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1.
Conscious Cogn ; 123: 103728, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39018832

RESUMEN

Humans experience feelings of confidence in their decisions. In perception, these feelings are typically accurate - we tend to feel more confident about correct decisions. The degree of insight people have into the accuracy of their decisions is known as metacognitive sensitivity. Currently popular methods of estimating metacognitive sensitivity are subject to interpretive ambiguities because they assume people have normally shaped distributions of different experiences when they are repeatedly exposed to a single input. If this normality assumption is violated, calculations can erroneously underestimate metacognitive sensitivity. Here, we describe a means of estimating metacognitive sensitivity that is more robust to violations of the normality assumption. This improved method can easily be added to standard behavioral experiments, and the authors provide Matlab code to help researchers implement these analyses and experimental procedures.

2.
J Exp Clin Cancer Res ; 43(1): 169, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38880883

RESUMEN

BACKGROUND: Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process. METHODS: Databases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α. RESULTS: The expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth. CONCLUSION: These findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.


Asunto(s)
Regulación hacia Abajo , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas con Dominio LIM , Mitocondrias , Especies Reactivas de Oxígeno , Humanos , Proteínas con Dominio LIM/metabolismo , Proteínas con Dominio LIM/genética , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Carcinoma Pulmonar de Lewis/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino
3.
Eur Thyroid J ; 13(4)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38847819

RESUMEN

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.


Asunto(s)
Oftalmopatía de Graves , Inmunoglobulinas Estimulantes de la Tiroides , Humanos , Femenino , Masculino , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/epidemiología , Oftalmopatía de Graves/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Anciano , Músculos Oculomotores/diagnóstico por imagen , Hong Kong/epidemiología , Imagen por Resonancia Magnética , Diplopía/epidemiología , Exoftalmia/epidemiología , Exoftalmia/sangre
4.
J Am Chem Soc ; 146(25): 17334-17347, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38767615

RESUMEN

Manipulation of cell-cell interactions via cell surface modification is crucial in tissue engineering and cell-based therapy. To be able to monitor intercellular interactions, it can also provide useful information for understanding how the cells interact and communicate. We report herein a facile bioorthogonal strategy to promote and monitor cell-cell interactions. It involves the use of a maleimide-appended tetrazine-caged boron dipyrromethene (BODIPY)-based fluorescent probe and a maleimide-substituted bicyclo[6.1.0]non-4-yne (BCN) to modify the membrane of macrophage (RAW 264.7) and cancer (HT29, HeLa, and A431) cells, respectively, via maleimide-thiol conjugation. After modification, the two kinds of cells interact strongly through inverse electron-demand Diels-Alder reaction of the surface tetrazine and BCN moieties. The coupling also disrupts the tetrazine quenching unit, restoring the fluorescence emission of the BODIPY core on the cell-cell interface, and promotes phagocytosis. Hence, this approach can promote and facilitate the detection of intercellular interactions, rendering it potentially useful for macrophage-based immunotherapy.


Asunto(s)
Compuestos de Boro , Comunicación Celular , Colorantes Fluorescentes , Humanos , Compuestos de Boro/química , Ratones , Animales , Colorantes Fluorescentes/química , Células RAW 264.7 , Maleimidas/química , Células HeLa
5.
Cogn Res Princ Implic ; 9(1): 29, 2024 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735013

RESUMEN

Auditory stimuli that are relevant to a listener have the potential to capture focal attention even when unattended, the listener's own name being a particularly effective stimulus. We report two experiments to test the attention-capturing potential of the listener's own name in normal speech and time-compressed speech. In Experiment 1, 39 participants were tested with a visual word categorization task with uncompressed spoken names as background auditory distractors. Participants' word categorization performance was slower when hearing their own name rather than other names, and in a final test, they were faster at detecting their own name than other names. Experiment 2 used the same task paradigm, but the auditory distractors were time-compressed names. Three compression levels were tested with 25 participants in each condition. Participants' word categorization performance was again slower when hearing their own name than when hearing other names; the slowing was strongest with slight compression and weakest with intense compression. Personally relevant time-compressed speech has the potential to capture attention, but the degree of capture depends on the level of compression. Attention capture by time-compressed speech has practical significance and provides partial evidence for the duplex-mechanism account of auditory distraction.


