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This study aimed to investigate the galectin-3 and associated cytokines levels in the cerebrospinal fluid (CSF) of severe traumatic brain injury (sTBI) patients. Temporal CSF expression of galectin-3 and associated cytokines levels in sTBI patients within 1-week post-injury were studied using the multiplex bead array. STBI patient group was stratified using the Modified Rankin Score (mRS) into 3 groups: mRS 6 (died), mRS 5 (severely disabled) and mRS 1-4 (mild-to-moderately disabled) group. Analysis for bead array data using Kruskal-Wallis test with post hoc Dunn's multiple comparisons test, and temporal changes and correlation analysis using Spearman's correlation were carried out. At day 1 post-injury, CSF galectin-3 and interleukin-6 (IL-6), interleukin-10 (IL-10), cysteine-cysteine motif chemokine ligand-2 (CCL-2), and cysteine-cysteine motif chemokine ligand-20 (CCL-20), but not interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) levels were significantly elevated in mRS 5 group compared to non-TBI controls. Temporal correlation analysis at 1-7 days showed decreased IL-10 level in the mRS 6 group, decreased IL-10 and CCL-2 levels in mRS 5 group, and decreased IL-6, CCL-2, and CCL-20 levels in the mRS 1-4 group. Receiver operating characteristic curve analyses revealed a significant area under the curve for comparison between mRS 6 and mRS 5 groups for galectin-3 and IL-6. No significant differences in sex, age, Glasgow Coma Scale score, C-reactive protein levels and types of TBI-induced hemorrhages were observed between the groups. CSF galectin-3 and associated cytokines, especially IL-6, CCL-2 and CCL-20 levels were different within sub-groups of sTBI patients, suggesting their potential use in sTBI prognostics.
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Lesiones Traumáticas del Encéfalo , Citocinas , Galectina 3 , Humanos , Lesiones Traumáticas del Encéfalo/líquido cefalorraquídeo , Masculino , Femenino , Persona de Mediana Edad , Citocinas/líquido cefalorraquídeo , Adulto , Galectina 3/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Galectinas/líquido cefalorraquídeo , Anciano , Adulto Joven , Proteínas SanguíneasRESUMEN
Gonadotropin-Releasing Hormone Agonist (GnRH-a) and levonorgestrel releasing intrauterine system (LNG-IUS) are conventional conservative treatments for adenomyosis, and high-intensity focused ultrasound (HIFU) is a novel ablation technique. This study aimed to investigate the effectiveness of HIFU combined with GnRH-a or LNG-IUS for adenomyosis patients. In this systematic review and meta-analysis, Pubmed, Embase, Cochrane Library and Scopus databases were searched up to December 2021. Published studies comparing HIFU plus GnRH-a with HIFU plus LNG-IUS in adenomyosis patients were assessed for eligibility by two independent authors. Risk of bias tool was utilized for risk evaluation. We selected treatment effective rate of dysmenorrhea (pain during menstruation) as the primary outcome; effective rate of menorrhagia severity and reduction rate of adenomyotic lesion as the secondary outcomes. Adverse effects were assessed. Four studies with a total 729 patients were enrolled in the meta-analysis. HIFU plus LNG-IUS showed lower dysmenorrhea [within 6 months: risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83-0.93, p < 0.00001; over 1 year: RR 0.73, 95% CI 0.65-0.82, p < 0.00001] and less menorrhagia severity (RR 0.63, 95% CI 0.60-0.66, p < 0.00001) than HIFU plus GnRH-a. Both groups demonstrated equal efficacy in adenomyotic lesion reduction rate (RR 1.03, 95% CI 0.97-1.09, p = 0.30). Adverse effects happened equally in both groups. Combination therapy of HIFU and LNG-IUS revealed better effectiveness in treating dysmenorrhea and menorrhagia than that of HIFU and GnRH-a. However, interpreting the conclusion should be approached with caution as a result of significant heterogeneity.
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Adenomiosis , Hormona Liberadora de Gonadotropina , Ultrasonido Enfocado de Alta Intensidad de Ablación , Dispositivos Intrauterinos Medicados , Levonorgestrel , Adulto , Femenino , Humanos , Adenomiosis/terapia , Adenomiosis/tratamiento farmacológico , Terapia Combinada , Dismenorrea/terapia , Hormona Liberadora de Gonadotropina/agonistas , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Levonorgestrel/administración & dosificación , Menorragia/terapia , Menorragia/etiología , Resultado del TratamientoRESUMEN
Lingual splints have been used to treat mandibular fractures, particularly in cases of complicated mandibular fractures, and serve as a noninvasive adjunctive procedure for reduction and fixation. Furthermore, when used in conjunction with open reduction and internal fixation, the lingual splint provides feasible external fixation against displacing forces exerted by the robust musculature of the mandible. However, the conventional method for lingual splint fabrication is performed preoperatively, and the procedure is time-consuming. This technical note describes a simplified and efficient technique for the intraoperative manufacture of a lingual splint for mandibular fractures using a thermoplastic material, polycaprolactone. Our results demonstrated satisfactory fixation outcomes, reduced lingual splint fabrication time, and superior cost-effectiveness, offering an alternative option for adjunctive external fixation of mandibular fractures.
