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1.
Support Care Cancer ; 32(11): 715, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377915

RESUMEN

BACKGROUND: Using granulocyte colony-stimulating factor (G-CSF) after completing chemotherapy reduces the duration of neutropenia and infections. However, the efficacy and safety of prophylactic pegfilgrastim in acute lymphoblastic leukemia (ALL) patients have not yet been evaluated after intensive cytotoxic chemotherapy compared to the daily G-CSF. This study aimed to evaluate the efficacy of pegfilgrastim for ALL patients who received intensive chemotherapy compared with a short-acting G-CSF. PATIENTS AND METHODS: Clinical data of 145 patients treated with hyper-CVAD, modified VPDL/VPD, or KALLA 1406/1407 regimen were retrospectively evaluated. Pegfilgrastim or the short-acting G-CSF was selected according to the clinician's discretion. Patients not receiving pegfilgrastim were treated with the short-acting G-CSF. RESULTS: The median age of enrolled patients was 45 years. Sixty newly diagnosed ALL patients were treated with hyper-CVAD regimen, while KALLA and VPDL regimens were administered to 39 and 46 patients, respectively. Among the 60 patients treated with hyper-CVAD, 20 patients received pegfilgrastim. Patients who received pegfilgrastim had a significantly shorter duration of neutropenia and hospitalization and reduced incidence of severe infections compared to patients receiving the short-acting G-CSF. Consistent results were also confirmed in an analysis targeting only patients who achieved remission during hyper-CVAD induction therapy. There was no significant difference in neutrophil recovery ability and hospitalization duration when the daily short-acting G-CSF was used prophylactically after completing hyper-CVAD, KALLA, and VPDL regimens as induction therapy. CONCLUSION: Using pegfilgrastim after hyper-CVAD therapy was more effective than the short-acting G-CSF in terms of infection, neutropenia recovery, and hospitalization in patients with newly diagnosed ALL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Filgrastim , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Polietilenglicoles , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas Recombinantes , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Polietilenglicoles/administración & dosificación , Masculino , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adolescente , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Anciano , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico
2.
Artículo en Inglés | MEDLINE | ID: mdl-39402009

RESUMEN

Solid pseudopapillary neoplasms (SPNs) are uncommon pancreatic tumors that primarily affect young females. We report a case of a 24-year-old female diagnosed with SPN and liver metastasis during a routine examination. Imaging revealed an 8-cm pancreatic mass with multiple liver metastases. Histopathology confirmed SPN. Subsequent next-generation sequencing revealed a CTNNB1 mutation. The patient underwent a total pancreatectomy with splenectomy, right hemihepatectomy, and intraoperative radiofrequency ablation. Two years after the surgery, she remained complication-free. She is under regular surveillance. This case underscores the importance of early detection and comprehensive management of SPN.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39410849

RESUMEN

Background: Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression. Methods: OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia. Results: TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia. Conclusion: Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.

4.
ArXiv ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-39398214

RESUMEN

Purpose: To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods: This retrospective study included contrast-enhanced and non-contrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years ± 11 [s.d.]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results: On NIH-LC (25 patients; mean age, 59 years ± 14 [s.d.]; 14 male) and NIH-OV (166 patients; mean age, 65 years ± 9 [s.d.]; all female), the model achieved Dice scores of 0.855±0.061 (CI: 0.831-0.878) and 0.826±0.153 (CI: 0.764-0.887), with median volume estimation errors of 19.6% (IQR: 13.2-29.0) and 5.3% (IQR: 2.4-9.7) respectively. On UofW-LC (124 patients; mean age, 46 years ± 12 [s.d.]; 73 female), the model had a Dice score of 0.830±0.107 (CI: 0.798-0.863) and median volume estimation error of 9.7% (IQR: 4.5-15.1). The model showed strong agreement with expert assessments, with r 2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion: The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments.

