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1.
Heliyon ; 10(15): e35117, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39170279

RÉSUMÉ

Nurses in intensive care units are subjected to high levels of work-related stress and must cope with psychological distress. This preliminary study explored the effects of an online supportive music and imagery intervention on these nurses' perceived stress, psychological distress, and sleep quality. A prospective pre-post design was employed to investigate the effectiveness of online supportive music and imagery interventions. The intervention comprised five weekly sessions, each lasting 50-60 min, which included verbal interactions and listening to music, and were facilitated by trained music therapists. Perceived stress and psychological distress were measured before and after the five-week program to investigate its effectiveness, and the current stress level and emotional state were measured before and after each session to explore changes over the intervention period. Sleep quality was measured weekly. In total, 29 participants completed the program. The results showed a significant decrease in perceived stress (d = 0.45, p = .045) and psychological distress (d = 0.53, p = .045) after the intervention. Regarding changes over the intervention period, the findings demonstrated a significant main effect of the number of sessions on perceived stress (p = 0.001), energy (p = 0.001), and tension (p = 0.023), whereas the effects on perceived valence and scores on the Korean version of the Insomnia Severity Index were not significant. Moreover, a significant post-session main effect was observed for all perceived stress and emotion ratings (p < 0.001). Online supportive music and imagery interventions may help reduce stress levels and enhance positive emotional states among nurses in intensive care units. Integrating self-work into supportive music imagery interventions may increase adherence to the intervention and extend its effect.

2.
Neuroimage ; 299: 120806, 2024 Aug 22.
Article de Anglais | MEDLINE | ID: mdl-39179011

RÉSUMÉ

Recent studies indicate that differences in cognition among individuals may be partially attributed to unique brain wiring patterns. While functional connectivity (FC)-based fingerprinting has demonstrated high accuracy in identifying adults, early studies on neonates suggest that individualized FC signatures are absent. We posit that individual uniqueness is present in neonatal FC data and that conventional linear models fail to capture the rapid developmental trajectories characteristic of newborn brains. To explore this hypothesis, we employed a deep generative model, known as a variational autoencoder (VAE), leveraging two extensive public datasets: one comprising resting-state functional MRI (rs-fMRI) scans from 100 adults and the other from 464 neonates. VAE models trained on rs-fMRI from both adults and newborns produced superior age prediction performance (with r between predicted- and actual age ∼ 0.7) and individual identification accuracy (∼45 %) compared to models trained solely on adult or neonatal data. The VAE model also showed significantly higher individual identification accuracy than linear models (=10∼30 %). Importantly, the VAE differentiated connections reflecting age-related changes from those indicative of individual uniqueness, a distinction not possible with linear models. Moreover, we derived 20 latent variables, each corresponding to distinct patterns of cortical functional network (CFNs). These CFNs varied in their representation of brain maturation and individual signatures; notably, certain CFNs that failed to capture neurodevelopmental traits, in fact, exhibited individual signatures. CFNs associated with neonatal neurodevelopment predominantly encompassed unimodal regions such as visual and sensorimotor areas, whereas those linked to individual uniqueness spanned multimodal and transmodal brain regions. The VAE's capacity to extract features from rs-fMRI data beyond the capabilities of linear models positions it as a valuable tool for delineating cognitive traits inherent in rs-fMRI and exploring individualized imaging phenotypes.

3.
Nanoscale Adv ; 6(16): 4137-4148, 2024 Aug 06.
Article de Anglais | MEDLINE | ID: mdl-39114153

RÉSUMÉ

Over more than a decade, lead halide perovskites (LHPs) have been popular as a next-generation semiconductor for optoelectronics. Later, all-inorganic CsPbX3 (X = Cl, Br, and I) nanocrystals (NCs) were synthesized via supersaturated recrystallization (SR) at room temperature (RT). However, compared to the hot injection (HI) method, the formation mechanism of NCs via SR-RT has not been well studied. Hence, this study will contribute to elucidating SR-RT based on the LaMer model and Hansen solubility parameter. Herein, we also demonstrate the entropy-driven mixing between two dissimilar polar-nonpolar (DMF-toluene) solvents. Next, we find that, in a poor solvent (toluene ≫ DMF in volume), ∼60 nm sized CsPbBr3 NCs were synthesized in one step, whereas in a marginal solvent (toluene ≈ DMF), ∼3.5 nm sized NCs were synthesized in two steps, indicating the importance of solvent polarity, specifically the 'solubility parameter'. In addition, in the presence of a CuBr2 additive, high-quality cubic NCs (with ∼3.8 nm and ∼21.4 nm edge sizes) were synthesized. Hence, through this study, we present a 'solubility parameter-based nanocrystal-size control model' for SR-RT processes.

