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1.
Small ; : e2405272, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319479

RESUMO

Polycrystalline perovskite light-emitting diodes (PeLEDs) have shown great promise with high efficiency and easy processability. However, PeLEDs using single-cation polycrystalline perovskite emitters have demonstrated low efficiency due to defects within the grains and at the interfaces between the perovskite layer and the charge injection contact. Thus, simultaneous defect engineering of perovskites to suppress exciton loss within the grains and at the interfaces is crucial for achieving high efficiency in PeLEDs. Here, 1,8-octanedithiol which is a strong nucleophile, is used to increase the luminescence efficiency of a single-cation perovskite by suppressing non-radiative recombination within the grains of their polycrystalline emitter film as well as at their interface with an anode. The dithiol additive performs a multifunctional role in defect passivation, spatial confinement of excitons, and prevention of exciton quenching at the interface between the perovskite layer and the underlying hole-injection layer. Photoluminescence studies demonstrate that incorporating the dithiol additive significantly enhances the charge carrier dynamics in perovskites, resulting in an external quantum efficiency (EQE) of up to 23.46% even in a simplified PeLED that does not use a hole-injection layer. This represents the highest level of EQE achieved among devices utilizing polycrystalline single-cation perovskites.

2.
Medicina (Kaunas) ; 60(9)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39336481

RESUMO

Background and Objectives: This study is a retrospective analysis aimed at understanding the incidence and risk factors of proximal junctional kyphosis (PJK) following long-instrumented spinal fusion from L1 to the sacrum in patients with mild to moderate sagittal imbalance. Materials and Methods: It recruited consecutive patients undergoing instrumented fusion from L1 to the sacrum for degenerative lumbar disease between June 2006 and November 2019 in a single institution. The patients' preoperative clinical data, muscle status at T12-L1 on magnetic resonance images, and sagittal spinopelvic parameters were analyzed. Univariate analysis was used to compare clinical and radiographic data between PJK and non-PJK patients. Logistic regression analysis was used to investigate the independent risk factors for PJK. Results: A total of 56 patients were included in this study. The mean age at surgery was 67.3 years and mean follow-up period was 37.3 months. In total, 10 were male and 46 were female. PJK developed in 23 (41.1%) out of 56; of these patients, 20 (87.0%) developed PJK within 1 year postoperatively. In the univariate analysis between PJK and non-PJK patients, the PJK group showed more frequent osteoporosis, lower body mass index, smaller cross-sectional area (CSA) and more fat infiltration (FI) in erector spinae muscle at T12-L1 and larger preoperative TLK and PT with statistical significance (p < 0.05). In the logistic regression analysis, severe (>50%) FI in erector spinae muscle (OR = 43.60, CI 4.10-463.06, R2N = 0.730, p = 0.002) and osteoporosis (OR = 20.49, CI 1.58-264.99, R2N = 0.730, p = 0.021) were statistically significant. Conclusions: Preexisting severe (>50%) fat infiltration in the erector spinae muscle and osteoporosis were independent risk factors associated with PJK following instrumented fusion from L1 to the sacrum, but age was not a risk factor.


Assuntos
Cifose , Vértebras Lombares , Sacro , Fusão Vertebral , Humanos , Masculino , Feminino , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Cifose/etiologia , Idoso , Fatores de Risco , Estudos Retrospectivos , Pessoa de Meia-Idade , Sacro/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Fatores Etários , Modelos Logísticos
3.
BMC Cancer ; 24(1): 1197, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334005

RESUMO

BACKGROUND: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). METHODS: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. DISCUSSION: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02613988.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Isocitrato Desidrogenase , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Estudos Prospectivos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Masculino , Isocitrato Desidrogenase/genética , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Idoso , Progressão da Doença , Quimiorradioterapia/métodos , Microambiente Tumoral , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos
4.
Arch Virol ; 169(10): 209, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39327326

RESUMO

Noroviruses are the most common cause of acute gastroenteritis (AGE) outbreaks in childcare centers and kindergartens. Their high transmissibility is partly due to their genetic diversity. AGE outbreaks that occurred in Seoul childcare centers and kindergartens from 2019 to 2022 were investigated, and 68 epidemiological reports prepared by public health centers in Seoul were used for data collection. In the three quarters of 2022, there were 40 outbreaks of AGE in Seoul childcare centers and kindergartens, which exceeded the 35 total outbreaks that occurred during the previous three years. The proportion of childcare centers and kindergartens with AGE outbreaks among all facilities in Seoul increased from 12.6% in 2019 to 58.8% in 2022. Noroviruses were the most common pathogens responsible for AGE outbreaks in these cases. From 2019 to 2021, norovirus GII.2 was the predominant genotype, and GII.4 was detected in about 25% of cases. However, in 2022, GII.4 became predominant and was detected in about 79% of cases. The attack rate and infection source of AGE outbreaks from 2019 to 2021 were not significantly different from those in 2022. In conclusion, the number of AGE outbreaks in Seoul childcare centers and kindergartens increased significantly, primarily because of increased norovirus GII.4 transmission in 2022.


