bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demographic Diversity of Clinical Trials for Therapeutic Drug Products: A Systematic Review of Recently Published Articles, 2017‐2022
Authors: Chege Wambui , Poddar Atasi , Samson Marsha E. , Almeida Cecilia , Miller Rihana , Raafat Dina , Fakhouri Tala , Fienkeng Mathilda , Omokaro Stephanie O. , Crentsil Victor 
Published: December 2023

AbstractThe US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit‐risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile and greater confidence in clinical trial results. The objective of this systematic review was to assess recent literature on the demographic diversity of clinical trial participants, describe the methods used in defining clinical trial diversity, and address knowledge gaps to enhance clinical trial diversity. Our literature search initially yielded 246 articles. After applying our eligibility criteria, we conducted a full‐text review and analyzed the contents of the 28 remaining articles in our systematic review. Eleven (39%) of the 28 articles used a reference standard to compare the participation of populations in clinical trials to assess diversity. The majority of the 28 articles reported on adult participants; only 5 included pediatric populations. Most articles found that women and minority populations were underrepresented in clinical trials. Some articles proposed solutions to improve clinical trial diversity; however, several did not comment on clinical trial diversity. Despite a growing emphasis on demographic diversity in research, certain populations continue to be underrepresented in clinical trials. There is a need to standardize the definition of diversity in clinical trials. Future research into effective enrollment approaches and appropriate reference standards could improve demographic diversity.
Necrotizing apoptosis‐related genes prognosis and treatment effect analysis of osteosarcoma in children
Authors: Chen Yuanling , Wu Ling , Li Yunyan , Zheng Jika , Zhong Shiling , Gu Shirong , Chen Jingyang 
Published: December 2023

AbstractBackgroundImmune cell homeostasis plays a crucial role in cancer research and therapeutic response. While chemotherapy and immunotherapy hold promise in treating osteosarcoma (OS), identifying patients who are likely to respond would significantly improve clinical practices. Necroptosis, a fundamental mechanism mediating chemotherapy and immunotherapy efficacy, offers valuable insights. In this context, subtypes based on necroptosis‐related genes have been established to predict the response of OS patients to immunotherapy and chemotherapy.MethodsWe conducted a high‐throughput screening test to identify necroptosis‐associated genes that regulate the development of osteosarcoma. Subsequently, the ConsensusClusterPlus package was employed to classify OS patients into subtypes, enabling comparisons of prognosis and clinical information between these subtypes. Patients from the TARGET‐OS and GSE21257 datasets were stratified into high‐risk and low‐risk groups, and their prognoses were compared. Additionally, we assessed the accuracy of the Risk Scoring Model in predicting prognosis, identified independent prognostic factors and explored potential chemotherapeutic agents and immunotherapy drugs.ResultsThrough the intersection of expression profiles from the TARGET‐OS and GSE21257 datasets, we have identified a total of 92 genes associated with necroptosis. Based on differences in the expression of these genes, patients were divided into three subtypes, and we investigated the differences in tumor‐infiltrating immune cells, immune‐related pathways, and prognosis among these subtypes. Our nomogram effectively differentiated subtypes with distinct responses to chemotherapy and immunotherapy. The established signature demonstrated superior prediction ability compared with single clinical indicators.ConclusionsThis pioneering study unveils the prognostic role of necroptosis‐related genes in OS patients, providing a promising alternative for prognostic prediction in clinical disease management. Moreover, our findings highlight the significance of immune cell homeostasis in cancer research and therapeutic response, underscoring its relevance in advancing current treatment strategies.
An analysis of medical malpractice claims against medical oncologists from a national database: Implications for safer practice
Authors: Doolin Jim W. , Schaffer Adam C. , Tishler Roy B. , Jacobson Joseph O. 
Published: December 2023

