bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes
Authors: Diehl Kyra , Stoos Elizabeth , Becker Alyssa , Orfaly Victoria E. , Nelson Jacob , Gillespie Jordan , Ng Justin , Tobey Tayler , Latour Emile , Ludzik Joanna , Berry Elizabeth G. , Geller Alan C. , Jacobe Heidi , Leitenberger Justin , McClanahan Danielle , Tran Jessica , Prasad Smriti , Mengden-Koon Stephanie , Nelson Kelly C. , Petering Ryan , Verdieck Alex , Savory Stephanie , Smith Emily H. , Tofte Susan , Weinstock Martin A. , White Kevin , Wisco Oliver , Curiel-Lewandrowski Clara , Swetter Susan M. , Witkowski Alexander M. , Ferris Laura , Black Samantha , Xu Rebecca , Xu Shuai , Leachman Sancy 
Published: December 2024

IntroductionPrimary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.MethodsWe have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.) that suits their learning style and time availability. Here we present the toolkit, the development and validation of the curriculum, and report on 1-year outcomes of a nested survey study. Because the goal of the program is to maximize participation by allowing PCPs to tailor their experience to their own needs and interests, the majority of participants did not complete every element of the program.ResultsA total of 8,683 PCPs have accessed at least one element of the toolkit from 2019–2024. Participants completed a pre-survey, online training module, and post-survey that included self-reported screening behaviors, changes in confidence, and malignant and benign lesion categorization based on clinical images. A total of 139 pre-surveys and 92 post-surveys were completed, including 55 matched participants that completed both the pre- and post-training surveys. There were significant improvements in PCP confidence (P &lt; 0.001) and malignant (P &lt; 0.001) and benign image (P = 0.029) identification respectively.DiscussionPCPs may serve as a valuable aid in skin cancer screening efforts, but additional studies are needed to evaluate the impact of these curricula in clinical practice.
Association between red cell distribution width and 30-day mortality in patients with sepsis-associated liver injury: a retrospective cohort study
Authors: Ao Ting , Huang Yingxiu , Zhen Peng , Hu Ming 
Published: December 2024

BackgroundSepsis-associated liver injury (SALI) is a critical component of sepsis-induced multiple organ dysfunction with high mortality. Identifying biomarkers for risk stratification is essential. Red cell distribution width (RDW), indicating variation in red blood cell volume, has been linked to adverse outcomes in various diseases. This study aimed to evaluate the association between RDW and 30-day mortality in SALI patients.MethodsA retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care-IV database. Patients admitted to the intensive care unit (ICU) with SALI were included. RDW was recorded within the initial 24 h. The primary outcome was 30-day mortality. A multivariable Cox regression analysis was performed to examine the relationship between RDW and mortality.ResultsAmong 529 SALI patients (mean age 68.7 years, 61.8% male), 46.1% had RDW &gt; 15.5%. The 30-day mortality rate was 35.5%. RDW was significantly higher in non-survivors compared to survivors (17.2 ± 3.0 vs. 15.4 ± 2.3, P &lt; 0.001). Cox regression identified RDW as an independent risk factor for 30-day mortality (HR 1.14, 95% CI 1.09 to 1.19, P &lt; 0.001). Subgroup analyses demonstrated that the findings were consistent across the various groups.ConclusionElevated RDW is independently associated with higher 30-day mortality in patients with SALI, suggesting its potential role in risk stratification and clinical management.
The application of ChatGPT in nursing: a bibliometric and visualized analysis
Authors: Wang Peng , Zhang Qian , Zhang Wenyu , Sun Jing 
Published: December 2024

