Tag: pubmed

Cell Mol Biol Lett. 2024 Jul 8;29(1):100. doi: 10.1186/s11658-024-00614-5.

ABSTRACT

OBJECTIVE: Osteoporosis is a global health issue characterized by decreased bone mass and microstructural degradation, leading to an increased risk of fractures. This study aims to explore the molecular mechanism by which P2X7 receptors influence osteoclast formation and bone resorption through the PI3K-Akt-GSK3β signaling pathway.

METHODS: An osteoporosis mouse model was generated through ovariectomy (OVX) in normal C57BL/6 and P2X7^f/f; LysM-cre mice. Osteoclasts were isolated for transcriptomic analysis, and differentially expressed genes were selected for functional enrichment analysis. Metabolite analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and multivariate statistical analysis and pattern recognition were used to identify differential lipid metabolism markers and their distribution. Bioinformatics analyses were conducted using the Encyclopedia of Genes and Genomes database and the MetaboAnalyst database to assess potential biomarkers and create a metabolic pathway map. Osteoclast precursor cells were used for in vitro cell experiments, evaluating cell viability and proliferation using the Cell Counting Kit 8 (CCK-8) assay. Osteoclast precursor cells were induced to differentiate into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-beta ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) staining was performed to compare differentiation morphology, size, and quantity between different groups. Western blot analysis was used to assess the expression of differentiation markers, fusion gene markers, and bone resorption ability markers in osteoclasts. Immunofluorescence staining was employed to examine the spatial distribution and quantity of osteoclast cell skeletons, P2X7 protein, and cell nuclei, while pit assay was used to evaluate osteoclast bone resorption ability. Finally, in vivo animal experiments, including micro computed tomography (micro-CT), hematoxylin and eosin (HE) staining, TRAP staining, and immunohistochemistry, were conducted to observe bone tissue morphology, osteoclast differentiation, and the phosphorylation level of the PI3K-Akt-GSK3β signaling pathway.

RESULTS: Transcriptomic and metabolomic data collectively reveal that the P2X7 receptor can impact the pathogenesis of osteoporosis through the PI3K-Akt-GSK3β signaling pathway. Subsequent in vitro experiments showed that cells in the Sh-P2X7 + Recilisib group exhibited increased proliferative activity (1.15 versus 0.59), higher absorbance levels (0.68 versus 0.34), and a significant increase in resorption pit area (13.94 versus 3.50). Expression levels of osteoclast differentiation-related proteins MMP-9, CK, and NFATc1 were markedly elevated (MMP-9: 1.72 versus 0.96; CK: 2.54 versus 0.95; NFATc1: 3.05 versus 0.95), along with increased fluorescent intensity of F-actin rings. In contrast, the OE-P2X7 + LY294002 group showed decreased proliferative activity (0.64 versus 1.29), reduced absorbance (0.34 versus 0.82), and a significant decrease in resorption pit area (5.01 versus 14.96), accompanied by weakened expression of MMP-9, CK, and NFATc1 (MMP-9: 1.14 versus 1.79; CK: 1.26 versus 2.75; NFATc1: 1.17 versus 2.90) and decreased F-actin fluorescent intensity. Furthermore, in vivo animal experiments demonstrated that compared with the wild type (WT) + Sham group, mice in the WT + OVX group exhibited significantly increased levels of CTX and NTX in serum (CTX: 587.17 versus 129.33; NTX: 386.00 versus 98.83), a notable decrease in calcium deposition (19.67 versus 53.83), significant reduction in bone density, increased trabecular separation, and lowered bone mineral density (BMD). When compared with the KO + OVX group, mice in the KO + OVX + recilisib group showed a substantial increase in CTX and NTX levels in serum (CTX: 503.50 versus 209.83; NTX: 339.83 versus 127.00), further reduction in calcium deposition (29.67 versus 45.33), as well as decreased bone density, increased trabecular separation, and reduced BMD.

CONCLUSION: P2X7 receptors positively regulate osteoclast formation and bone resorption by activating the PI3K-Akt-GSK3β signaling pathway.

PMID:38977961 | DOI:10.1186/s11658-024-00614-5

J Headache Pain. 2024 Jul 8;25(1):110. doi: 10.1186/s10194-024-01815-1.

ABSTRACT

BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH.

METHODS: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics.

RESULTS: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction.

CONCLUSIONS: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

PMID:38977951 | DOI:10.1186/s10194-024-01815-1

Can Urol Assoc J. 2024 Jun 17. doi: 10.5489/cuaj.8714. Online ahead of print.

ABSTRACT

INTRODUCTION: We aimed to evaluate the novel use of a 1.9 mm Trilogy lithotripter probe with varying locations and composition of renal stones.

