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1.
Am J Dermatopathol ; 46(9): 593-596, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39150181

RESUMEN

ABSTRACT: Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is a rare yet highly aggressive subtype of primary cutaneous lymphoma. Characterized by its challenging diagnosis and poor prognosis, PCGD-TCL presents unique clinical and histopathological features that distinguish it from other primary cutaneous lymphoma subtypes. Here, we report the case of a 75-year-old man who initially presented with multiple erythematous indurated plaques over his back and bilateral lower extremities. The initial biopsy suggested primary cutaneous T-cell lymphoma (PCTCL) with a CD30-negative phenotype. However, within a 2-month interval, the disease progressed rapidly, manifesting as extensive skin involvement across the chest and upper extremities. A repeat skin biopsy was performed, revealing dermal atypical lymphocytes without epidermotropism. Immunohistochemical analysis demonstrated positivity for CD3, CD5, and CD4, as well as T-cell receptor delta (TCR delta) expression, along with the loss of CD8 and CD30 expression. These findings were consistent with a diagnosis of PCGD-TCL. Despite therapeutic interventions, including systemic treatments, the patient's condition deteriorated rapidly, ultimately leading to his demise within a month of receiving the PCGD-TCL diagnosis. This case highlights the diagnostic complexities associated with PCGD-TCL, emphasizing the importance of careful histopathological examination and immunophenotypic characterization. Given its aggressive nature and propensity for rapid dissemination, early recognition of PCGD-TCL is paramount for initiating appropriate therapeutic interventions. However, effective treatment options for PCGD-TCL remain limited, and the disease typically carries an unfavorable prognosis. Further research is needed to elucidate the underlying molecular mechanisms driving the pathogenesis of PCGD-TCL, to identify novel therapeutic targets, and to improve patient outcomes. In addition, increased awareness among clinicians and pathologists regarding the clinical presentation and diagnostic criteria of PCGD-TCL is crucial for facilitating timely diagnosis and management of this challenging malignancy.


Asunto(s)
Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Masculino , Anciano , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/diagnóstico , Resultado Fatal , Receptores de Antígenos de Linfocitos T gamma-delta , Biomarcadores de Tumor/análisis , Biopsia , Progresión de la Enfermedad
2.
Int J Gynecol Pathol ; 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38085960

RESUMEN

Endometrial stromal tumors (ESTs) are uncommon uterine mesenchymal lesions. Nuclear expression of ß-catenin, an indication of activated Wnt/ß-catenin signaling pathway, was described in 50% to 92% of low-grade ESTs, including endometrial stromal nodule and low-grade endometrial stromal sarcoma. Activation of the Wnt/ß-catenin signaling pathway leads to the translocation of ß-catenin into the nucleus and interaction with the T-cell factor/lymphoid enhancer-binding factor-1 (LEF1) family of transcription factors to regulate cell proliferation, differentiation, migration, and survival. Immunohistochemical analysis of ß-catenin and LEF1 was performed in 2 endometrial stromal nodules and 20 low-grade endometrial stromal sarcomas and demonstrated 90.9% and 81.8% positive rates for ß-catenin and LEF1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ß-catenin and LEF1 were 90.9% versus 81.8%, 81.0% versus 85.7%, 83.3% versus 85.7%, 89.5% versus 81.8%, respectively, in the diagnosis of low-grade ESTs. There is no statistical significance of the performance of ß-catenin and LEF1 in all ESTs (P = 0.664) or in primary or metastatic/recurrent settings (P = 0.515 and 0.999, respectively). Only 3 smooth muscle tumors showed focal and weak positivity for LEF1. Our results indicate LEF1 can be a useful marker in aiding a diagnosis of low-grade EST and differentiating from smooth muscle tumors alone or in combination with ß-catenin.

