bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations
Authors: Heriyanto Didik Setyo , Yoshuantari Naomi , Akbariani Gilang , Lau Vincent , Hanini Hanifa , Hidayati Zulfa , Arief Muhammad Zulfikar , Gunawan Andrew Nobiantoro , Ridwanuloh Asep Muhamad , Kusharyoto Wien , Handaya Adeodatus Yuda , Ilyas Mohammad , Kurnianda Johan , Hutajulu Susanna Hilda , Susanti Susanti 
Published: March 2024

AbstractBackgroundIn Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients <50 years old compared to western populations, possibly due to a higher frequency of Lynch Syndrome (LS) in CRC patients. We aim to examine the association of KRAS and PIK3CA mutation with LS.MethodsIn this cross-sectional study, the PCR-HRM-based test was used for screening of MSI mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF(V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples.ResultsAll the samples (n=244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples respectively. PIK3CA mutation was significantly associated with female sex and lower levels of TILs in 62/107 (57.94%) and 26/107 (30.23%) samples respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients.ConclusionsHigh probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.
Oncology Researchers’ and Clinicians’ Perceptions of Complementary, Alternative, and Integrative Medicine: An International, Cross-Sectional Survey
Authors: Ng Jeremy Y. , Kochhar Jassimar , Cramer Holger 
Published: March 2024

AbstractBackgroundComplementary, alternative, and integrative medicine (CAIM) has become an increasingly popular supportive therapy option for patients with cancer. The objective of this study was to investigate how researchers and clinicians in the oncology field perceive CAIM.MethodsWe conducted an online, anonymous, cross-sectional survey for researchers and clinicians who have published their work in oncology journals that are indexed in MEDLINE. The link to the survey was sent to 47, 991 researchers and clinicians whose contact information was extracted from their publications. The survey included various multiple-choice questions, and one open-ended question at the end to allow for any additional comments.Results751 respondents completed the survey, and they mostly identified themselves as researchers (n=329, 45.13%), or as both researchers and clinicians (n=332, 45.45%) in the field of oncology. Over half of the respondents perceive mind-body therapies (n=354, 54.97%) to be the most promising CAIM category with regards to the prevention, treatment, and/or management of diseases related to oncology, and many respondents agreed that most CAIM therapies are safe (n=218, 37.39%), and that clinicians should receive training on CAIM therapies via formal (n=225, 38.59%) and supplemental education (n=290, 49.83%). However, many respondents were unsure when asked if most CAIM therapies are effective (n=202, 34.77%).ConclusionsThe findings from this study demonstrated great current interest in the use of CAIM in oncology. This information can serve as a foundation for conducting additional research and creating customized educational materials for researchers and clinicians in oncology.
Multichannel tDCS with Advanced Targeting for Major Depressive Disorder: A Tele-Supervised At-Home Pilot Study
Authors: Ruffini Giulio , Salvador Ricardo , Castaldo Francesca , Baleeiro Thais , Camprodon Joan A. , Chopra Mohit , Cappon Davide , Pascual-Leone Alvaro 
Published: March 2024

AbstractIntroductionProof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS).MethodsParticipants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits.Results34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge’sg= −3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements.ConclusionsThese results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.
Meditation Experience is Associated with Increased Structural Integrity of the Pineal Gland and greater total Grey Matter maintenance
Authors: Plini Emanuele RG , Melnychuk Michael C , Dockree Paul M 
Published: March 2024