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Molecular classification, particularly microsatellite instability-high (MSI-H), has gained attention for immunotherapy in endometrial cancer (EC). MSI-H is associated with DNA mismatch repair defects and is a crucial treatment predictor. The NCCN guidelines recommend pembrolizumab and nivolumab for advanced or recurrent MSI-H/mismatch repair deficient (dMMR) EC. However, evaluating MSI in all cases is impractical due to time and cost constraints. To overcome this challenge, we present an effective and efficient deep learning-based model designed to accurately and rapidly assess MSI status of EC using H&E-stained whole slide images. Our framework was evaluated on a comprehensive dataset of gigapixel histopathology images of 529 patients from the Cancer Genome Atlas (TCGA). The experimental results have shown that the proposed method achieved excellent performances in assessing MSI status, obtaining remarkably high results with 96%, 94%, 93% and 100% for endometrioid carcinoma G1G2, respectively, and 87%, 84%, 81% and 94% for endometrioid carcinoma G3, in terms of F-measure, accuracy, precision and sensitivity, respectively. Furthermore, the proposed deep learning framework outperforms four state-of-the-art benchmarked methods by a significant margin (p < 0.001) in terms of accuracy, precision, sensitivity and F-measure, respectively. Additionally, a run time analysis demonstrates that the proposed method achieves excellent quantitative results with high efficiency in AI inference time (1.03 seconds per slide), making the proposed framework viable for practical clinical usage. These results highlight the efficacy and efficiency of the proposed model to assess MSI status of EC directly from histopathological slides.
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The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 µg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 µg/mL). In vitro, SCH agents significantly enhance cell-cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.
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Neoplasias de la Mama , Fibrosis , Ácido Hialurónico , Ácido Hialurónico/química , Animales , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Ratones , Fibrosis/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Ratones Endogámicos BALB C , Cistamina/química , Cistamina/farmacología , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Movimiento Celular/efectos de los fármacos , InyeccionesRESUMEN
BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.
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Células Dendríticas , Tolerancia Inmunológica , FN-kappa B , Transducción de Señal , Linfocitos T Reguladores , Animales , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , FN-kappa B/metabolismo , Ratas , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Receptor Notch1/metabolismo , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Proteína Jagged-1/metabolismo , Técnicas de Cocultivo , Células Madre/metabolismo , Células Madre/citología , Diferenciación CelularRESUMEN
We are documenting the case of An 11-year-old girl who has been followed up at our out-patient clinic since birth with clinical presentations including intrauterine growth restriction, recurrent periodic fever in infancy, hypotonia, global developmental delay, liver function impairment with cirrhotic changes, and clinodactyly. Congenital abnormalities were suspected but a series of examinations including brain MRI, liver biopsy and muscle biopsy yielded insignificant findings. Whole genome sequencing (WGS) was conducted and revealed three novel mutations (c2T > G, c1826T > C, c.556-560delAGTAAinsCT) of the COG5 gene. A diagnosis of COG5-congenital disorders of glycosylation (COG5-CDG, or CDG IIi), with neurologic presentation was established. Sanger sequencing in the patient and her parents confirmed the compound heterozygous mutation. Upon literature review, we identified the patient as the first case of COG5-CDG in Taiwan. Our study enhances the clarity of the correlation between the mutative genes and the presentation of COG5-CDG.