Assuntos
Infecções por Caliciviridae , Creches , Surtos de Doenças , Gastroenterite , Genótipo , Norovirus , Norovirus/genética , Norovirus/classificação , Norovirus/isolamento & purificação , Gastroenterite/epidemiologia , Gastroenterite/virologia , Humanos , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/transmissão , Infecções por Caliciviridae/virologia , Pré-Escolar , Criança , Lactente , Seul/epidemiologia
5.
Sci Rep ; 14(1): 20319, 2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223169

RESUMO

Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P < 0.001) and miR-29c (AUC = 0.795; P < 0.001) showed good predictive accuracy for IFTA. In the No IFTA group, the eGFR level at 1 week after transplantation was significantly higher compared to the IFTA group (41.34 mL/min/1.73m2 vs. 28.65 mL/min/1.73m2, P = 0.012). These findings signify the potential of urinary exosomal miRNAs as valuable biomarker candidates for evaluating the severity of IFTA in deceased donor kidneys before they undergo recovery.


Assuntos
Aloenxertos , Biomarcadores , Exossomos , Fibrose , Transplante de Rim , MicroRNAs , Humanos , Biomarcadores/urina , Masculino , Exossomos/metabolismo , Feminino , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , MicroRNAs/urina , MicroRNAs/genética , Adulto , Rim/patologia , Taxa de Filtração Glomerular
6.
Am J Clin Pathol ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255263

RESUMO

OBJECTIVES: This study aimed to evaluate whether a 2-week period of daily isoagglutinin titer testing after ABO-incompatible kidney transplantation (ABOi-KT) is sufficient to ensure successful engraftment and to advocate for an extension of the monitoring duration in specific situations. METHODS: We reviewed patients from January 2022 to December 2023 at Asan Medical Center who underwent therapeutic plasma exchange (TPE) due to elevated ABO antibody titers and suspected acute antibody-mediated rejection (AMR) after ABOi-KT. Data collected included pre- and posttransplantation laboratory results, clinical and procedural information, imaging studies, and needle biopsy results of the renal graft. RESULTS: We encountered 3 cases of acute AMR 2 weeks after transplantation. All cases exhibited simultaneous increases in anti-ABO antibody isoagglutinin titers, creatinine, and C-reactive protein levels. Clinical signs, including fever, suggested possible infection, and renal graft biopsy, confirmed AMR in all cases. Two cases underwent graftectomy, while the third recovered renal function after conservative treatment, including TPE. CONCLUSIONS: Our findings suggest that a 2-week monitoring period for isoagglutinin titers after ABOi-KT may not be sufficient to detect late AMR. Extending the monitoring duration and considering lifelong fresh-frozen plasma transfusion with graft-compatible blood types, along with periodic isoagglutinin titer testing in cases of suspected AMR, may improve long-term graft outcomes.

7.
Telemed J E Health ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39348339

RESUMO

Introduction: The role of telemedicine should be reassessed in the post-COVID-19 pandemic era. This study aimed to evaluate the perception and satisfaction of medical staff with telemedicine after the COVID-19 pandemic and compare these findings with those during the COVID-19 pandemic. Methods: Between January and February 2023, a questionnaire regarding the utilization, safety, and satisfaction with telemedicine was administered to 200 medical staff members (100 doctors and 100 nurses). Additionally, open-ended questions were included to gather insights on the strengths, weaknesses, and prerequisites of telemedicine. The satisfaction levels of the medical staff were compared with those from a previous study conducted during the COVID-19 pandemic. Results: The response rate among medical staff was 60.0% (50 doctors and 70 nurses). Concerning patient safety, 83.3% of respondents indicated a risk of worsening symptoms in chronic patients, and 68.3% expressed concerns about emergencies related to patient safety. Eighty-two percent of doctors preferred in-person visits over telemedicine, while 48.6% of nurses reported equal or greater satisfaction with telemedicine (p = 0.003). The reported strengths of telemedicine included the convenience of outpatient clinics (67%), while its primary weakness was the incomplete assessment of patient conditions (73%). The likelihood of partial substitution of telemedicine for in-person visits was significantly higher in the post-COVID-19 pandemic period compared to during the pandemic (71.7% vs. 49.0%, p < 0.001). Conclusion: In the post-COVID-19 pandemic era, telemedicine continues to offer significant benefits in enhancing patient access to medical care. However, medical staff remain concerned about its safety and show lower satisfaction compared to in-person visits. In response to these concerns, an effective telemedicine platform and legal standards, including practical guidelines, should be developed.