AbstractGrowing evidence demonstrates that meditation practice supports cognitive functions including attention and interoceptive processing, and is associated with structural changes across cortical networks including prefrontal regions, and the insula. However, the extent of subcortical morphometric changes linked to meditation practice is less appreciated. A noteworthy candidate is the Pineal Gland, a key producer of melatonin, which regulates circadian rhythms that augment sleep-wake patterns, and may also provide neuroprotective benefits to offset cognitive decline. Increased melatonin levels as well as increased fMRI BOLD signal in the Pineal Gland has been observed in mediators vs. controls. However, it is not known if long-term meditators exhibit structural change in the Pineal Gland linked to lifetime duration of practice. In the current study we performed Voxel-based morphometry (VBM) analysis to investigate: 1) whether long-term meditators (LTMs) (n=14) exhibited greater Pineal Gland integrity compared to a control group (n=969), 2) a potential association between the estimated lifetime hours of meditation (ELHOM) and Pineal Gland integrity, and 3) whether LTMs show greater Grey Matter (GM) maintenance (BrainPAD) that is associated with Pineal Gland integrity. The results revealed greater Pineal Gland integrity and lower BrainPAD scores (younger brain age) in LTMs compared to controls. Exploratory analysis revealed a positive association between ELHOM and greater signal intensity in the Pineal Gland but not with GM maintenance as measured by BrainPAD score. However, greater Pineal integrity and lower BrainPAD scores were correlated in LTMs. The potential mechanisms by which meditation influences Pineal Gland function, hormonal metabolism, and GM maintenance are discussed – in particular melatonin’s roles in sleep, immune response, inflammation modulation, and stem cell and neural regeneration.
Multi-omics Integration Identifies Genes Influencing Traits Associated with Cardiovascular Risks: The Long Life Family Study
Authors: Acharya Sandeep , Liao Shu , Jung Wooseok J. , Kang Yu S. , Moghaddam Vaha A. , Feitosa Mary , Wojczynski Mary , Lin Shiow , Anema Jason A. , Schwander Karen , Connell Jeff O , Province Mike , Brent Michael R. 
Published: March 2024

AbstractThe Long Life Family Study (LLFS) enrolled 4,953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8×10−7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein-Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genesFCER1A, MS4A2, GATA2, HDC, andHRH4in atherosclerosis risks. Our findings also suggest that lower expression ofATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest thatENPP3may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform (https://nf-co.re/omicsgenetraitassociation).
Leveraging molecular-QTL co-association to predict novel disease-associated genetic loci using a graph convolutional neural network
Authors: Ng-Kee-Kwong Julian , Bretherick Andrew D. 
Published: March 2024

AbstractGenome-wide association studies (GWAS) have successfully uncovered numerous associations between genetic variants and disease traits to date. Yet, identifying significantly associated loci remains a considerable challenge due to the concomitant multiple-testing burden of performing such analyses genome-wide. Here, we leverage the genetic associations of molecular traits – DNA CpG-site methylation status and RNA expression – to mitigate this problem. We encode their co-association across the genome using PinSage, a graph convolutional neural network-based recommender system previously deployed at Pinterest. We demonstrate, using this framework, that a model trained only on methylation quantitative trait locus (QTL) data could recapitulate over half (554,209/1,021,052) of possible SNP-RNA associations identified in a large expression QTL meta-analysis. Taking advantage of a recent ‘saturated’ map of height associations, we then show that height-associated loci predicted by a model trained on molecular-QTL data replicated comparably, following Bonferroni correction, to those that were genome-wide significant in UK Biobank (88% compared to 91%). On a set of 64 disease outcomes in UK Biobank, the same model identified 143 independent novel disease associations, with at least one additional association for 64% (41/64) of the disease outcomes examined. Excluding associations involving the MHC region, we achieve a total uplift of over 8% (128/1,548). We successfully replicated 38% (39/103) of the novel disease associations in an independent sample, with suggestive evidence for six additional associations from GWAS Catalog. Replicated associations included for instance that between rs10774625 (nearest gene: SH2B3/ATXN2) and coeliac disease, and that between rs12350420 (nearest gene: MVB12B) and glaucoma. For many GWAS, attaining such an enhancement by simply increasing sample size may be prohibitively expensive, or impossible depending on disease prevalence.
Cognitive Effects ofToxoplasmaand CMV Infections: A Cross-Sectional Study of 557 Young Adults Considering Modulation by Sex and Rh Factor
Authors: Flegr Jaroslav , Chvátalová Veronika , Příplatová Lenka , Tureček Petr , Kodym Petr , Šebánková Blanka , Kaňková Šárka 
Published: March 2024