4.
Hepatol Commun ; 8(8)2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39101773

RÉSUMÉ

BACKGROUND: Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet. METHODS: RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma. RESULTS: Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number-dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade. CONCLUSIONS: Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.


Sujet(s)
Carcinome hépatocellulaire , Cholangiocarcinome , Analyse de profil d'expression de gènes , Tumeurs du foie , Humains , Tumeurs du foie/génétique , Tumeurs du foie/anatomopathologie , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/anatomopathologie , Cholangiocarcinome/génétique , Cholangiocarcinome/anatomopathologie , Transcriptome , Mâle , Methyltransferases/génétique , Methyltransferases/métabolisme , Transduction du signal/génétique , Régulation de l'expression des gènes tumoraux , Tumeurs des canaux biliaires/génétique , Tumeurs des canaux biliaires/anatomopathologie , Femelle , Adulte d'âge moyen
5.
Article de Anglais | MEDLINE | ID: mdl-39109557

RÉSUMÉ

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

6.
Clin Orthop Surg ; 16(4): 586-593, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39092301

RÉSUMÉ

Background: The morphology of the suprascapular notch (SSN) and the ossification of the superior transverse suprascapular ligament (STSL) are risk factors for injury of the suprascapular nerve (SN) during arthroscopic shoulder procedures. The purpose of the current study was to compare preoperative clinical and radiologic characteristics between patients with and without STSL ossification and to evaluate SSN morphology in patients who underwent arthroscopic rotator cuff repair using a 3-dimensional (3D) reconstructed model. Methods: Patients who underwent arthroscopic rotator cuff repair and were given a computed tomography (CT) scan from March 2018 to August 2019 were included in this study. Patients were divided into 2 groups: those without STSL ossification (group I) and those with STSL ossification (group II). Tear size of the rotator cuff and fatty infiltration of rotator cuff muscles were assessed in preoperative magnetic resonance imaging. The morphology of the SSN was classified following Rengachary's classification. The transverse and vertical diameters of the SSN and the distances from anatomical landmarks to the STSL were measured. All measurements were completed using a 3D CT reconstructed scapula model. Results: A total of 200 patients were included in this study. One hundred seventy-eight patients (89.0%) without STSL ossification were included in group I, and 22 patients (11.0%) with STSL ossification were included in group II. Group II showed a significantly advanced age (61.0 ± 7.4 vs. 71.0 ± 7.3 years, p < 0.001) and a shorter transverse diameter of SSN (10.7 ± 3.1 mm vs. 6.1 ± 3.7 mm, p < 0.001) than group I. In the logistic regression analysis, age was an independent prognostic factor for STSL ossification (odds ratio, 1.201; 95% confidence interval, 1.112-1.296; p < 0.001). Patients in type VI showed significantly shorter transverse diameters than other types (p < 0.001). The patient with type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than those with other types (p < 0.001). Conclusions: In the 3D morphological analysis, age was the independent factor associated with STSL ossification in patients who underwent arthroscopic rotator cuff repair. Type VI showed significantly shorter transverse diameters than other types. Type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than other types.


Sujet(s)
Arthroscopie , Imagerie tridimensionnelle , Lésions de la coiffe des rotateurs , Tomodensitométrie , Humains , Arthroscopie/méthodes , Femelle , Mâle , Adulte d'âge moyen , Lésions de la coiffe des rotateurs/chirurgie , Lésions de la coiffe des rotateurs/imagerie diagnostique , Sujet âgé , Études rétrospectives , Ossification hétérotopique/imagerie diagnostique , Ossification hétérotopique/chirurgie , Coiffe des rotateurs/chirurgie , Coiffe des rotateurs/imagerie diagnostique , Scapula/imagerie diagnostique , Scapula/chirurgie , Ligaments articulaires/chirurgie , Ligaments articulaires/imagerie diagnostique , Adulte
7.
Nucleic Acids Res ; 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39087553

RÉSUMÉ

Transient halting of transcription activity on the damaged chromatin facilitates DNA double-strand break (DSB) repair. However, the molecular mechanisms that facilitate transcription recovery following DSB repair remain largely undefined. Notably, failure to restore gene expression in a timely manner can compromise transcriptome signatures and may impose deleterious impacts on cell identity and cell fate. Here, we report PHF8 as the major demethylase that reverses transcriptionally repressive epigenetic modification laid down by the DYRK1B-EHMT2 pathway. We found that PHF8 concentrates at laser-induced DNA damage tracks in a DYRK1B-dependent manner and promotes timely resolution of local H3K9me2 to facilitate the resumption of transcription. Moreover, PHF8 also assists in the recovery of ribosomal DNA (rDNA) transcription following the repair of nucleolar DSBs. Taken together, our findings uncover PHF8 as a key mediator that coordinates transcription activities during the recovery phase of DSB responses.

