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1.
Signal Transduct Target Ther ; 9(1): 242, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271680

RESUMEN

Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Enfermedad Injerto contra Huésped/terapia , Investigación Biomédica Traslacional , Esclerosis Amiotrófica Lateral/terapia
2.
Plants (Basel) ; 13(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39273869

RESUMEN

Phalaenopsis is the most popular potted plant worldwide. However, its typically long stalks often lead to increased shipping costs and risks. This study investigates the effectiveness of varying the concentration, timing, and frequency of paclobutrazol (PP333) applications on shortening the stalk of Phalaenopsis Join Grace 'TH288-4'. Concurrently, it also examines the potential for producing visually appealing and single-flower potted phalaenopsis products by means of truncation. Mature phalaenopsis plants were moved to a cool room in the seventh week to induce flowering. Four experimental groups were established based on different PP333 application schedules: the control (CK) group, with reverse osmosis water application in the second week; the T2 group, with a single application in the second week; the T2T3 group, with applications in both the second and third weeks; and the T7T8 group, with applications in the seventh and eighth weeks. The PP333 concentrations used were 250, 500, 750, and 1000 mg·L-1, applied as foliar sprays. The results showed that the shortest stalks, measured from the base to the first flower, were observed in the T2 group treated with PP333 at 750 mg·L-1 and in the T2T3 group with PP333 at 500, 750, and 1000 mg·L-1. These treatments resulted in stalk lengths of 19.18-22.17 cm, which are 67.2-71.6% shorter than the controls. PP333 application had minimal effect on the stalk diameter, pedicel length, flower width, length, and length/width ratio. However, root diameter was thicker in plants treated with PP333 compared with the control plants. For producing single-flower phalaenopsis, a foliar spray of 750 mg·L-1 PP333 is recommended approximately a month before moving the plants to cooler conditions, followed by truncation, retaining only the first flower. As a result, this study establishes a PP333 treatment protocol for phalaenopsis, offering a strategy to effectively shorten the stalks.

3.
J Plast Reconstr Aesthet Surg ; 98: 272-280, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39305535

RESUMEN

BACKGROUND: Chronic osteomyelitis poses a formidable challenge for orthopedic practitioners in clinical practice. Chimeric perforator flap is a commonly used repair method for chronic osteomyelitis. The purpose of this study was to compare the clinical efficacy of chimeric anterolateral thigh flap (C-ALTP) and chimeric thoracodorsal artery perforator flap (C-TDAP) for the treatment of chronic osteomyelitis. METHODS: A retrospective analysis was performed on patients with chronic osteomyelitis of the lower extremity who underwent two kinds of treatment with chimeric perforator flaps from January 2014 to March 2022. The preoperative basic data and the operative and postoperative basic information of the two groups were collected and statistically analyzed. RESULTS: Sixty-six patients were included in this study, and both groups achieved satisfactory aesthetic and functional results. Intraoperative results showed that the intraoperative blood loss and flap acquisition time in the C-TDAP group were less than those in the C-ALTP group. The incidence of postoperative complications in the donor and recipient sites in the C-TDAP group was significantly lower than that in the C-ALTP group, which led to a high reoperation rate in the C-ALTP group. Long-term follow-up showed that the wound healing time and weight-bearing walking time in the C-TDAP group were less than those in the C-ALTP group. CONCLUSIONS: Chimeric perforator flaps can effectively be used to treat osteomyelitis with composite tissue defects, eliminate inflammation of the affected limbs, and promote wound healing. However, C-TDAP flaps have more reliable healing effects on wounds and donor sites, and have fewer complications. LEVEL OF EVIDENCE: III, Case-control study.