5.
Sci Rep ; 14(1): 23676, 2024 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-39389994

RESUMEN

This study aimed to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with central retinal artery occlusion (CRAO) by analyzing changes in visual acuity (VA) and enhanced depth imaging optical coherence tomography (EDI-OCT) parameters. A comparative retrospective study was conducted by reviewing the medical records of all HBO-treated RAO patients in our department and comparing them with matched RAO patients who did not receive HBO treatment. All patients treated with HBO received treatment within 7 days of the onset of visual symptoms. Baseline characteristics were compared, and VA and OCT parameters were evaluated at baseline and follow-up visits. A total of 50 eyes from 50 patients were included, with 29 eyes in the HBOT group and 21 eyes in the control group. The mean BCVA of the HBOT group at the initial visit was 2.03 logMAR, which improved to 1.55 logMAR at 6 months, with the change being statistically significant (P < 0.01), while the control group's BCVA remained almost unchanged, from 2.1 to 2.11 logMAR (P = 0.762). The central choroidal thickness increased significantly in the HBOT group over the subsequent period. The central fovea, and outer retinal layer thickness in the HBOT group were significantly greater than those in the control group at the 6-month follow-up after treatment. HBOT appears to be effective in improving VA and inducing favorable changes in OCT parameters in patients with CRAO. It helps to preserve retinal layer thickness, especially in the outer retinal layer.


Asunto(s)
Oxigenoterapia Hiperbárica , Oclusión de la Arteria Retiniana , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Tomografía de Coherencia Óptica/métodos , Oclusión de la Arteria Retiniana/terapia , Oclusión de la Arteria Retiniana/diagnóstico por imagen , Oxigenoterapia Hiperbárica/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Agudeza Visual/fisiología , Estudios Retrospectivos , Resultado del Tratamiento , Retina/diagnóstico por imagen , Retina/patología
6.
J Clin Oncol ; : JCO2400683, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39361946

RESUMEN

PURPOSE: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725). CONCLUSION: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

7.
Int J Mol Sci ; 25(19)2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39408777

RESUMEN

Exosomes derived from mesenchymal stem cells have shown promise in treating metabolic disorders, yet their specific mechanisms remain largely unclear. This study investigates the protective effects of exosomes from human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) against adiposity and insulin resistance in high-fat diet (HFD)-induced obese mice. HFD-fed mice treated with hWJMSC-derived exosomes demonstrated improved gut barrier integrity, which restored immune balance in the liver and adipose tissues by reducing macrophage infiltration and pro-inflammatory cytokine expression. Furthermore, these exosomes normalized lipid metabolism including lipid oxidation and lipogenesis, which alleviate lipotoxicity-induced endoplasmic reticulum (ER) stress, thereby decreasing fat accumulation and chronic tissue inflammation in hepatic and adipose tissues. Notably, hWJMSC-derived exosomes also promoted browning and thermogenic capacity of adipose tissues, which was linked to reduced fibroblast growth factor 21 (FGF21) resistance and increased adiponectin production. This process activated the AMPK-SIRT1-PGC-1α pathway, highlighting the role of the FGF21-adiponectin axis. Our findings elucidate the molecular mechanisms through which hWJMSC-derived exosomes counteract HFD-induced metabolic dysfunctions, supporting their potential as therapeutic agents for metabolic disorders.


Asunto(s)
Adiponectina , Dieta Alta en Grasa , Exosomas , Factores de Crecimiento de Fibroblastos , Resistencia a la Insulina , Células Madre Mesenquimatosas , Obesidad , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Adiponectina/metabolismo , Obesidad/metabolismo , Obesidad/terapia , Masculino , Humanos , Ratones Obesos , Hígado Graso/metabolismo , Hígado Graso/etiología , Hígado Graso/terapia , Ratones Endogámicos C57BL , Tejido Adiposo/metabolismo , Transducción de Señal , Hígado/metabolismo , Hígado/patología , Metabolismo de los Lípidos
8.
Biomed Eng Lett ; 14(5): 1079-1085, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39220028

