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1.
J Educ Health Promot ; 13: 268, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39310018

RESUMEN

INTRODUCTION: Dental education assumes an indispensable role in adequately equipping students for a successful career in dentistry. Error-based active learning, an innovative approach in dental education, is a combination of mistake-driven learning (MDL) and case-based learning (CBL) to provide a transformative learning atmosphere for students. While active learning has gained popularity in dental education, the effectiveness of error-based active learning remains unexplored. This study aims to evaluate the effectiveness of error-based active learning among final-year dental undergraduate students in comparison with the conventional lecture-based approach. MATERIALS AND METHODS: A parallel-arm single-blind randomized controlled trial was conducted in a dental institute in India from November 2022 to December 2022. A total of 74 students were randomly allocated to two groups: Group A (n = 37) received error-based active learning and group B (n = 37) received conventional lecture-based learning approach. Atraumatic restorative treatment (ART) was chosen as the topic for the study. The knowledge of students was assessed at three intervals: baseline, post-intervention, and 4 weeks after the intervention, using a self-designed and validated questionnaire with Cronbach's alpha of 0.87 and a content validity ratio of 0.84. A standard survey questionnaire was employed to evaluate students' perceptions of the teaching methods. RESULTS: Error-based active learning group outperformed the lecture-based group significantly in the post-intervention test (20.92 ± 1.42 vs 16.97 ± 3.06), with better knowledge retention (18.30 ± 2.02 vs 14.05 ± 4.26) and positive feedback from the students. CONCLUSIONS: The error-based active learning approach proved superior to the conventional lecture-based method in enhancing and retaining knowledge regarding ART.

2.
Hum Pathol ; 153: 105667, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39305965

RESUMEN

Pure intertubular seminoma (PITS) of the testis is described as the presence of seminoma cells within the interstitium of testis without any evidence of diffuse growth pattern or mass lesion of classical seminoma. These tumors are clinically and grossly inconspicuous and are diagnosed incidentally or during investigations for testicular pain, infertility or other symptoms. Rarely metastasis is the first presentation. Microscopic identification can be difficult and poses a diagnostic challenge in the absence of a mass lesion. Seminomas with exclusive intertubular growth patterns were gathered in an international cohort. Diagnoses were confirmed by fellowship-trained or specialized urologic pathologists. Cases with the presence of a classical diffuse or nested pattern of seminoma or any other germ cell tumor component were excluded. The patient's age, tumor characteristics and additional clinicopathologic features were recorded and analyzed. 15 patients of pure intertubular seminoma (PITS) were collated. The mean age of presentation was 29 years. Patients presented with variable symptoms, including undescended testis (26%, n = 4/15), testicular heaviness/pain (20%, n = 3/15) infertility (20%, n = 3/15) and metastasis (6%, n = 1/15); presentation was unknown in 4 patients. Of note, none of the patients presented because of testicular mass. Serum markers were within normal limits in most patients (93%, n = 14/15) with available data. No tumors were identified macroscopically; however, an ill-defined, grey-white, firm area was noted in one orchiectomy specimen. Microscopically, tumor cells were seen in intertubular spaces as dispersed individual cells or small clusters. Tumor cells were round to polygonal with large nuclei and prominent nucleoli. Mild to moderate lymphocytic infiltrates were seen admixed with tumor cells in 40% (n = 6/15) of the tumors. GCNIS was present in association with most PITS (73%, n = 11/15). Tubular atrophy with thickening of the basement membrane and Leydig cell hyperplasia was observed in one tumor. Thirty-three percent (n = 5/15) of the tumors showed pagetoid involvement of rete testis, including the tumor with metastasis. All tumors showed the classical immunohistochemical profile of seminoma, with PLAP, c-KIT, OCT3/4, D2-40 and SALL4 positivity. PITS can be clinically & pathologically inconspicuous, difficult to stage and liable to be misdiagnosed especially if presented with metastasis. Despite the inconspicuousness, PITS may represent an aggressive growth pattern of seminoma with the propensity for rete testis invasion.

3.
Virchows Arch ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287823

RESUMEN

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.