3.
J Foot Ankle Surg ; 60(6): 1188-1192, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34130931

RESUMEN

Talus osteochondral lesions are a commonly underdiagnosed problem in young athletes. Talus osteochondral lesions surgical algorithm remains controversial. Current metrics suggest that conventional treatment of osteochondral lesions of the talus is promising; yet return to sport is poorly studied. Fifty-seven patients following talus osteochondral lesion surgical intervention were included in this study. About 63.1% were female with mean age 37.1 years, mean lesion size 10 × 12.5 mm, and mean follow-up 79.9 months postoperatively. Patients were divided into 4 groups by surgery performed: antegrade arthroscopic bone marrow stimulation, retrograde arthroscopic drilling, osteochondral autograft transfer, and allograft cartilage implantation. Outcome metrics include Visual Analog Scale for pain and function, Short Form-12, Foot and Ankle Disability Scale, Tegner, Marx activity scores, Naal Sports inventory, and patient satisfaction. Over 77% of patients were satisfied with surgical intervention. Each intervention significantly decreased pain and increased function, except retrograde drilling. All interventions trended toward decreased Tegner score; only antegrade drilling showed significant decrease. Based on Naal's sports inventory, 85.7% of surgically treated patients reported participating in sport activities, on average 3 times/week and 50.6 minutes/session. Traditionally, talus osteochondral lesions present a difficult problem that is marred by unsatisfactory nonoperative outcomes in typically active patients. As our surgical understanding has evolved, we've continued to improve on outcomes. Our patients demonstrated 77.2% overall satisfaction rate, a statistically significant improvement in pain and function, at an average follow-up of 79.9 months postoperatively, and a high rate of return to sport with little difference between surgical interventions.


Asunto(s)
Cartílago Articular , Astrágalo , Adulto , Articulación del Tobillo , Artroscopía , Femenino , Humanos , Volver al Deporte , Astrágalo/cirugía , Trasplante Autólogo , Resultado del Tratamiento
4.
Proc Natl Acad Sci U S A ; 113(37): E5434-43, 2016 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-27578867

RESUMEN

Rapid clearance of adoptively transferred Cd47-null (Cd47(-/-)) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47(-/-) mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background. Studying our recently established Sirpα-KO (Sirpα(-/-)) mice, as well as Cd47(-/-) mice, we reveal additional activation and inhibitory mechanisms besides the CD47-SIRPα axis dominantly controlling macrophage behavior. Sirpα(-/-) mice and Cd47(-/-) mice, although being normally healthy, develop severe anemia and splenomegaly under chronic colitis, peritonitis, cytokine treatments, and CFA-/LPS-induced inflammation, owing to splenic macrophages phagocytizing self-red blood cells. Ex vivo phagocytosis assays confirmed general inactivity of macrophages from Sirpα(-/-) or Cd47(-/-) mice toward healthy self-cells, whereas they aggressively attack toward bacteria, zymosan, apoptotic, and immune complex-bound cells; however, treating these macrophages with IL-17, LPS, IL-6, IL-1ß, and TNFα, but not IFNγ, dramatically initiates potent phagocytosis toward self-cells, for which only the Cd47-Sirpα interaction restrains. Even for macrophages from WT mice, phagocytosis toward Cd47(-/-) cells does not occur without phagocytic activation. Mechanistic studies suggest a PKC-Syk-mediated signaling pathway, to which IL-10 conversely inhibits, is required for activating macrophage self-targeting, followed by phagocytosis independent of calreticulin Moreover, we identified spleen red pulp to be one specific tissue that provides stimuli constantly activating macrophage phagocytosis albeit lacking in Cd47(-/-) or Sirpα(-/-) mice.


Asunto(s)
Antígeno CD47/genética , Inflamación/genética , Interleucina-10/genética , Receptores Inmunológicos/genética , Animales , Citocinas/biosíntesis , Citocinas/genética , Endocitosis/genética , Humanos , Inflamación/patología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Noqueados , Fagocitosis/genética , Proteína Quinasa C/genética , Transducción de Señal/genética
5.
J Immunol ; 197(8): 3293-3301, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27619992