RESUMEN

Supramalleolar osteotomy (SMO) is a representative procedure to restore a malalignment in the varus ankle deformity by shifting the concentrated pressure on the medial ankle joint to the lateral area. Additionally, fibula osteotomy (FO) is selectively selected and performed according to the surgeon's preference. However, it is controversial whether FO is effective in shifting the abnormal pressure from the medial to the lateral area on the ankle joint. Some cadaveric studies have been performed to prove this. However, it is difficult to consistently reconstruct amount of the varus ankle deformities angle in cadavers and to guarantee reliable contact pressure between the ankle joint. Thus, the aim of this study was predicted and quantitatively compared a peak pressure between single SMO and SMO with FO procedure by using a finite element analysis as a powerful biomechanical tool to those limitations of cadaveric study. This study reconstructed total 4 3D foot and ankle models including a normal and pre-op model and 2 post-op models. The pre-op model was modified by assigning 10° varus tilting corresponding to stage 3b in the classification of varus ankle osteoarthritis based on the validated normal model. Also, the post-op models were reconstructed by applying single SMO and SMO with FO, respectively. All of the models were assumed as one-leg standing position and to mimic smooth ankle joint motion. Peak contact pressure change was predicted at the medial ankle joint by using computational simulation. As a result, 2 post-op models showed a remarkably peak pressure reduction by up to 5.5 times on the medial tibiotalar joint. However, a comparison between single SMO and SMO with FO model showed no appreciable differences. In conclusion, this study predicted that single SMO may be as effective as SMO with FO in reducing peak contact pressure on the medial tibiotalar joint in varus ankle osteoarthritis.

9.
J Microbiol Biotechnol ; 34(10): 1969-1980, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39252632

RESUMEN

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.


Asunto(s)
Citocinas , Dermatitis Atópica , Dinitroclorobenceno , Modelos Animales de Enfermedad , Proteínas Filagrina , Células HaCaT , Interferón gamma , Queratinocitos , Extractos Placentarios , Factor de Necrosis Tumoral alfa , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Animales , Humanos , Ratones , Femenino , Factor de Necrosis Tumoral alfa/metabolismo , Interferón gamma/metabolismo , Citocinas/metabolismo , Extractos Placentarios/farmacología , Queratinocitos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos BALB C , Antiinflamatorios/farmacología , Embarazo , Inmunoglobulina E/sangre , Bazo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Placenta/metabolismo , Placenta/efectos de los fármacos
10.
Medicina (Kaunas) ; 60(8)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39202567

RESUMEN

Background and Objective: Obesity is associated with difficult or failed intubation attempts, making general anesthesia challenging for anesthesiologists to perform. The purpose of this study was to evaluate and compare the efficacy of a McCoy laryngoscope and a C-MAC D-blade video laryngoscope for intubation in obese patients with a body mass index (BMI) ≥ 35 kg/m2. Methods: In total, 104 patients were randomly assigned to be intubated with a McCoy (McCoy group) or C-MAC D-blade video laryngoscope (C-MAC group). The primary outcome was intubation time. The secondary outcomes were vocal cord exposure time, vocal cord passage time, proportion of successful intubation, mask ventilation scale, intubation difficulty scale (IDS), percentage of glottis opening (POGO) score, and hemodynamic variables. Results: Although the intubation time did not significantly differ, the C-MAC group showed shorter vocal cord exposure times and a higher rate of successful vocal cord exposure within 5 s. The IDS value was significantly lower in the C-MAC group than in the McCoy group. The proportion of patients who required an increase in lifting force during laryngoscopy was higher in the McCoy group than in the C-MAC group, which may explain the difference in MAP between the groups. Conclusions: Both the McCoy laryngoscope and the C-MAC D-blade video laryngoscope were useful during the intubation of obese patients. The C-MAC D-blade video laryngoscope might be more useful for obese patients in terms of hemodynamic stability.


Asunto(s)
Intubación Intratraqueal , Laringoscopios , Laringoscopía , Obesidad , Humanos , Masculino , Femenino , Obesidad/complicaciones , Obesidad/fisiopatología , Obesidad/terapia , Persona de Mediana Edad , Intubación Intratraqueal/métodos , Intubación Intratraqueal/instrumentación , Adulto , Laringoscopía/métodos , Laringoscopía/instrumentación , Índice de Masa Corporal , Anciano , Anestesia General/métodos
11.
Exp Dermatol ; 33(8): e15155, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39133009

RESUMEN

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/ß-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/ß-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/ß-catenin pathway and highlight its therapeutic potential in hair loss treatment.


