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The uncertainty of true labels in medical images hinders diagnosis owing to the variability across professionals when applying deep learning models. We used deep learning to obtain an optimal convolutional neural network (CNN) by adequately annotating data for oral exfoliative cytology considering labels from multiple oral pathologists. Six whole-slide images were processed using QuPath for segmenting them into tiles. The images were labeled by three oral pathologists, resulting in 14,535 images with the corresponding pathologists' annotations. Data from three pathologists who provided the same diagnosis were labeled as ground truth (GT) and used for testing. We investigated six models trained using the annotations of (1) pathologist A, (2) pathologist B, (3) pathologist C, (4) GT, (5) majority voting, and (6) a probabilistic model. We divided the test by cross-validation per slide dataset and examined the classification performance of the CNN with a ResNet50 baseline. Statistical evaluation was performed repeatedly and independently using every slide 10 times as test data. For the area under the curve, three cases showed the highest values (0.861, 0.955, and 0.991) for the probabilistic model. Regarding accuracy, two cases showed the highest values (0.988 and 0.967). For the models using the pathologists and GT annotations, many slides showed very low accuracy and large variations across tests. Hence, the classifier trained with probabilistic labels provided the optimal CNN for oral exfoliative cytology considering diagnoses from multiple pathologists. These results may lead to trusted medical artificial intelligence solutions that reflect diverse diagnoses of various professionals.
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Aprendizado Profundo , Redes Neurais de Computação , Humanos , Citodiagnóstico/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , PatologistasRESUMO
Retroperitoneal sarcoma (RPS) is a rare disease. RPS invading the abdominal aorta is exceedingly rare and has a poor prognosis. There have been scattered cases of RPS treated with combined abdominal aortic replacement. However, the average survival time for these cases was only 8 months, with a 2-year survival rate of 21%, indicating a poor prognosis. In this case study, a 44-year-old man presented to our hospital complaining of abdominal pain. Multiple imaging findings suggested a retroperitoneal mass that was diagnosed as a malignant tumor. The patient underwent tumor resection with abdominal aortic replacement due to an RPS tumor invading the abdominal aorta. The histopathological grade was determined to be grade 3, the most malignant grade tumor, according to the Fédération Nationale des Centres de Lutte Contre le Cancer grading system. Postoperative chemotherapy with doxorubicin and ifosfamide was administered for five cycles. The patient has been alive for over 8 years after the operation without any recurrence. This case presents a long-term survival of RPS requiring abdominal aortic replacement.
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The aVR sign characterized by ST-segment elevation in lead aVR and diffuse ST-segment depression on the electrocardiogram indicates potential life-threatening conditions. We report the case of a 53-year-old male with a history of ascending aortic replacement for acute aortic dissection, who presented to our institution in shock. The initial electrocardiogram revealed the aVR sign, consisting of ST-segment elevation in lead aVR and ST-segment depression in leads II, III, aVF, and V3-6, leading to the initiation of salvage veno-arterial extracorporeal membrane oxygenation (ECMO) due to deteriorating hemodynamics. The aVR sign resolved shortly after ECMO initiation, and hemodynamics stabilized even with reduced ECMO flow. Subsequent coronary angiography showed no impaired coronary perfusion, whereas contrast-enhanced CT revealed severe supra-valvular stenosis due to pseudoaneurysm-induced graft kinking. The patient was then managed with emergency surgery for the pseudoaneurysm. In this report, we encountered a salvaged case of critical circulatory failure presenting with the aVR sign due to severe graft kinking caused by pseudoaneurysm formation.
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PURPOSE: Achieving a secure anastomosis and complete hemostasis is essential for surgically treating type A acute aortic dissection (TAAAD). This study assessed the clinical feasibility of "tailored stand-up collar (TSC)" technique for constructing the distal stump. METHODS: We enrolled 68 patients who underwent ascending aortic repair for TAAAD. Patients were categorized according to the technique for distal stump construction: conventional (C) group using only a felt strip (32 cases); post-aortotomy (P) group, with a Hydrofit-felt strip attached after aortotomy (18 cases), and TSC group, where a Hydrofit-felt strip attached during cooling (18 cases). Pre-operative characteristics, procedural profiles, and post-operative outcomes were evaluated. RESULTS: The pre-operative characteristics were identical among the groups. The durations of cardiopulmonary bypass, hemostasis, and surgery were significantly shorter in the P and TSC groups. The duration of open distal in the TSC group (21 min) was significantly shorter than the other two groups. Post-operative additional procedures were not required for the TSC group and their post-operative hospital stay was significantly shorter (47.1% of patients were discharged within 2 weeks). CONCLUSION: The TSC technique would be practical because of its high reproducibility in terms of ease of use, shorter anastomotic time, and secure hemostasis.