RESUMEN

Chronic diseases are often associated with altered inflammatory response, leading to increased host vulnerability to new inflammatory challenges. Employing streptozotocin (STZ)-induced diabetes as a model, we further investigate mechanisms leading to enhanced neutrophil (polymorphonuclear leukocytes [PMN]) responses under hyperglycemia and compare them with those under chronic colitis. We show that, different from colitis under which the PMN response is significantly potentiated, the existence of a proinflammatory state associated with broad increases in macrophages in various organs plays a dominant role in promoting the PMN inflammatory response in diabetic mice. Studies of PMN infiltration during zymosan-induced peritonitis reveal that hyperglycemia enhances PMN recruitment not through inducing a high level of IL-17, which is the case in colitis, but through increasing F4/80+ macrophages in the peritoneal cavity, resulting in elevations of IL-6, IL-1ß, TNF-α, and CXCL1 production. Insulin reversal of hyperglycemia, but not the neutralization of IL-17, reduces peritoneal macrophage numbers and ameliorates PMN infiltration during peritonitis. Significantly increased macrophages are also observed in the liver, kidneys, and intestines under hyperglycemia, and they are attributable to exacerbated nephropathy and colitis when inflammatory conditions are induced by doxorubicin and dextran sulfate sodium, respectively. Furthermore, analyses of monocyte production and macrophage proliferation in tissues suggest that significant monocytosis of inflammatory F4/80+Gr-1+ monocytes from the spleen and macrophage proliferation in situ synergistically contribute to the increased macrophage population under hyperglycemia. In conclusion, our results demonstrate that STZ-induced hyperglycemic mice develop a systemic proinflammatory state mediated by broad infiltration of macrophages.


Asunto(s)
Diabetes Mellitus Tipo 1/inmunología , Hiperglucemia/inmunología , Inflamación/inmunología , Macrófagos/inmunología , Animales , Diabetes Mellitus Tipo 1/inducido químicamente , Modelos Animales de Enfermedad , Hiperglucemia/inducido químicamente , Interleucina-17/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Neutrófilos/inmunología , Estreptozocina
6.
J Immunol ; 195(2): 661-71, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-26085683

RESUMEN

CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells. Previous studies suggested that cells may lose surface CD47 during aging or apoptosis to enable phagocytic clearance. In the current study, we demonstrate that the level of cell surface CD47 is not decreased, but the distribution pattern of CD47 is altered, during apoptosis. On nonapoptotic cells, CD47 molecules are clustered in lipid rafts forming punctates on the surface, whereas on apoptotic cells, CD47 molecules are diffused on the cell surface following the disassembly of lipid rafts. We show that clustering of CD47 in lipid rafts provides a high binding avidity for cell surface CD47 to ligate macrophage SIRPα, which also presents as clusters, and elicits SIRPα-mediated inhibitory signaling that prevents phagocytosis. In contrast, dispersed CD47 on the apoptotic cell surface is associated with a significant reduction in the binding avidity to SIRPα and a failure to trigger SIRPα signal transduction. Disruption of plasma membrane lipid rafts with methyl-ß-cyclodextrin diffuses CD47 clusters, leading to a decrease in the cell binding avidity to SIRPα and a concomitant increase in cells being engulfed by macrophages. Taken together, our study reveals that CD47 normally is clustered in lipid rafts on nonapoptotic cells but is diffused in the plasma membrane when apoptosis occurs; this transformation of CD47 greatly reduces the strength of CD47-SIRPα engagement, resulting in the phagocytosis of apoptotic cells.


Asunto(s)
Antígenos de Diferenciación/inmunología , Apoptosis/efectos de la radiación , Antígeno CD47/inmunología , Células Epiteliales/efectos de la radiación , Macrófagos/efectos de la radiación , Receptores Inmunológicos/inmunología , Animales , Antígenos de Diferenciación/genética , Apoptosis/efectos de los fármacos , Sitios de Unión , Antígeno CD47/química , Antígeno CD47/genética , Línea Celular Tumoral , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Fibroblastos/efectos de la radiación , Regulación de la Expresión Génica , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/efectos de la radiación , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Microdominios de Membrana/efectos de los fármacos , Microdominios de Membrana/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Fagocitosis/efectos de los fármacos , Fagocitosis/efectos de la radiación , Cultivo Primario de Células , Unión Proteica , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/efectos de la radiación , Receptores Inmunológicos/genética , Transducción de Señal , Bazo/citología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/efectos de la radiación , Rayos Ultravioleta , beta-Ciclodextrinas/farmacología
7.
Phys Chem Chem Phys ; 19(8): 6164-6168, 2017 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-28191553