4.
Am J Clin Pathol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136261

RESUMEN

OBJECTIVES: This review summarizes the current and potential uses of artificial intelligence (AI) in the current state of clinical microbiology with a focus on replacement of labor-intensive tasks. METHODS: A search was conducted on PubMed using the key terms clinical microbiology and artificial intelligence. Studies were reviewed for relevance to clinical microbiology, current diagnostic techniques, and potential advantages of AI in routine microbiology workflows. RESULTS: Numerous studies highlight potential labor, as well as diagnostic accuracy, benefits to the implementation of AI for slide-based and macroscopic digital image analyses. These range from Gram stain interpretation to categorization and quantitation of culture growth. CONCLUSIONS: Artificial intelligence applications in clinical microbiology significantly enhance diagnostic accuracy and efficiency, offering promising solutions to labor-intensive tasks and staffing shortages. More research efforts and US Food and Drug Administration clearance are still required to fully incorporate these AI applications into routine clinical laboratory practices.

6.
Indian J Pharmacol ; 56(3): 178-185, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-39078181

RESUMEN

OBJECTIVE: In the present study, the effect of sildenafil on the pharmacokinetics of metformin was studied in experimental rats, and we also postulated the molecular mechanism by performing molecular docking studies. MATERIALS AND METHODS: Analysis of metformin and sildenafil (SIL) from rat plasma was done by high performance liquid chromatography. Optimum chromatographic separation and quantification of MET, SIL and Cetirizine was achieved on Phenomenex EVO C18 column with triethyl amine (0.3%): Methanol: Acetonitrile (70:05:25 v/v) as mobile phase maintaining flow rate of 1 ml/min, the detector was tuned at 224 nm. The extraction of MET and sildenafil from rat plasma was achieved by solid-phase extraction using Strata-X cartridges. The method was validated as per the ICH guidelines. For docking studies, the crystal structure of organic cation transporter 1 (OCT1) protein and multidrug and toxin extrusion (MATE) protein (5XJJ) were downloaded from the PubChem database. The docking study was performed by PyRx virtual screening software, and the results were analyzed by BIOVIA Discovery Studio. RESULTS: The validation of HPLC method was done, intraday and interday precision study of HPLC method demonstrated %RSD values less than 5%, the extraction recovery for MET and SIL were near to 80 % for low, medium and high QC samples. The plasma stability of MET and SIL showed % RSD values <10% for low, medium, and high QC samples. A sensitivity study for MET and SIL in rat plasma suggested a lower limit of quantification values of 8 and 10 ng/mL, respectively. The pharmacokinetic parameters were recorded, Cmax of experimental and control rats was 611.2 and 913.2 ng/mL; t1/2 1.66 and 1.98, AUC (0-t) 1637.5 and 2727.24, AUC (0-∞) 1832.38 and 2995.24 for MET. The results suggested that the Cmax of MET in experimental rats (MET + SIL) was 33.07% lower than the control (MET only) and also the t1/2 was 0.32 h shorter. Docking analysis suggested a higher binding affinity of sildenafil with MATE protein (5XJJ) compared to OCT1, suggesting possible involvement of MATE family proteins for pharmacokinetic alterations of MET. CONCLUSIONS: The HPLC and solid-phase extraction method were developed and applied successfully for the pharmacokinetics of MET and SIL. Intake of SIL altered the pharmacokinetics of MET in rats. Molecular docking studies suggested the involvement of MATE family proteins for alterations of MET pharmacokinetics.