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Dissecção Aórtica , Implante de Prótese Vascular , Estudos de Viabilidade , Tempo de Internação , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Feminino , Masculino , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Fatores de Tempo , Doença Aguda , Estudos Retrospectivos , Duração da Cirurgia , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Adulto , Complicações Pós-Operatórias/etiologiaRESUMO
Hemophagocytic lymphohistiocytosis (HLH) represents a fatal immunopathology derived from excessive inflammatory reactions. In particular, lymphoma-associated hemophagocytic syndrome (LAHS) is associated with a dismal prognosis. The current study presented a challenging case of splenic LAHS. A 71-year-old man presented with fatigue and anorexia. Laboratory test results revealed anemia, thrombocytopenia, lactate dehydrogenase elevation and markedly elevated levels of ferritin (6,210 ng/ml) and soluble interleukin 2 receptor (sIL-2R; 11,328 U/ml). Abdominal computed tomography revealed marked splenomegaly, while fluorodeoxyglucose positron emission tomography revealed increased tracer uptake in the spleen. An elective splenectomy was performed, which led to the diagnosis of B-cell splenic lymphoma with transformation from indolent to aggressive lymphoma. Prior to the splenectomy, thrombocytopenia and hepatic dysfunction with rapidly progressing jaundice appeared, accompanying further elevation of ferritin (25,197 ng/ml) and sIL-2R levels (30,420 U/ml). On postoperative day 5, the patient was transferred to a tertiary care institution and corticosteroid pulse therapy was immediately initiated after establishing the diagnosis of LAHS. Liver dysfunction gradually recovered and subsequent chemotherapy resulted in complete remission with improved performance status. At eight months after the onset, the patient remains alive without any signs of residual lymphoma. Although splenic lymphoma typically manifests with low-grade lymphoma, it can transform into high-grade lymphoma associated with severe complications, such as HLH and multiple organ failure. In this case, splenectomy assisted in not only establishing the diagnosis but also in tumor cytoreduction before commencing chemotherapy. Through interdisciplinary collaboration, the patient was successfully treated by performing a timely splenectomy, followed by steroid pulse therapy and chemotherapy.
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For the practical application of fuel cells in vehicles, it is a challenge to develop a proton solid electrolyte that coexhibits thermal stability and high proton conductivity at wide intermediate temperatures. Here, we report on the tunnel structured phosphate KNi1-xH2x(PO3)3·yH2O, which exhibits high proton conductivity at room temperature up to 500 °C, with the conductivity value reaching 1.7 × 10-2 S cm-1 at 275 °C for x = 0.18. This material, composed of the smallest cations that form the tunnel framework with face-shared (KO6) and (NiO6) chains and PO4 tetrahedral chains, retained the rigid framework up to 600 °C. Two oxygen sites of water molecules located adjacent to each other along the PO4 tetrahedral chains in the tunnel provided the proton conduction pathway. The sample maintained a conductivity of 5.0 × 10-3 S cm-1 for 10 h at 150 °C while changing the measurement atmosphere to a N2 gas flow, a 4% H2-96% Ar gas flow, and an O2 gas flow. The conductivity value at x = 0.18 obtained from the DC measurement was in the order of 10-6 S cm-1, close to the instrument's measurement limit. These results demonstrate that tunnel phosphate has potential as a proton solid electrolyte for next-generation fuel cells.
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Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.
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Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by recurrent, pruritic, and localized eczema. Various types of new drugs have been recently investigated for treating AD. The efficacy and safety of abrocitinib in treating AD has been reported in clinical trials, but the real-world data from Japan has not been reported. Herein, we analyzed 12 Japanese patients with AD treated with 100 mg of abrocitinib using our real-world data. We also performed transcriptome analysis with peripheral blood to investigate the effects of abrocitinib on cytokine expressions and inflammatory pathways in AD from three patients. This study included patients with moderate to severe AD treated with abrocitinib at Gunma University Hospital, Japan. All patients were systemic treatment-naïve. All patients received a 100-mg dose of abrocitinib daily, and used strong or very strong topical steroids and moisturizers. The Eczema Area and Severity Index (EASI) response analysis revealed that after 4 weeks, 25% (three of 12) of the cases reached a 75% reduction in the EASI score (EASI-75) and a 90% reduction in the EASI score (EASI-90). After 12 weeks, 83.3.% (10 of 12), 41.6% (five of 12), and 16.7% (two of 12) of the patients reached EASI-50, a 75% reduction in the EASI score (EASI-75), and EASI-90. Peak Pruritus Numerical Rating Scale was achieved in nine patients (75%) at week 12. The most frequent adverse reaction was acne (six cases [50%]). Gene Ontology pathway analysis using Differentially expressed genes from RNA sequencing analysis revealed attenuation of defense responses to biotic stimulus, virus, and cytokines. Th2 cytokine expression was not suppressed, but several chemokines, especially CXCL1, were suppressed by abrocitinib treatment. Our results indicate abrocitinib as a fast-acting and highly antipruritic agent that is effective for moderate skin eruptions.