METHODS: We prospectively enrolled patients to undergo mini percutaneous nephrolithotomy (mPCNL) procedures using the 1.9 mm (instead of the standard 1.5 mm) Trilogy probe from August 2021 to April 2022. Several adjunctive irrigation measures compensated for reduced flow with the larger probe. Primary outcome was treatment efficiency. Patient demographics, preoperative demographics, and comorbidities, as well as real-time surgical data were extracted. Statistical analysis was performed using Kruskal-Wallis tests to compare stone type and location.

RESULTS: A total of 110 patients were included in this study. The median total treatment time was 6.8 minutes, median lithotripsy time was 3.3 minutes, median stone treatment efficiency was 0.34 mm/min, and treatment efficacy was 50.4 (lithotripter time/treatment time). Overall median lithotripter efficiency was 104.6 mm³/min. Treatment efficiency was similar among stone composition (p=0.245) and location (p=0.263). Lithotripter 3D and 1D efficiency was also similar among stone composition (p=0.637 and p=0.766, respectively). Lithotripter 1D efficiency was nearly twice as fast in the lower pole compared to other stone locations (p=0.010). Overall broken probe rate for this procedure was 12%, mostly at the beginning, suggesting a learning curve. Five patients had minor complications, including one patient that required admission to the hospital for postoperative pain management.

CONCLUSIONS: The 1.9 mm Trilogy lithotripter can be effective in mPCNL procedures with the use of easily implementable adjunctive irrigation techniques, decreasing the gap between lithotripsy time and total treatment time.

PMID:38976894 | DOI:10.5489/cuaj.8714

J Med Internet Res. 2024 Jul 8;26:e51931. doi: 10.2196/51931.

ABSTRACT

BACKGROUND: Online appointment booking is a commonly used tool in several industries. There is limited evidence about the benefits and challenges of using online appointment booking in health care settings. Potential benefits include convenience and the ability to track appointments, although some groups of patients may find it harder to engage with online appointment booking. We sought to understand how patients in England used and experienced online appointment booking.

OBJECTIVE: This study aims to describe and compare the characteristics of patients in relation to their use of online appointment booking in general practice and investigate patients’ views regarding online appointment booking arrangements.

METHODS: This was a mixed methods study set in English general practice comprising a retrospective analysis of the General Practice Patient Survey (GPPS) and semistructured interviews with patients. Data used in the retrospective analysis comprised responses to the 2018 and 2019 GPPS analyzed using mixed-effects logistic regression. Semistructured interviews with purposively sampled patients from 11 general practices in England explored experiences of and views on online appointment booking. Framework analysis was used to allow for comparison with the findings of the retrospective analysis.

RESULTS: The retrospective analysis included 1,327,693 GPPS responders (2018-2019 combined). We conducted 43 interviews with patients with a variety of experiences and awareness of online appointment booking; of these 43 patients, 6 (14%) were from ethnic minority groups. In the retrospective analysis, more patients were aware that online appointment booking was available (581,224/1,288,341, 45.11%) than had experience using it (203,184/1,301,694, 15.61%). There were deprivation gradients for awareness and use and a substantial decline in both awareness and use in patients aged >75 years. For interview participants, age and life stage were factors influencing experiences and perceptions, working patients valued convenience, and older patients preferred to use the telephone. Patients with long-term conditions were more aware of (odds ratio [OR] 1.43, 95% CI 1.41-1.44) and more likely to use (OR 1.65, 95% CI 1.63-1.67) online appointment booking. Interview participants with long-term conditions described online appointment booking as useful for routine nonurgent appointments. Patients in deprived areas were clustered in practices with low awareness and use of online appointment booking among GPPS respondents (OR for use 0.65, 95% CI 0.64-0.67). Other key findings included the influence of the availability of appointments online and differences in the registration process for accessing online booking.

CONCLUSIONS: Whether and how patients engage with online appointment booking is influenced by the practice with which they are registered, whether they live with long-term conditions, and their deprivation status. These factors should be considered in designing and implementing online appointment booking and have implications for patient engagement with the wider range of online services offered in general practice.

PMID:38976870 | DOI:10.2196/51931

J Med Internet Res. 2024 Jul 8;26:e56110. doi: 10.2196/56110.

ABSTRACT

BACKGROUND: OpenAI’s ChatGPT is a pioneering artificial intelligence (AI) in the field of natural language processing, and it holds significant potential in medicine for providing treatment advice. Additionally, recent studies have demonstrated promising results using ChatGPT for emergency medicine triage. However, its diagnostic accuracy in the emergency department (ED) has not yet been evaluated.

OBJECTIVE: This study compares the diagnostic accuracy of ChatGPT with GPT-3.5 and GPT-4 and primary treating resident physicians in an ED setting.

METHODS: Among 100 adults admitted to our ED in January 2023 with internal medicine issues, the diagnostic accuracy was assessed by comparing the diagnoses made by ED resident physicians and those made by ChatGPT with GPT-3.5 or GPT-4 against the final hospital discharge diagnosis, using a point system for grading accuracy.