Asunto(s)
Metformina , Simulación del Acoplamiento Molecular , Citrato de Sildenafil , Animales , Citrato de Sildenafil/farmacocinética , Metformina/farmacocinética , Ratas , Masculino , Cromatografía Líquida de Alta Presión/métodos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/química , Interacciones Farmacológicas , Ratas Wistar
7.
J Oral Biol Craniofac Res ; 14(5): 522-529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055999

RESUMEN

Objectives: Achyranthes aspera (Apamarga) and Trachyspermum ammi (Ajwain) have been used in many clinical conditions, and it displays valuable properties as an alternative to Chlorhexidine (CHX) in the management of gingivitis. Therefore, this study aims to assess the effect of Achyranthes aspera and Trachyspermum ammi (AA + TA) based herbal mouthwash, 0.2 % CHX, and placebo mouthwash on gingival health, plaque control and antibacterial activity against specific periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia) using quantitative real-time PCR (RT-PCR). Methods: This was a randomized controlled non-inferiority trial involving 108 children with plaque-induced gingivitis who were randomly assigned to three groups of 36 children each: Group A, AA + TA mouthwash; Group B, CHX mouthwash; and Group C, placebo mouthwash. Gingival index and plaque index were recorded at baseline, 7th and 21st day. RT-PCR was employed to determine the bacterial counts of each plaque sample at baseline and after 21 days. Results: All three groups exhibited a gradual and significant reduction in both gingival and plaque scores from baseline to days 7 and 21. However, the placebo group did not demonstrate a significant difference in scores between days 7 and 21. Furthermore, a significant reduction in bacterial counts of P. gingivalis and T. forsythia was observed in the groups receiving CHX and AA + TA mouthwash after 21 days of intervention compared to the placebo group. Conclusion: AA + TA mouthwash demonstrated non-inferiority in anti-gingivitis and anti-plaque properties compared to CHX, suggesting its potential suitability as an alternative to CHX when used in conjunction with mechanical plaque control measures.

8.
Nature ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866050

RESUMEN

Computational pathology1,2 has witnessed considerable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders3,4. However, despite the explosive growth of generative artificial intelligence (AI), there have been few studies on building general-purpose multimodal AI assistants and copilots5 tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We built PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and fine-tuning the whole system on over 456,000 diverse visual-language instructions consisting of 999,202 question and answer turns. We compare PathChat with several multimodal vision-language AI assistants and GPT-4V, which powers the commercially available multimodal general-purpose AI assistant ChatGPT-4 (ref. 6). PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases with diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive vision-language AI copilot that can flexibly handle both visual and natural language inputs, PathChat may potentially find impactful applications in pathology education, research and human-in-the-loop clinical decision-making.

9.
Cells ; 13(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38920635

RESUMEN

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).


Asunto(s)
Reprogramación Celular , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/patología , Masculino , Reprogramación Celular/genética , Animales
10.
Front Chem ; 12: 1394191, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882214

RESUMEN

This review provides a comprehensive overview of the production and modification of CZTS nanoparticles (NPs) and their application in electrocatalysis for water splitting. Various aspects, including surface modification, heterostructure design with carbon nanostructured materials, and tunable electrocatalytic studies, are discussed. A key focus is the synthesis of small CZTS nanoparticles with tunable reactivity, emphasizing the sonochemical method's role in their formation. Despite CZTS's affordability, it often exhibits poor hydrogen evolution reaction (HER) behavior. Carbon materials like graphene, carbon nanotubes, and C60 are highlighted for their ability to enhance electrocatalytic activity due to their unique properties. The review also discusses the amine functionalization of graphene oxide/CZTS composites, which enhances overall water splitting performance. Doping with non-noble metals such as Fe, Co., and Ni is presented as an effective strategy to improve catalytic activity. Additionally, the synthesis of heterostructures consisting of CZTS nanoparticles attached to MoS2-reduced graphene oxide (rGO) hybrids is explored, showing enhanced HER activity compared to pure CZTS and MoS2. The growing demand for energy and the need for efficient renewable energy sources, particularly hydrogen generation, are driving research in this field. The review aims to demonstrate the potential of CZTS-based electrocatalysts for high-performance and cost-effective hydrogen generation with low environmental impact. Vacuum-based and non-vacuum-based methods for fabricating CZTS are discussed, with a focus on simplicity and efficiency. Future developments in CZTS-based electrocatalysts include enhancing activity and stability, improving charge transfer mechanisms, ensuring cost-effectiveness and scalability, increasing durability, integrating with renewable energy sources, and gaining deeper insight into reaction processes. Overall, CZTS-based electrocatalysts show great promise for sustainable hydrogen generation, with ongoing research focused on improving performance and advancing their practical applications.

