bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genomic alteration and prognosis using pathomics-based artificial intelligence in oral leukoplakia and head and neck squamous cell carcinoma: a multicenter experimental study
Authors: Cai Xin-Jia , Peng Chao-Ran , Cui Ying-Ying , Li Long , Huang Ming-Wei , Zhang He-Yu , Zhang Jian-Yun , Li Tie-Jun 
Published: September 2024

Background:
Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP).

Materials and methods:
Three hundred thirty-three OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42 and n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis.

Results:
9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction).

Conclusion:
To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC.
Utilization of recurrent laryngeal nerve monitoring during thyroid surgery in China: a point prevalence survey (2015–2023)
Authors: Zhao Yishen , Wang Peiyao , Dionigi Gianlorenzo , Kou Jiedong , Li Changlin , Li Fang , Wang Tie , Tian Wen , Jiang Kewei , Wang Ping , Zhang Hao , Sun Hui ,   Chinese Neuromonitoring Study Group (CNMSG)
Published: September 2024

Background:
The survey aimed to elucidate the complete range of national practices, including all technical and non-technical aspects, as well as surgical stratification and maturation, of the use of intraoperative neuromonitoring (IONM) during thyroid surgery in China.

Materials and methods:
Six national questionnaires, developed by the Chinese Neural Monitoring Study Group (CNMSG) between 2015 and 2023, were used to collect and analyze data regarding the clinical application, education, and scientific research related to IONM in Chinese medical institutions.

Results:
Among the surveyed hospitals, 45% reported an average annual surgical volume exceeding 3000 cases, with 82.5% performing more than 80% of the surgeries for malignant thyroid tumors. Additionally, 97.5% of the hospitals reported a less than 3% incidence of postoperative hoarseness with IONM. Statistical analysis from 2011 to 2015 found that the incidence of postoperative hoarseness decreased by 30% in 2013 compared with 2011, when the technology was introduced. Preoperative and postoperative laryngoscopies were routinely performed by 82.5% and 15% of the hospitals, respectively. For 65% of the hospitals, the publication of the Chinese edition of neuromonitoring guidelines in 2013 prompted the utilization of IONM technology. An average annual number of IONM applications exceeding 500 cases (18.5% the average volume) was reported by 80% of the hospitals, while 62.5% reported a cumulative number of applications greater than 5000 cases (47.1% the average cumulative volume). Regarding technical parameters, 75% of the hospitals reported an intraoperative V1 amplitude of greater than 500 µV, and 70% reported an intraoperative loss of signal (LOS) rate of less than 3%. 92.5% of the surveyed hospitals believed that IONM could help identify dissociated nerves, and 95% of the surveyed hospitals believed that IONM could reduce nerve damage. However, 72.5% of the respondents thought that cost was the main limitation. Furthermore, 67.5% of the hospitals reported that half of their thyroid surgical team members were trained in IONM, with 17.5% reporting that all team members were trained. Areas for reinforced training included IONM research methods and directions (72.5%) and analysis and treatment of abnormal EMG signals (72.5%). Research projects related to IONM were conducted by 42.5% of the hospitals, while 52.5% had published papers on neuromonitoring.

Conclusions:
IONM was independently and incrementally associated with the annual surgical volume. This survey emphasized the importance of national collaboration and/or a registry for the uptake, consolidation, and development of CNMSG consensus.
Whole Blood Program: Implementation in a Rural Trauma Center
Authors: Orr Lanny C. , Peterson Alexa L. , Savell Tessa C. , McCotter Elizabeth L. , Palm Craig E. , Arnold Sadie L. , Riha Gordon M. , Thompson Simon J. 
Published: September 2024

BACKGROUND:
The balanced transfusion of blood components plays a leading role in traumatic hemostatic resuscitation. Yet, previous whole blood studies have only focused on urban trauma center settings.

OBJECTIVE:
To compare component vs whole blood therapy on wastage rates and mortality in the rural setting.

METHODS:
This study was a nonrandomized, retrospective, observational, single-center study on a cold-stored whole blood program implementation for adult massive transfusions from 2020 to 2022 at a Level II trauma center. Trauma registry data determined the facility’s whole blood needs and facilitated sustainable blood supplies. Whole blood use protocols were established, and utilization and laboratory compliance for incompatible ABO antibody hemolysis was monitored and reviewed monthly at stakeholder and trauma services meetings.