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PURPOSE: Transgender young adults (TYA) are burdened by adverse mental health outcomes. Guided by intersectionality and minority stress frameworks, we compared prevalence of psychological distress and suicidality among TYA of different social identities to inform future interventions. METHODS: In this secondary data analysis of 12,738 TYA, ages 18-25 years, from the 2015 United States Transgender Survey, we developed multivariable regression models examining associations between social identities and psychological distress and suicidality, adjusting for relevant covariates. Self-reported identities were used as proxies for minority stress resulting from structural oppressions related to gender binarism, transmisogyny, heterosexism, and racism. RESULTS: Overall, 53% met criteria for serious psychological distress, and 66% reported suicidal ideation. Statistically higher odds of serious psychological distress and suicidal ideation and plan were found for TYA assigned male compared to assigned female at birth (adjusted odds ratios [aORs] = 1.14-1.50). Nonbinary TYA assigned male at birth also had lower odds of all outcomes compared to all other TYA (aORs = 0.6-0.7). Compared to White TYA, Latiné/x TYA were more likely to experience serious psychological distress (aOR = 1.19, 95% confidence interval: 1.02, 1.39) and multiracial TYA were more likely to report suicide plan(s) and attempt(s) (aORs = 1.25-1.30). Finally, compared to heterosexual TYA, bisexual/pansexual TYA were more likely to report suicide plan(s) (aOR = 1.28, 95% confidence intervals: 1.04, 1.52), and all sexual minority TYA were more likely to report serious psychological distress and suicidal ideation (aORs = 1.31-2.00). DISCUSSION: Results highlight complex associations between intersectional minority stress and mental health outcomes among TYA. Associations between identities and mental health morbidity highlight an urgent need for targeted mental health interventions.
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Distrés Psicológico , Ideación Suicida , Personas Transgénero , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Personas Transgénero/psicología , Personas Transgénero/estadística & datos numéricos , Adulto Joven , Adolescente , Adulto , Prevalencia , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Encuestas y CuestionariosRESUMEN
Mushroom poisoning occurs frequently after the ingestion of toxic wild mushrooms misidentified as edible species. The goal of this study is to develop a mass spectrometric platform to bypass the need for morphological recognition of poisonous mushrooms by experts and rapidly identify the toxins in the mushrooms for emergency care. Trace mushroom toxins were collected by penetrating and removing the mushrooms surface for 3 mm with a direct electrospray probe (DEP). The analytes on the DEP were then dissolved in the solution (70% isopropanol containing 0.1% acetic acid) flowing out of a solvent reservoir on the DEP. Electrospray ionization was induced from the sample solution as a high electric field was generated between the DEP and MS inlet. The obtaining mass spectrometric results were further analyzed with principal component analysis (PCA) to classify mushroom toxins. The mass spectrometric platform for detecting mushroom toxins was assessed for its sensitivity, precision, and efficiency by determining its limit-of-detection (LOD), repeatability, and turnaround time, respectively. As a result, the LODs of the mushroom toxins in pure methanol and spiked in human vomitus by DEP/MS were within 0.001-0.5 ng/µL and 0.01-1 ng/µL, respectively. Linear responses of the mushroom toxins in pure methanol with concentrations between 0.01 and 5 ng/µL (R2 between 0.9922 and 0.998) were obtained. The repeatability of the approach (n = 10) was shown in the low relative standard deviation value (<15%) from ten repeat analysis of mushroom toxins standard solution. The corresponding toxic compounds were identified through matching of the obtained mass spectrometric data with those provided by its companion database library of mushroom toxins. Since no time-consuming pretreatment of the samples is required, identification of mushroom toxins with DEP/MS was complete within 1 min. This will be helpful for the emergency physicians to make correct clinical judgment and prescribe appropriate medical treatment in a timely manner.
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Agaricales , Servicios Médicos de Urgencia , Micotoxinas , Humanos , Metanol , Espectrometría de MasasRESUMEN
Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.
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Carcinoma de Células Escamosas , Colgajo Perforante , Procedimientos de Cirugía Plástica , Masculino , Humanos , Persona de Mediana Edad , Colgajo Perforante/irrigación sanguínea , Recurrencia Local de Neoplasia/cirugía , Cabeza/cirugía , Extremidad Inferior/cirugía , Muslo/cirugía , Muslo/irrigación sanguínea , Carcinoma de Células Escamosas/cirugíaRESUMEN
Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.
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Hemorragia de los Ganglios Basales , Neuroendoscopía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Neuroendoscopía/métodos , Hemorragia de los Ganglios Basales/diagnóstico por imagen , Hemorragia de los Ganglios Basales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Hematoma/cirugíaRESUMEN
Purpose: Glioblastoma is a highly aggressive brain tumor with universally poor outcomes. Recent progress in immune checkpoint inhibitors has led to increased interest in their application in glioblastoma. Nonetheless, the unique immune milieu in the brain has posed remarkable challenges to the efficacy of immunotherapy. We aimed to leverage the radiation-induced immunogenic cell death to overcome the immunosuppressive network in glioblastoma. Methods: We developed a novel approach using the gold-core silica-shell nanoparticles (Au@SiO2 NPs) in combination with low-dose radiation to enhance the therapeutic efficacy of the immune checkpoint inhibitor (atezolizumab) in brain tumors. The biocompatibility, immune cell recruitment, and antitumor ability of the combinatorial strategy were determined using in vitro assays and in vivo models. Results: Our approach successfully induced the migration of macrophages towards brain tumors and promoted cancer cell apoptosis. Subcutaneous tumor models demonstrated favorable safety profiles and significantly enhanced anticancer effects. In orthotopic brain tumor models, the multimodal therapy yielded substantial prognostic benefits over any individual modalities, achieving an impressive 40% survival rate. Conclusion: In summary, the combination of Au@SiO2 NPs and low-dose radiation holds the potential to improve the clinical efficacy of immune checkpoint inhibitors. The synergetic strategy modulates tumor microenvironments and enhances systemic antitumor immunity, paving a novel way for glioblastoma treatment.
