on a voxel’s position along the anterior-posterior anatomical axis of V1, with voxels within the calcarine sulcus being capable of preserving close to 25% of their amplitude as the frequency of stimulation increased from 0.05 Hz to 0.20 Hz, and voxels nearest to the occipital pole preserving less than 18%. These results indicate that detection biases in high-resolution fMRI will depend on the anatomical and vascular features of the area being imaged, and that these biases will differ depending on the timing of the underlying neuronal activity. While we attribute this variance primarily to hemodynamic effects, neuronal non-linearities may also influence response timing. Importantly, this spatial heterogeneity of temporal specificity suggests that it could be exploited to achieve higher specificity in some locations, and that tailored data analysis strategies may help improve the detection and interpretation of fast fMRI responses.
Assessing the impact of environmental education in a critical orangutan landscape in West Kalimantan, Indonesia
Authors: Robinson Natalie J. , Achmad Mariamah , Freund Cathryn A. , Naruri Ranti , O’Connell Caitlin A. , Rahman Edi , Selfiany Widiya Octa , Knott Cheryl D. 
Published: December 2024

Abstract
Gunung Palung National Park (GPNP) and the surrounding region in West Kalimantan, Indonesia, host a significant population of Critically Endangered Bornean orangutans (Pongo pygmaeus wurmbii) amidst various conservation challenges, including habitat destruction, the illegal pet trade, and human-wildlife conflict. The Gunung Palung Orangutan Conservation Program (GPOCP) employs diverse strategies, including environmental education, to address these challenges. Environmental education helps to connect local students with conservation efforts, educate them about endangered endemic species, and highlight the relationship between human behavior and ecosystem health. Environmental education is critical in fostering sustainable behaviors and raising awareness about conservation issues, particularly in areas where human activities threaten primate biodiversity. Such programs can promote long-term conservation outcomes by engaging communities and empowering individuals to take action. Here, we review the effectiveness of GPOCP’s environmental education initiatives, focusing on school visits conducted between 2016 and 2023 that concentrated on orangutan conservation. We analyze data from standardized pre- and post-activity surveys administered to students participating in puppet shows and lectures. Results indicate a substantial increase in knowledge and positive shifts in attitudes toward orangutan conservation among students. However, challenges remain in evaluating long-term behavioral changes and the relative contribution of different conservation interventions. Future efforts will explore tailored educational approaches and impact assessments to enhance conservation outcomes and foster community engagement in safeguarding Bornean orangutans and their habitat.
Helluari Libris
Authors: Walsh Robyn Faith 
Published: December 2024

Abstract
This essay engages the theme “Manufacturing Religion: From Christian Origins to Classical Islam” by challenging scholarly assumptions about the rapid reception and cohesion of new or developing philosophical and religious movements in Greek and Roman antiquity. To illustrate this issue, I present two interrelated case studies: late Republic/early imperial Stoicism and its possible intersections with the later Christ movement of the first century. At a time when engagement with literate culture conferred a great deal of social capital, I suggest that the relative flexibility and “openness” of these two movements allowed for those seeking prestige, social mobility, or distinction – or those who were otherwise excluded from the top tiers of society – to participate in intellectual practices that emulated the standards of the elite. This model for understanding early Christianity counters traditional approaches within the study of religion that tend to foreground notions like belief, conversion and so forth as an explanatory model for membership over sociological and material motivations. This discussion also troubles understandings of Stoicism that tend to link it anachronistically with its later and more exalted imperial associations.
The Impact of Cumulus Clouds and CCN Regeneration on Aerosol Vertical Distribution and Size
Authors: Arieli Yael , Khain Alexander , Gavze Ehud , Altaratz Orit , Eytan Eshkol , Koren Ilan 
Published: December 2024

Abstract
This study employs a high-resolution (10 m) System for Atmospheric Modeling (SAM) coupled with the spectral bin microphysical (SBM) scheme to thoroughly investigate the processes governing the evolution of aerosol properties within and outside a shallow cumulus cloud. The model encompasses the complete life cycle of cloud droplets, starting from their formation through their evolution until their complete evaporation or sedimentation to the ground. Additionally, the model tracks the aerosols’ evolution both within the droplets and in the air. Aerosols are transported within the droplets, grow by droplet coalescence, and are released into the atmosphere after droplet evaporation (regeneration process). The aerosol concentration increases by droplet evaporation and decreases along with falling drops. So, the effects of clouds on the surrounding aerosols depend on the microphysical and dynamic processes, which in turn depend on the amount of background aerosols; here, we compare clean and polluted conditions. It is shown that the regeneration process is highly important and that shallow trade cumulus clouds significantly impact the vertical profile of aerosol concentration in the lower troposphere, as well as their size distribution, and can serve as a source of large cloud condensation nuclei. Furthermore, it is shown that both precipitating and nonprecipitating boundary layer clouds contribute to a substantial increase in aerosol concentration within the inversion layer due to intense evaporation.
The Impact of Sit-Stand Desks on Full-Day and Work-Based Sedentary Behavior of Office Workers: A Systematic Review
Authors: Silva Hélio , Ramos Pedro G. F. , Teno Sabrina C. , Júdice Pedro B. 
Published: December 2024