8.
Article de Anglais | MEDLINE | ID: mdl-39102648

RÉSUMÉ

Type III effectors (T3Es) are major determinants of Xanthomonas virulence and targets for resistance breeding. XopJ2 (syn. AvrBsT) is a highly conserved YopJ-family T3E acquired by X. perforans, the pathogen responsible for bacterial spot disease of tomato. In this study, we characterized a new variant (XopJ2b) of XopJ2, which is predicted to have a similar 3D structure as the canonical XopJ2 (XopJ2a) despite sharing only 70% sequence identity. XopJ2b carries an acetyltransferase domain and the critical residues required for its activity, and the positions of these residues are predicted to be conserved in 3D structure of the proteins. We demonstrated that XopJ2b is a functional T3E and triggers hypersensitive response when translocated into pepper cells. Like XopJ2a, XopJ2b triggers HR in Arabidopsis that is suppressed by the deacetylase, SOBER1. We found xopJ2b in genome sequences of X. euvesicatoria, X. campestris, X. citri, X. guizotiae, and X. vasicola strains, suggesting widespread horizontal transfer. In X. perforans, xopJ2b was present in strains collected in North and South America, Africa, Asia, Australia, and Europe, whereas xopJ2a had a more narrow geographic distribution. This study expands the Xanthomonas T3E repertoire, demonstrates functional conservation in T3E evolution, and further supports the importance of XopJ2 in X. perforans fitness on tomato.

9.
Article de Anglais | MEDLINE | ID: mdl-39099390

RÉSUMÉ

Treatment patterns and preferences for patients with Graves' disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

10.
Nurs Rep ; 14(3): 1859-1870, 2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39189269

RÉSUMÉ

Older Korean immigrants are one of the most understudied and marginalized Asian ethnic groups in the United States, despite their rapid population growth. Many older Korean immigrants encounter distinct challenges in assimilating into their new country as first-generation immigrants, including cultural conflict, language barriers, low economic status, and a lack of social support. These issues may be compounded for those who live alone, which is considered a negative factor in their mental and physical health. However, little is known about the correlates and health issues of older Korean immigrants living alone. This study's objective was to explore correlates and health issues among older Korean immigrants living alone. Based on established scoping review methodology five databases, CINAHL, PubMed, MEDLINE, SocINDEX, and Health Source Nursing/Academic Edition, were used to find relevant studies. Twelve articles were reviewed, and four major themes were identified as correlates and health issues among older Korean immigrants living alone in the United States: depression, changed family relationships, social interactions, and factors on general health and well-being. The findings have significant implications for healthcare professionals for understanding the unique culture, situation, and physical and psychosocial vulnerability of older Korean immigrants living alone.

11.
Article de Anglais | MEDLINE | ID: mdl-39126454

RÉSUMÉ

INTRODUCTION: Cementless fixation has become increasingly popular in hip arthroplasty due to its shorter operation time, easier technique, biologic fixation, and avoidance of bone cement implantation syndrome compared to cemented fixation. However, intraoperative periprosthetic femoral fracture (IOPFx) is a disconcerting complication during cementless hip arthroplasty. Our purpose was to identify the features of cementless stem that increase the risk of IOPFx during primary hip arthroplasty. MATERIALS AND METHODS: We retrospectively reviewed all 4806 hip arthroplasties that was performed in a single institution from May 2003 to December 2020. Age at the index arthroplasty, sex, body mass index, physical status, ambulatory function, side of the operation, operational history, cause of the index arthroplasty, type of arthroplasty, surgical approach, surgeon, implant information, and events during the operation were investigated. The shoulder geometry and length of stem were also reviewed. The event of interest was narrowed down to IOPFx among various records of intraoperative events. RESULTS: We found IOPFx of 2.6% among all the hips operated with cementless stem. In the multivariable analysis, female (OR = 1.52), childhood hip disease (OR = 2.30), stove-pipe femur (OR = 2.43), combined approach (OR = 2.60), and standard length of stem (OR = 1.59) were found to be significant risk factors of IOPFx. CONCLUSIONS: In conclusion, a stem with a standard length is significantly associated with risk of IOPFx compared to a shortened stem. These findings highlight the importance of careful consideration in terms of the risk of IOPFx when standard length cementless stem is chosen.