AbstractMalpractice claims data include valuable information about patient safety. We used mixed methods to analyze claims against medical oncologists (MO) from 2008 to 2019 using a national database. MO claims were compared to a group of other internal medicine subspecialties (OIMS). Logistic regression was used to examine correlates of closing with an indemnity payment. A subset of claims against MO were thematically analyzed using a validated safety incident taxonomy as a framework. 456 claims against MO were compared with 5771 claims against OIMS. MO claims closed with indemnity payments 29.8% of the time versus OIMS 30.3% (p = 0.87). Median MO and OIMS indemnity payments were similar ($190,591 vs. $233,432; p = 0.20). Correlates of MO claims closing with payment included patient assessment, communication among providers, and safety and security as contributing factors. Thematic analysis identified provider cognitive error, adverse drug events and relational problems as the most common safety incidents. MO malpractice claims have similar outcomes to OIMS. We demonstrate the proof‐of‐concept of applying a safety incident taxonomy to medical malpractice. Finding ways to reduce patient exposure to provider cognitive errors, adverse drug reactions, and communication breakdowns should be strategic priorities for safer cancer care.
Evaluation of the Reproducibility of MR Elastography Measurements of the Lumbar Back Muscles
Authors: Chevalier Benjamin , Bedretdinova Dina , Pellot‐Barakat Claire , Maître Xavier , Creze Maud 
Published: December 2023

BackgroundMR elastography (MRE) may provide quantitative imaging biomarkers of lumbar back muscles (LBMs), complementing MRI in spinal diseases by assessing muscle mechanical properties. However, reproducibility analyses for MRE of LBM are lacking.PurposeTo assess technical failure, within‐day and inter‐day reproducibility, robustness with the excitation source positioning, and inter‐observer agreement of MRE of muscles.Study TypeProspective.SubjectsSeventeen healthy subjects (mean age 28 ± 4 years; 11 females).Field Strength/Sequence1.5 T, gradient‐echo MRE, T1‐weighted turbo spin echo.AssessmentThe pneumatic driver was centered at L3 level. Four MRE were performed during two visits, 2–4 weeks apart, each consisting of two MRE with less than 10 minutes inter‐scan interval. At Visit 1, after the first MRE, the coil and driver were removed, then reinstalled. The MRE was repeated. At Visit 2, following the first MRE, only the driver was moved down 5 cm. The MRE was repeated. Two radiologists segmented the multifidus and erector spinae muscles.Statistical TestsPaired t‐test, analysis of variance, intraclass correlation coefficients (ICCs). P‐values <0.05 were considered statistically significant.ResultsMean stiffness of LBM ranged from 1.44 to 1.60 kPa. Mean technical failure rate was 2.5%. Inter‐observer agreement was excellent (ICC ranging from 0.82 [0.64–0.96] to 0.99 [0.98–0.99] in the multifidus, and from 0.85 [0.69–0.92] to 0.99 [0.97–0.99] in the erector spinae muscles). Within‐day reproducibility was fair in the multifidus (ICC: 0.53 [0.47–0.77]) and good in the erector spinae muscles (ICC: 0.74 [0.48–0.88]). Reproducibility after moving the driver was excellent in both multifidus (ICC: 0.85 [0.69–0.93]) and erector spinae muscles (ICC: 0.84 [0.67–0.92]). Inter‐day reproducibility was excellent in the multifidus (ICC: 0.76 [0.48–0.89]) and poor in the erector spinae muscles (ICC: 0.23 [−0.61 to 0.63]).Data ConclusionMRE of LBM provides measurements of stiffness with fair to excellent reproducibility and excellent inter‐observer agreement. However, inter‐day reproducibility in the multifidus muscles indicated that the herein used MRE protocol may not be optimal for this muscle.Evidence Level2Technical EfficacyStage 1
Preparation of Novel Sea Cucumber Intestinal Peptides to Promote Tibial Fracture Healing in Mice by Inducing Differentiation of Hypertrophic Chondrocytes to the Osteoblast Lineage
Authors: Yin Haowen , Yue Hao , Wang Meng , Zhang Tianqi , Zhao Yun‐Tao , Liu Hongying , Wang Jingfeng , Zheng Hongwei , Xue Changhu 
Published: December 2023