Objective To gather the existing evidence on the impact of sit-stand desk-based interventions on working-time and full-day sedentary behavior and compare their impact across different intervention lengths. Background Reducing sedentary behavior is vital for improving office workers’ health. Sit-stand desks promote sitting and standing alternation, but understanding their effects outside the workplace is essential for success. Methods Studies published between January 2008 and January 2024 were searched through electronic databases (PubMed, Google Scholar, and Cochrane Library). The quality of the studies was assessed using the Quality Assessment Tool for Quantitative Studies of the Effective Public Health Practice Project. Results Twelve included studies showed that the intervention group experienced average reductions in full-day sedentary behavior of 68.7 min/day at 3 months, 77.7 min/day at 6 months, and 62.1 min/day at 12 months compared to the control group. For working hours sedentary behavior, reductions were observed in the intervention group at 9 weeks (73.0 min/day), 3 months (88.0 min/day), 6 months (80.8 min/day), and 12 months (48.0 min/day) relative to the control group. Conclusions Sit-stand desk interventions can be effective in helping office workers reduce sedentary behavior in the short, medium, and long-term both at work and throughout the full-day. Application Active workstation interventions, including sit-stand desks, educational sessions, and alert software, aim to reduce sedentary behavior among office workers. While sit-stand desks show promise in decreasing sitting time during working hours, their long-term effectiveness and impact beyond the workplace remain uncertain. This review evaluates their effectiveness across different durations, addressing both workplace and full-day impact.
Ensuring quality information for patients tool to assess patient information on CABG websites: Systemic search and evaluation
Authors: Wai Tai Chun , Wing Kwan Lam , Chan Jeremy , Angelini Gianni D 
Published: December 2024

Background Coronary artery bypass surgery (CABG) is the most common cardiac surgical procedure worldwide. The Internet is often the first place for patients to obtain medical information and may influence their health-seeking behaviour. This study aimed to assess the quality of online CABG information for patients. Methods A review was conducted on the available CABG information online using four search terms in Google: “coronary artery bypass grafting”, “CABG”, “bypass surgery”, and “coronary surgery”. Websites on the first three pages of each search term were assessed by two independent assessors using the Ensuring Quality Information for Patients (EQIP) tool (score 0-36). Results 71 websites in total were eligible for the evaluation. Most websites originated from the USA and the UK (35% for both). The median EQIP score was 16.5. Most websites used everyday language (94%) in short sentences (83%). More than half (60%) of the websites addressed qualitative complications and risks of surgery. Only 1/3 of the websites described treatment alternatives, precautions before surgery, and warning signs after surgery. Only about 1/10 of websites could address quality-of-life issues and resolution of complications. Conclusion Most online sites concerning CABG scores were low in EQIP tool assessment in terms of quality and readability with insufficient sources. Minimal information is provided regarding the quantitative risks and complications. Enhancement of the credibility and informativeness of websites is needed to reduce patients’ anxiety about surgical procedures and help with treatment options for coronary artery disease. Education and investigation on the consistency of high-quality websites may help patient identify high quality medical information.
Occupational therapy in pain management: An exploration and description of current UK practice
Authors: Slee Rebecca , Warren Alison , Noonan Miriam , Henderson Tristan 
Published: December 2024

Introduction: There is a growing body of evidence regarding the contribution to the management of chronic pain by occupational therapists. However, there is limited research available regarding contemporary practice in the United Kingdom (UK). Method: An on-line questionnaire was circulated via social media, profession specific publications and specialist interest groups. Responses were requested from UK-based Health and Care Professions Council registered occupational therapists who identified working with those living with chronic pain and their friends, family and supporters. Findings: A total of 26 occupational therapists responded. Occupational therapists are working in diverse service settings, offering a range of interventions and recognised the unique contribution by occupational therapists to this area of practice. Perceived barriers to delivering intervention included staffing levels, understanding of the occupational therapists’ role and suggestions for additional interventions were stated. Conclusion: This research increases understanding of UK-based occupational therapist’s current practice in pain management and views of their role. It provides considerations for further research including how to increase awareness of occupational therapy’s contribution to this area of practice, exploring the occupational needs of individuals and those of friends, family and supporters to ensure intervention is designed to best meet the needs of this population.
Examining the Digital Technology Usage of Older Adults as Determinants of Life Satisfaction in the Digital Divide
Authors: Jun Mina , Kim Miyea , Han Jeongsoo 
Published: December 2024

The digital divide has become a growing source of inequality, as older adults face challenges in adopting and using digital technologies in daily life. Few studies have explored how different types of digital technology usage in various life domains among older adults impact their overall well-being. This study addresses this gap by suggesting effective directions for reducing the cross-generational digital divide. To this end, it analyzed de-identified secondary data from 864 South Korean adults above 65 years, surveyed by the National Information Society Agency (NIA). The findings show that digital efficacy positively affects older adults’ life satisfaction, mediated by their perceptions of digital technology. Additionally, social networking through digital technology positively influences their life satisfaction through the same mediation. Our findings suggest that policymakers should prioritize the development of educational programs to improve digital efficacy and social networking, which will ultimately enhance older adults’ well-being.