12.
J Invest Dermatol ; 2024 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-39127093

RÉSUMÉ

Lipid-lowering agents have been suggested as a therapeutic option for vitiligo based on the potential pathogenic role of lipid metabolism abnormalities. We aimed to explore the impact of genetically proxied lipid-lowering agents on the risk of vitiligo and potentially associated mediators. Genome-wide association study summary statistics for European ancestry were extracted from the largest available meta-analysis for vitiligo, the Global Lipids Genetics Consortium for seven lipid profiles, and two large biobanks, UKB and deCODE, for 4,719 proteins. After identifying lipid-lowering agents with genetically proxied protective effects against vitiligo using lipid-lowering and protein-inhibition Mendelian randomization (MR) analyses, multivariable and two-step MR analyses were conducted to identify potential mediators between lipid-lowering agents and vitiligo. Lipid-lowering MR indicated a potential role of PCSK9 in reducing the vitiligo risk (OR[95%CI] = 0.71[0.52-0.95]), which was replicated in PCSK9-inhibition MR analyses across two separate biobanks (UKB: OR[95%CI]=0.82[0.71-0.96]; deCODE: OR[95%CI]=0.78[0.67-0.91]). Multivariable MR suggested that well-known lipid profiles do not mediate the relationship between PCSK9 and vitiligo, while two-step MR analyses identified five potential protein mediators (CCN5, CXCL12, FCRL1, LGMN, and FGF2). Hence, PCSK9 inhibitor may attenuate the vitiligo risk; PCSK9 and the potential protein mediators can serve as promising novel therapeutic targets for its effective treatment.

13.
14.
Cardiovasc Diabetol ; 23(1): 287, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39113067

RÉSUMÉ

BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.


Sujet(s)
Atorvastatine , Maladie des artères coronaires , Diabète , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase , Rosuvastatine de calcium , Humains , Rosuvastatine de calcium/effets indésirables , Rosuvastatine de calcium/usage thérapeutique , Atorvastatine/effets indésirables , Atorvastatine/usage thérapeutique , Maladie des artères coronaires/épidémiologie , Maladie des artères coronaires/sang , Maladie des artères coronaires/diagnostic , Maladie des artères coronaires/traitement médicamenteux , Mâle , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/effets indésirables , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Femelle , Adulte d'âge moyen , Sujet âgé , Diabète/diagnostic , Diabète/épidémiologie , Diabète/sang , Diabète/traitement médicamenteux , Incidence , Résultat thérapeutique , Facteurs de risque , Facteurs temps , Marqueurs biologiques/sang , Appréciation des risques
15.
Eur Radiol ; 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39112752

RÉSUMÉ

OBJECTIVES: To develop and validate imaging-based models for predicting the malignancy risk of intraductal papillary mucinous neoplasm (IPMN). MATERIALS AND METHODS: We retrospectively analyzed data from 241 IPMN patients who underwent preoperative CT and MRI for model development. Cyst size, presence and size of the enhancing mural nodule (EMN), main pancreatic duct (MPD) diameter, thickened/enhancing cyst wall, abrupt MPD caliber change with distal atrophy, and lymphadenopathy were assessed. Multiple logistic regression models predicting malignancy risk were created using either continuous (Model C) or dichotomized variables (Model D) using these imaging features. Validation included internal (n = 55) and external (n = 43) datasets. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and compared with that of the international guideline-based model (Model F). RESULTS: Model C identified age, EMN size, MPD diameter, and lymphadenopathy as independent predictors on CT, and age and presence and size of EMN on MRI. Model D identified age ≥ 68, cyst size ≥ 31 mm, EMN ≥ 6 mm, MPD ≥ 7 mm, and lymphadenopathy as independent predictors on CT, and age ≥ 68, EMN ≥ 4.5 mm, and lymphadenopathy on MRI. Model C (AUC, 0.763-0.899) performed slightly better than Model D (AUC, 0.753-0.912) without statistical significance. No significant difference was observed between Models C and F (AUC, 0.729-0.952). Combining Model C with obstructive jaundice improved performance (AUC, 0.802-0.941) without statistical significance. CONCLUSION: Our imaging-based models effectively predicted the malignancy risk of IPMNs, comparable to international consensus guidelines. CLINICAL RELEVANCE STATEMENT: Imaging features are important for predicting the malignant potential of IPMNs. Our imaging-based model may help determine surgical candidacy for patients with IPMNs. KEY POINTS: Non-invasively determining the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) allows for appropriate treatment decision-making We identified multiple imaging features that are associated with malignant transformation and developed models for this prediction. Our model performs comparably with international consensus guidelines in predicting the malignant potential of IPMNs.