8.
J Neurosurg ; : 1-10, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39270314

RESUMO

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39221061

RESUMO

The recently established non-thermal, single-shot pulsed field ablation (PFA) is a potential tool for achieving rapid pulmonary vein isolation (PVI) to cause cell death by electroporation, yet data regarding this state-of-the-art technology remain sparse. In this meta-analysis, we included 3,857 patients from 20 studies. There was no significant difference in AF recurrence between the PFA and control groups. Subgroup analysis showed that additional ablation beyond PVI has a similar rate of AF recurrence to PVI alone (10% versus 13%, respectively). PVI durability was achieved in 83% (mean), 95% CI [65-99%] of the PFA group and in 79% (mean), 95% CI [60-98%] of the control group, with no significant difference in the rate of PVI durability between the two groups. The PFA group had considerably reduced procedure duration, but not fluoroscopy time. No statistically significant differences in periprocedural complications were observed. PFA is associated with shorter procedural time than thermal ablation. Cardiac complications were uncommon and mainly reversible in both the PFA and control groups.

10.
Small ; : e2404784, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39205546

RESUMO

Wide-bandgap perovskite solar cells (PSCs) with high open-circuit voltage (Voc) represent a compelling and emerging technological advancement in high-performing perovskite-based tandem solar cells. Interfacial engineering is an effective strategy to enhance Voc in PSCs by tailoring the energy level alignments between the constituent layers. Herein, n-type quinoxaline-phosphine oxide-based small molecules with strong dipole moments is designed and introduce them as effective cathode interfacial layers. Their strong dipole effect leads to appropriate energy level alignment by tuning the work function of the Ag electrode to form an ohmic contact and enhance the built-in potential within the device, thereby improving charge-carrier transport and mitigating charge recombination. The organic interfacial layer-modified wide-bandgap PSCs exhibit a high Voc of 1.31 V (deficit of <0.44 V) and a power conversion efficiency (PCE) of 20.3%, significantly improved from the device without an interface dipole layer (Voc of 1.26 V and PCE of 16.7%). Furthermore, the hydrophobic characteristics of the small molecules contribute to improved device stability, retaining 95% of the initial PCE after 500 h in ambient air.

11.
Neuro Oncol ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177498

RESUMO

BACKGROUND: To spatially validate intratumoral subregions (tumor habitat) using physiologic MRI on pathology of the isocitrate dehydrogenase (IDH)-wildtype whole-glioblastoma sample. METHODS: Data of 20 patients (168 slides) were obtained from the Ivy Glioblastoma Atlas Project. On MRI, tumor habitats were defined using voxel-wise clustering of apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps for contrast-enhancing lesion (CEL) and non-enhancing lesion (NEL). On pathology slides, normalized areas of leading edge (LE), infiltrating tumor (IT), cellular tumor (CT), hypervascular lesion (CThypervascular), and perinecrotic lesion (CTperinecrotic) were obtained. Gross specimen was co-registered on MRI and correlation between pathology-MRI habitats was calculated. RNA sequencing of 67 samples was assessed using 4 Neftel subtypes and further correlated with pathology. RESULTS: Six tumor habitats were identified: hypervascular, hypovascular cellular, and hypovascular hypocellular habitats for CEL and NEL. CT was correlated with hypovascular cellular habitat in CEL (r= 0.238, p =.005). IT was correlated with hypovascular cellular habitat in NEL (r= 0.294, p =.017). CThypervascular was correlated with hypervascular habitat in NEL (r= 0.195, p = .023). CTperinecrotic was correlated with imaging necrosis (r= 0.199, p =.005). Astrocyte-like subtypes were correlated with IT (r= 0.256, p <.001), while mesenchymal-like subtypes were correlated with CTperinecrotic area (r= 0.246, p <.001). CONCLUSION: Pathologically matched tumor subregions were cellular tumor with hypovascular cellular habitat in CEL and infiltrative tumor with hypovascular cellular habitat in NEL. Identification of the most aggressive as well as infiltrative tumor portion can be achieved using non-invasive MRI tumor habitats.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39093062