RESULTS: The study enrolled 100 patients with a median age of 72 (IQR 58.5-82.0) years who were admitted to our internal medicine ED primarily for cardiovascular, endocrine, gastrointestinal, or infectious diseases. GPT-4 outperformed both GPT-3.5 (P<.001) and ED resident physicians (P=.01) in diagnostic accuracy for internal medicine emergencies. Furthermore, across various disease subgroups, GPT-4 consistently outperformed GPT-3.5 and resident physicians. It demonstrated significant superiority in cardiovascular (GPT-4 vs ED physicians: P=.03) and endocrine or gastrointestinal diseases (GPT-4 vs GPT-3.5: P=.01). However, in other categories, the differences were not statistically significant.

CONCLUSIONS: In this study, which compared the diagnostic accuracy of GPT-3.5, GPT-4, and ED resident physicians against a discharge diagnosis gold standard, GPT-4 outperformed both the resident physicians and its predecessor, GPT-3.5. Despite the retrospective design of the study and its limited sample size, the results underscore the potential of AI as a supportive diagnostic tool in ED settings.

PMID:38976865 | DOI:10.2196/56110

Prehosp Emerg Care. 2024 Jul 8:1-12. doi: 10.1080/10903127.2024.2376757. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assesses the feasibility, inter-rater reliability, and accuracy of using OpenAI’s ChatGPT-4 and Google’s Gemini Ultra large language models (LLMs), for Emergency Medical Services (EMS) quality assurance. The implementation of these LLMs for EMS quality assurance has the potential to significantly reduce the workload on medical directors and quality assurance staff by automating aspects of the processing and review of patient care reports. This offers the potential for more efficient and accurate and identification of areas requiring improvement, thereby potentially enhancing patient care outcomesMETHODS: Two expert human reviewers, ChatGPT GPT-4, and Gemini Ultra assessed and rated 150 consecutively sampled and anonymized prehospital records from 2 large urban EMS agencies for adherence to 2020 National Association of State EMS metrics for cardiac care. We evaluated the accuracy of scoring, inter-rater reliability, and review efficiency. The inter-rater reliability for the dichotomous outcome of each EMS metric was measured using the kappa statistic.RESULTS: Human reviewers showed high interrater reliability, with 91.2% agreement and a kappa coefficient, 0.782 (0.654-0.910). ChatGPT-4 achieved substantial agreement with human reviewers in EKG documentation and aspirin administration (76.2% agreement, kappa coefficient, 0.401 (0.334-0.468), but performance varied across other metrics. Gemini Ultra’s evaluation was discontinued due to poor performance. No significant differences were observed in median review times: 01:28 minutes (IQR 1:12 – 1:51 min) per human chart review, 01:24 minutes (IQR 01:09 – 01:53 min) per ChatGPT-4 chart review (p = 0.46), and 01:50 minutes (IQR 01:10-03:34 min) per Gemini Ultra review (p = 0.06).CONCLUSIONS: Large language models demonstrate potential in supporting quality assurance by effectively and objectively extracting data elements. However, their accuracy in interpreting non-standardized and time-sensitive details remains inferior to human evaluators. Our findings suggest that current LLMs may best offer supplemental support to the human review processes, but their value remains limited. Enhancements in LLM training and integration are recommended for improved and more reliable performance in the quality assurance processes.

PMID:38976859 | DOI:10.1080/10903127.2024.2376757

J Psychosoc Nurs Ment Health Serv. 2024 Jul;62(7):11-15. doi: 10.3928/02793695-20240620-01. Epub 2024 Jul 1.

ABSTRACT

The mental health needs of Asian American older adults are complex and multifaceted. Despite their rich diversity, Asian American older adults face significant challenges, including mental health stigma, cultural stress, limited English proficiency, and historical trauma. In addition, the coronavirus disease 2019 pandemic reignited preexisting anti-Asian attitudes of hostility, discrimination, blame, and scapegoating. The historical context of Asian immigration to the United States, impact of race-based discrimination, and recent resurgence of anti-Asian hate crimes impact mental health in Asian American older adults. Thus, there is a need for a culturally sensitive and competent mental health care workforce, culturally tailored interventions, and family involvement. In the context of research and policy, it is critical to prioritize increased funding and research focus on culturally tailored instrument development, interventions, and policy initiatives informed by recent findings to safeguard this population from hate crimes and discrimination. [Journal of Psychosocial Nursing and Mental Health Services, 62(7), 11-15.].

PMID:38976856 | DOI:10.3928/02793695-20240620-01

Orthopedics. 2024 Jul 10:1-5. doi: 10.3928/01477447-20240702-02. Online ahead of print.