16.
Sci Rep ; 14(1): 17994, 2024 08 03.
Article de Anglais | MEDLINE | ID: mdl-39097625

RÉSUMÉ

CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects.


Sujet(s)
5'-Nucleotidase , Tumeurs du côlon , Cystéine , Tomographie par émission de positons , Zirconium , Animaux , 5'-Nucleotidase/métabolisme , Zirconium/composition chimique , Tumeurs du côlon/imagerie diagnostique , Tumeurs du côlon/métabolisme , Tumeurs du côlon/immunologie , Tumeurs du côlon/anatomopathologie , Souris , Lignée cellulaire tumorale , Tomographie par émission de positons/méthodes , Cystéine/métabolisme , Humains , Radio-isotopes , Femelle , Souris de lignée BALB C , Distribution tissulaire , Souris nude , Protéines liées au GPI/métabolisme , Protéines liées au GPI/immunologie , Immunoglobuline G/immunologie , Immunoglobuline G/métabolisme
17.
JAMA Netw Open ; 7(8): e2426304, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39115845

RÉSUMÉ

Importance: Limited data suggest that early palliative care (EPC) improves quality of life (QOL) and survival in patients with advanced cancer. Objective: To evaluate whether comprehensive EPC improves QOL; relieves mental, social, and existential burdens; increases survival rates; and helps patients develop coping skills. Design, Setting, and Participants: This nonblinded randomized clinical trial (RCT) recruited patients from 12 hospitals in South Korea from September 2017 to October 2018. Patients aged 20 years or older with advanced cancer who were not terminally ill but for whom standard chemotherapy has not been effective were eligible. Participants were randomized 1:1 to the control (receiving usual supportive oncological care) or intervention (receiving EPC with usual oncological care) group. Intention-to-treat data analysis was conducted between September and December 2022. Interventions: The intervention group received EPC through a structured program of self-study education materials, telephone coaching, and regular assessments by an integrated palliative care team. Main Outcomes and Measures: The primary outcome was the change in overall QOL score (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) from baseline to 24 weeks after enrollment, with evaluations also conducted at 12 and 18 weeks. Secondary outcomes were social and existential burdens (assessed with the McGill Quality of Life Questionnaire) as well as crisis-overcoming capacity and 2-year survival. Results: A total of 144 patients (83 males [57.6%]; mean [SD] age, 60.7 (7.2) years) were enrolled, of whom 73 were randomized to the intervention group and 71 to the control group. The intervention group demonstrated significantly greater changes in scores in overall health status or QOL from baseline, especially at 18 weeks (11.00 [95% CI, 0.78-21.22] points; P = .04; effect size = 0.42). However, at 12 and 24 weeks, there were no significant differences observed. Compared with the control group, the intervention group also showed significant improvement in self-management or coping skills over 24 weeks (20.51 [95% CI, 12.41-28.61] points; P < .001; effect size = 0.93). While the overall survival rate was higher in the intervention vs control group, the difference was not significant. In the intervention group, however, those who received 10 or more EPC interventions (eg, telephone coaching sessions and care team meetings) showed a significantly increased probability of 2-year survival (53.6%; P < .001). Conclusions and Relevance: This RCT demonstrated that EPC enhanced QOL at 18 weeks; however, no significant improvements were observed at 12 and 24 weeks. An increased number of interventions sessions was associated with increased 2-year survival rates in the intervention group. Trial Registration: ClinicalTrials.gov Identifier: NCT03181854.


Sujet(s)
Tumeurs , Soins palliatifs , Qualité de vie , Humains , Mâle , Femelle , Soins palliatifs/méthodes , Adulte d'âge moyen , Tumeurs/thérapie , Tumeurs/psychologie , Tumeurs/mortalité , République de Corée , Sujet âgé , Adaptation psychologique , Adulte
18.
Nat Commun ; 15(1): 6506, 2024 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-39090079

RÉSUMÉ

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.