Asunto(s)
Atención , Nombres , Percepción del Habla , Humanos , Atención/fisiología , Femenino , Masculino , Percepción del Habla/fisiología , Adulto , Adulto Joven , Habla/fisiología , Tiempo de Reacción/fisiología , Estimulación Acústica
7.
Front Endocrinol (Lausanne) ; 15: 1368944, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756997

RESUMEN

Background: The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET). Methods: A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses. Results: Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease. Conclusion: The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Organización Mundial de la Salud , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/metabolismo , Adulto , Anciano , Pronóstico , Adulto Joven , Estudios de Seguimiento , Proteínas de Dominio T Box/metabolismo
8.
J Contemp Brachytherapy ; 16(2): 150-155, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38808204

RESUMEN

Patients with primary tumor progression after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) have a second chance at complete tumor eradication with salvage local therapies, including lung resection, repeat course of SBRT, and percutaneous ablative therapies. In this paper, we presented our institution's initial experience with percutaneous high-dose-rate (HDR) brachyablation for a relapsed stage I NSCLC that had been treated with SBRT 4.3 years earlier. Lung tumor measuring approximately 5 cm in maximum tumor dimension at the time of relapse was histopathologically confirmed to be persistent squamous cell carcinoma, and successfully treated with a single fraction of 24 Gy with HDR brachyablation. Treatment was delivered via two percutaneous catheters inserted under CT-guidance, and treated in less than 20 minutes. The patient was discharged home later the same day without the need for a chest tube, and has been monitored with serial surveillance scans every 3 to 6 months without evidence of further lung cancer progression or complications at 2.8 years post-HDR brachyablation procedure and 7.8 years after initial SBRT.

9.
Phys Ther ; 104(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38513257

RESUMEN

A clinical practice guideline on telerehabilitation was developed by an American Physical Therapy Association volunteer guideline development group consisting of international physical therapists and physiotherapists, a physician, and a consumer. The guideline was based on systematic reviews of current scientific literature, clinical information, and accepted approaches to telerehabilitation in physical therapist practice. Seven recommendations address the impact of, preparation for, and implementation of telerehabilitation in physical therapist practice. Research recommendations identify current gaps in knowledge. Overall, with shared decision-making between clinicians and patients to inform patients of service delivery options, direct and indirect costs, barriers, and facilitators of telerehabilitation, the evidence supports the use of telerehabilitation by physical therapists for both examination and intervention. The Spanish and Chinese versions of this clinical practice guideline, as well as the French version of the recommendations, are available as supplementary material (Suppl. Materials).


Asunto(s)
Telerrehabilitación , Humanos , Estados Unidos , Especialidad de Fisioterapia/normas , Modalidades de Fisioterapia/normas , Fisioterapeutas
10.
Eur Urol ; 85(6): 517-520, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38494380

RESUMEN

Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16-22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32-67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. PATIENT SUMMARY: We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951.


Asunto(s)
Leuprolida , Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Radiocirugia , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Anciano , Leuprolida/uso terapéutico , Persona de Mediana Edad , Acetato de Abiraterona/uso terapéutico , Tiohidantoínas/uso terapéutico , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Antígeno Prostático Específico/sangre , Metástasis de la Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Antagonistas de Andrógenos/uso terapéutico , Resultado del Tratamiento , Antineoplásicos Hormonales/uso terapéutico
11.
Eur J Ophthalmol ; : 11206721241229470, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38444235

RESUMEN

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

13.
Work ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38393878

RESUMEN

BACKGROUND: Telehealth is becoming more prevalent in physical therapy, involving a whole host of clinical services. These services are often provided without structured training in telehealth, and no formal curricula currently exist for this purpose. OBJECTIVE: To develop a set of educational competencies (ECs) to guide instruction of telehealth-related skills in entry-level programs (i.e., Doctor of Physical Therapy), existing programs (i.e., residencies and fellowships), and potential future post-graduate programs specific to telehealth physical therapy. METHODS: Physical therapists and physical therapist assistants from diverse geographic locations and practice areas were invited to participate on an expert panel. A modified Delphi process was then used to evaluate the acceptability of draft ECs gathered from the extant literature by a steering group. Draft ECs were presented to the expert panel on a questionnaire, which asked expert participants to rate each draft EC according to applicability and clarity. Draft ECs were accepted if they met a priori established criteria for acceptability and clarity. Unendorsed ECs were revised by the steering group according to open-ended comments from respondents and presented during a subsequent round. Three rounds of surveys were undertaken. RESULTS: Thirty-eight participants formed the expert panel; 38 participants completed the Round 1 survey, 28 participants completed the Round 2 survey, and 24 participants completed the Round 3 survey. Delphi group members approved 48 ECs in the first round, 23 ECs in the second round, and 2 ECs in the third round. There were 4 ECs that remained unendorsed after the modified Delphi process. Endorsed ECs spanned 7 conceptual areas. Distinct sets of ECs characterized expected end points of first professional degree, existing residency and fellowship, and potential future telehealth physical therapy post-graduate program. CONCLUSIONS: Consensus-based ECs identified in this study may guide instruction in knowledge and skills relevant to physical therapy telehealth.