RESULTS:
From 2018 to 2019, the facility initiated component therapy massive transfusions every 9 days (n = 41). Therefore, four units of low-titer, O-positive whole blood delivered fortnightly was determined to provide patient coverage and minimize wastage. Across the study time frame (2020–2022), there were n = 68 hemodynamically unstable patients, consisting of those receiving whole blood, n = 37, and patients receiving component therapy, n = 31. Mortality rates were significantly lower (p = .030) in the whole blood population (n = 3, 8%) compared to those solely receiving component therapy (n = 9, 29%). Wastage rates were constantly evaluated; in 2021, 43.4% was not utilized, and in 2022, this was reduced to 38.7%. Anecdotally, nurses appreciated the ease of administration and documentation of transfusing whole blood, as it negated ratio compliance.

CONCLUSION:
This evidence-based whole blood program provides vital care to severely injured trauma patients in a vast, rural region.
A study of attention allocation mode in clinical decision-making in nurses with different professional titles: An eye-tracking experiment
Authors: Hou Chenxin , Jin Xiaoyan , Xu Weiran , Zhang Jianxia , Ma Li , Guo Jinyu , Shang Shaomei 
Published: September 2024

Abstract

Objective:
The aim of this experiment was to investigate the way in which attention is allocated in the clinical decision-making process of nurses of different professional ranks and titles and associated factors.

Methods:
Seventy-six subjects from the emergency departments of 3 hospitals in Beijing were recruited in this experiment using the convenience sampling method, including 28 junior nurses, 24 senior nurses, and 24 supervisor nurses. Subjects were required to complete clinical decision tasks, and data on subjects’ visual behavior were recorded and analyzed using a Tobii Pro eye-tracker during the decision-making process.

Results:
Nurses with high professional titles had a higher correct response rate in the nursing diagnosis and ranking of nursing diagnoses part (P < 0.05), and it was found that nurses with high professional titles would pay attention to pathophysiological mechanisms of illness earlier when making decisions (F = 3.808, P = 0.024). The heat maps showed differences in the attention allocation modes of nurses with different titles during the decision-making process.

Conclusions:
Lower-titled nurses focused more on the symptoms and signs section when making clinical decisions and paid less attention to the auxiliary examination results section, demonstrating a poorer level of active attention. Nurses with higher titles were relatively more comprehensive in their distribution of attention to patient disease information when making decisions and paid attention to the information in the patient’s auxiliary examination section earlier.
Alar base symmetry in orthognathic surgery: Patients with unilateral cleft
Authors: Fukuyama Sotatsu , Saito Takafumi , Lo Lun-Jou 
Published: September 2024

Background:
Patients with unilateral cleft lip and palate (UCLP) could present with a notable nasal deformity with alar base retrusion, which should be considered when planning orthognathic surgery (OGS).

Methods:
This retrospective study included 84 patients with Class III malocclusion. Cone beam computed tomographic data were used for the investigation. 42 patients had complete UCLP, and the other 42 did not have a cleft. All the patients underwent preoperative virtual surgical planning. Preoperative and postoperative images were used to measure anteroposterior changes in the bone and soft tissue at the alar bases.

Results:
In the UCLP group, varying degrees of alar base discrepancies were observed before surgery. In the piriform region of the cleft side, the bone was retruded in 32 cases, but the soft tissue was thicker in 38 cases, and the mean skin surface was anterior in 28 cases. After surgery, the bone discrepancy was not significantly changed (p = 0.288), however, the skin surface symmetry was improved (p = 0.013). Relating to the bone advancement, the ratio of soft tissue change was smaller on the cleft side than the noncleft side (0.56 ± 0.30 vs. 0.77 ± 0.33, p < 0.001). In the control group, a consistent ratio change was observed on both sides (0.76 ± 0.19 vs. 0.79 ± 0.27, p = 0.544).

Conclusions:
This study revealed improved alar base symmetry in patients with UCLP after OGS. The soft tissue change ratios were different across the cleft, which should be considered during treatment planning.
Education for people with serious chronic respiratory diseases and their informal caregivers: how to address challenges that impact learning
Authors: Muijsenberg Anouk J.L. , Houben-Wilke Sarah , Spruit Martijn A. , Janssen Daisy J.A. 
Published: September 2024

Purpose of review
Shared decision making is crucial in palliative care for people with serious chronic respiratory diseases and their informal caregivers. Patient education is a critical component in this process, as it provides patients and their informal caregivers the necessary knowledge for informed decisions regarding symptom management, coping with breathlessness, and advance care planning. However, education does not automatically lead to acquiring knowledge. This review describes challenges for education for people with serious chronic respiratory diseases and their informal caregivers and describes how learner-centered education can address these.