11.
J Am Soc Cytopathol ; 13(5): 319-328, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38744615

RESUMEN

INTRODUCTION: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force. MATERIALS AND METHODS: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed. RESULTS: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice. CONCLUSIONS: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed.


Asunto(s)
Inteligencia Artificial , Citodiagnóstico , Humanos , Encuestas y Cuestionarios , Citodiagnóstico/métodos , Sociedades Médicas , Comités Consultivos , Estados Unidos , Interpretación de Imagen Asistida por Computador/métodos , Patología Quirúrgica/métodos , Citología
12.
Pathology ; 56(5): 633-642, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38719771

RESUMEN

Prostate and breast cancer incidence rates have been on the rise in Japan, emphasising the need for precise histopathological diagnosis to determine patient prognosis and guide treatment decisions. However, existing diagnostic methods face numerous challenges and are susceptible to inconsistencies between observers. To tackle these issues, artificial intelligence (AI) algorithms have been developed to aid in the diagnosis of prostate and breast cancer. This study focuses on validating the performance of two such algorithms, Galen Prostate and Galen Breast, in a Japanese cohort, with a particular focus on the grading accuracy and the ability to differentiate between invasive and non-invasive tumours. The research entailed a retrospective examination of 100 consecutive prostate and 100 consecutive breast biopsy cases obtained from a Japanese institution. Our findings demonstrated that the AI algorithms showed accurate cancer detection, with AUCs of 0.969 and 0.997 for the Galen Prostate and Galen Breast, respectively. The Galen Prostate was able to detect a higher Gleason score in four adenocarcinoma cases and detect a previously unreported cancer. The two algorithms successfully identified relevant pathological features, such as perineural invasions and lymphovascular invasions. Although further improvements are required to accurately differentiate rare cancer subtypes, these findings highlight the potential of these algorithms to enhance the precision and efficiency of prostate and breast cancer diagnosis in Japan. Furthermore, this validation paves the way for broader adoption of these algorithms as decision support tools within the Asian population.


Asunto(s)
Algoritmos , Inteligencia Artificial , Neoplasias de la Mama , Clasificación del Tumor , Neoplasias de la Próstata , Humanos , Estudios Retrospectivos , Masculino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Femenino , Japón , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Estudios de Cohortes , Pueblos del Este de Asia
13.
Cell ; 187(10): 2502-2520.e17, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38729110

RESUMEN

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.


Asunto(s)
Imagenología Tridimensional , Neoplasias de la Próstata , Aprendizaje Automático Supervisado , Humanos , Masculino , Aprendizaje Profundo , Imagenología Tridimensional/métodos , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Microtomografía por Rayos X/métodos
14.
J Prev Med Hyg ; 65(1): E65-E72, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38706762

RESUMEN

Background: Occupation significantly influences oral health, with factors like the work environment, stress levels, access to dental care, and job-related habits playing crucial roles. The oral health of construction workers, especially migrant workers, is a noteworthy concern. Understanding the oral health of this population is crucial for enhancing their quality of life through various means. This study aimed to investigate the prevalence of dental caries, oral hygiene status, and deleterious habits in this occupational group of Belagavi district, Karnataka. Materials and methods: Study design was cross-sectional in nature. Before commencement of the study a pilot study was conducted. Multi-stage random sampling technique was employed, and 610 participants were recruited for the study. Trained and calibrated examiners recorded WHO dentition status and treatment needs (2013) and Oral Hygiene Index Simplified (OHI-S). Collected data was analyzed using descriptive analysis, chi-square, one-way ANOVA, and multiple linear regression analysis. Results: The prevalence of dental caries among construction workers was significantly high (81%), and poor oral hygiene was observed among 36.9% of them. The prevalence of smoking, the tobacco chewing habit, and alcohol consumption among the construction workers was found to be 21.6%, 59.9%, and 37.3%, respectively. The dependence of OHI-S and DMFT on predictors (age, gender and deleterious habits) was found to be 21.5% and 39.6%, respectively. Conclusions: Migrant construction workers in Belagavi had a high caries prevalence, poor oral hygiene status, and a high prevalence of deleterious habits such as tobacco use. These results emphasize the necessity of awareness and dental health education programs to improve the oral health of construction workers.