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Dermatite Atópica , Perfilação da Expressão Gênica , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Compostos de Boro/efeitos adversos , Compostos de Boro/uso terapêutico , Citocinas/sangue , Citocinas/metabolismo , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/genética , População do Leste Asiático , Japão , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Transcriptoma , Resultado do TratamentoRESUMO
The gene for ATP binding cassette subfamily A member 2 (ABCA2) is located at chromosome 9q34.3. Biallelic ABCA2 variants lead to intellectual developmental disorder with poor growth and with or without seizures or ataxia (IDPOGSA). In this study, we identified novel compound heterozygous ABCA2 variants (NM_001606.5:c.[5300-17C>A];[6379C>T]) by whole exome sequencing in a 28-year-old Korean female patient with intellectual disability. These variants included intronic and nonsense variants of paternal and maternal origin, respectively, and are absent from gnomAD. SpliceAI predicted that the intron variant creates a cryptic acceptor site. Reverse transcription-PCR using RNA extracted from a lymphoblastoid cell line of the patient confirmed two aberrant transcripts. Her clinical features are compatible with those of IDPOGSA.
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Deficiência Intelectual , Humanos , Feminino , Adulto , Deficiência Intelectual/genética , Mutação , Família , Síndrome , Ataxia/genéticaRESUMO
Background: Despite advances in technology, glycemic outcomes in people with type 1 diabetes (T1D) remain suboptimal. The MiniMed 780G (MM780G) advanced hybrid closed-loop (AHCL) system is the latest technology for T1D management with established safety and efficacy. This study explores the cost-effectiveness of MM780G AHCL compared against multiple daily injections (MDI) plus intermittently scanned continuous glucose monitor (isCGM). Methods: A cost-utility analysis was conducted, simulating lifetime outcomes for 1000 T1D individuals, with baseline hemoglobin A1c of 8.4%, using the IQVIA Core Diabetes Model (CDM) v9.5. A Singapore health care payer perspective was taken with 2023 costs applied. Treatment effects were taken from the ADAPT study and treatment-related events from a combination of sources. T1D complication costs were derived from local literature, and health state utilities and disutilities from published literature. Scenario analyses and probabilistic sensitivity analyses (PSAs) explored uncertainty. Cost-effectiveness was assessed based on willingness-to-pay (WTP) thresholds set to Singapore Dollars (SGD) 45,000 (United States Dollars [USD] 33,087) per quality-adjusted life year (QALY) and Singapore's gross domestic product (GDP) per capita of SGD 114,165 (USD 83,941) per QALY. Results: A switch from MDI plus isCGM to MM780G resulted in expected gains in life-years (+0.78) and QALYs (+1.45). Cost savings through reduction in T1D complications (SGD 25,465; USD 18,723) partially offset the higher treatment costs in the AHCL arm (+SGD 74,538; +USD 54,805), resulting in an estimated incremental cost-effectiveness ratio of SGD 33,797 (USD 24,850) per QALY gained. Findings were robust, with PSA outputs indicating 81% and 99% probabilities of cost-effectiveness at the stated WTP thresholds. Conclusion: MM780G is a cost-effective option for people with T1D managed in a Singapore setting.
