bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression
Authors: Huang Lanshan , Winter Sarah J. , Olsson Linnea T. , Hamilton Alina M. , Halliday Sophia R. , Kirk Erin L. , Farnan Laura , Gerstel Adrian , Craig Stephanie G. , Finn Stephen P. , LaBonte Wilson Melissa , Jain Suneil , Troester Melissa A. , Butler Eboneé N. , Bensen Jeannette T. , Wobker Sara E. , Allott Emma H. 
Published: September 2024

Abstract

Background:
Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood.

Methods:
We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy and 101 radiation-treated patients with prostate cancer in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of hematoxylin and eosin–stained tissues was applied to quantify tumor-infiltrating lymphocytes in segmented regions. NanoString gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue, and a 50-gene signature utilized to predict immune cell types.

Results:
Vigorous recreational activity, reported by 34 (29.1%) UNC CSC men, was inversely associated with tumor-infiltrating lymphocyte abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression–predicted abundance of Th, exhausted CD4 T cells, and macrophages. T-cell subsets, including regulatory T cells, Th, Tfh, exhausted CD4 T cells, and macrophages, were associated with an increased risk of biochemical recurrence, only among men with ERG-positive tumors.

Conclusions:
Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T-cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer.

Impact:
Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression and may provide insights into how vigorous exercise could affect prostate tumor biology.
Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group
Authors: Wyatt Alexander W. , Litiere Saskia , Bidard Francois-Clément , Cabel Luc , Dyrskjøt Lars , Karlovich Chris A. , Pantel Klaus , Petrie Joan , Philip Reena , Andrews Hillary S. , Vellanki Paz J. , Tolmeijer Sofie H. , Villalobos Alberu Xenia , Alfano Christian , Bogaerts Jan , Calvo Emiliano , Chen Alice P. , Toledo Rodrigo A. , de Vries Elisabeth G.E. , Seymour Lesley , Laurie Scott A. , Garralda Elena ,   for the RECIST ctDNA workshop group
Published: September 2024

Abstract
Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggest that measuring on-treatment changes in the amount or proportion of ctDNA in peripheral blood plasma may accurately identify responding and nonresponding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class and must be assessed before ctDNA can be considered a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST and offer opportunities for developing novel early endpoints for modern clinical trials.
The Dark Knight: Functional Reprogramming of Neutrophils in the Pathogenesis of Colitis-Associated Cancer
Authors: Ghosh Sreya , Zanoni Ivan 
Published: September 2024

Abstract
Neutrophils are the primary myeloid cells that are recruited to inflamed tissues, and they are key players during colitis, being also present within the tumor microenvironment during the initiation and growth of colon cancer. Neutrophils fundamentally serve to protect the host against microorganism invasion, but during cancer development, they can become protumoral and lead to tumor initiation, growth, and eventually, metastasis—hence, playing a dichotomic role for the host. Protumoral neutrophils in cancer patients can be immunosuppressive and serve as markers for disease progression but their characteristics are not fully defined. In this review, we explore the current knowledge on how neutrophils in the gut fluctuate between an inflammatory or immunosuppressive state and how they contribute to tumor development. We describe neutrophils’ antitumoral and protumoral effects during inflammatory bowel diseases and highlight their capacity to provoke the advent of inflammation-driven colorectal cancer. We present the functional ambivalence of the neutrophil populations within the colon tumor microenvironment, which can be potentially exploited to establish therapies that will prevent, or even reverse, inflammation-dependent colon cancer incidence in high-risk patients.
Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment
Authors: Rahal Zahraa , Liu Yuejiang , Peng Fuduan , Yang Sujuan , Jamal Mohamed A. , Sharma Manvi , Moreno Hannah , Damania Ashish V. , Wong Matthew C. , Ross Matthew C. , Sinjab Ansam , Zhou Tieling , Chen Minyue , Tarifa Reischle Inti , Feng Jiping , Chukwuocha Chidera , Tang Elizabeth , Abaya Camille , Lim Jamie K. , Leung Cheuk Hong , Lin Heather Y. , Deboever Nathaniel , Lee Jack J. , Sepesi Boris , Gibbons Don L. , Wargo Jennifer A. , Fujimoto Junya , Wang Linghua , Petrosino Joseph F. , Ajami Nadim J. , Jenq Robert R. , Moghaddam Seyed Javad , Cascone Tina , Hoffman Kristi , Kadara Humam 
Published: September 2024