AbstractOne-third of humanity harbors a lifelong infection withToxoplasma gondii. This parasite undergoes sexual reproduction in cats and asexual reproduction in any warm-blooded intermediate hosts. The cycle progresses as cats ingest these hosts, containing the parasite’s tissue cysts. Such infections can alter behaviors in both animals and humans, potentially increasing predation risk by felines—usually seen as parasite-induced manipulations. This study aims to delineate toxoplasmosis’s effects on cognitive abilities and compare these to the effects of human cytomegalovirus (CMV), which also infects the brain but is not spread through predation. We evaluated the cognitive performance of 557 students, who had been examined forToxoplasmaand CMV infections, using intelligence, memory, and psychomotor tests. Results indicated cognitive impairments in seropositive individuals for both pathogens, with variations in cognitive impact related to sex and Rh factor. Specifically,Toxoplasmawas associated with lower IQ in men, whereas CMV predominantly with worse women’s memory and reaction speeds. Analysis of antibody concentrations hinted that certainToxoplasma-associated cognitive detriments may wane (impaired intelligence) or worsen (impaired reaction times) over time following infection. The findings imply that cognitive impairments from both neurotropic pathogens are likely due to pathological changes in the brain rather than direct manipulative actions by the parasites.
DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers
Authors: Øgaard Nadia , Iden Cecilie R. , Jensen Sarah Østrup , Mustafa Salah Mohammad , Aagaard Emilie , Bramsen Jesper Bertram , Ahlborn Lise Barlebo , Hasselby Jane Preuss , Rohrberg Kristoffer Staal , Achiam Michael Patrick , Andersen Claus Lindbjerg , Mau-Sørensen Morten 
Published: March 2024

AbstractBackgroundPatients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ AC) face poor outcomes. Thus, sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ AC.MethodsTumor DNA from 29 patients, and plasma cell-free DNA from 17 patients with advanced- and 17 patients with resectable G-GEJ AC, and from 50 healthy controls was analyzed. A tumor-agnostic, digital PCR test – TriMeth - targeting the gastrointestinal cancer-specific methylated genesC9orf50, KCNQ5, andCLIP4, was performed.ResultsTriMeth detected tumor DNA in 29/29 (100%) of the tumor tissue samples. Furthermore, TriMeth detected ctDNA in plasma from 13/17 (76%) of patients with advanced disease, 7/17 (41%) of patients with resectable disease, and in 0/50 (0%) of healthy controls.ConclusionsThis study demonstrates that TriMeth may hold potential as a biomarker for identification of ctDNA in patients with G-GEJ AC. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.
Modelling long COVID using Bayesian networks
Authors: Pérez Chacón Gladymar , Mascaro Steven , Estcourt Marie J. , Phetsouphanh Chan , Nicholson Ann E. , Snelling Tom , Wu Yue 
Published: March 2024

AbstractMotivated by the ambiguity of operational case definitions for long COVID and the impact of the lack of a common causal language on long COVID research, in early 2023 we began developing a research framework on this post-acute infection syndrome. We used directed acyclic graphs (DAGs) and Bayesian networks (BNs) to depict the hypothesised mechanisms of long COVID in an agnostic fashion. The DAGs were informed by the evolving literature and subsequently refined following elicitation workshops with domain experts. The workshops were structured online sessions guided by an experienced facilitator. The causal DAGs aim to summarise the hypothesised pathobiological pathways from mild or severe COVID-19 disease to the development of pulmonary symptoms and fatigue over four different time points. The DAG was converted into a BN using qualitative parametrisation. These causal models aim to assist the identification of disease endotypes, as well as the design of randomised controlled trials and observational studies. The framework can also be extended to a range of other post-acute infection syndromes.
The Emerging Applications of Synthetic Data in Neurosurgery Research and Practice: A Systematic Review
Authors: Bouras Andrew 
Published: March 2024