14.
Clin Endocrinol (Oxf) ; 100(3): 230-237, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38127469

RESUMEN

OBJECTIVE: Baseline circulating thrombospondin-2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography. DESIGN: Serum TSP2 levels were measured in participants from a randomized, open-label intervention study, at baseline and after 24-weeks treatment of either dapagliflozin 10 mg (N = 30) or sitagliptin 100 mg daily (N = 30). Vibration-controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively. PATIENTS AND MEASUREMENTS: Among all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p = .012), CAP (p = .015) and LS (p = .011) after 24 weeks. RESULTS: Serum TSP2 level decreased significantly from baseline in dapagliflozin-treated participants (p = .035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (r = .487, p = .006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment. CONCLUSIONS: Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes.


Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Diagnóstico por Imagen de Elasticidad , Glucósidos , Enfermedad del Hígado Graso no Alcohólico , Humanos , Hígado/diagnóstico por imagen , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Hemoglobina Glucada , Cirrosis Hepática/tratamiento farmacológico , Fosfato de Sitagliptina/uso terapéutico , Biomarcadores , Trombospondinas/uso terapéutico
15.
Front Med (Lausanne) ; 10: 1246796, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116038

RESUMEN

Here, we report the first adult case of pancreatic yolk sac tumor with ectopic adrenocorticotropic hormone (ACTH) syndrome. The patient was a 27-year-old woman presenting with abdominal distension, Cushingoid features, and hyperpigmentation. Endogenous Cushing's syndrome was biochemically confirmed. The ACTH level was in the normal range, which raised the suspicion of ACTH precursor-dependent disease. Elevated ACTH precursors were detected, supporting the diagnosis of ectopic ACTH syndrome. Functional imaging followed by tissue sampling revealed a pancreatic yolk sac tumor. The final diagnosis was Cushing's syndrome due to a yolk sac tumor. The patient received a steroidogenesis inhibitor and subsequent bilateral adrenalectomy for control of hypercortisolism. Her yolk sac tumor was treated with chemotherapy and targeted therapy. Cushing's syndrome secondary to a yolk sac tumor is extremely rare. This case illustrated the utility of ACTH precursor measurement in confirming an ACTH-related pathology and distinguishing an ectopic from a pituitary source for Cushing's syndrome.

16.
J Vis ; 23(10): 7, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37695612

RESUMEN

Visual confidence generally depends on performance in targeted perceptual tasks. However, it remains unclear how factors unrelated to performance affect confidence. Given the hierarchical nature of visual processing, both local and global stimulus features can influence confidence, but their strengths of influence remain unknown. To address this question, we independently manipulated the local contrast signals and the global coherence signals in a multiple-aperture motion pattern. The drifting-Gabor elements were individually manipulated to give rise to a coherent global motion percept. In both dichotomous direction-discrimination task (Experiment 1) and analog direction-judgment task (Experiment 2), we found stimulus-dependent biases in metacognition despite matched perceptual performance. Specifically, participants systematically gave higher confidence ratings to an incoherent pattern with clear elements (i.e., strong local but weak global signals) than a coherent pattern with noisy elements (i.e., weak local but strong global signals). We did not find any systematic effects of local/global stimulus features on metacognitive sensitivity. Model comparisons show that variation in local/global signals in the stimulus should be considered a factor influencing confidence, even after controlling for the effects of performance. Our results suggest that the metacognitive system, when generating confidence for a perceptual task, puts more weights on local than global signals.


Asunto(s)
Metacognición , Humanos , Sesgo , Juicio , Movimiento (Física) , Percepción Visual
17.
Physiother Can ; 75(2): 132-133, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37736374
18.
Cancer Sci ; 114(10): 3857-3872, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37525561