Abstract
Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.
The effectiveness of progressive muscle relaxation for air traffic controller in Indonesia
Authors: Saleh Lalu Muhammad , Russeng Syamsiar S. , Tadjuddin Istiana , Yanti Iva Hardi , Syafitri Nurul Mawaddah , Rahmadani Yulianah , Yusbud Mahfuddin 
Published: September 2024

<span>Evaluation of progressive muscle relaxation (PMR) intervention testing is deemed necessary for air traffic controllers as their role in controlling aircraft airways requires high focus with stable physical and mental conditions. This study aimed to analyze the effectiveness of progressive muscle relaxation in improving health status, quality of life, and reducing psychological fatigue in air traffic controllers. A quasi-experimental pre-test post-test control group design was employed, involving 184 participants separated into intervention and control groups. The results showed that there was a significant difference in the pulse rate, oxygen level, specific diastolic blood pressure, depression, anxiety, quality of life domains 1 and 2, as well as feelings of fatigue before and after progressive muscle relaxation was implemented with p&lt;0.05 but not in control group at the end of the observation. The Mann-Whitney U-Test results indicated that anxiety and pulse rate are variables reduced significantly in the two groups. It can be concluded that the implementation of PMR is effective to improve the health status, quality of life, and reduce psychological fatigue among controller in Indonesia. </span>
Tokens of Reality: On the Prospective Nature of Virtual Consciousness
Authors: Hancock P.A. 
Published: September 2024

Abstract
This work concerns the distinction of the nature of an individual's conscious reality via the use of a “truth token.” The latter can, most readily, be represented as a unique object or bespoken pattern that is exclusively associated with that person's originating reality. It is a talisman that permits an unequivocal return to that reality upon demand. These objects, or even neurocognitive patterns, access sensory-perceptual, memorial, and/or action-based profiles to characterize their individuality and to subsequently activate their function. The advantages of, and barriers to, achieving the successful implementation of such touchstones are considered here in light of contemporary problems with verifying currently reported expressions of reality, and future challenges to unique distinctions amongst the potentialities for technologically-enabled multi-worlds.
Grey Areas in Maritime Delimitation
Authors: Gaja Giorgio 
Published: September 2024

Abstract
This article considers some recent jurisprudence in maritime boundary delimitation that results in the creation of ‘grey areas’. Such grey areas have generated uncertainty in practice, specifically concerning claims to entitlements and the rights that States may exercise in such areas. The article reviews the two Bay of Bengal cases (International Tribunal for the Law of the Sea 2012 and the Annex VII Tribunal 2014) and two cases before the International Court of Justice (Somalia v. Kenya 2021; Nicaragua v. Colombia 2023), indicating the need for delimitation of maritime areas and legal rights to reflect the ‘physical reality at the time of delimitation’.
Ferrostatin-1 ameliorates Cis-dichlorodiammineplatinum(II)-induced ovarian toxicity by inhibiting ferroptosis
Authors: Zhang Lu , Dong Zhe , Jiang Fan , Huang Huaju , Ding Hui , Liu Meimei 
Published: September 2024

AbstractCis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets.
Distinguishing word identity and sequence context in DNA language models
Authors: Sanabria Melissa , Hirsch Jonas , Poetsch Anna R. 
Published: September 2024