RESUMEN

Palladium (Pd)-catalyzed selective hydrogenation of alkynes has been one of the most studied hydrogenation reactions in the last century. However, kinetic studies conducted to reveal the catalyst's active centers have been hindered because of dynamic surface changes on Pd during the reaction. In the present study, bimetallic Pd-Au nanoparticles supported on carbon nanotubes have been synthesized at room temperature as catalysts for selective hydrogenation of phenylacetylene, which show effectively enhanced selectivity compared to their monometallic counterparts. Structural and surface analyses of fresh and reacted catalysts reveal that selective hydrogenation of phenylacetylene is favored over nanosized Pd-Au bimetallic phases due to modifications in the Pd surface in terms of neighboring site isolation and electron density reduction.

8.
Phys Chem Chem Phys ; 19(36): 25214-25219, 2017 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-28885634

RESUMEN

Phosphorous oxide (PxOy)-incorporated carbon nanotubes (PCNTs) and nitric acid treated carbon nanotubes (OCNTs) are first synthesized, then phosphorous modified palladium nanoparticles (Pd-P NPs) supported on PCNTs (Pd-P/PCNTs) and OCNTs (Pd-P/OCNTs) are synthesized and employed as electrocatalysts in a methanol oxidation reaction. Pd-P/PCNTs show enhanced electrocatalytic activity and stability in comparison to Pd-P/OCNTs. Combining surface analysis and electrochemical performance, PxOy incorporated into CNTs could create anchoring sites for Pd ions and P precursors, which could facilitate the synthesis of Pd-P NPs in an aqueous solution containing Pd ions and sodium hypophosphite serving as a reducing agent and a P source. The electronic modification of embedded Pd-P NPs on PxOy-incorporated CNTs accounts for the enhanced electrochemical performance of Pd-P/PCNTs.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39106145

RESUMEN

Although multiple instance learning (MIL) methods are widely used for automatic tumor detection on whole slide images (WSI), they suffer from the extreme class imbalance WSIs containing small tumors where the tumor may include only a few isolated cells. For early detection, it is important that MIL algorithms can identify small tumors. Existing studies have attempted to address this issue using attention-based architectures and instance selection-based methodologies but have not produced significant improvements. This paper proposes crossattention-based salient instance inference MIL (CASiiMIL), which involves a novel saliency-informed attention mechanism to identify small tumors (e.g., breast cancer lymph node micro-metastasis) on WSIs without needing any annotations. In addition to this new attention mechanism, we introduce a negative representation learning algorithm to facilitate the learning of saliencyinformed attention weights for improved sensitivity on tumor WSIs. The proposed model outperforms the state-ofthe-art MIL methods on two popular tumor metastasis detection datasets. The proposed approach demonstrates great cross-center generalizability, high accuracy in classifying WSIs with small tumor lesions, and excellent interpretability attributed to the saliency-informed attention weights. We expect that the proposed method will pave the way for training algorithms for early tumor detection on large datasets where acquiring fine-grained annotations is is not practical.