4.
Chemosphere ; : 143360, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303793

RESUMEN

Anaerobic ammonium oxidizing (anammox) bacteria have been proven weak-electroactive. However, the impact of exogenous anthraquinone-2,6-disulfonate (AQDS) on the anammox activity, although it usually plays essential roles in the life activities of many other electroactive microorganisms, is still unknown. Therefore, this study further explored the influences of AQDS on the anammox activity and the interaction mechanism with anammox bacteria, as well as the behaviors of NH4+, NO2-, and NO3-. The results showed that exogenous AQDS increased the ammonium and total nitrogen removal rates by 12.8% and 10.7%, respectively. Interestingly, the conversion from NO2- to NO3- was significantly reduced after adding AQDS, resulting in a 40.1% reduction in NO3- production of anammox process. In this study, we found for the first time that anammox bacteria could not only carry out the conventional anammox process but also perform a weak redox mediators-mediated anammox process, which could achieve the 1:1 consumption of NH4+ and NO2-. The redox mediators-mediated anammox process was related to an endogenous redox mediator (ERM) synthesized and secreted by anammox bacteria, whose redox midpoint potential was around -0.26 V (vs. Ag/AgCl). After adding AQDS, not only the ERM-mediated anammox process was enhanced, but also two novel redox mediators-mediated anammox processes were introduced, including the AQDS-mediated anammox process and ERM-AQDS-mediated anammox process. These three redox mediators-mediated anammox processes significantly improved the nitrogen removal performance of anammox bacteria and reduced energy consumption. These findings will help reduce the dependence of anammox technology on NO2-, reduce the cost of subsequent treatment of NO3-, and provide new visions for optimizing and applying anammox technology.

5.
Inorg Chem ; 63(38): 17435-17448, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39231304

RESUMEN

The photophysical properties and luminescent mechanism of a series of tripod-type Cu(I) complexes in solution and solids were comprehensively investigated through theoretical simulations. From a microscopic perspective, the experimental phenomenon is explained: (1) The intrinsic reason for the quenching of complex 1 in solution was attributed to the significant nonradiative transition caused by structural deformation; (2) In the solid, the reduced ΔEST for complex 2 effectively facilitate reverse intersystem crossing (RISC) and improves its luminescence efficiency; (3) The enhanced performance of complex 3 in solution is attributed to that its stronger steric hindrance is advantageous to decrease not only the ΔEST but also the reorganization energy through intramolecular weak interactions. Based on complex 3, the tert-butyl substituted isomeric complex 4 was designed. Complex 4 further amplifies the advantages of 3 to further promote the RISC to make full use of excitons. Meanwhile, it has an emission wavelength of 462.6 nm, which makes it an excellent candidate for high-efficiency deep-blue TADF materials. This study provides valuable information for obtaining efficient blue phosphorescence and TADF dual-channel luminescent materials.

6.
J Thromb Haemost ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307246

RESUMEN

BACKGROUND: The functions of critical platelet proteins are controlled by thiol-disulfide exchanges, which are mediated by the protein disulfide isomerase (PDI) family. It has been shown that some PDI family members are important in platelet activation and thrombosis with distinct functions. TMX4, a membrane-type PDI family member, is expressed in platelets, whether it has a role in platelet activation remains unknown. OBJECTIVES: To determine the role of TMX4 in platelet activation and thrombosis. METHODS: The phenotypes of TMX4-deficient mice were evaluated in tail bleeding time assay and laser-induced and FeCl3-induced arterial injury models. The functions of TMX4 in platelets were assessed in vitro using TMX4-null platelets, recombinant TMX4 protein and anti-TMX4 antibody. RESULTS: Compared with the control mice, Tie2-Cre/TMX4fl/fl mice deficient of hematopoietic and endothelial TMX4 exhibited prolonged tail bleeding times and reduced platelet thrombus formation. Pf4-Cre/TMX4fl/fl mice deficient of platelet TMX4 also had prolonged tail bleeding times and decreased thrombus formation, which was rescued by injection of recombinant TMX4 protein. Consistently, TMX4 deficiency inhibited platelet aggregation, integrin αIIbß3 activation, P-selectin expression, phosphatidylserine exposure and thrombin generation, without affecting tyrosine phosphorylation of intracellular signaling molecules Syk, LAT and PLCγ2 and calcium mobilization. Recombinant TMX4 protein enhanced platelet aggregation and reduced integrin αIIbß3 disulfide bond, and TMX4 deficiency decreased free thiols of integrin αIIbß3, consistent with a potent reductase activity of TMX4. In contrast, an inactive TMX4 protein and a specific anti-TMX4 antibody inhibited platelet aggregation. CONCLUSIONS: TMX4 is a novel PDI family member that enhances platelet activation and thrombosis.