ObjectiveWith the development of ChatGPT, the number of studies within the nursing field has increased. The sophisticated language capabilities of ChatGPT, coupled with its exceptional precision, offer significant support within the nursing field, which includes clinical nursing, nursing education, and the clinical decision-making process. Preliminary findings suggest positive outcomes, underscoring its potential as a valuable resource for enhancing clinical care. However, a comprehensive analysis of this domain is lacking, and the application of bibliometric methods remains rare. This study aims to describe and predict the developmental trajectory of the discipline, identify research hotspots and trends, and provide a comprehensive framework for the integration of ChatGPT in nursing.MethodsFollowing the development of a search strategy in collaboration with librarians, the implementation of this strategy occurred in the Web of Science Core Collection (WoSCC) on June 30, 2024. For bibliometric and visual analyses—including evaluations of sources, institutions, countries, author collaboration networks, and keywords—Bibliometrix (version 4.4.2) and CiteSpace (version 6.2.R2 Basic) were employed.ResultsA total of 81 articles published by 67 authors were retrieved from the Web of Science Core Collection database, covering the period of June 30, 2024. The number of published studies has exhibited an increasing trend. The “European Journal of Cardiovascular Nursing” emerged as the most productive journals, while the USA, the UK, and China were identified as the leading countries in terms of publication output. The top 10 keywords identified in this study include artificial intelligence, nursing education, large language models, ChatGPT, natural language processing, generative artificial intelligence, care, nursing practice, clinical decision-making, and deep learning.ConclusionChatGPT is an emerging tool in the nursing field, currently in the foundational research phase. While there is significant international collaboration, cooperation among author groups remains somewhat limited. Studies focusing on ChatGPT in nursing primarily concentrate on two key themes: (1) the deep learning of ChatGPT in nursing and (2) the feasibility of its application. It is essential for nurses across various specialties to collaborate in exploring the diverse applications of ChatGPT within their domains, thereby fostering the ongoing development and enhancement of this technology.
Biomarker discovery and development of prognostic prediction model using metabolomic panel in breast cancer patients: a hybrid methodology integrating machine learning and explainable artificial intelligence
Authors: Yagin Fatma Hilal , Gormez Yasin , Al-Hashem Fahaid , Ahmad Irshad , Ahmad Fuzail , Ardigò Luca Paolo 
Published: December 2024

BackgroundBreast cancer (BC) is a significant cause of morbidity and mortality in women. Although the important role of metabolism in the molecular pathogenesis of BC is known, there is still a need for robust metabolomic biomarkers and predictive models that will enable the detection and prognosis of BC. This study aims to identify targeted metabolomic biomarker candidates based on explainable artificial intelligence (XAI) for the specific detection of BC.MethodsData obtained after targeted metabolomics analyses using plasma samples from BC patients (n = 102) and healthy controls (n = 99) were used. Machine learning (ML) models based on raw data were developed, then feature selection methods were applied, and the results were compared. SHapley Additive exPlanations (SHAP), an XAI method, was used to clinically explain the decisions of the optimal model in BC prediction.ResultsThe results revealed that variable selection increased the performance of ML models in BC classification, and the optimal model was obtained with the logistic regression (LR) classifier after support vector machine (SVM)-SHAP-based feature selection. SHAP annotations of the LR model revealed that Leucine, isoleucine, L-alloisoleucine, norleucine, and homoserine acids were the most important potential BC diagnostic biomarkers. Combining the identified metabolite markers provided robust BC classification measures with precision, recall, and specificity of 89.50%, 88.38%, and 83.67%, respectively.ConclusionIn conclusion, this study adds valuable information to the discovery of BC biomarkers and underscores the potential of targeted metabolomics-based diagnostic advances in the management of BC.
Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice
Authors: Wang Yarong , Zhang Rongxing , Jiang Yumin , Liao Jingwen , Mu Lianwei , Hu Min 
Published: December 2024

ObjectiveAnxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.MethodsAfter eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer’s disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.ResultsWe first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.ConclusionThese findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.
Apolipoprotein E dysfunction in Alzheimer’s disease: a study on miRNA regulation, glial markers, and amyloid pathology
Authors: Wijesinghe Printha , Li Hao Ran , Ai Zhengyuan , Campbell Matthew , Chen Si Xuan , Xi Jeanne , Pham Wellington , Matsubara Joanne A. 
Published: December 2024