Recent findings
People with serious chronic respiratory diseases and their informal caregivers face diverse information needs and learning challenges, with low health literacy and cognitive problems being common. Healthcare professionals can facilitate learner-centered education by enhancing motivation for knowledge acquisition by meeting information needs and learning preferences of patients and their informal caregivers, and by ensuring that information is understandable and readable for those with low health literacy and cognitive problems. E-health applications may serve as valuable tools in this process.

Summary
Learner-centered education may enhance knowledge acquisition in people with serious chronic respiratory diseases and their informal caregivers aiming to gain control over symptoms and optimize shared decision making and advance care planning.
Identifying deleterious noncoding variation through gain and loss of CTCF binding activity
Authors: Tubbs Colby , Benton Mary Lauren , McArthur Evonne , Capra John A. , Ruderfer Douglas M. 
Published: September 2024

AbstractNoncoding single nucleotide variants are the predominant class of genetic variation in whole genome sequencing and are key drivers of phenotypic variation. However, their functional annotation remains challenging. To address this, we develop a hypothesis-driven functional annotation scheme for CTCF binding sites given CTCF’s critical roles in gene regulation and extensive profiling in regulatory datasets. We synthesize CTCF’s binding patterns at 1,063,879 genomic loci across 214 biological contexts into a summary metric, which we refer to as binding activity. We find that binding activity is significantly enriched for both conserved nucleotides (Pearson R = 0.31, p < 2.2 x 10-16) and sequences that contain high-quality CTCF binding motifs (Pearson R = 0.63, p = 2.9 x 10-12). We then integrate binding activity with high confidence change in precision weight matrix scores. By applying this framework to 1,253,330 SNVs in gnomAD, we explore signatures of selection acting against the disruption of CTCF binding. We find a strong, positive relationship between the mutability adjusted proportion of singletons (MAPS) metric and the loss of CTCF binding at loci with highin vitroactivity (Pearson R = 0.67, p = 1.5 x 10-14). To contextualize these findings, we apply MAPS to other functional classes of variation and find that a subset of 198,149 loss of CTCF binding variants are observed as infrequently as missense variants. This work implicates these thousands of rare, noncoding variants that disrupt CTCF binding for further functional studies while providing a blueprint for the interpretable annotation of noncoding variants.
Machine Learning Driven Optimization for High Precision Cellular Droplet Bioprinting
Authors: Shin Jaemyung , Kang Minseok , Hyun Kinam , Li Zhangkang , Kumar Hitendra , Kim Kangsoo , Park Simon S. , Kim Keekyoung 
Published: September 2024

AbstractControlled volume microliter cell-laden droplet bioprinting is important for precise biologics deposition, reliably replicating 3D microtissue environments for building cell aggregates or organoids. To achieve this, we propose an innovative machine-learning approach to predict cell-laden droplet volumes according to input parameters. We developed a novel bioprinting platform capable of collecting high-throughput droplet images and generating an extensive dataset for training machine learning and deep learning algorithms. Our research compared the performance of three machine learning and two deep learning algorithms that predict droplet volume based on numerous bioprinting parameters. By adjusting bioink viscosity, nozzle size, printing time, printing pressure, and cell concentration as input parameters, we precisely could control droplet sizes, ranging from 0.1 µL to 50 µL in volume. We utilized a hydrogel precursor composed of 5% gelatin methacrylate and a mixture of 0.5% and 1% alginate, respectively. Additionally, we optimized the cell bioprinting process using green fluorescent protein-tagged 3T3 fibroblast cells. These models demonstrated superior predictive accuracy and revealed the interrelationships among parameters while taking minimal time for training and testing. This method promises to advance the mass production of organoids and microtissues with precise volume control for various biomedical applications.
Interference with Systemic Negative Feedback Regulation as a Potential Mechanism for Nonmonotonic Dose-Responses of Endocrine-Disrupting Chemicals
Authors: Shi Zhenzhen , Xiao Shuo , Zhang Qiang 
Published: September 2024