ScopeHypertrophic chondrocytes have a decisive regulatory role in the process of fracture healing, and the fate of hypertrophic chondrocytes is not only apoptosis. However, the mechanism of sea cucumber (Stichopus japonicus) intestinal peptide (SCIP) on fracture promotion is still unclear. This study aims to investigate the effect of sea cucumber intestinal peptide on the differentiation fate of hypertrophic chondrocytes in a mouse tibial fracture model.Methods and resultsMice are subjected to open fractures of the right tibia to establish a tibial fracture model. The results exhibit that the SCIP intervention significantly promotes the mineralization of cartilage callus, decreases the expression of the hypertrophic chondrocyte marker Col X, and increases the expression of the osteoblast marker Col I. Mechanically, SCIP promotes tibial fracture healing by promoting histone acetylation and inhibiting histone methylation, thereby upregulating pluripotent transcription factors induced the differentiation of hypertrophic chondrocytes to the osteoblast lineage in a manner distinct from classical endochondral ossification.ConclusionThis study is the first to report that SCIP can promote tibial fracture healing in mice by inducing the differentiation of hypertrophic chondrocytes to the osteoblast lineage. SCIP may be considered raw material for developing nutraceuticals to promote fracture healing.
A simulation of a high‐resolution cadmium zinc telluride positron emission tomography system
Authors: Stanford‐Hill Riley , Groll Andrew , Levin Craig S. 
Published: December 2023

AbstractBackgroundA CZT (cadmium zinc telluride) PET (positron emission tomography) system is being developed at Stanford University. CZT has the promise of outperforming scintillator‐based systems in energy and spatial resolution but has relatively poor coincidence timing resolution.PurposeTo supplement GATE (GEANT 4 Application for Emission Tomography) simulations with charge transport and electronics modeling for a high‐resolution CZT PET system.MethodsA conventional GATE simulation was supplemented with electron‐hole transport modeling and experimentally measured single detector energy resolution to improve the system‐level understanding of a CZT high‐resolution PET system in development at Stanford University. The modeling used GATE hits data and applied charge transport in the crystal and RC‐CR processing of the simulated signals to model the electronics, including leading‐edge discriminators and peak pick‐off. Depth correction was also performed on the simulation data. Experimentally acquired data were used to determine energy resolution parameters and were compared to simulation data.ResultsThe distributions of the coincidence timing, anode energy, and cathode energy are consistent with experimental data. Numerically, the simulation achieved 153 ns FWHM coincidence time resolution (CTR), which is of the same order of magnitude as the raw 210 ns CTR previously found experimentally. Further, the anode energy resolution was found to be 5.9% FWHM (full width at half maximum) at 511 keV in the simulation, which is between the experimental value found for a single crystal of 3% and the value found for the dual‐panel setup of 8.02%, after depth correction.ConclusionsDeveloping this advanced simulation improves upon the limitations of GATE for modeling semiconductor PET systems and provides a means for deeper analysis of the coincidence timing resolution and other complementary electron‐hole dependent system parameters.
Intracellular pyruvate–lactate–alanine cycling detected using real‐time nuclear magnetic resonance spectroscopy of live cells and isolated mitochondria
Authors: Nagana Gowda G. A. , Lusk John A. , Pascua Vadim 
Published: December 2023

AbstractPyruvate, an end product of glycolysis, is a master fuel for cellular energy. A portion of cytosolic pyruvate is transported into mitochondria, while the remaining portion is converted reversibly into lactate and alanine. It is suggested that cytosolic lactate and alanine are transported and metabolized inside mitochondria. However, such a mechanism continues to be a topic of intense debate and investigation. As a part of gaining insight into the metabolic fate of the cytosolic lactate and alanine; in this study, the metabolism of mouse skeletal myoblast cells (C2C12) and their isolated mitochondria was probed utilizing stable isotope‐labeled forms of the three glycolysis products, viz. [3‐13C1]pyruvate, [3‐13C1]lactate, and [3‐13C1]alanine, as substrates. The uptake and metabolism of each substrate was monitored, separately, in real‐time using 1H‐13C 2D nuclear magnetic resonance (NMR) spectroscopy. The dynamic variation of the levels of the substrates and their metabolic products were quantitated as a function of time. The results demonstrate that all three substrates were transported into mitochondria, and each substrate was metabolized to form the other two metabolites, reversibly. These results provide direct evidence for intracellular pyruvate–lactate–alanine cycling, in which lactate and alanine produced by the cytosolic pyruvate are transported into mitochondria and converted back to pyruvate. Such a mechanism suggests a role for lactate and alanine to replenish mitochondrial pyruvate, the primary source for adenosine triphosphate (ATP) synthesis through oxidative phosphorylation and the electron transport chain. The results highlight the potential of real‐time NMR spectroscopy for gaining new insights into cellular and subcellular functions.
Machine learning‐based amide proton transfer imaging using partially synthetic training data
Authors: Viswanathan Malvika , Yin Leqi , Kurmi Yashwant , Zu Zhongliang 
Published: December 2023