AbstractBackgroundThe integration of data-driven technologies into neurosurgery, particularly through the advent of synthetic data, marks a significant evolution in the field. This qualitative systematic review explores the impact of synthetic data on neurosurgical practices, including preoperative planning, intraoperative navigation, postoperative care, training, and research. The goal is to provide a comprehensive assessment of the current applications, benefits, challenges, and future directions of synthetic data in neurosurgery.MethodsA thorough literature review was conducted, focusing on peer-reviewed articles and conference proceedings that detail the use of synthetic data in neurosurgery. The review prioritized studies offering qualitative evaluations, case studies, technological developments, and expert perspectives on synthetic data’s integration into neurosurgical practices. Inclusion criteria were established to select studies that explicitly discuss the generation, utilization, and impact of synthetic data in the discipline.ResultsThe analysis reveals that synthetic data contributes significantly to neurosurgery, enhancing surgical planning precision, training simulation accuracy, and enabling personalized care. Identified benefits include addressing the scarcity of clinical data, maintaining patient privacy, and facilitating machine learning model development. Challenges such as ensuring data realism and variability, along with the integration of synthetic data into clinical workflows, were also identified. The review further highlights synthetic data’s role in supporting collaborative research, navigating data sharing obstacles, and fostering innovation in neurosurgical methods and patient outcomes.ConclusionsSynthetic data presents a transformative opportunity for neurosurgery, addressing historical challenges and fostering advancements. Despite existing hurdles, its application across neurosurgical domains indicates a shift towards more personalized, precise, and effective patient care. Overcoming these challenges requires ongoing interdisciplinary cooperation and technological progress. The review emphasizes the necessity for standardized methodologies, ethical considerations, and a proactive stance to leverage synthetic data’s potential fully in neurosurgical advancements.
Visualization ofBacillus subtilisSpore Structure and Germination using Quick-Freeze Deep-Etch Electron Microscopy
Authors: Jalil Kiran , Tahara Yuhei O. , Miyata Makoto 
Published: March 2024

AbstractBacterial spores, known for their complex and resilient structures, have been the focus of visualization using various methodologies. In this study, we applied quick-freeze and replica electron microscopy techniques, allowing observation ofBacillus subtilisspores in high-contrast and three-dimensional detail. This method facilitated visualization of the spore structure with enhanced resolution and provided new insights into the spores and their germination processes. We identified and described five distinct structures: (i) hair-like structures on the spore surface, (ii) spike formation on the surface of lysozyme-treated spores, (iii) the fractured appearance of the outer spore cortex during germination, (iv) potential connections between small vesicles and the core membrane, and (v) the evolving surface structure of nascent vegetative cells during germination.
Gretl - Variation GRaph Evaluation TooLkit
Authors: Vorbrugg Sebastian , Bezrukov Ilja , Bao Zhigui , Weigel Detlef 
Published: March 2024

AbstractMotivation: As genome graphs are powerful data structures for representing the genetic diversity within populations, they can help identify genomic variations that traditional linear references miss, but their complexity and size makes the analysis of genome graphs challenging. We sought to develop a genome graph analysis tool that helps these analyses to become more accessible by addressing the limitations of existing tools. Specifically, we improve scalability and user-friendliness, and we provide many new statistics for graph evaluation.Results: We developed an efficient, comprehensive, and integrated tool,gretl, to analyse genome graphs and gain insights into their structure and composition by providing a wide range of statistics.gretlcan be utilised to evaluate different graphs, compare the output of graph construction pipelines with different parameters, as well as perform an in-depth analysis of individual graphs, including sample-specific analysis. With the assistance ofgretl, novel patterns of genetic variation and potential regions of interest can be identified, for later, more detailed inspection. We demonstrate thatgretloutperforms other tools in terms of speed, particularly for larger genome graphs.Availability and implementation:gretlis implemented in Rust. Commented source code is available under MIT licence athttps://github.com/MoinSebi/gretl. Examples of how to rungretlare provided in the documentation. Several Jupyter notebooks are part of the repository and can help visualisegretlresults.