Asunto(s)
Fibronectinas , Glucógeno Sintasa Quinasa 3 beta , Folículo Piloso , Cabello , Ratones Endogámicos C57BL , Vía de Señalización Wnt , beta Catenina , Animales , Humanos , Fibronectinas/metabolismo , Ratones , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Cabello/crecimiento & desarrollo , beta Catenina/metabolismo , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/metabolismo , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Proliferación Celular , Proteína Wnt-5a/metabolismo , Proteínas Wnt/metabolismo , Masculino , Femenino , Proteínas Proto-Oncogénicas
12.
ACS Appl Mater Interfaces ; 16(35): 46044-46052, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39103250

RESUMEN

Lipid nanoparticles (LNPs) are gaining recognition as potentially effective carriers for delivery of therapeutic agents, including nucleic acids (DNA and RNA), for the prevention and treatment of various diseases. Much effort has been devoted to the implementation of microfluidic techniques for the production of monodisperse and stable LNPs and the improvement of encapsulation efficiency. Here, we developed three-dimensional (3D)-printed ring micromixers for the production of size-controllable and monodispersed LNPs with a high mRNA delivery efficiency. The effects of flow rate and ring shape asymmetry on the mixing performance were initially examined. Furthermore, the physicochemical properties (such as hydrodynamic diameter, polydispersity, and encapsulation efficiency) of the generated LNPs were quantified as a function of these physical parameters via biochemical analysis and cryo-electron microscopy imaging. With a high production rate of 68 mL/min, our 3D-printed ring micromixers can be used to manufacture LNPs with diameters less than 90 nm, low polydispersity (<0.2), and high mRNA encapsulation efficiency (>91%). Despite the simplicity of the ring-shaped mixer structure, we can produce mRNA-loaded LNPs with exceptional quality and high throughput, outperforming costly commercial micromixers.


Asunto(s)
Nanopartículas , Tamaño de la Partícula , Impresión Tridimensional , ARN Mensajero , ARN Mensajero/genética , ARN Mensajero/metabolismo , Nanopartículas/química , Lípidos/química , Humanos , Liposomas
14.
Sci Rep ; 14(1): 17459, 2024 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075200

RESUMEN

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18-0.51, p < 0.0001]; median OS 19.8 vs. 10.0 months [HR: 0.38, 95% CI: 0.23-0.64, p < 0.001]) independent of BRCA mutation status, platinum-sensitivity, previous PARP inhibitor therapy, ECOG performance status, and FIGO stage. Notably, GCIG CA125 response had a high negative predictive value (NPV: 93%, 95% CI: 80-98), but poor positive predictive value (PPV: 53%, 95% CI: 35-71) in predicting RECIST response. CA125 PD criteria also showed poor concordance with RECIST PD (PPV 56%, 95% CI: 40-71; NPV 33%, 95% CI: 17-54). Therefore, serum CA125 may be useful as a highly accessible prognostic and predictive biomarker to CHK1i therapy in recurrent HGSOC.


Asunto(s)
Antígeno Ca-125 , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Antígeno Ca-125/sangre , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Anciano , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/antagonistas & inhibidores , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Pronóstico , Anciano de 80 o más Años , Pirazoles/uso terapéutico , Pirazoles/farmacología , Pirazinas/uso terapéutico , Pirazinas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Criterios de Evaluación de Respuesta en Tumores Sólidos , Supervivencia sin Progresión , Biomarcadores de Tumor/sangre , Proteínas de la Membrana
15.
Biomed Eng Lett ; 14(4): 747-754, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38946821