AbstractPurposeMachine learning (ML) has been increasingly used to quantify CEST effect. ML models are typically trained using either measured data or fully simulated data. However, training with measured data often lacks sufficient training data, whereas training with fully simulated data may introduce bias because of limited simulations pools. This study introduces a new platform that combines simulated and measured components to generate partially synthetic CEST data, and to evaluate its feasibility for training ML models to predict amide proton transfer (APT) effect.MethodsPartially synthetic CEST signals were created using an inverse summation of APT effects from simulations and the other components from measurements. Training data were generated by varying APT simulation parameters and applying scaling factors to adjust the measured components, achieving a balance between simulation flexibility and fidelity. First, tissue‐mimicking CEST signals along with ground truth information were created using multiple‐pool model simulations to validate this method. Second, an ML model was trained individually on partially synthetic data, in vivo data, and fully simulated data, to predict APT effect in rat brains bearing 9 L tumors.ResultsExperiments on tissue‐mimicking data suggest that the ML method using the partially synthetic data is accurate in predicting APT. In vivo experiments suggest that our method provides more accurate and robust prediction than the training using in vivo data and fully synthetic data.ConclusionPartially synthetic CEST data can address the challenges in conventional ML methods.
Activation of dopamine 2 receptors modulates glutamate decarboxylases 65 and 67 during stroke recovery in mice
Authors: Talhada Daniela , Nilsson Robert , Walser Severin , Michalettos Georgios , Ruscher Karsten 
Published: December 2023

AbstractBackgroundsTreatment with levodopa enhances recovery of lost neurological functions in preclinical stroke models and patients. Here, we studied whether dopamine signaling modulates GABAergic neurotransmission in parvalbumin‐positive interneurons after experimental stroke.MethodsFollowing block randomization, mice were subjected to experimental stroke induced by photothrombosis (PT). Two days after the insult, mice were treated either with the D1 receptor antagonist by R(+)‐SCH‐23390 (0.1 mg/kg), the selective D1 receptor agonist (R)‐(+)‐SKF‐38393 hydrochloride (1 mg/kg), the D2 receptor agonist R(−)‐2,10,11‐trihydroxy‐N‐propyl‐noraporphine hydrobromide hydrate (TNPA) (1 mg/kg), the D2 receptor antagonist S‐(−)‐eticlopride hydrochloride (0.3 mg/kg), or vehicle (saline) by daily intraperitoneal injection for five consecutive days, respectively. Recovery of function was assessed by paw placement and foot fault test before and on Days 2 and 7 after surgery.ResultsMice treated with TNPA showed a statistically significant improvement of recovery compared to all other treatment conditions. Synthesis of gamma‐aminobutyric acid (GABA) was quantified by levels of full‐length and cleaved glutamate acid decarboxylase 67 and 65 (GAD65 and GAD67) in the peri‐infarct area and homotypic regions of the contralateral cortex. Compared to the other treatments, TNPA significantly reduced the level of the GAD67 isoform both in the ischemic and contralateral hemispheres. Levels of GAD65 were found significantly higher in the contralateral hemisphere in TNPA‐treated mice after PT accompanied by an increase in the 58 kDa‐truncated form.ConclusionOur results point toward reduced GABA synthesis in a D2 receptor‐mediated mechanism possibly contributing to counteract functional inhibition after stroke.
Sleep and its association with dental caries or myopia in first graders
Authors: Tsai Han‐Yi , Tsai Tzu‐I , Wang Yin‐Lin , Chen Hung‐Chi , Lee Chien‐Chang , Tsai Shao‐Yu 
Published: December 2023