10.
Exp Ther Med ; 28(1): 283, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38800044

RESUMEN

Osteoarthritis (OA) is a disease of the joints, characterized by chronic inflammation, cartilage destruction and extracellular matrix (ECM) remodeling. Aberrant chondrocyte hypertrophy promotes cartilage destruction and OA development. Collagen X, the biomarker of chondrocyte hypertrophy, is upregulated by runt-related transcription factor 2 (Runx2), which is mediated by the bone morphogenetic protein 4 (BMP4)/Smad1 signaling pathway. BMP binding endothelial regulator (BMPER), a secreted glycoprotein, acts as an agonist of BMP4. 5,7,3',4'-tetramethoxyflavone (TMF) is a natural flavonoid derived from Murraya exotica L. Results of our previous study demonstrated that TMF exhibits chondroprotective effects against OA development through the activation of Forkhead box protein O3a (FOXO3a) expression. However, whether TMF suppresses chondrocyte hypertrophy through activation of FOXO3a expression and inhibition of BMPER/BMP4/Smad1 signaling remains unknown. Results of the present study revealed that TMF inhibited collagen X and Runx2 expression, inhibited BMPER/BMP4/Smad1 signaling, and activated FOXO3a expression; thus, protecting against chondrocyte hypertrophy and OA development. However, BMPER overexpression and FOXO3a knockdown impacted the protective effects of TMF. Thus, TMF inhibited chondrocyte hypertrophy in OA cartilage through mediating the FOXO3a/BMPER signaling pathway.

11.
Spine J ; 24(3): 417-423, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37844629

RESUMEN

BACKGROUND CONTEXT: Multilevel cervical myelopathy is a common cause of spinal cord dysfunction in adults. Surgical intervention via laminoplasty can provide satisfactory clinical outcomes by expansive decompression of the spinal cord. Traditional suture or bone graft techniques have been associated with insufficient fixation, leading to premature closure and subsequent neurological deterioration. In contrast, plated laminoplasty has been shown to provide stable fixation to maintain canal enlargement, but longer-term outcomes are lacking. PURPOSE: To evaluate longer-term clinical outcomes and reoperations associated with plate-only open-door laminoplasty. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Postoperative patients who underwent plate-only open door laminoplasty with minimum 5-year follow up. OUTCOME MEASURES: modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and 12-item Short Form Health Survey (SF-12). METHODS: All patients at a single academic institution who underwent plate-only open-door cervical laminoplasty from 9/1/2006 to 9/1/2016 were identified to ensure minimum 5 year follow up. Clinical outcomes included the modified Japanese Orthopaedic Association (mJOA) score, the Neck Disability Index (NDI), and the 12-item Short Form Health Survey (SF-12). The occurrence of any repeat operations on the cervical spine was evaluated, as well as its cause. The study team attempted to contact all eligible patients to achieve at least 5 years postoperative follow-up. Pairwise t tests were performed to compare clinical outcomes at preoperative, 6 months, 1-year, and final postoperative follow-up with an α level of 0.05. RESULTS: A total of 774 met the initial inclusion criteria, of which 157 were included in the study (20.3%). Most common reasons for exclusion included inability to reach after 3 attempts (49.48%), inactive phone numbers (20.28%), and patient declining (3.49%). Included patients had an average age of 60.66±10.63 and an average follow-up time of 8.37±2.57 years (minimum 5 years). mJOA scores (preoperative 11.59±2.16) improved significantly at 6-months (14.57±2.07, p<.001), 1-year (15.19±1.95, p<.001), and final follow-up (14.59±2.63, p<.001). NDI (preoperative 33.89±18.54) improved significantly at 6 months (27.89±19.72, p=.03), 1-year (25.96±19.79, p=.01) and final follow-up (17.88±17.17, p<.001). SF-12 MCS (preoperative 44.73) improved significantly at 6 months (52.01, p=.001), 1-year (51.62, p=.008), and final follow-up (52.32, p<.001). No patient underwent reoperations for plate failure or canal closure with recurrent stenosis. Reoperations for progressive spondylosis during the follow up period were rare and occurred in only three patients for new onset radiculopathy (1.9%) and two patients for myelopathy (1.3%) at an average of 3.2 years postoperative. There were no reoperations performed for adjacent segment disease. CONCLUSIONS: At a minimum of 5 years and an average of more than 8 years postoperative, laminoplasty was associated with significant and sustained improvements in mJOA, NDI, and SF-12 MCS. Importantly, no patients underwent revision surgery for plate failure or recurrent canal closure. Reoperations for new onset radiculopathy and myelopathy were also very rare over the 8-year average follow-up period, with no reoperations for adjacent segment disease. Plate-only laminoplasty is a durable means of treating multilevel myelopathy with excellent longer-term outcomes and a very low risk of reoperation, either for premature closure or the inevitable spondylotic changes that occur over time in patients with similar baseline characteristics to the study population.


