Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

In this study, we systematically tested the hypothesis that during the critical developmental period of adolescence, on a macro scale, the concentrations of major excitatory and inhibitory neurotransmitters (glutamate/glutamine and γ‑aminobutyric acid [GABA]) in the dorsal and ventral lateral prefrontal cortex are associated with the brain's functional connectivity and an individual's psychopathology. Neurotransmitters were measured via magnetic resonance spectroscopy while functional connectivity was measured with resting-state fMRI (n = 121). Seed-based and network-based analyses revealed associations of neurotransmitter concentrations and functional connectivities between regions/networks that are connected to prefrontal cortices via structural connections that are thought to be under dynamic development during adolescence. These regions tend to be boundary areas between functional networks. Furthermore, several connectivities were found to be associated with individual's levels of internalizing psychopathology. These findings provide insights into specific neurochemical mechanisms underlying the brain's macroscale functional organization, its development during adolescence, and its potential associations with symptoms associated with internalizing psychopathology.
Humans ; Adolescent ; Glutamic Acid/metabolism* ; Prefrontal Cortex/diagnostic imaging* ; Male ; Glutamine/metabolism* ; Female ; gamma-Aminobutyric Acid/metabolism* ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Nerve Net/metabolism* ; Neural Pathways ; Connectome

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Recent advancements in the field of medical artificial intelligence (AI) have led to the widespread adoption of foundational and large language models. This review paper explores their applications within medical AI, introducing a novel classification framework that categorizes them as disease-specific, general-domain, and multi-modal models. The paper also addresses key challenges such as data acquisition and augmentation, including issues related to data volume, annotation, multi-modal fusion, and privacy concerns. Additionally, it discusses the evaluation, validation, limitations, and regulation of medical AI models, emphasizing their transformative potential in healthcare. The importance of continuous improvement, data security, standardized evaluations, and collaborative approaches is highlighted to ensure the responsible and effective integration of AI into clinical applications.

Background: Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS). Methods: Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships. Results: Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years).The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and  MM-GLS > 18%. Conclusions MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.

Background: Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS). Methods: Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships. Results: Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years).The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and  MM-GLS > 18%. Conclusions MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.

Background: Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS). Methods: Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships. Results: Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years).The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and  MM-GLS > 18%. Conclusions MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.

Background: There is considerable heterogeneity in findings and a lack of consensus regarding the interplay between osteoporosis and outcomes in patients with lumbar degenerative spine disease. Therefore, the purpose of this systematic review and meta-analysis was to gather and analyze existing data on the effect of osteoporosis on radiographic, surgical, and clinical outcomes following surgery for lumbar degenerative spinal disease. Methods: A systematic review was performed to determine the effect of osteoporosis on the incidence of adverse outcomes after surgical intervention for lumbar degenerative spinal diseases. The approach focused on the radiographic outcomes, reoperation rates, and other medical and surgical complications. Subsequently, a meta-analysis was performed on the eligible studies. Results: The results of the meta-analysis suggested that osteoporotic patients experienced increased rates of adjacent segment disease (ASD; p=0.015) and cage subsidence (p=0.001) while demonstrating lower reoperation rates than non-osteoporotic patients (7.4% vs. 13.1%; p=0.038). The systematic review also indicated that the length of stay, overall costs, rates of screw loosening, and rates of wound and other medical complications may increase in patients with a lower bone mineral density. Fusion rates, as well as patient-reported and clinical outcomes, did not differ significantly between osteoporotic and non-osteoporotic patients. Conclusions Osteoporosis was associated with an increased risk of ASD, cage migration, and possibly postoperative screw loosening, as well as longer hospital stays, incurring higher costs and an increased likelihood of postoperative complications. However, a link was not established between osteoporosis and poor clinical outcomes.

Objective : To identify the main components in the extracts of different parts of Juandan Baihe (Lilium lancifolium) by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology and investigate their hypoglycemic activities. Methods: The MS fragmentation pathways of the main types of compounds in Juandan Baihe (Lilium lancifolium) were studied, and the main components in the extracts were systematically identified using MS fragmentation pathways combined with MS mining technology. Based on the hyperglycemia male mouse model [specific pathogen free (SPF)-grade Kunming mice] induced by streptozotocin (intragastric administration of 80 mg/kg for 3 d), the hypoglycemic effects of extracts of Juandan Baihe (Lilium lancifolium) roots, stems, corms, leaves, and flowers were evaluated by measuring the changes of blood glucose, daily water consumption, daily food intake, and body weight. Result: The MS fragmentation pathways of regalosides, dioscins, phenylpropanoids, flavonoids, and chlorogenic acids in Juandan Baihe (Lilium lancifolium) were clarified, and a mining method for compounds in this plant was constructed. A total of 58 compounds, including 6 chlorogenic acids, 14 regalosides, 13 phenylpropanoids, 5 flavonoids, and 20 dioscins, were identified from the roots, stems, corms, leaves, and flowers of Juandan Baihe (Lilium lancifolium). Among them, 30 compounds were reported for the first time from this plant. The root and corm extracts demonstrated significant hypoglycemic activities by reducing blood glucose levels from 23.76 ± 1.21 and 24.29 ± 1.35 mmol/L to 17.21 ± 1.23 and 18.78 ± 1.49 mmol/L, respectively (P < 0.05). The roots and corms extracts could also attenuate the symptoms of polydipsia (P < 0.01), polyphagia (P < 0.05), and weight loss caused by diabetes. Conclusion This study clarifies that the roots of Juandan Baihe (Lilium lancifolium) are rich in regalosides and dioscins for the first time, and have significant hypoglycemic activities, providing the foundation for the comprehensive utilization of this plant and the development of hypoglycemic drugs.