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Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Dióxido de Silicio/uso terapéutico , Glioblastoma/tratamiento farmacológico , Oro/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: Refractory apraxia of eyelid opening (AEO) is mostly unresponsive to botulinum toxin (BTx) and inevitably leads to functional blindness. To treat this challenging condition, an innovative surgical technique was proposed. METHODS: The extended frontalis orbicularis oculi muscle (FOOM) flap shortening consisting of frontalis suspension, partial myectomy, and myotomy in situ of eyelid protractors was applied to treat refractory AEO associated with blepharospasm. The postoperative outcomes and patient satisfaction were evaluated. RESULTS: Seven patients (mean ages 64.1 ± 3.9 years) of 14 eyelids in total had an average flap shortening distance of 24.4 ± 1.3 mm. During a mean follow-up of 31.6 ± 11.4 months, the average BTx dosage reduced from 58.6 ± 12. 1 units to 30.0 ± 8.2 units, with a mean injection interval decreasing from 2.3 ± 0.5 months to 4.1 ± 0.9 months (p < 0.05). Palpebral fissure height increased from 1.4 ± 0.5 mm to 7.9 ± 0.7 mm, and the disability scale decreased from 78.8% ± 7.2% to 12.6% ± 7.0% (p < 0.05). The postoperative BTx dosage and frequency were significantly reduced. All patients restored voluntary eyelid opening and reported high postoperative satisfaction (average Likert scale 4.6 ± 0.5). CONCLUSION: Extended FOOM flap shortening is an effective treatment to solve refractory AEO associated with blepharospasm.
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Apraxias , Blefaroespasmo , Humanos , Persona de Mediana Edad , Anciano , Blefaroespasmo/tratamiento farmacológico , Blefaroespasmo/cirugía , Párpados/cirugía , Satisfacción del Paciente , Apraxias/cirugía , MúsculosRESUMEN
Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.
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Hidrogeles , Osteoartritis de la Rodilla , Ratas , Animales , Osteoartritis de la Rodilla/tratamiento farmacológico , Articulación de la RodillaRESUMEN
Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecologic cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors have been identified as inducing tumor angiogenesis. According to several clinical trials, anti-vascular endothelial growth factor-targeted therapy with bevacizumab was effective in all phases of EOC treatment. However, there are currently no biomarkers accessible for regular therapeutic use despite the importance of patient selection. Microsatellite instability (MSI), caused by a deficiency of the DNA mismatch repair system, is a molecular abnormality observed in EOC associated with Lynch syndrome. Recent evidence suggests that angiogenesis and MSI are interconnected. Developing predictive biomarkers, which enable the selection of patients who might benefit from bevacizumab-targeted therapy or immunotherapy, is critical for realizing personalized precision medicine. In this study, we developed 2 improved deep learning methods that eliminate the need for laborious detailed image-wise annotations by pathologists and compared them with 3 state-of-the-art methods to not only predict the efficacy of bevacizumab in patients with EOC using mismatch repair protein immunostained tissue microarrays but also predict MSI status directly from histopathologic images. In prediction of therapeutic outcomes, the 2 proposed methods achieved excellent performance by obtaining the highest mean sensitivity and specificity score using MSH2 or MSH6 markers and outperformed 3 state-of-the-art deep learning methods. Moreover, both statistical analysis results, using Cox proportional hazards model analysis and Kaplan-Meier progression-free survival analysis, confirm that the 2 proposed methods successfully differentiate patients with positive therapeutic effects and lower cancer recurrence rates from patients experiencing disease progression after treatment (P < .01). In prediction of MSI status directly from histopathology images, our proposed method also achieved a decent performance in terms of mean sensitivity and specificity score even for imbalanced data sets for both internal validation using tissue microarrays from the local hospital and external validation using whole section slides from The Cancer Genome Atlas archive.