AbstractTransformer-based large language models (LLMs) are very suited for biological sequence data, because of analogies to natural language. Complex relationships can be learned, because a concept of "words" can be generated through tokenization. Training the models with masked token prediction, they learn both token sequence identity and larger sequence context. We developed methodology to interrogate model learning, which is both relevant for the interpretability of the model and to evaluate its potential for specific tasks. We used DNABERT, a DNA language model trained on the human genome with overlapping k-mers as tokens. To gain insight into the model′s learning, we interrogated how the model performs predictions, extracted token embeddings, and defined a fine-tuning benchmarking task to predict the next tokens of different sizes without overlaps. This task evaluates foundation models without interrogating specific genome biology, it does not depend on tokenization strategies, vocabulary size, the dictionary, or the number of training parameters. Lastly, there is no leakage of information from token identity into the prediction task, which makes it particularly useful to evaluate the learning of sequence context. We discovered that the model with overlapping k-mers struggles to learn larger sequence context. Instead, the learned embeddings largely represent token sequence. Still, good performance is achieved for genome-biology-inspired fine-tuning tasks. Models with overlapping tokens may be used for tasks where a larger sequence context is of less relevance, but the token sequence directly represents the desired learning features. This emphasizes the need to interrogate knowledge representation in biological LLMs.
scBubbletree: computational approach for visualization of single cell RNA-seq data
Authors: Kitanovski Simo , Cao Yingying , Ttoouli Dimitris , Farahpour Farnoush , Wang Jun , Hoffmann Daniel 
Published: September 2024

Abstract
Background
Visualization approaches transform high-dimensional data from single cell RNA sequencing (scRNA-seq) experiments into two-dimensional plots that are used for analysis of cell relationships, and as a means of reporting biological insights. Yet, many standard approaches generate visuals that suffer from overplotting, lack of quantitative information, and distort global and local properties of biological patterns relative to the original high-dimensional space.

Results
We present scBubbletree, a new, scalable method for visualization of scRNA-seq data. The method identifies clusters of cells of similar transcriptomes and visualizes such clusters as “bubbles” at the tips of dendrograms (bubble trees), corresponding to quantitative summaries of cluster properties and relationships. scBubbletree stacks bubble trees with further cluster-associated information in a visually easily accessible way, thus facilitating quantitative assessment and biological interpretation of scRNA-seq data. We demonstrate this with large scRNA-seq data sets, including one with over 1.2 million cells.

Conclusions
To facilitate coherent quantification and visualization of scRNA-seq data we developed the R-package scBubbletree, which is freely available as part of the Bioconductor repository at: https://bioconductor.org/packages/scBubbletree/
Centering the role of community health workers in social risk screening, referral, and follow-up within the primary care setting
Authors: Larson Emily K. , Ingram Maia , Dougherty Erin , Velasco Maria , Guzman Vanessa , Jackson Azel , Patel Kiran , Carvajal Scott C. , Wilkinson-Lee Ada M. 
Published: September 2024

Abstract
Background
Community health workers (CHWs) remain an underutilized resource in social risk diagnostics in the primary care setting. This process evaluation study seeks to assess the role of CHWs in social risk screening, referral, and follow-up through process mapping to identify barriers to the process for future quality improvement efforts.

Methods
Researchers at the Arizona Prevention Research Center (AzPRC) engaged with two Federally Qualified Health Centers (FQHCs) in two of Arizona’s major urban areas to evaluate their internal processes for social risk screening and intervention. The Consolidated Framework for Implementation Research (CFIR) was used to direct a process mapping exercise to visually describe the workflow, gaps, and barriers to identifying and addressing social risk.

Results
The process unveiled key areas for health system improvements in the community setting, the organizational setting, and in the implementation of social risk screening, referral, and follow-up. Further, process maps highlight the potential resources needed for effective CHW integration to address social risk in the primary care setting.

Conclusions
Our findings demonstrate the importance of organizational tools, such as process mapping, to assist primary care settings in evaluating internal processes for quality improvement in addressing social risk and in effectively integrating the CHW workforce. Subsequent research will evaluate rates of social risk screening, referral, and follow-up within all of Arizona’s FQHCs and propose models for CHW integration to address social risk in primary care and strengthen social risk screening reach and effectiveness.
Coronavirus disease-19 vaccine uptake, willingness for vaccination, and associated Factors among chronic follow patients attending in the two comprehensive specialized hospitals of Bahir Dar, Ethiopia
Authors: Tegegne Dessie , Kebede Mulu , Biresaw Henok , Andargie Astewle , Ewunetu Mengistu , Dessie Getenet 
Published: September 2024

Abstract
Background
Even though the disease has spread throughout the world, with millions killed, global COVID-19 vaccination coverage remains low, particularly in developing countries. However, epidemiological data is lacking in the area. Hence, this study aimed to assess COVID-19 uptake, willingness for vaccination, and associated factors.