ABSTRACT

BACKGROUND: Displaced diaphyseal fractures can be reduced using the push-pull technique, wherein a plate is affixed to the distal fragment of the fracture, a post screw is placed proximal to the plate, and a lamina spreader creates distraction. This study evaluated the load to failure and mechanism of failure of bicortical and unicortical post screws during reduction.

MATERIALS AND METHODS: Four matched pairs of cadaver legs were subjected to a 2-cm oblique osteotomy simulating a displaced, oblique diaphyseal fracture. A 6-hole compression plate was affixed to the distal fragment with 2 unicortical locking screws, and a 12-mm uni-cortical or 20-mm bicortical screw was inserted as a post screw proximal to the plate. A lamina bone spreader was used to exert a distraction force between the plate and the post screw. A mechanical actuator simulated the distraction procedure until failure. Maximum applied load, displacement, and absorbed energy were recorded and compared across unicortical and bicortical groups by paired t tests.

RESULTS: At maximum load, we found statistically significant differences in displacement (P=.003) and energy absorbed (P=.022) between the two groups. All unicortical screws failed through screw toggle and bone cut-out. Bicortical screws failed through bending, with no visible damage to the bone at the screw site.

CONCLUSION: When diaphyseal fractures are significantly shortened and require a greater distraction force to achieve reduction, bicortical screws demonstrate a higher mechanical load to failure and increased bone loss from the screw-removal site. A unicortical post screw may be used if minimal distraction is needed. [Orthopedics. 202x;4x(x):xx-xx.].

PMID:38976846 | DOI:10.3928/01477447-20240702-02

JCO Precis Oncol. 2024 Jun;8:e2300718. doi: 10.1200/PO.23.00718.

ABSTRACT

PURPOSE: To use modern machine learning approaches to enhance and automate the feature extraction from the longitudinal circulating tumor DNA (ctDNA) data and to improve the prediction of survival and disease progression, risk stratification, and treatment strategies for patients with 1L non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS: Using IMpower150 trial data on patients with untreated metastatic NSCLC treated with atezolizumab and chemotherapies, we developed a machine learning algorithm to extract predictive features from ctDNA kinetics, improving survival and progression prediction. We analyzed kinetic data from 17 ctDNA summary markers, including cell-free DNA concentration, allele frequency, tumor molecules in plasma, and mutation counts.

RESULTS: Three hundred and ninety-eight patients with ctDNA data (206 in training and 192 in validation) were analyzed. Our models outperformed existing workflow using conventional temporal ctDNA features, raising overall survival (OS) concordance index to 0.72 and 0.71 from 0.67 and 0.63 for C3D1 and C4D1, respectively, and substantially improving progression-free survival (PFS) to approximately 0.65 from the previous 0.54-0.58, a 12%-20% increase. Additionally, they enhanced risk stratification for patients with NSCLC, achieving clear OS and PFS separation. Distinct patterns of ctDNA kinetic characteristics (eg, baseline ctDNA markers, depth of ctDNA responses, and timing of ctDNA clearance, etc) were revealed across the risk groups. Rapid and complete ctDNA clearance appears essential for long-term clinical benefit.

CONCLUSION: Our machine learning approach offers a novel tool for analyzing ctDNA kinetics, extracting critical features from longitudinal data, improving our understanding of the link between ctDNA kinetics and progression/mortality risks, and optimizing personalized immunotherapies for 1L NSCLC.

PMID:38976829 | DOI:10.1200/PO.23.00718

J Chem Theory Comput. 2024 Jul 8. doi: 10.1021/acs.jctc.4c00514. Online ahead of print.

ABSTRACT

Alchemical free energy methods are useful in computer-aided drug design and computational protein design because they provide rigorous statistical mechanics-based estimates of free energy differences from molecular dynamics simulations. λ dynamics is a free energy method with the ability to characterize combinatorial chemical spaces spanning thousands of related systems within a single simulation, which gives it a distinct advantage over other alchemical free energy methods that are mostly limited to pairwise comparisons. Recently developed methods have improved the scalability of λ dynamics to perturbations at many sites; however, the size of chemical space that can be explored at each individual site has previously been limited to fewer than ten substituents. As the number of substituents increases, the volume of alchemical space corresponding to nonphysical alchemical intermediates grows exponentially relative to the size corresponding to the physical states of interest. Beyond nine substituents, λ dynamics simulations become lost in an alchemical morass of intermediate states. In this work, we introduce new biasing potentials that circumvent excessive sampling of intermediate states by favoring sampling of physical end points relative to alchemical intermediates. Additionally, we present a more scalable adaptive landscape flattening algorithm for these larger alchemical spaces. Finally, we show that this potential enables more efficient sampling in both protein and drug design test systems with up to 24 substituents per site, enabling, for the first time, simultaneous simulation of all 20 amino acids.

PMID:38976796 | DOI:10.1021/acs.jctc.4c00514