Asunto(s)
Laminoplastia , Radiculopatía , Enfermedades de la Médula Espinal , Espondilosis , Adulto , Humanos , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Reoperación/efectos adversos , Resultado del Tratamiento , Laminoplastia/efectos adversos , Laminoplastia/métodos , Radiculopatía/cirugía , Enfermedades de la Médula Espinal/cirugía , Vértebras Cervicales/cirugía , Laminectomía/efectos adversos , Espondilosis/complicaciones , Estudios Retrospectivos
12.
Int J Surg Pathol ; 32(6): 1117-1122, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38166430

RESUMEN

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.


Asunto(s)
Biomarcadores de Tumor , Mesotelioma Maligno , Neoplasias Testiculares , Humanos , Masculino , Anciano , Neoplasias Testiculares/patología , Neoplasias Testiculares/diagnóstico , Mesotelioma Maligno/patología , Mesotelioma Maligno/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Mesotelioma/diagnóstico , Mesotelioma/patología , Testículo/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología
13.
Cancers (Basel) ; 16(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272955

RESUMEN

Lung cancer is the leading cause of cancer-related death in the United States. Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer that can be treated with resection. While resection can be curative, there is a significant risk of recurrence, which necessitates close monitoring and additional treatment planning. Traditionally, microscopic evaluation of tumor grading in resected specimens is a standard pathologic practice that informs subsequent therapy and patient management. However, this approach is labor-intensive and subject to inter-observer variability. To address the challenge of accurately predicting recurrence, we propose a deep learning-based model to predict the 5-year recurrence of LUAD in patients following surgical resection. In our model, we introduce an innovative dual-attention architecture that significantly enhances computational efficiency. Our model demonstrates excellent performance in recurrent risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69-3.09, p < 0.005), which outperforms several existing deep learning methods. This study contributes to ongoing efforts to use deep learning models for automatically learning histologic patterns from whole slide images (WSIs) and predicting LUAD recurrence risk, thereby improving the accuracy and efficiency of treatment decision making.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38756441

RESUMEN

Current deep learning methods in histopathology are limited by the small amount of available data and time consumption in labeling the data. Colorectal cancer (CRC) tumor budding quantification performed using H&E-stained slides is crucial for cancer staging and prognosis but is subject to labor-intensive annotation and human bias. Thus, acquiring a large-scale, fully annotated dataset for training a tumor budding (TB) segmentation/detection system is difficult. Here, we present a DatasetGAN-based approach that can generate essentially an unlimited number of images with TB masks from a moderate number of unlabeled images and a few annotated images. The images generated by our model closely resemble the real colon tissue on H&E-stained slides. We test the performance of this model by training a downstream segmentation model, UNet++, on the generated images and masks. Our results show that the trained UNet++ model can achieve reasonable TB segmentation performance, especially at the instance level. This study demonstrates the potential of developing an annotation-efficient segmentation model for automatic TB detection and quantification.

15.
Biomed Pharmacother ; 166: 115401, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37651799

RESUMEN

Lipid metabolism is a complex process that maintains the normal physiological function of the human body. The disorder of lipid metabolism has been implicated in various human diseases, such as cardiovascular diseases and bone diseases. Intervertebral disc degeneration (IDD), an age-related degenerative disease in the musculoskeletal system, is characterized by high morbidity, high treatment cost, and chronic recurrence. Lipid metabolism disorder may promote the pathogenesis of IDD, and the potential mechanisms are complex. Leptin, resistin, nicotinamide phosphoribosyltransferase (NAMPT), fatty acids, and cholesterol may promote the pathogenesis of IDD, while lipocalin, adiponectin, and progranulin (PGRN) exhibit protective activity against IDD development. Lipid metabolism disorder contributes to extracellular matrix (ECM) degradation, cell apoptosis, and cartilage calcification in the intervertebral discs (IVDs) by activating inflammatory responses, endoplasmic reticulum (ER) stress, and oxidative stress and inhibiting autophagy. Several lines of agents have been developed to target lipid metabolism disorder. Inhibition of lipid metabolism disorder may be an effective strategy for the therapeutic management of IDD. However, an in-depth understanding of the molecular mechanism of lipid metabolism disorder in promoting IDD development is still needed.