AbstractBackgroundEndocrine-disrupting chemicals (EDCs) often exhibit nonmonotonic doseresponse (NMDR) relationships, posing significant challenges to health risk assessment and regulations. Several molecular mechanisms operating locally in cells have been proposed, including opposing actions via different receptors, mixed-ligand heterodimer formation, and receptor downregulation. Systemic negative feedback regulation of hormone homeostasis, which is a common feature of many endocrine systems, has also been invoked as a mechanism; however, whether and how exactly such global feedback structure may underpin NMDRs is poorly understood.ObjectivesWe hypothesize that an EDC may compete with the endogenous hormone for receptors (i) at the central site to interfere with the feedback regulation thus altering the physiological hormone level, and (ii) at the peripheral site to disrupt the hormone action; this dual-action may oppose each other, producing nonmonotonic endocrine effects. The objective here is to explore – through computational modeling – how NMDRs may arise through this potential mechanism and the relevant biological variabilities that enable susceptibility to nonmonotonic effects.MethodsWe constructed a dynamical model of a generic hypothalamic-pituitary-endocrine (HPE) axis with negative feedback regulation between a pituitary hormone and a terminal effector hormone (EH). The effects of model parameters, including receptor binding affinities and efficacies, on NMDR were examined for EDC agonists and antagonists. Monte Carlo human population simulations were then conducted to systemically explore biological parameter conditions that engender NMDR.ResultsWhen an EDC interferes sufficiently with the central feedback action of EH, the net endocrine effect at the peripheral target site can be opposite to what is expected of an agonist or antagonist at low concentrations. J/U or Bell-shaped NMDRs arise when the EDC has differential binding affinities and/or efficacies, relative to EH, for the peripheral and central receptors. Quantitative relationships between these biological variabilities and associated distributions were discovered, which can distinguish J/U and Bell-shaped NMDRs from monotonic responses.ConclusionsThe ubiquitous negative feedback regulation in endocrine systems can act as a universal mechanism for counterintuitive and nonmonotonic effects of EDCs. Depending on key receptor kinetic and signaling properties of EDCs and endogenous hormones, some individuals may be more susceptible to these complex endocrine effects.
Projection Statistics – ProST: Online statistical assessment of group separation in data projection analysis
Authors: Salem Danny , Surendra Anuradha , McDowell Graeme SV , Čuperlović-Culf Miroslava 
Published: September 2024

AbstractMotivationUnsupervised data projection for the determination of trends in the data, visualization of multidimensional data in a reduced dimension space or feature space reduction through combination of data is a major step in data mining. Methods such as Principal Component Analysis or t-Distribution Stochastic Neighbor Embedding are regularly used as one of the first steps in computational biology or omics investigation. However, the significance of the separation of sample groups by these methods generally relies on visual assessment. User-friendly application for different projection methods, each focusing on distinct data properties, are needed as well as a rigorous method for statistical determination of the significance of separation of groups of interest in each dataset.ResultsWe present Projection STatistics (ProST), a user-friendly solution for data projection analysis providing three unsupervised (PCA, t-SNE and UMAP) and one supervised (LDA) approach. For each method we are including a novel statistical investigation of the significance of group separation with Mann-Whitney U-rank or t-test analysis as well as necessary preprocessing steps. ProST provides an unbiased, objective application of the determination of the significance of the separation of measurement groups through either linear or manifold projection analysis with methods ranging from a focus on the separation of points based on major variances or on point proximities based on distance.AvailabilityThe ProST software application is freely available athttps://complimet.ca/shiny/ProST/with source code provided onhttps://github.com/complimet/prost.Contactdanny.salem@nrc-cnrc.gc.caorMiroslava.cuperlovic-culf@nrc-cnrc.gc.caSupplementary informationSupplementary help pages are provided athttps://complimet.ca/shiny/ProST/.
Genome-wide identification of stable RNA-chromatin interactions
Authors: Wen Xingzhao , Zhong Sheng 
Published: September 2024

SummaryRNA-chromatin interactions play crucial roles in gene regulation and genome organization, but the interaction landscape remains poorly understood. In this study, we conducted an in-depth analysis of a previously published dataset on RNase-treated in situ mapping of the RNA–genome interactome in human embryonic stem cells. This dataset globally profiles RNase-insensitive RNA-chromatin interactions. Our analysis revealed that RNase treatment selectively preserved long-range RNA-chromatin interactions while removing promiscuous interactions resulting from the local diffusion of nascent transcripts. RNase-insensitive chromatin-associated RNAs (RI-caRNAs) exhibited high sequence conservation and preferentially localized to functional genomic regions, including promoters, transcription factor binding sites, and regions with specific histone modifications. Interestingly, coding and non-coding RNA transcripts showed distinct sensitivities to RNase, with lncRNAs and disease-associated transcripts being enriched among RI-caRNAs. Furthermore, we identified specific caRNA classes associated with individual transcription factors and histone modifications. Altogether, our findings reveal a RNase-inaccessible regulatory RNA-chromatin interactome and provide a resource for understanding RNA-mediated chromatin regulation.