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Automonitorização da Glicemia , Análise Custo-Benefício , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 1/sangue , Singapura , Hipoglicemiantes/economia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina/economia , Masculino , Feminino , Automonitorização da Glicemia/economia , Insulina/administração & dosagem , Insulina/economia , Insulina/uso terapêutico , Adulto , Glicemia/análise , Hemoglobinas Glicadas/análise , Pessoa de Meia-IdadeRESUMO
Ischemia-reperfusion (I/R) injury is a key player in the pathogeneses of pressure ulcer formation. Our previous work demonstrated that inducing the transcription factor SOX2 promotes cutaneous wound healing through EGFR signaling pathway enhancement. However, its protective effect on cutaneous I/R injury was not well-characterized. We aimed to assess the role of SOX2 in cutaneous I/R injury and the tissue-protective effect of SOX2 induction in keratinocytes (KCs) in cutaneous I/R injury. SOX2 was transiently expressed in KCs after cutaneous I/R injury. Ulcer formation was significantly suppressed in KC-specific SOX2-overexpressing mice. SOX2 in skin KCs significantly suppressed the infiltrating inflammatory cells, apoptotic cells, vascular damage, and hypoxic areas in cutaneous I/R injury. Oxidative stress-induced mRNA levels of inflammatory cytokine expression were suppressed, and antioxidant stress factors and amphiregulin were elevated by SOX2 induction in skin KCs. Recombinant amphiregulin administration suppressed pressure ulcer development after cutaneous I/R injury in mice and suppressed oxidative stress-induced ROS production and apoptosis in vitro. These findings support that SOX2 in KCs might regulate cutaneous I/R injury through amphiregulin production, resulting in oxidative stress suppression. Recombinant amphiregulin can be a potential therapeutic agent for cutaneous I/R injury.
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Úlcera por Pressão , Traumatismo por Reperfusão , Animais , Camundongos , Anfirregulina/genética , Anfirregulina/metabolismo , Apoptose , Queratinócitos/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Pele/metabolismoRESUMO
A 38-year-old male, he was diagnosed with a giant pulmonary bulla occupying 2/3 of the right thoracic cavity on chest computed tomography( CT). The preoperative pulmonary function was unfavorable, so bullectomy of right upper lobe with video-assisted thoracoscopic surgery( VATS) was performed. The outpatient follow-up was completed at 6 months after surgery. However, one year and eleven months postoperatively, the patient returned to the clinic complaining of dyspnea. Chest X-ray and CT showed a recurrence of a giant emphysematous bulla in the right upper lobe. Two years and three months after the initial surgery, the recurrent giant bulla was resected by right upper lobectomy with VATS. About four years after the reoperation, no recurrence of giant pulmonary bulla has been seen. Although there are some reports on surgical treatment and results of giant pulmonary bulla, there are few reports on recurrent cases, so we report this case.
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Pneumopatias , Enfisema Pulmonar , Masculino , Humanos , Adulto , Vesícula/diagnóstico por imagem , Vesícula/cirurgia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Pulmão/cirurgiaRESUMO
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-ß (TGF-ß) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-ß inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-ß has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H2O2) and examined the effects of three TGF-ß inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-ß inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-ß inhibitors. In our present study, TGF-ß inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-ß inhibitor.
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Cistite Intersticial , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Cistite Intersticial/tratamento farmacológico , Cistite Intersticial/patologia , Fibrose , Peróxido de Hidrogênio/efeitos adversos , Fator de Crescimento Transformador beta/antagonistas & inibidores , Modelos Animais de DoençasRESUMO
Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.
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Ácidos Nucleicos Livres , Telomerase , Neoplasias da Bexiga Urinária , Humanos , Regiões Promotoras Genéticas , Detecção Precoce de Câncer , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Mutação , Telomerase/genética , Biomarcadores Tumorais/genéticaRESUMO
Although recent clinical trials of new therapeutic agents for metastatic urothelial carcinoma have shown prolonged overall survival, there are few real-world evidence. To assess the impact of new therapeutic agents, we performed retrospective analysis for consecutive 158 metastatic urothelial carcinoma patients who performed systemic therapy in our institution between May 2008 and August 2023. We defined a period from May 2008 to December 2017, when pembrolizumab was first introduced to the clinical setting in the new therapeutic agents for metastatic urothelial carcinoma in Japan, as "pre new drug era" and a period from January 2018 to August 2023 as "post new drug era". We compared overall survival between pre- and post- new drug era using Kaplan-Meier method with log rank test. Median overall survival of pre- and post- new drug era were 14.5 months (95% confidence intervals: 11.6-16.7) and 23.1 months (95% confidence intervals: 14.5-NA), respectively (p < 0.001). Five-year survival rate of pre- and post- new drug era was 7.0% (95% confidence intervals: 2.3-15.3) and 36.3% (95% confidence intervals: 21.4-51.5), respectively. Multivariable Cox proportional hazards regression analysis of factors associated with overall survival showed that enfortumab vedotin administration, administration of second-line or more systemic therapy, best overall response of SD, PR and CR in first-line systemic therapy, higher serum albumin and lower CRP were factors for overall survival prolongation. Introduction of new therapeutic agents for metastatic urothelial carcinoma contributed to the improvement of overall survival in comparison with the era without these agents.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , JapãoRESUMO
BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown. OBJECTIVE: To investigate the role of TRPV4 in cutaneous wound healing in a mouse model. METHODS: Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro. RESULTS: TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-ß stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts. CONCLUSION: TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.