7.
ACS Cent Sci ; 10(8): 1585-1593, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39220690

RESUMEN

DNA aptamers have been developed as sensors to detect metabolites with high sensitivity, selectivity, and biocompatibility. While they are effective in sensing important targets in the brain, the lack of methods for their efficient delivery across the blood-brain barrier (BBB) has significantly hindered their applications in brain research. To address this issue, we herein report the development of brain cell-derived exosomes as endogenous BBB delivery vehicles to deliver an ATP-responsive aptamer across the BBB of live mice for noninvasive live brain imaging. We found that the system uses endosome recycling to transfer the sensors between the delivered exosomes and native recycling endosomes, resulting in high delivery efficiencies. Using this system, we observed unique signal distributions for ATP across different brain regions, with significant accumulation in the subiculum and cortex in healthy mice. In an Alzheimer's disease transgenic mouse model, ATP levels decreased in the subiculum and cortex, demonstrating this method's capability to determine metabolite location and relative abundance with high spatial resolution in vivo. Since DNA aptamers have been obtained for many other targets, the method developed in this work can be applied to deliver sensors across the BBB to image a wide range of other brain-related metabolites.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39237671

RESUMEN

Psoriasis is a prevalent chronic disease affecting 2-3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.

9.
Eur Spine J ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39245779

RESUMEN

PURPOSE: Short-term efficacy of percutaneous kyphoplasty (PKP) for treating osteoporotic vertebral compression fracture (OVCF) in elderly patients is good, but long-term complications such as vertebral recompression (VRC) and adjacent vertebral fracture (AVF) may arise. Identifying risk factors in patients with poor prognoses, we developed a nomogram model to mitigate these potential complications. METHODS: Patients with OVCFs who underwent PKP had their medical data retrospectively evaluated. Analysis of the sample included their pre- and postoperative conditions. Stepwise logistic regression analyses were conducted to identify independent risk factors for postoperative complications. For forecasting the likelihood of postoperative comorbidities, we offered a nomogram. The prognostic performance was assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analyses (DCA). Internal model validation using the Bootstrap method. RESULTS: A total of 235 patients were included in this study. Among them, 147 patients were utilized to develop nomograms and for internal validation, while the remaining 88 patients from a different time period were designated as the external validation cohort. The results of stepwise logistic regression analysis showed that thoracolumbar (TL) fracture, posterior wall of vertebral fracture, vertebral compression > 30%, and lack of continuous anti-osteoporosis therapy after surgery as independent risks associated with poor prognosis. The nomogram exhibited outstanding predictive accuracy and clinical utility. CONCLUSIONS: This study identified four independent predictors of poor prognosis following PKP and devised a straightforward yet efficient predictive model. This model offers valuable insights for guiding clinical decision-making in the management of elderly patients with OVCFs.

10.
Int J Pharm ; 665: 124657, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226987

RESUMEN

Surfactants are crucial in formulating poorly soluble drugs but lead to serious side effects due to PEG chains. Novel supra-amphiphiles consisting of fatty acids and choline are developed, which spontaneously form ionic co-aggregates (ICAs) in water and exhibit strong solubilizing capacity. Paclitaxel (PTX) is adopted as a model drug here to evaluate the feasibility of choline oleate-based ICAs in the intravenous delivery of poorly soluble drugs by comparing the kinetics and distribution of payloads and nanocarriers. Choline oleate presents a maximum 10-fold enhancement in solubilizing capacity to PTX than Cremophor EL (CreEL), enabling a one-tenth use level in the formulation. Aggregation-caused quenching probes are utilized to evaluate the kinetics and biodistribution of ICAs or CreEL-based micelles (MCs). A huge gap is found between the pharmacokinetic and particokinetic curves of either nanocarrier, indicating fast leakage. ICAs lead to faster PTX leakage in blood circulation but higher PTX distribution to organs than MCs. MCs present a longer circulation in blood but a slower distribution to organs than ICAs. ICAs do not arise adverse reactions in rats following repeated injections, while MCs cause pathological changes in varying degrees. In conclusion, choline oleate-based ICAs provide an alternative to surfactants in formulating poorly soluble drugs.

11.
Stem Cell Res Ther ; 15(1): 296, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256886

RESUMEN

BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.