RESUMEN

The suppressive regulatory T cells (Treg) are frequently upregulated in cancer patients. This study aims to demonstrate the hypothesis that arecoline could induce the secretion of mitochondrial (mt) DNA D-loop and programmed cell death-ligand 1 (PD-L1) in extracellular vesicles (EVs), and attenuate T-cell immunity by upregulated Treg cell numbers. However, the immunosuppression could be reversed by whole glucan particle (WGP) ß-glucan in oral squamous cell (OSCC) patients. Arecoline-induced reactive oxygen specimen (ROS) production and cytosolic mtDNA D-loop were analyzed in OSCC cell lines. mtDNA D-loop, PD-L1, IFN-γ, and Treg cells were also identified for the surgical specimens and sera of 60 OSCC patients. We demonstrated that higher mtDNA D-loop, PD-L1, and Treg cell numbers were significantly correlated with larger tumor size, nodal metastasis, advanced clinical stage, and areca quid chewing. Furthermore, multivariate analysis confirmed that higher mtDNA D-loop levels and Treg cell numbers were unfavorable independent factors for survival. Arecoline significantly induced cytosolic mtDNA D-loop leakage and PD-L1 expression, which were packaged by EVs to promote immunosuppressive Treg cell numbers. However, WGP ß-glucan could elevate CD4+ and CD8+ T-cell numbers, mitigate Treg cell numbers, and promote oral cancer cell apoptosis. To sum up, arecoline induces EV production carrying mtDNA D-loop and PD-L1, and in turn elicits immune suppression. However, WGP ß-glucan potentially enhances dual effects on T-cell immunity and cell apoptosis and we highly recommend its integration with targeted and immune therapies against OSCC.


Asunto(s)
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , beta-Glucanos , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Arecolina , Antígeno B7-H1/genética , Neoplasias de la Boca/patología , Glucanos , beta-Glucanos/farmacología , ADN Mitocondrial/genética , Terapia de Inmunosupresión , Vesículas Extracelulares/metabolismo
19.
Cancers (Basel) ; 15(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37568732

RESUMEN

PURPOSE/OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura with a poor prognosis. We aimed to develop a model, via interpretable machine learning (ML) methods, predicting overall survival for MPM following radiotherapy based on dosimetric metrics as well as patient characteristics. MATERIALS/METHODS: Sixty MPM (37 right, 23 left) patients treated on a Tomotherapy unit between 2013 and 2018 were retrospectively analyzed. All patients received 45 Gy (25 fractions). The multivariable Cox regression (Cox PH) model and Survival Support Vector Machine (sSVM) were applied to build predictive models of overall survival (OS) based on clinical, dosimetric, and combined variables. RESULTS: Significant differences in dosimetric endpoints for critical structures, i.e., the lung, heart, liver, kidney, and stomach, were observed according to target laterality. The OS was found to be insignificantly different (p = 0.18) between MPM patients who tested left- and right-sided, with 1-year OS of 77.3% and 75.0%, respectively. With Cox PH regression, considering dosimetric variables for right-sided patients alone, an increase in PTV_Min, Total_Lung_PTV_Mean, Contra_Lung_Volume, Contra_Lung_V20, Esophagus_Mean, and Heart_Volume had a greater hazard to all-cause death, while an increase in Total_Lung_PTV_V20, Contra_Lung_V5, and Esophagus_Max had a lower hazard to all-cause death. Considering clinical variables alone, males and increases in N stage had greater hazard to all-cause death; considering both clinical and dosimetric variables, increases in N stage, PTV_Mean, PTV_Min, and esophagus_Mean had greater hazard to all-cause death, while increases in T stage and Heart_V30 had lower hazard to all-cause-death. In terms of C-index, the Cox PH model and sSVM performed similarly and fairly well when considering clinical and dosimetric variables independently or jointly. CONCLUSIONS: Clinical and dosimetric variables may predict the overall survival of mesothelioma patients, which could guide personalized treatment planning towards a better treatment response. The identified predictors and their impact on survival offered additional value for translational application in clinical practice.

20.
J Chiropr Educ ; 37(2): 137-150, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37270710

RESUMEN

OBJECTIVE: To investigate if a written guide or augmented reality (AR) guide improves free recall of diversified chiropractic adjusting technique and to capture participants' impressions of the study in a poststudy questionnaire. METHODS: Thirty-eight chiropractic students were evaluated for diversified listing (a nomenclature denoting vertebral malposition and correction) recall, pre-AR and post-AR, or written guide review. The vertebral segments used were C7 and T6. Two randomized groups reviewed an original course written guide (n = 18) or a new AR guide (n = 20). A Wilcoxon-Mann-Whitney (C7) and t test (T6) compared group differences in reevaluation scores. A poststudy questionnaire was given to capture participants' impressions of the study. RESULTS: Both groups showed no significant differences in free recall scores after reviewing the guides for C7 or T6. The poststudy questionnaire suggested a number of strategies could be used to improve current teaching material such as more detail in the written guides and organizing content into smaller blocks. CONCLUSION: Use of an AR or written guide does not seem to change participants' free recall ability when used to review diversified technique listings. The poststudy questionnaire was useful to identify strategies to improve currently used teaching material.

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