RESUMEN

This study was performed to investigate the effects of fibular osteotomy and release of medial soft tissues including posterior tibial tendon (PTT), and deep deltoid ligaments, which act as medial stabilizing structures in medial open wedge SMO. Twelve fresh frozen human legs were obtained and disarticulated below the knee. Experiments were conducted in four steps. First, medial open wedge tibial osteotomy was performed. Second, fibular osteotomy was performed in an inferomedial direction at the same level as the tibial osteotomy. Third, the deep deltoid ligament was released from tibial attachments. Forth, total tenotomy of the PTT was performed behind the medial malleolus. After finishing each step, contact area and peak and mean pressures were measured in the tibiotalar and talofibular joints. Fibular osteotomy after medial open wedge SMO significantly decreased mean pressure in the tibiotalar joint, mean and peak pressures in the talofibular joint. Medial soft tissue release resulted in a remarkable lateral shift and decreased tibiotalar joint loading. However, no remarkable change was observed in the tibiotalar joint during releasing medial soft tissues. The overall peak pressure distribution tended to shift more laterally compared to the value of normal alignment. In conclusion, concomitant fibular osteotomy and release of the deltoid ligament and PTT provide a useful means of minimizing tibiotalar joint stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00370-7.

16.
Mycobiology ; 52(3): 172-182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948453

RESUMEN

Truffles, belonging to the genus Tuber, are ectomycorrhizal (ECM) fungi that form underground ascocarps and primarily establish symbiosis with oaks and hazels. The cultivation of Tuber spp. involves transplanting inoculated seedlings that have formed ectomycorrhiza with Tuber species, with mulching being effective for truffle cultivation. In this study, we investigated the effects of mulching on the mycelial growth of four Tuber species (T. himalayense, T. koreanum, T. melanosporum, and T. borchii) in the Korean natural environment, highlighting the potential for Korea as a truffle cultivation site. We developed and tested species-specific primers for quantifying the soil mycelial biomass of Tuber spp. by qRT-PCR, determined the superior mulch color for mycelial growth, and identified the Tuber species exhibiting the highest growth rate in the Korean field environment. Our results demonstrated that white mulch significantly enhanced mycelial growth in Tuber species than black mulch, likely owing to its ability to maintain low soil temperatures, control weeds, and improve host plant growth. Among the Tuber species, T. himalayense showed the greatest growth potential in the Korean natural environment. Additionally, a significant and positive correlation was observed between the mycelial biomass of Tuber species and the growth of inoculated seedlings, as measured by the total stem length and the number of leaves, thereby indicating the importance of symbiosis between ECM fungi and host plants. This study provides valuable insights into truffle cultivation in Korea and highlights the potential of using white mulch to promote mycelial growth, thereby contributing essential data for understanding the appropriate environmental conditions for Tuber spp. cultivation in Korea. Further study is needed to assess the long-term impact of mulching and to explore the effectiveness of other mulching materials.

17.
IEEE Trans Biomed Eng ; PP2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990742

RESUMEN

OBJECTIVE: Recent years have seen an increase in machine learning (ML)-based blood glucose (BG) forecasting models, with a growing emphasis on potential application to hybrid or closed-loop predictive glucose controllers. However, current approaches focus on evaluating the accuracy of these models using benchmark data generated under the behavior policy, which may differ significantly from the data the model may encounter in a control setting. This study challenges the efficacy of such evaluation approaches, demonstrating that they can fail to accurately capture an ML-based model's true performance in closed-loop control settings. METHODS: Forecast error measured using current evaluation approaches was compared to the control performance of two forecasters-a machine learning-based model (LSTM) and a rule-based model (Loop)-in silico when the forecasters were utilized with a model-based controller in a hybrid closed-loop setting. RESULTS: Under current evaluation standards, LSTM achieves a significantly lower (better) forecast error than Loop with a root mean squared error (RMSE) of 11.57 ±0.05 mg/dL vs. 18.46 ±0.07 mg/dL at the 30-minute prediction horizon. Yet in a control setting, LSTM led to significantly worse control performance with only 77.14% (IQR 66.57-84.03) time-in-range compared to 86.20% (IQR 78.28-91.21) for Loop. CONCLUSION: Prevailing evaluation methods can fail to accurately capture the forecaster's performance when utilized in closed-loop settings. SIGNIFICANCE: Our findings underscore the limitations of current evaluation standards and the need for alternative evaluation metrics and training strategies when developing BG forecasters for closed-loop control systems.