Asunto(s)
Adenocarcinoma , Células Madre Neoplásicas , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Ratones , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Nitrilos/farmacología , Feniltiohidantoína/farmacología
12.
Neuroreport ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39292961

RESUMEN

Our study aims to explore the differences in functional connectivity in the nucleus accumbens (NAc) between patients with melancholic depression and non-melancholic depression (NMD) and their relation to melancholic depression's pathogenesis. We recruited 60 melancholic depression, 58 NMD, and 80 healthy controls, all matched for gender, age, and education. Functional connectivity analysis focused on bilateral NAc as the region of interest, comparing it with the whole brain and correlating significant differences with clinical scores. Melancholic depression patients showed reduced functional connectivity between the left NAc and anterior brain regions, and between the right NAc and temporal and frontal areas, compared to healthy controls. In contrast, NMD patients displayed reduced functional connectivity only between the left NAc and the posterior cingulate cortex. Melancholic depression patients also exhibited increased functional connectivity between the right NAc and the middle frontal gyrus, unlike NMD patients. The findings suggest that melancholic depression patients exhibit unique NAc functional connectivity patterns, particularly with the default mode network and prefrontal areas, suggesting atypical reward-circuitry interactions. The right NAc's connection to the prefrontal gyrus may distinguish melancholic depression from NMD.

13.
Crit Rev Oncol Hematol ; 204: 104496, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284518

RESUMEN

BACKGROUND: Early detection of fatigue is crucial for cancer patients. Although single-item scales are convenient, their diagnostic accuracy remain unclear, and the variability across studies may affect generalizability. This systematic review and meta-analysis evaluates the diagnostic value of single-item fatigue detection scales. METHODS: We systematically searched CINAHL, Cochrane Library, Embase, and PubMed. Meta-analyses were conducted to calculate pooled sensitivity, specificity, likelihood ratios, predictive values, and diagnostic odds ratios (DOR). We also calculated the area under a hierarchical summary receiver operating characteristic curve. Subgroup analyses were performed to address heterogeneity. All analyses were done R (version 4.3.1). The study registered in PROSPERO (CRD42023457658). RESULTS: Eleven studies involving 3509 participants were included. Pooled results revealed a sensitivity of 0.89 (95 % CI: 0.82-0.93), specificity of 0.72 (95 % CI: 0.63-0.80), DOR of 19.95 (95 % CI: 10.47-38.04), and an AUC of 0.90 (95 % CI: 0.89-0.91). Moderate to high heterogeneity was observed, influenced by variations in cancer types, study designs, and gold standard references. CONCLUSION: Single-item fatigue scales demonstrate commendable diagnostic accuracy, comparable to multidimensional scales. Despite study variability, they are effective for routine clinical use to detect and manage fatigue in cancer patients. Future research should focus on standardizing assessment criteria and optimizing the balance between simplicity and diagnostic precision.

14.
iScience ; 27(9): 110739, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39280611

RESUMEN

Mast cell tryptases, a family of serine proteases involved in inflammatory responses and cancer development, present challenges in structural characterization and inhibitor development. We employed state-of-the-art protein structure prediction algorithms to model the three-dimensional structures of tryptases α, ß, δ, γ, and ε with high accuracy. Computational docking identified potential substrates and inhibitors, suggesting overlapping yet distinct activities. Tryptases ß, δ, and ε were predicted to act on phenolic compounds, with ß and ε additionally hydrolyzing cyanides. Tryptase δ may possess unique formyl-CoA dehydrogenase activity. Virtual screening revealed 63 compounds exhibiting strong binding to tryptase ß (TPSB2), 12 exceeding the affinity of the known inhibitor. Notably, the top hit (3-chloro-4-methylbenzimidamide) displayed over 10-fold selectivity for tryptase ß over other isoforms. Our integrative approach combining protein modeling, functional annotation, and molecular docking provides a framework for characterizing tryptase isoforms and developing selective inhibitors of therapeutic potential in inflammatory and cancer conditions.