Asunto(s)
Industria de la Construcción , Caries Dental , Higiene Bucal , Migrantes , Humanos , India/epidemiología , Caries Dental/epidemiología , Estudios Transversales , Masculino , Adulto , Migrantes/estadística & datos numéricos , Prevalencia , Femenino , Persona de Mediana Edad , Consumo de Bebidas Alcohólicas/epidemiología , Fumar/epidemiología , Adulto Joven , Salud Bucal , Proyectos Piloto , Índice de Higiene Oral , Índice CPO
15.
Appl Immunohistochem Mol Morphol ; 32(6): 255-263, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38725126

RESUMEN

Programmed cell death receptor 1/Programmed cell death ligand 1 (PD-L1) checkpoint pathway is responsible for the control of immune cell responses. Immunotherapy using checkpoint inhibitors, such as anti-PD-L1 therapy, aids disease management and potentiates clinical outcomes. This study aimed to analyze the performance of the Leica Biosystems (LBS) USA FDA class I in vitro diagnostic monoclonal antibody (clone 73-10) to detect PD-L1 expression in breast, colorectal, and hepatocellular carcinomas compared with the class III FDA-approved PD-L1 detecting antibodies [SP263 (Ventana), 22C3 (Dako), and 28-8 (Dako)] using 208 unique tissue microarray-based cases for each tumor type. The interassay concordances between LBS 73-10 clone and other PD-L1 antibodies ranged from 0.59 to 0.95 Cohen kappa coefficient (K) and from 0.66 to 0.90 (K) for cutoff values of 1% and 50% tumor proportion score (TPS), respectively. The 73-10 clones showed inter-pathologist agreements ranging from 0.53 to 1.0 (K) and 0.34 to 0.94 (K) for cutoff values of 1% and 50% TPS, respectively. For the immune cell proportion score (IPS) using a cutoff of 1%, the Kappa coefficient of interassay concordances and inter-pathologist agreements ranged from 0.34 to 0.94. The 73-10 clone assay's sensitivity ranged from 78.3% to 100% (TPS ≥1%), 100% (TPS ≥50%), and 77.4% to 93.5% (IPS ≥1%), while its specificity was 97.9% to 100% (TPS ≥1%), 99.5% to 99.8% (TPS ≥50%), and 97.9% to 100% (IPS ≥1%). This exploratory evaluation of LBS 73-10 monoclonal antibody on a large set of breast, colorectal, and hepatocellular carcinomas showed the assay's technical performance is comparable to the FDA-approved companion/complementary diagnostics PD-L1 detection assays.


Asunto(s)
Anticuerpos Monoclonales , Antígeno B7-H1 , Neoplasias de la Mama , Carcinoma Hepatocelular , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/inmunología , Anticuerpos Monoclonales/inmunología , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Inmunohistoquímica/métodos , Masculino , Biomarcadores de Tumor/metabolismo
16.
Sci Rep ; 14(1): 10876, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740810