IntroductionApolipoprotein E (ApoE) plays a crucial role in lipid homeostasis, predominantly expressed in astrocytes and to a lesser extent in microglia within the central nervous system (CNS). While the APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), its precise role in AD pathogenesis remains elusive. Apoe-knockout (Apoe-ko) mice, mice expressing human APOE4, and human APOE4 carriers exhibit similar deficits in lipid metabolism, cognitive and behavioral functions, and neurodegeneration. The retina, as part of the CNS, has been studied to investigate the underlying mechanisms of AD, including neuroinflammation, amyloid aggregation, and neurodegeneration. This study explores ApoE’s role in AD by analyzing brain and eye samples from Apoe-ko mice, focusing on identifying potential retinal biomarkers associated with ApoE dysfunction.MethodsWe compared female Apoe-ko mice on a regular diet to age-matched C57BL/6J controls at 3 and 9 months. Our investigations included microRNAs (miRNAs), their target messenger RNAs (mRNAs), and selected protein markers, including astroglial (Gfap), microglial/macrophage (Iba1 and Trem2) markers, and amyloid precursor protein (APP)/amyloid-β (Aβ) peptides implicated in AD pathogenesis. We also examined female Apoe-ko mice on a high-fat diet versus a regular diet at 9 months for differential miRNA and mRNA expressions.ResultsOur findings demonstrated that miRNA levels were generally lower in 3-month-old Apoe-ko mice but increased in 9-month-old mice across five distinct brain regions, as well as in eye tissue and tear fluid. A high-fat diet further enhanced miRNA dysregulation in brain and eye tissues, but not in tear fluid. Target mRNAs were generally higher in the neocortex-hippocampus and eye tissue of 3-month-old Apoe-ko mice but decreased with age, except for glial cell mRNAs like Gfap and Aif1. Protein analysis revealed elevated Gfap expression, and increased APP/Aβ peptide accumulation in the neocortex-hippocampus, including brain endothelial cells at the meninges, as well as in the retina of 9-month-old Apoe-ko mice. These findings highlight ApoE’s pivotal role in AD, demonstrating its impact on inflammatory and amyloidogenic/angiogenic miRNA expression, glial homeostasis, and APP/Aβ peptide clearance. The observed upregulation of proinflammatory miR-146a and anti-amyloidogenic/angiogenic miR-15a in 9-month-old Apoe-ko mice suggests their potential as tear-based biomarkers for ApoE dysfunction.
Targeted plasma metabolomics reveals potential biomarkers of the elderly with mild cognitive impairment in Qingdao rural area
Authors: Meng Yuchi , Cheng Murong , Qu Hongyan , Song Zhenxue , Zhang Ling , Zeng Yuanjun , Zhang Dongfeng , Li Suyun 
Published: December 2024

IntroductionPrevious research has suggested a link between the onset of Alzheimer’s disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.MethodWe included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using t-tests or Wilcoxon rank-sum tests, with p-values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR &lt; 0.05 and fold change (FC) &gt; 1.5 or &lt; 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP &gt; 1 and FDR &lt; 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.ResultsA total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.DiscussionThese findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.
Establishment and evaluation of a carotid artery dissection model in rats
Authors: Zhang Shufan , Han Zhenxiang , Cao Ying , Wu Weicheng , Liu Yuanzeng , Yang Shilin , Feng Xiaochao , Yu Chun , Zhu Zhu , Dong Qiang , Han Xiang 
Published: December 2024

BackgroundGiven the lack of models for carotid artery dissections (CAD), we aim to investigate effects of beta-aminopropionitrile (BAPN) combined with physical damage on the arterial walls of rats, and to establish a high-incidence and low-mortality CAD model.MethodsSixteen SPF SD rats (3-week-old) were divided into two groups. Group B was given 0.25% BAPN solution and group W was given water. Then we established an animal model of CAD by carotid artery torsion. One of the two carotid arteries in each rat was randomly selected for torsion. We got four groups of blood vessels following above-mentioned methods: BAPN plus torsion group (group Bt), BAPN plus non-torsion group (group Bn), water plus torsion group (group Wt), and water plus non-torsion group (group Wn). The hematoxylin and eosin (HE) staining and Verhoeff’s Van Gieson (EVG) staining were performed to observe structures of arteries. Immunofluorescence staining was used to detect structural proteins in vessels. We used triphenyltetrazolium chloride (TTC) staining and neurological function assessment to detect the infarct area of brain and neurological deficits in rats with carotid dissection to verify the validity of the rat model.ResultsBAPN treatment significantly affected the weight gain of rats, but had little effect on survival during the first 5 weeks. The group Bt had the highest incidence of CAD among all groups (p = 0.014). HE staining of carotid artery tissue sections showed that the vascular walls were the thickest in group Bt (p &lt; 0.001). EVG staining showed the arrangement of elastic fibers was the most irregular in group Bt. Immunofluorescence staining revealed that the expression of a-SMA and SM22a were decreased remarkably in group Bt (p &lt; 0.001). Both motor and sensory deficits were more severe in CAD group than control group (p = 0.0004; p = 0.0036). The relative infarction volumes of CAD group rats were significantly larger than control group (p &lt; 0.001).ConclusionThe animal model of CAD can be feasible to establish by mechanical torsion combined with BAPN free drinking. With this method, the animal mortality was low and the model formation rate was high. This model will enable further studies on CAD.
Changes in serum concentration of perioperative inflammatory cytokines following the timing of surgery among mild–moderate traumatic brain injury patients and factors associated
Authors: Lekuya Hervé Monka , Cose Stephen , Nakibuule Marjorie , Ahimbisibwe Gift , Fuller Anthony , Kamabu Larrey Kasereka , Biryabarema Emmanuel , Olweny Geoffrey , Kateete David Patrick , Kirabira Anthony , Makumbi Fredrick , Vandersteene Jelle , Baert Edward , Galukande Moses , Kalala Jean-Pierre Okito 
Published: December 2024