18.
Sensors (Basel) ; 24(14)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39066055

RESUMEN

The purpose of this study was to examine the validity of two wearable smartwatches (the Apple Watch 6 (AW) and the Galaxy Watch 4 (GW)) and smartphone applications (Apple Health for iPhone mobiles and Samsung Health for Android mobiles) for estimating step counts in daily life. A total of 104 healthy adults (36 AW, 25 GW, and 43 smartphone application users) were engaged in daily activities for 24 h while wearing an ActivPAL accelerometer on the thigh and a smartwatch on the wrist. The validities of the smartwatch and smartphone estimates of step counts were evaluated relative to criterion values obtained from an ActivPAL accelerometer. The strongest relationship between the ActivPAL accelerometer and the devices was found for the AW (r = 0.99, p < 0.001), followed by the GW (r = 0.82, p < 0.001), and the smartphone applications (r = 0.93, p < 0.001). For overall group comparisons, the MAPE (Mean Absolute Percentage Error) values (computed as the average absolute value of the group-level errors) were 6.4%, 10.5%, and 29.6% for the AW, GW, and smartphone applications, respectively. The results of the present study indicate that the AW and GW showed strong validity in measuring steps, while the smartphone applications did not provide reliable step counts in free-living conditions.


Asunto(s)
Acelerometría , Actividades Cotidianas , Aplicaciones Móviles , Teléfono Inteligente , Dispositivos Electrónicos Vestibles , Humanos , Masculino , Femenino , Adulto , Acelerometría/instrumentación , Acelerometría/métodos , Adulto Joven , Monitoreo Ambulatorio/métodos , Monitoreo Ambulatorio/instrumentación , Caminata/fisiología , Persona de Mediana Edad
19.
Prev Med Rep ; 43: 102772, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952432

RESUMEN

Objectives: This study aims to investigate the influence of socioeconomic status (SES) on variations in physical activity (PA) levels and diabetes-related cognitive dysfunction and impairment amidst disruptions caused by the COVID-19 pandemic. Methods: With the sample of old population, comprising about 20 thousand from the Fact-Finding Survey on the Status of Senior Citizens (FSSSC) released by Ministry of Health and Welfare of South Korea in 2017 and 2020, we empirically tested the direct and indirect effects of SES on cognitive dysfunction using structural equation modeling (SEM). Two SEMs provided the comparison on the effects of COVID-19. Results: Household income had a negative impact on the likelihood of dementia diagnosis via PA related diabetes during the pandemic (p < 0.001), whereas no effects of household income on dementia diagnosis were found in 2017, due to no direct effect of PA on diabetes confirmation in 2017. The disparity in PA based on SES becomes more prominent among the older individuals during the pandemic (z = 11.7) than 2017 (z = 6.0), emphasizing the significance of PA in mitigating diabetes-induced cognitive dysfunction during the pandemic. SES affects access to PA, contributing to diabetes-induced cognitive dysfunctions in the older population with lower SES during the pandemic. Conclusion: PA may serve as a preventive measure against diabetes-induced cognitive dysfunction and dementia in the older population. Thorough investigation of these mechanisms is imperative to establish the role of PA in preventing diabetes-induced cognitive impairment, particularly among the older population with lower SES.

20.
Exp Dermatol ; 33(7): e15137, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39031460

RESUMEN

AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3ß(Ser9) and ß-catenin(Ser675), indicating the activation of the GSK-3ß/ß-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health.


Asunto(s)
Glucógeno Sintasa Quinasa 3 beta , Folículo Piloso , Cabello , beta Catenina , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , beta Catenina/metabolismo , Humanos , Ratones , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Proliferación Celular/efectos de los fármacos , Transducción de Señal , Colágeno/metabolismo , Fosforilación , Células Cultivadas , Péptidos/farmacología
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