Asunto(s)
Degeneración del Disco Intervertebral , Trastornos del Metabolismo de los Lípidos , Humanos , Metabolismo de los Lípidos , Adiponectina , Apoptosis
16.
Huan Jing Ke Xue ; 44(6): 3619-3626, 2023 Jun 08.
Artículo en Zh | MEDLINE | ID: mdl-37309976

RESUMEN

Applying machine learning methods to resolve the cadmium (Cd) uptake characteristics of regional soil-wheat systems can contribute to the accuracy and rationality of risk decisions. Based on a regional survey, we constructed a Freundlich-type transfer equation, random forest (RF) model, and neural network (BPNN) model to predict wheat Cd enrichment factor (BCF-Cd); verified the prediction accuracy; and assessed the uncertainty of different models. The results showed that both RF (R2=0.583) and BPNN (R2=0.490) were better than the Freundlich transfer equation (R2=0.410). The RF and BPNN were further trained repeatedly, and the results showed that the mean absolute error (MAE) and root mean square error (RMSE) of RF and BPNN were close to each other. Additionally, the accuracy and stability of RF (R2=0.527-0.601) was higher than that of BPNN (R2=0.432-0.661). Feature importance analysis showed that multiple factors led to the heterogeneity of wheat BCF-Cd, in which soil phosphorus (P) and zinc (Zn) were the key variables affecting the change in wheat BCF-Cd. Parameter optimization can further improve the accuracy, stability, and generalization ability of the model.


Asunto(s)
Cadmio , Triticum , Aprendizaje Automático , Fósforo , Suelo
17.
Huan Jing Ke Xue ; 44(2): 984-990, 2023 Feb 08.
Artículo en Zh | MEDLINE | ID: mdl-36775621

RESUMEN

The interaction of zinc (Zn) and cadmium (Cd) is an important research direction in the prevention and control of Cd pollution of wheat in recent years. In this study, a typical wheat field in North China was selected as the object to explore the control effect and application risk of Zn fertilizer on Cd pollution in a soil-wheat system through field experiments. The results showed that under the treatment of a low dosage of Zn, the Cd concentrations in wheat grains in Jiyuan City and Kaifeng City decreased by 33.4% and 25.3% compared with those in the control, respectively. By contrast, Cd concentrations in wheat grains treated with a high dosage of Zn increased by 22.4% and 34.2% compared with that of the low-dosage Zn treatment. After the application of Zn, the total amount and available Zn concentrations increased significantly, and Cd was partially activated in these two locations. Canonical correlation analysis (CCA) showed that when the Zn concentrations in the soils were less than 200 mg·kg-1, soil Zn was the main factor affecting Cd accumulation in the soil-wheat system, whereas when Zn concentrations in soils were greater than 200 mg·kg-1, the activation of soil Cd was the main factor affecting Cd accumulation in wheat grains. Regression analysis showed that when the soil Cd/Zn ratio decreased to 0.0089 (low dosage of Zn), Zn and Cd showed an antagonistic effect, whereas when the soil Cd/Zn ratio decreased to 0.0078 (high dosage of Zn), Zn and Cd showed a synergistic effect. According to the characteristics of regional Cd pollution, adjusting the amount of Zn fertilizer can improve the efficiency of pollution control and avoid aggravating the harm of Cd pollution.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/análisis , Zinc , Triticum , Fertilizantes/análisis , Contaminantes del Suelo/análisis , Grano Comestible/química , Suelo
18.
Int J Surg Pathol ; : 10668969231211337, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37908107