RESUMEN

The Himalayas are highly susceptible to various natural disasters, such as the tectonically induced land deformation, earthquakes, landslides, and extreme climatic events. Recently, the Joshimath town witnessed a significantly large land subsidence activity. The phenomenon resulted in the development of large cracks in roads and in over 868 civil structures, posing a significant risk to inhabitants and infrastructure of the area. This study uses a time-series synthetic aperture radar (SAR) interferometry-based PSInSAR approach to monitor land deformation utilizing multi-temporal Sentinel-1 datasets. The line of sight (LOS) land deformation velocity for the Joshimath region, calculated for the year 2022-2023 using a PSInSAR-based approach, varies from - 89.326 to + 94.46 mm/year. The + ve sign indicates the LOS velocity/displacement away from the SAR sensor, whereas - ve sign signifies the earth's movement towards the SAR sensor in the direction of LOS. In addition, the study investigates feature tracking land displacement analysis using multi-temporal high-resolution Planet datasets. The result of this analysis is consistent with the PSInSAR results. The study also estimated the land deformation for the periods 2016-2017, 2018-2019, and 2020-2021 separately. Our results show that the Joshimath region experienced the highest land deformation during the year 2022-2023. During this period, the maximum land subsidence was observed in the north-western part of the town. The maximum LOS land deformation velocity + 60.45 mm/year to + 94.46 mm/year (2022-2023), occurred around Singhdwar, whereas the north and central region of the Joshimath town experienced moderate to high subsidence of the order of + 10.45 mm/year to + 60.45 mm/year (2022-2023), whereas the south-west part experienced an expansion of the order of 84.65 mm/year to - 13.13 mm/year (2022-2023). Towards the south-east, the town experienced rapid land subsidence, - 13.13 mm/year to - 5 mm/year (2022-2023). The study analyzes the causative factors of the observed land deformation in the region. Furthermore, this work assesses the ground conditions of the Joshimath region using UAV datasets acquired in the most critically affected areas such as Singhdhaar, Hotel Mountain View, Malhari Hotel, and Manoharbagh. Finally, the study provides recommendations and future prospects for the development policies that need to be adopted in the critical Himalayan regions susceptible to land deformation. The study suggests that land deformation in the region is primarily attributed to uncontrolled anthropogenic activities, infrastructural development, along with inadequate drainage systems.

17.
J Dent Educ ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693655

RESUMEN

BACKGROUND: Dental education in India predominantly relies on traditional lecture-based learning (LBL), which may hinder student engagement and learning outcomes. To address these limitations, innovative learning methodologies, such as spaced repetition learning (SRL), are imperative. SRL prioritizes active recall and can enhance long-term knowledge retention. This study aims to assess the effectiveness of SRL delivered through a mobile flashcard application, in enhancing knowledge retention among dental undergraduates. METHODS: This single-blind randomized controlled trial (CTRI/2023/10/059347), conducted in Belagavi, India, involved 90 dental students who were equally distributed into control (LBL) and test (lecture followed by SRL demonstration) groups after randomization. Rigorous expert review ensured the quality of PowerPoint presentation and mobile flashcard contents. Knowledge assessments were conducted at baseline, first, and third months using a validated and reliable questionnaire. A perception survey on learning techniques was administered after the first month. Analysis methods included descriptive analysis, Pearson's chi-square test, independent t-test, and repeated measures ANOVA with Bonferroni's post hoc test. RESULTS: The pre- and post-intervention knowledge showed no significant differences, but the SRL group exhibited significantly higher retention at both first month (p ≤ 0.001) and third months (p ≤ 0.001) than the LBL group. Repeated measures ANOVA revealed significant pairwise differences in mean knowledge scores in SRL group. Students had significantly favorable perception toward SRL than LBL group. CONCLUSION: SRL delivered through mobile flashcards significantly enhances knowledge retention compared to LBL among dental students. Positive student perceptions support SRL's integration into dental curricula, with implications for improving knowledge retention among them.