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Canais de Cátion TRPV , Cicatrização , Animais , Camundongos , Movimento Celular/genética , Movimento Celular/fisiologia , Colágeno/metabolismo , Modelos Animais de Doenças , Fibroblastos/metabolismo , Queratinócitos/metabolismo , RNA Mensageiro/metabolismo , Pele/patologia , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Cicatrização/genética , Cicatrização/fisiologiaRESUMO
BACKGROUND: Atopic dermatitis is a common skin disease caused by genetic susceptibility, environmental factors, immune response, and skin barrier dysfunction. Kaempferol is a natural flavonoid widely found in tea, vegetables, and fruits and has been reported to have excellent anti-inflammation activity. However, the therapeutic effect of kaempferol on atopic dermatitis is unclear. OBJECTIVE: This study aimed to elucidate the effect of kaempferol on skin inflammation in atopic dermatitis. METHODS: The suppressive effect of kaempferol administration on skin inflammation was examined using MC903-induced atopic dermatitis-like skin inflammation mouse model. Quantification of skin dermatitis and transepidermal water loss was performed. A histopathological study was performed to examine thymic stromal lymphopoietin expression, cornified envelope proteins such as filaggrin, loricrin, and involucrin, and the numbers of infiltrating inflammatory cells, including lymphocytes, macrophages, and mast cells in the dermatitis area. The expressions of IL-4 and IL-13 were investigated by qPCR and flow cytometry analysis using skin tissues. The expression of HO-1 was investigated by western blot and qPCR. RESULTS: Kaempferol therapy significantly suppressed MC903-induced dermatitis, TEWL, TSLP, and HO-1 expression, and infiltration of inflammatory cells. Kaempferol therapy improved the decreased expressions of filaggrin, loricrin, and involucrin in MC903-induced dermatitis skin site. The expressions of IL-4, and IL-13 were partially decreased in kaempferol-treated mice. CONCLUSION: Kaempferol might improve MC903-induced dermatitis via suppression of type 2 inflammation and improvement of barrier dysfunction by inhibition of TSLP expression and oxidative stress. Kaempferol might have the potential to be a new treatment for atopic dermatitis.
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Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Proteínas Filagrinas , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Citocinas/metabolismo , Pele/patologia , Inflamação/metabolismo , Estresse OxidativoRESUMO
The study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis.
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Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Patologistas , Neoplasias Bucais/diagnósticoRESUMO
PURPOSE: Children with undescended testes (UDTs) undergoing orchiopexy at a later age reportedly experience more negative effects on post-orchiopexy testicular volume (TV). This study aimed to investigate the effect of orchiopexy according to the age at operation. METHODS: We included 93 patients (127 testes) who underwent orchiopexy between 2008 and 2020. According to their age at orchiopexy, they were divided into Group 1 (< 24 months; n = 36, median follow-up: 17 [14-39] months) and Group 2 (≥ 24 months; n = 57, median follow-up: 16 [13-34] months). TV was measured with ultrasonography preoperatively and postoperatively. In unilateral UDTs, the testicular volume rates (TVR) were calculated as diseased-side TV/intact-side TV × 100%. A TVR < 50% indicated preoperative testicular atrophy (pre-op TA), whereas volume loss ≥ 50% from baseline indicated postoperative testicular atrophy (post-op TA). RESULTS: Only seven patients experienced pre-op TA. The TV of these 14 atrophic testes improved after orchiopexy (TVR: 100% (7/7) in Group 1 and 85% (6/7) in Group 2). Furthermore, the median TVR significantly improved after orchiectomy, from 27 to 58% (p < 0.01) and from 32 to 61% in Groups 1 and 2 (p < 0.05), respectively. Post-op TA was found in four testes (8%) in Group 1 and three testes (4%) in Group 2. Multivariate analysis showed that only preoperative testicular location predicted post-op TA. CONCLUSION: Post-orchiopexy TA may occur regardless of the patient's age at orchiopexy, and orchiopexy is recommended irrespective of age at diagnosis.