RESUMEN

Pseudoangiomatous spindle cell lipoma is a rare pattern within the spindle cell lipoma spectrum that exhibits a remarkable histological pattern characterized by its resemblance to vascular lesions, creating a pseudoangiomatous appearance. Approximately 20 to 30 reports have been described in the literature. In this context, we present an intriguing report of pseudoangiomatous spindle cell lipoma showcasing a unique low-fat pseudo angiomatous pattern in a 61-year-old male patient presented with a 6-cm subcutaneous mass on his right arm, which was thoroughly investigated and subsequently excised. Microscopic examination revealed bland spindle cells infiltrates within a fibromyxoid stroma. Notably, the tumor exhibited distinctive branching and dilated vascular-like spaces that formed pseudopapillary (villiform) projections. Interestingly, the tumor displayed certain regions featuring mature adipose tissue components, alongside hyalinized blood vessels. No necrosis, atypical spindle cells, increased mitotic activity, or pleomorphic lipoblasts were observed. The immunohistochemical evaluation demonstrated diffuse positive staining for CD34 and negative staining for STAT6. This report of a low-fat pattern of pseudoangiomatous spindle cell lipoma underscores the importance of recognizing and characterizing rare entity subtype for accurate diagnosis and appropriate management. This report contributes to the expanding understanding of the diverse presentations of pseudo angiomatous spindle cell lipomas and underscores the significance of comprehensive histopathological assessment.

19.
PLoS One ; 18(4): e0283562, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37014891

RESUMEN

Breast cancer is the most common malignancy in women, with over 40,000 deaths annually in the United States alone. Clinicians often rely on the breast cancer recurrence score, Oncotype DX (ODX), for risk stratification of breast cancer patients, by using ODX as a guide for personalized therapy. However, ODX and similar gene assays are expensive, time-consuming, and tissue destructive. Therefore, developing an AI-based ODX prediction model that identifies patients who will benefit from chemotherapy in the same way that ODX does would give a low-cost alternative to the genomic test. To overcome this problem, we developed a deep learning framework, Breast Cancer Recurrence Network (BCR-Net), which automatically predicts ODX recurrence risk from histopathology slides. Our proposed framework has two steps. First, it intelligently samples discriminative features from whole-slide histopathology images of breast cancer patients. Then, it automatically weights all features through a multiple instance learning model to predict the recurrence score at the slide level. On a dataset of H&E and Ki67 breast cancer resection whole slides images (WSIs) from 99 anonymized patients, the proposed framework achieved an overall AUC of 0.775 (68.9% and 71.1% accuracies for low and high risk) on H&E WSIs and overall AUC of 0.811 (80.8% and 79.2% accuracies for low and high risk) on Ki67 WSIs of breast cancer patients. Our findings provide strong evidence for automatically risk-stratify patients with a high degree of confidence. Our experiments reveal that the BCR-Net outperforms the state-of-the-art WSI classification models. Moreover, BCR-Net is highly efficient with low computational needs, making it practical to deploy in limited computational settings.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Femenino , Humanos , Neoplasias de la Mama/patología , Antígeno Ki-67 , Mama/patología , Riesgo
20.
Proc (Bayl Univ Med Cent) ; 36(4): 524-527, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334098

RESUMEN

A 36-year-old pregnant woman with a prior history of depression and recent gunshot wounds presented with sudden deterioration in her mental status. Clinical examination revealed psychosis, hallucinations, and lack of orientation, with an otherwise normal neurological and cardiorespiratory examination. Computed tomographic scan of her head was normal, and she was diagnosed with acute psychosis and excited delirium. She did not respond to supraphysiologic dosages of antipsychotic therapy and needed physical restraints for combativeness and agitation. Her cerebrospinal fluid analysis was negative for an infectious etiology, but was positive for anti-N-methyl-D-aspartate receptor encephalitis antibodies. Abdominal imaging revealed a right-sided ovarian cyst. Subsequently she underwent right-sided oophorectomy. Postoperatively the patient continued to have intermittent episodes of agitation requiring antipsychotic medications. Later, she was safely transitioned to home care with family support.

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