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Aprendizaje Profundo , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Bevacizumab/genética , Inestabilidad de Microsatélites , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patologíaRESUMEN
Changes in sexual orientation identity (SOI) and gender identity (GI) have rarely been studied in transgender and/or nonbinary youth (TNBY), but documenting such changes is important for understanding identity development and gender transition and supporting the needs of TNBY. This study examined the frequency and patterning of changes in GI and SOI across 3 months (T1-T2) and 1.5 years (T1-T4) among 183 TNBY (baseline age 14-17 years; 83.6% White, 16.9% Hispanic/Latinx) who participated in a longitudinal US study. Participants completed online surveys including measures of GI and SOI. The most common gender identity selected at T1 (with or without another gender identity) was nonbinary (56.3%), and more than half (57.4%) of youth identified with a plurisexual identity (e.g., bisexual, pansexual). GI fluidity from T1-T2 was 13.2% and from T1-T4 was 28.9%. It was equally common to move toward a nonbinary gender identity as toward a binary gender identity. SOI fluidity was more common (30.6% from T1-T2; 55.8% from T1-T4) than GI fluidity. Shifts toward plurisexual identities were more common than shifts toward monosexual identities (e.g., straight, gay). Findings highlight the need to assess changes in GI and SOI in research and clinical practice to address the unique needs of TNBY accurately and effectively.
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BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.
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Hidrocefalia , Adulto , Humanos , Derivaciones del Líquido Cefalorraquídeo/métodos , Estudios de Seguimiento , Hidrocefalia/etiología , Hidrocefalia/cirugía , Prótesis e Implantes , Estudios Retrospectivos , Derivación Ventriculoperitoneal/métodosRESUMEN
BACKGROUND: Rathke's cleft cyst is rare, with variable characteristics and no unified categorization system. This study aimed to evaluate long-term outcomes, based on different categorizations, of symptomatic Rathke's cleft cysts treated with endoscopic endonasal approach. METHODS: This retrospective study of 38 patients with symptomatic Rathke's cleft cyst treated with endoscopic endonasal approach from 2006/06-2021/08 recorded pre- and post-operative clinical presentation, endocrine and visual tests, radiological findings, and resection status. Rathke's cleft cysts were categorized by both cyst consistency and radiological features and clinical characteristics were analyzed. RESULTS: The most common pre-operative symptoms were visual field deficit (65.8%) and hypopituitarism (39.5 %). Visual field deficit improved in 84% of affected patients, and hyperprolactinemia improved in 80% of affected patients. Pre-operative hypothyroidism and hypogonadism were associated with radiological type 3 cysts, while headache was more common in type B and C. Type 3 cysts were also associated post-operative hypogonadism and hypothyroidism. Permanent Diabetes insipidus was found in 3 patients (7.9%). Cyst height was a significant factor related to pre-operative visual field deficit and post-operative Diabetes insipidus. Residual cysts were found in 11 cases (30.6%) and 9 patients experienced regrowth/recurrence. Residual cysts were a significant factor in regrowth/recurrence. Recurrence rate and post-operative complications were not correlated with different subtypes. CONCLUSIONS: Endoscopic endonasal approach for removal of Rathke's cleft cyst is a safe and effective intervention. It leads to significant improvement in visual field deficit and recovery of hyperprolactinemia. Although the incidence of post-operative Diabetes insipidus is high, it is usually temporary. Although different categorizations are not correlated to recurrence rate, they could help predict the status of hormone deficit.
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This study investigated the effects of different drying methods on the drying characteristics, three-dimensional (3D) appearance, color, total polysaccharide content (TPC), antioxidant activity, and microstructure of Pleurotus eryngii slices. The drying methods included hot air drying (HAD), infrared drying (ID), and microwave drying (MD). The results showed that the drying method and conditions significantly influenced the drying time, with MD having a significant advantage in reducing the drying time. The 3D appearance of P. eryngii slices was evaluated based on shrinkage and roughness as quantitative indexes, and the best appearance was obtained by hot air drying at 55 and 65 °C. HAD and ID at lower drying temperatures obtained better color, TPC, and antioxidant activity, but MD significantly damaged the color and nutritional quality of P. eryngii. The microstructure of dried P. eryngii slices was observed using scanning electron microscopy, and the results showed that drying methods and conditions had an obvious effect on the microstructure of P. eryngii slices. Scattered mycelia were clearly observed in P. eryngii samples dried by HAD and ID at lower drying temperatures, while high drying temperatures led to the cross-linking and aggregation of mycelia. This study offers scientific and technical support for choosing appropriate drying methods to achieve a desirable appearance and quality of dried P. eryngii.