BackgroundThe safe timing window for surgery during the acute phase of inflammation due to traumatic brain injury (TBI) has not been studied extensively. We aimed to elucidate the relationship between the timing of surgery and changes in perioperative serum levels of inflammatory cytokines and factors associated to optimize TBI management in low-middle-income countries.MethodsA prospective cohort study was conducted among TBI Patients with depressed skull fractures with a GCS &gt; 8 operated at different timing from injury and followed up peri-operatively. We collected the clinical-radiological data, as well as pre-and postoperative venous samples from participants; we then did Luminex Assay to quantify the serum levels of pro/anti-inflammatory cytokines using the kits of 96-well human cytokine “27-Plex-Assay (#M500KCAF0Y®).” We performed the analysis with STATA version 17 and R_studio applying both descriptive and inferential methods.ResultsWe enrolled 82 TBI patients with a median (IQR) age of 25.5 (20–34) years, and the majority were male (85.4%). There were 48.8% victims of assaults, and 73.2% had a post-resuscitation admission GCS of 14–15. There were 38 (46.3%) who were operated within 48 h of injury versus 44 (53.7%) after 48 h. Serum levels of TNF-α were significantly higher after surgeries done &gt;48 h compared to those done ≤48 h (p = 0.0327); whereas, the difference in post-operative mean serum levels of IL-10 was significantly increased in patients who developed later SSI compared to those who did not (11.56 versus −0.58 pg./mL, p = 0.0489). In multivariate analysis, the history of post-traumatic seizure (PTS) was associated with a postoperative increase in TNF-α (p = 0.01), the hemoglobin of 10–12 with a postoperative decrease of IL-4 (p = 0.05); the presence of focal neurological deficit was associated with a significant postoperative increased of TNF-α, IL-6, and IL-4 (p = 0.05). The presence of extra-axial hemorrhage was associated with a postoperative increase of IL-10 (p = 0.05).ConclusionDelayed surgical intervention beyond 48 h post-injury in mild–moderate TBI patients results in a significantly increased postoperative inflammatory response, as evidenced by elevated serum levels of TNF-α and IL-6. Neurological deficits, PTS, reduced hemoglobin rate, and extra-axial intracranial hemorrhage are factors associated with this heightened response.
Remotely induced electrical modulation of deep brain circuits in non-human primates
Authors: Lybbert Carter , Webb Taylor , Wilson Matthew G. , Tsunoda Keisuke , Kubanek Jan 
Published: December 2024

IntroductionThe combination of magnetic and focused ultrasonic fields generates focused electric fields at depth entirely noninvasively. This noninvasive method may find particularly important applications in targeted treatments of the deep brain circuits involved in mental and neurological disorders. Due to the novelty of this method, it is nonetheless unknown which parameters modulate neural activity effectively.MethodsWe have investigated this issue by applying the combination of magnetic and focused ultrasonic fields to deep brain visual circuits in two non-human primates, quantifying the electroencephalographic gamma activity evoked in the visual cortex. We hypothesized that the pulse repetition frequency of the ultrasonic stimulation should be a key factor in modulating the responses, predicting that lower frequencies should elicit inhibitory effects and higher frequencies excitatory effects.ResultsWe replicated the results of a previous study, finding an inhibition of the evoked gamma responses by a strong magnetic field. This inhibition was only observed for the lowest frequency tested (5 Hz), and not for the higher frequencies (10 kHz and 50 kHz). These neuromodulatory effects were transient and no safety issues were noted.DiscussionWe conclude that this new method can be used to transiently inhibit evoked neural activity in deep brain regions of primates, and that delivering the ultrasonic pulses at low pulse repetition frequencies maximizes the effect.