Sujet(s)
Carcinome hépatocellulaire , Alimentation riche en graisse , Modèles animaux de maladie humaine , Tumeurs du foie , Animaux , Carcinome hépatocellulaire/métabolisme , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/génétique , Mâle , Tumeurs du foie/métabolisme , Tumeurs du foie/anatomopathologie , Tumeurs du foie/génétique , Souris , Alimentation riche en graisse/effets indésirables , Souris de lignée C57BL , Humains , Foie/métabolisme , Foie/anatomopathologie , Stéatose hépatique/métabolisme , Stéatose hépatique/anatomopathologie , Streptozocine , Cirrhose du foie/métabolisme , Cirrhose du foie/anatomopathologie , Transcriptome , Obésité/métabolisme , Obésité/complications , Diabète de type 2/complications , Diabète de type 2/métabolisme , Stéatose hépatique non alcoolique/métabolisme , Stéatose hépatique non alcoolique/anatomopathologie , Stéatose hépatique non alcoolique/complications
19.
J Clin Psychiatry ; 85(3)2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39145677

RÉSUMÉ

Abstract.Objective: The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a widely recognized tool with exceptional reliability and validity in evaluating and diagnosing PTSD. This study aimed to determine the predictive values of CAPS-5 assessed early postinjury for subsequent development of PTSD during a 2-year follow-up period.Methods: Patients with moderate to severe physical injuries were recruited from a trauma center at a university hospital in South Korea between June 2015 and January 2021. At baseline, 1,142 patients underwent evaluations using CAPS-5 for the diagnosis of acute stress disorder (ASD) along with total scores. They were followed up for PTSD using the CAPS-5 evaluations at 3, 6, 12, and 24 months post-baseline. Area under receiver operating curve (AUROC) analyses were conducted to identify predictive values of the CAPS-5 for later PTSD development.Results: CAPS-5 diagnosis of ASD at baseline displayed fair to failed performance (AUROCs: 0.555-0.722) for predicting follow-up PTSD. However, CAPS-5 scores of ≥15 exhibited good to fair predictive accuracy (AUROCs: 0.767-0.854) for later PTSD development. Notably, for patients with intentional injuries or a history of previous trauma, a higher CAPS-5 score of ≥16 showed improved predictive accuracy.Conclusion: A CAPS-5 score of ≥15 would be an effective and practical cutoff for early prediction of PTSD following physical injuries. In cases of intentional injuries or a documented trauma history, a cutoff of ≥16 may offer enhanced predictive precision. Future research in diverse settings and populations is needed to confirm the generalizability of our findings.


Sujet(s)
Troubles de stress post-traumatique , Humains , Troubles de stress post-traumatique/diagnostic , Mâle , Femelle , Adulte , Adulte d'âge moyen , République de Corée , Reproductibilité des résultats , Valeur prédictive des tests , Plaies et blessures/psychologie , Plaies et blessures/diagnostic , Échelles d'évaluation en psychiatrie/normes , Troubles de stress traumatique aigus/diagnostic , Études de suivi
20.
Clin Shoulder Elb ; 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39138940

RÉSUMÉ

Background: Several studies have investigated factors affecting patient satisfaction after arthroscopic rotator cuff repair (ARCR); however, it is unknown if these factors vary according to age. Therefore, this study aimed to evaluate the factors associated with satisfaction of ARCR in individuals 70 years and older versus younger patients. Methods: Among 319 consecutive patients who underwent ARCR, 173 were included. Patients were divided into an old age group (≥70 years) and a young age group (<70 years), and the two age groups were further divided into satisfied and unsatisfied subgroups. Patient satisfaction was evaluated at the final follow-up visit using a binary question (yes or no). Clinical outcomes were assessed preoperatively and at the final follow-up. Results: Satisfaction rates in the older and younger age groups were 75.41% and 79.47%, respectively. Mean changes in Constant and American Shoulder and Elbow Surgeons scores were significantly different between the satisfied and unsatisfied subgroups (P=0.031 and P=0.012, respectively) in the young patients. In the old patients, there was a significant difference in the mean change in depression subscale of the Hospital Anxiety and Depression Scale (P=0.031) and anxiety subscale of the Hospital Anxiety and Depression Scale (P=0.044) scores between the satisfied and unsatisfied subgroups. Conclusions: Factors affecting patient satisfaction after ARCR differed according to age. Psychological improvement was more important to elderly patients, whereas restoration of function was more important to younger patients. Pain relief was important for both age groups. Level of evidence: III.

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