15.
NPJ Precis Oncol ; 8(1): 193, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39244594

RESUMEN

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

16.
J Gastrointest Oncol ; 15(4): 1519-1533, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39279967

RESUMEN

Background: Randomized trials have shown a survival benefit for fruquintinib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies, but real-world prognostic analyses have been seldom reported. We evaluated survival, safety outcomes, and predictive and prognostic factors in patients treated with fruquintinib in a real-life setting. Methods: We conducted a multi-center study by collecting relevant data on patients with advanced colorectal cancer (CRC) who received fruquintinib, focusing on progression-free survival (PFS), overall survival (OS), and L3 skeletal muscle index (SMI), including safety follow-up. Results: From January 2020 to January 2022, a total of 140 patients were selected and included in this study. The cut-off date was 30 July 2022. The median follow-up time was 18.3 months (range, 6-29.3 months) and the median age of included cases was 63 years (range, 32-81 years). The median PFS and OS for the 140 patients was 6.3 and 12.6 months, respectively. The median PFS and OS for the 76 patients who were included in SMI analysis was 6.0 and 12.0 months, respectively. Multivariate analysis suggested brain metastasis {hazard ratio (HR) [95% confidence interval (CI)]: 2.779 (1.162-6.646), P=0.02}, decrease in SMI of >5% [HR (95% CI): 9.732 (2.201-43.028), P=0.003], and baseline carcinoembryonic antigen (CEA) level [HR (95% CI): 4.061 (1.391-11.858), P=0.01] as independent predictors of OS. The most common treatment-related adverse events (TRAEs) were hypertension (24, 17.1%), fatigue (21, 15%), and hand-foot syndrome (20, 14.3%); 9 (13.6%) and 15 (10.7%) patients had dose reduction and treatment discontinuation due to TRAEs respectively. Conclusions: The real-world efficacy and safety of fruquintinib in advanced CRC patients are numerically superior to that in the previous phase III studies. SMI, brain metastasis and CEA could serve as potential markers for patient selection.

17.
Eye (Lond) ; 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279010

RESUMEN

BACKGROUND: To investigate the morphologic features of iris in the highly myopic (HM) eyes using a novel swept-source optical coherence tomography (SS-OCT). METHODS: In this retrospective case-control study, 100 eyes of 100 patients scheduled to have cataract surgery were included, categorized into the control (22 mm< AL < 24.5 mm) and HM (AL ≥ 26 mm) groups. Iris volume (IV), area of anterior iris surface (IS), area of posterior IS, and average iris thickness (IT), as well as anterior chamber volume (ACV) and trabecular-iris space at 500 µm (TISA 500) were evaluated using SS-OCT. The associated factors with morphologic features of iris were also investigated. RESULTS: The HM group showed significantly larger IV and area of anterior and posterior IS than the control group (all P < 0.001), while no difference was identified in IT between the groups. Similar trend in IV was seen in the superior and nasal segments, and area of anterior and posterior IS showed similar trends in all segments except the temporal segment. The IV, area of anterior and posterior IS were all positively correlated with AL (all P < 0.001). Multivariate linear regression revealed that a larger IV was associated with greater ACV. Both larger areas of anterior IS and posterior IS were associated with male, longer AL, greater ACV, and smaller TISA 500. CONCLUSIONS: The HM eyes showed larger IV and area of IS than the control eyes, indicating a coronal expansion of the iris with AL. Iris morphology correlated with anterior chamber angle configuration.

18.
J Affect Disord ; 367: 545-553, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236887

RESUMEN

BACKGROUND: Social Anxiety Disorder is traditionally diagnosed using subjective scales that may lack accuracy. Recently, EEG technology has gained importance for anxiety detection due to its ability to capture stable and objective neurophysiological activities. However, existing methods mainly focus on extracting EEG features during resting states, with limited use of psychologically features like Event-Related Potential (ERP) in task-related states for anxiety detection in deep learning frameworks. METHODS: We collected EEG data from 63 participants exposed to four facial expressions and extracted task-relevant features. Using the EEGNet model, we predicted social anxiety and evaluated its performance using metrics such as accuracy, F1 score, sensitivity, and specificity. We compared EEGNet's performance with Deep Convolutional Neural Network (DeepConvNet), ShallowConvNet, Bi-directional Long Short-Term Memory (BiLSTM), and SVM. To assess the generalizability of the results, we carried out the same procedure on our prior dataset. RESULTS: EEGNet outperformed other models, achieving 99.16 % accuracy with Late Positive Potential (LPP). ERP components yielded higher accuracy than time-domain and frequency-domain features for social anxiety recognition. Accuracy was better for neutral and negative facial stimuli. Consistency across two datasets indicates stability of findings. LIMITATIONS: Due to limited publicly available task-state datasets, only our own were used. Future studies could assess generalizability on larger datasets from different sources. CONCLUSIONS: We conducted the first test of ERP features in anxiety recognition tasks. Results show ERP features have greater potential in social anxiety recognition, with LPP exhibiting high stability and accuracy. Outcomes indicate recognizing social anxiety with negative or neutral facial stimuli is more useful.