AbstractAimFirst grade is a transition from pre‐school to school‐age. The change in lifestyle behaviours such as sleep may have a physiological response, which contributes to the presence or absence of two highly incident diseases: dental caries or myopia. The aim of the study was to examine the association between sleep and myopia as well as sleep and dental caries in first graders.DesignIt is a cross‐sectional study.MethodsThis was a recruitment phase of an interventional study. A total of 338 children whose caregivers completed a Children's Sleep Habits Questionnaire. Caregivers also provided information regarding myopia and caries status of children and their parents. Binary logistic regression was applied to analyse the potential risk factors.ResultsDental caries and myopia rates were 45.9% and 9.5%, respectively. After adjusting for children's gender, children's age, fathers with caries and mothers with caries, the odds ratio for dental caries in children who slept less than 9 h when compared to those who slept for nine and more hours was 1.94. Mothers with caries were 3.37 times more likely to have children with caries than mothers without caries. However, sleep was not associated with myopia in first graders.ConclusionSleeping less than 9 h and maternal caries were risk factors of children developing dental caries. Future sleep and myopia studies can be conducted on higher graders who may present prolonged exposure and accumulations of myopic risk factors.ImplicationsScreening of children with insufficient sleep is needed for nurses to enable the early identification of high‐risk groups for dental caries in school settings. Family nurses are encouraged to work with family members to implement tailored sleep interventions, in order to facilitate better sleep and oral health practices in both school and home settings.RegistrationThis study protocol was registered on ClinicalTrials.gov (Registration number: Redacted).
The association between perceived social support and resilience among Chinese university students: A moderated mediation model
Authors: Hou Yan , Zhang Yan , Cao Xiaochen , Lei Guanghui , Liu Guohua 
Published: December 2023

AbstractThis study investigated the relationship between perceived social support and psychological resilience among university students while also exploring the mediating role of coping style and the moderating effect of perceived stress. The study collected data from 1356 university students, and a path analysis was used to test the proposed hypotheses. The results revealed that perceived social support had a significant positive effect on psychological resilience. Additionally, positive coping style partially mediated the relationship between perceived social support and psychological resilience. The study also found that the direct predictive effect of perceived social support on psychological resilience, as well as the mediating role of positive coping style, were both moderated by perceived stress. Specifically, the effect of perceived social support on psychological resilience was more significant among university students with lower perceived stress than among those with higher perceived stress. Our results underscore the importance of perceived social support, positive coping style, and perceived stress in promoting psychological resilience among Chinese university students.
Emerging role of carbonyl–carbonyl interactions in the classification of beta turns
Authors: D'Arminio Nancy , Ruggiero Valentina , Pierri Giovanni , Marabotti Anna , Tedesco Consiglia 
Published: December 2023

AbstractCarbonyl–carbonyl interactions in peptides and proteins attracted considerable interest in recent years. Here, we report a survey of carbonyl–carbonyl interactions in cyclic peptides, depsipeptides, peptoids and discuss the relationship between backbone torsion angles and CO∙∙∙CO distances. In general, φ values in the range between −40° and −90° and between 40° and 90° correspond to CO∙∙∙CO distances below 3.22 Å. By extending the analysis of carbonyl–carbonyl interactions in different types of beta turns in proteins, we also highlight the role of direct or reciprocal carbonyl–carbonyl interactions in stabilizing the beta turn conformation for each specific type. We confirmed the new type II beta turn, detected by Dunbrack and coworkers, and named Pa, and detect the presence of a direct carbonyl–carbonyl interaction between the second and third residues of the turn. We also evidenced the existence of another new type II beta turn, named pA (following Dunbrack's notation), which represents the alternative conformation of Pa with opposite φ and ψ values and is characterized by a direct carbonyl–carbonyl interaction between the second and third residues of the turn. Finally, we show that the occurrence of CO∙∙∙CO interactions could be also advocated to explain from a chemical point of view the diversity of turn types.