18.
Eur Urol ; 86(2): 114-127, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38670879

RESUMEN

BACKGROUND AND OBJECTIVE: TP53 loss-of-function (TP53LOF) mutations might be a driver of poor prognosis and chemoresistance in both human papillomavirus (HPV)-independent (HPV-) and HPV-associated (HPV+) penile squamous cell carcinoma (PSCC). Here, we aim to describe transcriptomic differences in the PSCC microenvironment stratified by TP53LOF and HPV status. METHODS: We used single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing to obtain a comprehensive atlas of the cellular architecture of PSCC. TP53LOF and HPV status were determined by targeted next-generation sequencing and sequencing HPV-DNA reads. Six HPV+ TP53 wild type (WT), six HPV- TP53WT, and four TP53LOF PSCC samples and six controls were included. Immunohistochemistry and hematoxylin-eosin confirmed the morphological context of the observed signatures. Prognostic differences between patient groups were validated in 541 PSCC patients using Kaplan-Meier survival estimates. KEY FINDINGS AND LIMITATIONS: Patients with aberrant p53 staining fare much worse than patients with either HPV- or HPV+ tumors and WT p53 expression. Using scRNA-seq, we revealed 65 cell subtypes within 83 682 cells. TP53LOF tumors exhibit a partial epithelial-to-mesenchymal transition, immune-excluded, angiogenic, and morphologically invasive environment, underlying their aggressive phenotype. HPV- TP53WT tumors show stemness and immune exhaustion. HPV+ TP53WT tumors mirror normal epithelial maturation with upregulation of antibody-drug-conjugate targets and activation of innate immunity. Inherent to the scRNA-seq analysis, low sample size is a limitation and validation of signatures in large PSCC cohorts is needed. CONCLUSIONS AND CLINICAL IMPLICATIONS: This first scRNA-seq atlas offers unprecedented in-depth insights into PSCC biology underlying prognostic differences based on TP53 and HPV status. Our findings provide clues for testing novel biomarker-driven therapies in PSCC. PATIENT SUMMARY: Here, we analyzed tissues of penile cancer at the level of individual cells, which helps us understand why patients who harbor a deactivating mutation in the TP53 gene do much worse than patients lacking such a mutation. Such an analysis may help us tailor future therapies based on TP53 gene mutations and human papillomavirus status of these tumors.


Asunto(s)
Mutación , Infecciones por Papillomavirus , Neoplasias del Pene , Fenotipo , Análisis de la Célula Individual , Proteína p53 Supresora de Tumor , Humanos , Masculino , Neoplasias del Pene/genética , Neoplasias del Pene/virología , Neoplasias del Pene/patología , Proteína p53 Supresora de Tumor/genética , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/patología , Medicina de Precisión , Persona de Mediana Edad , Papillomaviridae/genética , Pronóstico , Microambiente Tumoral/genética , Anciano , Virus del Papiloma Humano
19.
Cureus ; 16(3): e56304, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38629023

RESUMEN

Aim and objectives To assess oral hygiene status and salivary and microbiological parameters among 12 to 15-year-old visually impaired and normal-sighted children before and after oral health education (OHE). Methodology An interventional study was conducted among 25 visually impaired children (Group A) and 25 normal-sighted children (Group B) in the age range of 12 to 15 years. Simple random sampling was used to select the study participants. A questionnaire was designed to record socio-demographic data and the dietary habits of the children on pre-decided days. The oral hygiene practices and the Decayed Missing Filled Teeth (DMFT) index were recorded, and salivary physicochemical parameters for all the selected children were evaluated, followed by saliva collection for microbial analysis. After baseline assessment, the Audio-Tactile Performance technique for Group A and the animated visual performance technique for Group B children were used to impart OHE. Periodic assessments of salivary parameters were conducted at one-month and three-month intervals. Unpaired T test/Mann-Whitney U test, repeated measures analysis of variance (ANOVA)/Friedman test, followed by Bonferroni's post hoc test were carried out to determine the difference between and within groups, respectively. All statistical tests were performed at a significance level of 5%. Results Group A demonstrated a greater change in salivary pH (6.20 ± 0.41 to 6.96 ± 0.20), salivary buffering capacity (5.80 ± 0.82 to 7.20 ± 0.65), and Streptococcus mutans count (9.36 ± 0.41 to 8.7 ± 0.45 x 104 CFU/mL) when compared to Group B. Group B demonstrated a greater Lactobacillus acidophilus count reduction (7.96 ± 0.66 to 7.50 ± 0.64 x 104 CFU/mL) when compared to Group A. Conclusion The appropriate use of specialized OHE holds particular significance in the improvement of oral hygiene status and salivary parameters, along with a reduction in the bacterial count in both visually impaired children and normal-sighted children.

20.
Sci Rep ; 14(1): 8584, 2024 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-38615021

RESUMEN

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.


Asunto(s)
Síndrome Torácico Agudo , Anemia de Células Falciformes , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Síndrome Torácico Agudo/etiología , Anemia de Células Falciformes/complicaciones , Antibacterianos , Causalidad , Causas de Muerte , Factores de Riesgo
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