RESUMO

BACKGROUND: An evaluation of scapula position is important to predict spine curvature and shoulder function in patients with adolescent idiopathic scoliosis (AIS). Therefore, a reliable scapula position is required to assess posture in patients with AIS. OBJECTIVE: This study investigated the reliabilities of scapula position tests and differences in scapula position and shoulder function between individuals with and without AIS. METHODS: The study compared 18 patients with AIS and 18 healthy controls to identify differences in scapula position and shoulder function. The acromion-table distance, lateral displacement of the scapula, acromion depression, winged scapula, upward rotation of the scapula, and anterior tilt of the scapula were measured. Scapula position test reliabilities were assessed using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimum clinically important difference (MCID). Shoulder function was measured using the Shoulder Pain and Disability Index. RESULTS: The reliabilities of scapula position tests (ICC 0.85-0.93, SEM 0.1-1.2, and MCID 0.2-2.5) were good. There were significant differences in scapula position and shoulder function between patients with AIS and healthy controls (p< 0.05). CONCLUSION: Scapula position tests were highly reliable in patients with AIS; they can be used to evaluate scapula position during clinical assessment of posture in patients with AIS.

13.
Kidney Int Rep ; 9(8): 2474-2483, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39156155

RESUMO

Introduction: Kidney transplantation (KT) improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in KT recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes. Methods: A total of 750 KTRs with diabetes were enrolled from 6 tertiary hospitals. Among them, 129 patients (17.2%) were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes. Results: In the matched cohort, MACE occurred in 5 patients (3.9%) in the SGLT2i group and 15 patients (11.8%) in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group (P = 0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio [HR], 0.30 and 0.04; 95% confidence interval [CI], 0.10-0.88 and 0.004-0.40; P = 0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection (UTI) between the 2 groups. Conclusion: SGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes.

14.
J Phys Chem Lett ; 15(34): 8676-8681, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39159009

RESUMO

Organic charge-transfer complex (CTC) formation has emerged as an effective molecular engineering strategy for achieving the desired optical properties via intermolecular interactions. By synthesizing organic CTCs with carbazole-based electron donors and a 7,7,8,8-tetracyanoquinodimethane acceptor and adopting a molecular linker located remotely from the charge-transfer interface within the donors, we were able to modulate near-infrared absorptive and short-wavelength infrared emissive properties. Structural characterizations performed by using single-crystal X-ray diffraction confirmed that the unique molecular arrangements induced by the steric hindrance from the remotely located linker significantly influence the electronic interactions between the donor and acceptor molecules, resulting in different photophysical properties. Our findings offer an improved understanding of the interplay between molecular packing and optoelectronic properties, providing a foundation for designing advanced materials for optoelectronic applications.

15.
Neuro Oncol ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39097777

RESUMO

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

16.
Immunity ; 57(8): 1864-1877.e9, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39111315

RESUMO

Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARδ) activity, causing mitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARδ pathway to support bioenergetic fitness of CD8+ TILs.


Assuntos
Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral , Mitocôndrias , Microambiente Tumoral , Linfócitos T CD8-Positivos/imunologia , Animais , Mitocôndrias/metabolismo , Mitocôndrias/imunologia , Camundongos , Microambiente Tumoral/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Transdução de Sinais , Metabolismo Energético , PPAR delta/metabolismo , Linhagem Celular Tumoral , Neoplasias/imunologia , Glicólise , Camundongos Knockout , Fosforilação Oxidativa
17.
Int J Surg ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116448

RESUMO

BACKGROUND: Accurate forecasting of clinical outcomes after kidney transplantation is essential for improving patient care and increasing the success rates of transplants. Our study employs advanced machine learning (ML) algorithms to identify crucial prognostic indicators for kidney transplantation. By analyzing complex datasets with ML models, we aim to enhance prediction accuracy and provide valuable insights to support clinical decision-making. MATERIALS AND METHODS: Analyzing data from 4077 KT patients (June 1990 - May 2015) at a single center, this research included 27 features encompassing recipient/donor traits and peri-transplant data. The dataset was divided into training (80%) and testing (20%) sets. Four ML models-eXtreme Gradient Boosting (XGBoost), Feedforward Neural Network, Logistic Regression, and Support Vector Machine-were trained on carefully selected features to predict the success of graft survival. Performance was assessed by precision, sensitivity, F1 score, Area Under the Receiver Operating Characteristic (AUROC), and Area Under the Precision-Recall Curve. RESULTS: XGBoost emerged as the best model, with an AUROC of 0.828, identifying key survival predictors like T-cell flow crossmatch positivity, creatinine levels two years post-transplant and human leukocyte antigen mismatch. The study also examined the prognostic importance of histological features identified by the Banff criteria for renal biopsy, emphasizing the significance of intimal arteritis, interstitial inflammation, and chronic glomerulopathy. CONCLUSION: The study developed ML models that pinpoint clinical factors crucial for KT graft survival, aiding clinicians in making informed post-transplant care decisions. Incorporating these findings with the Banff classification could improve renal pathology diagnosis and treatment, offering a data-driven approach to prioritizing pathology scores.