19.
Transl Vis Sci Technol ; 13(9): 12, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39235401

RESUMEN

Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features. Methods: We enrolled 616 highly myopic eyes of 616 patients. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering. Results: With 83.35% total variance explained, highly myopic eyes were classified into four AI categories. The percentages of AI categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. Contrast acuity of the eyes in AI category 1 was the highest, which decreased by half in AI category 2. For AI categories 2 to 4, every increase in category led to a decrease of 0.23 logarithm of the minimum angle of resolution in contrast acuity. Compared with those in AI category 1, eyes in AI category 2 presented a higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in AI categories 3 and 4 presented significantly higher percentage of MMD ≥ 3, thinner nasal macular thickness and p-RNFL (P < 0.05). Multivariate regression showed AI category 4 had higher MMD grades and thinner macular compared with AI category 3. Conclusions: We proposed an AI-based classification of highly myopic eyes with clear relevance to visual function and fundus features. Translational Relevance: This classification helps to discover the early hidden visual deficits of highly myopic patients, becoming a useful tool to evaluate the disease comprehensively.


Asunto(s)
Inteligencia Artificial , Sensibilidad de Contraste , Fondo de Ojo , Tomografía de Coherencia Óptica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Anciano , Sensibilidad de Contraste/fisiología , Agudeza Visual/fisiología , Adulto , Miopía Degenerativa/fisiopatología , Miopía Degenerativa/diagnóstico por imagen , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/clasificación , Miopía Degenerativa/patología , Degeneración Macular/clasificación , Degeneración Macular/fisiopatología , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Degeneración Macular/diagnóstico por imagen , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/fisiopatología , Fibras Nerviosas/patología
20.
Soil Biol Biochem ; 1892024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39238778

RESUMEN

The soil region influenced by plant roots, i.e., the rhizosphere, is one of the most complex biological habitats on Earth and significantly impacts global carbon flow and transformation. Understanding the structure and function of the rhizosphere is critically important for maintaining sustainable plant ecosystem services, designing engineered ecosystems for long-term soil carbon storage, and mitigating the effects of climate change. However, studying the biological and ecological processes and interactions in the rhizosphere requires advanced integrated technologies capable of decoding such a complex system at different scales. Here, we review how emerging approaches in sensing, imaging, and computational modeling can advance our understanding of the complex rhizosphere system. Particularly, we provide our perspectives and discuss future directions in developing in situ rhizosphere sensing technologies that could potentially correlate local-scale interactions to ecosystem scale impacts. We first review integrated multimodal imaging techniques for tracking inorganic elements and organic carbon flow at nano- to microscale in the rhizosphere, followed by a discussion on the use of synthetic soil and plant habitats that bridge laboratory-to-field studies on the rhizosphere processes. We then describe applications of genetically encoded biosensors in monitoring nutrient and chemical exchanges in the rhizosphere, and the novel nanotechnology-mediated delivery approaches for introducing biosensors into the root tissues. Next, we review the recent progress and express our vision on field-deployable sensing technologies such as planar optodes for quantifying the distribution of chemical and analyte gradients in the rhizosphere under field conditions. Moreover, we provide perspectives on the challenges of linking complex rhizosphere interactions to ecosystem sensing for detecting biological traits across scales, which arguably requires using the best-available model predictions including the model-experiment and image-based modeling approaches. Experimental platforms relevant to field conditions like SMART (Sensors at Mesoscales with Advanced Remote Telemetry) soils testbed, coupled with ecosystem sensing and predictive models, can be effective tools to explore coupled ecosystem behavior and responses to environmental perturbations. Finally, we envision that with the advent of novel high-resolution imaging capabilities at nano- to macroscale, and remote biosensing technologies, combined with advanced computational models, future studies will lead to detection and upscaling of rhizosphere processes toward ecosystem and global predictions.

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