Method
A hospital-based cross-sectional study was conducted from May 1 to June 30, 2022, among patients attending chronic follow-up clinics in the two comprehensive specialized hospitals in Bahir Dar. The total sample size was 423. Participants were selected by a systematic random sampling technique. Data was gathered using a pre-tested questionnaire and analyzed using SPSS version 23. A descriptive analysis was performed. A binary logistic regression analysis was done to assess the association between variables. Variables with a p-value < 0.05 in the multi-variable logistic regression with a 95% confidence interval were considered statistically significant.

Results
The analysis included 400 out of 423 participants, representing a 95% response rate. The COVID-19 vaccination uptake was 46.8%, while the acceptance was 60.5%. About 56% and 68% of the respondents had good knowledge and a favorable attitude, respectively. Elderly people were 2.7 times more likely to be vaccinated. Similarly, urban residents were 3.94 times more vaccinated. The probability of being vaccinated among respondents with good knowledge and favorable attitudes was 70% and 79%, respectively. The willingness for vaccination increased among those individuals with favorable attitudes (AOR: 1.82). Urban people were less likely to accept vaccination (AOR: 0.46). Some participants misunderstood that vaccination may aggravate their disease condition.

Conclusion
The overall COVID-19 vaccine uptake and acceptance for vaccination were low compared to what was estimated by the WHO. Age, residence, knowledge, and attitude were associated with COVID-19 vaccine uptake and acceptance of vaccination. Besides, there was a high level of rumor about the status of the vaccine and risk factors. Hence, special emphasis is warranted to deliver centrally trusted information. Moreover, further nationwide studies are warranted in the future.
Patient perspectives and preferences for rehabilitation among people living with frailty and chronic kidney disease: a qualitative evaluation
Authors: Kennard Alice L , Rainsford Suzanne , Hamilton Kelly L , Glasgow Nicholas J , Pumpa Kate L , Douglas Angela M , Talaulikar Girish S 
Published: September 2024

Abstract
Background
Understanding the patient perspective of frailty is critical to offering holistic patient-centred care. Rehabilitation strategies for patients with advanced chronic kidney disease (CKD) and frailty are limited in their ability to overcome patient-perceived barriers to participation, resulting in high rates of drop-out and non-adherence. The aim of this study was to explore patient perspectives and preferences regarding experiences with rehabilitation to inform a CKD/Frailty rehabilitation model.

Methods
This qualitative study involved two focus groups, six individual semi-structured interviews and three caregiver semi-structured interviews with lived experience of advanced kidney disease and frailty. Interviews were recorded, transcribed, and coded for meaningful concepts and analysed using inductive thematic analysis using constant comparative method of data analysis employing Social Cognitive Theory.

Results
Six major themes emerged including accommodating frailty is an act of resilience, exercise is endorsed for rehabilitation but existing programs have failed to meet end-users’ needs. Rehabilitation goals were framed around return to normative behaviours and rehabilitation should have a social dimension, offering understanding for “people like us”. Participants reported on barriers and disruptors to frailty rehabilitation in the CKD context. Participants valued peer-to-peer education, the camaraderie of socialisation and the benefit of feedback for maintaining motivation. Patients undertaking dialysis described the commodity of time and the burden of unresolved symptoms as barriers to participation. Participants reported difficulty envisioning strategies for frailty rehabilitation, maintaining a focus on the immediate and avoidance of future uncertainty.

Conclusions
Frailty rehabilitation efforts in CKD should leverage shared experiences, address comorbidity and symptom burden and focus on goals with normative value.