18.
Adv Mater ; 36(36): e2403783, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39023001

RESUMO

In 2D noble metals like copper, the carrier scattering at grain boundaries has obscured the intrinsic nature of electronic transport. However, it is demonstrated that the intrinsic nature of transport by hole carriers in 2D copper can be revealed by growing thin films without grain boundaries. As even a slight deviation from the twin boundary is perceived as grain boundaries by electrons, it is only through the thorough elimination of grain boundaries that the hidden hole-like attribute of 2D single-crystal copper can be unmasked. Two types of Fermi surfaces, a large hexagonal Fermi surface centered at the zone center and the triangular Fermi surface around the zone corner, tightly matching to the calculated Fermi surface topology, confirmed by angle-resolved photoemission spectroscopy (ARPES) measurements and vivid nonlinear Hall effects of the 2D single-crystal copper account for the presence of hole carriers experimentally. This breakthrough suggests the potential to manipulate the majority carrier polarity in metals by means of grain boundary engineering in a 2D geometry.

19.
Oncol Lett ; 28(2): 388, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38966587

RESUMO

Atezolizumab/bevacizumab is the first line of treatment for unresectable hepatocellular carcinoma (HCC), combining immune checkpoint inhibitor and anti-VEGF monoclonal antibodies. Hepatic arterial infusion chemotherapy (HAIC) is administered when the above-described combination fails to confer sufficient clinical benefit. The present study aimed to explore the association between tumor programmed cell death-ligand 1 (PD-L1) positivity and HAIC response. A total of 40 patients with HCC who had undergone HAIC with available biopsy samples obtained between January 2020 and May 2023 were retrospectively enrolled. Tumor response, progression-free survival (PFS), disease control rate (DCR) and overall survival (OS) were evaluated. PD-L1 expression in tumor samples was assessed using a combined positivity score. The response rates of HAIC-treated patients with advanced HCC after failure of atezolizumab/bevacizumab combination therapy were recorded. OS (P=0.9717) and PFS (P=0.4194) did not differ between patients with and without PD-L1 positivity. The objective response rate (P=0.7830) and DCR (P=0.7020) also did not differ based on PD-L1 status. In conclusion, the current findings highlight the consistent efficacy of HAIC, regardless of PD-L1 positivity.

20.
Discov Oncol ; 15(1): 268, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971940

RESUMO

PURPOSE: Oligodendrogliomas (ODGs) are a subtype of diffuse lower-grade gliomas with overall survival of > 10 years. This study aims to analyze long-term outcomes and identify prognostic factors in patients with WHO grade 2 ODG. METHODS: We retrospectively reviewed 138 adult patients diagnosed with 1p/19q co-deleted ODG who underwent surgical resection or biopsy between 1994 and 2021, analyzing clinical data, treatment details, and outcomes. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were utilized to identify significant prognostic factors. RESULTS: In the gross total resection (GTR) group, 63 (45.7%) underwent observation and 5 (3.6%) received postoperative treatment; in the non-GTR group, 37 (26.8%) were observed and 33 (23.9%) received postoperative treatment. The median PFS and OS were 6.8 and 18.4 years, respectively. Between adjuvant treatment and observation, there was no significant difference in PFS or OS. However, GTR or STR with less than 10% residual tumor exhibited significantly better PFS and OS compared to PR or biopsy (p = 0.022 and 0.032, respectively). Multivariate analysis revealed that contrast enhancement on MRI was associated with worse PFS (HR = 2.36, p < 0.001) and OS (HR = 5.89, p = 0.001). And the presence of seizures at presentation was associated with improved OS (HR = 0.28, p = 0.006). CONCLUSION: This study underscores favorable long-term outcomes for patients with 1p/19q co-deleted ODG WHO grade 2. Our findings indicate that the EOR plays a crucial role as a significant prognostic factor in enhancing PFS and OS outcomes in WHO grade 2 ODG.

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