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BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.
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Enfermedad de Parkinson , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Método Simple Ciego , Estudios Prospectivos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Cognición , Factores de Tiempo , Recuperación de la Función , Corteza Motora/fisiopatologíaRESUMEN
Backgrounds: Freezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients. Methods: We recruited 14 PD patients and collected data from multiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model. Results: We found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to other models. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations. Conclusions: We demonstrated the potential of using wearable pressure sensors and machine learning models for FoG detection in PD patients. The TCNN model showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers.
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Background: The morphology of the suprascapular notch (SSN) and the ossification of the superior transverse suprascapular ligament (STSL) are risk factors for injury of the suprascapular nerve (SN) during arthroscopic shoulder procedures. The purpose of the current study was to compare preoperative clinical and radiologic characteristics between patients with and without STSL ossification and to evaluate SSN morphology in patients who underwent arthroscopic rotator cuff repair using a 3-dimensional (3D) reconstructed model. Methods: Patients who underwent arthroscopic rotator cuff repair and were given a computed tomography (CT) scan from March 2018 to August 2019 were included in this study. Patients were divided into 2 groups: those without STSL ossification (group I) and those with STSL ossification (group II). Tear size of the rotator cuff and fatty infiltration of rotator cuff muscles were assessed in preoperative magnetic resonance imaging. The morphology of the SSN was classified following Rengachary's classification. The transverse and vertical diameters of the SSN and the distances from anatomical landmarks to the STSL were measured. All measurements were completed using a 3D CT reconstructed scapula model. Results: A total of 200 patients were included in this study. One hundred seventy-eight patients (89.0%) without STSL ossification were included in group I, and 22 patients (11.0%) with STSL ossification were included in group II. Group II showed a significantly advanced age (61.0 ± 7.4 vs. 71.0 ± 7.3 years, p < 0.001) and a shorter transverse diameter of SSN (10.7 ± 3.1 mm vs. 6.1 ± 3.7 mm, p < 0.001) than group I. In the logistic regression analysis, age was an independent prognostic factor for STSL ossification (odds ratio, 1.201; 95% confidence interval, 1.112-1.296; p < 0.001). Patients in type VI showed significantly shorter transverse diameters than other types (p < 0.001). The patient with type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than those with other types (p < 0.001). Conclusions: In the 3D morphological analysis, age was the independent factor associated with STSL ossification in patients who underwent arthroscopic rotator cuff repair. Type VI showed significantly shorter transverse diameters than other types. Type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than other types.
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Artroscopía , Imagenología Tridimensional , Lesiones del Manguito de los Rotadores , Tomografía Computarizada por Rayos X , Humanos , Artroscopía/métodos , Femenino , Masculino , Persona de Mediana Edad , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Anciano , Estudios Retrospectivos , Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/cirugía , Manguito de los Rotadores/cirugía , Manguito de los Rotadores/diagnóstico por imagen , Escápula/diagnóstico por imagen , Escápula/cirugía , Ligamentos Articulares/cirugía , Ligamentos Articulares/diagnóstico por imagen , AdultoRESUMEN
This study aims to determine the prevalence of successful aging (SA) and examine the association of changes in the indicators of SA and variations in SA status between 2016 and 2020. The study included 548 participants recruited for the Korean Frailty and Aging Cohort Study (KFACS). Compared to participants who achieved SA in 2016 (N = 393, 71.7%), the number of older adults with SA decreased by 7.8% in 2020. Among older adults preserving SA (SAâSA group, 54%), there were relatively small numbers of older adults who successfully maintained indicators, including chronic diseases (noâno, 9.5%), employment (yesâyes, 12.2%), and volunteer activities (yesâyes, 2.9%). Our findings suggest that interventions to strengthen the physical and psychological function of older adults are needed, and social support needs to be guaranteed to improve social engagement for older adults.
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Dose-finding studies play a crucial role in drug development by identifying the optimal dose(s) for later studies while considering tolerability. This not only saves time and effort in proceeding with Phase III trials but also improves efficacy. In an era of precision medicine, it is not ideal to assume patient homogeneity in dose-finding studies as patients may respond differently to the drug. To address this, we propose a personalized dose-finding algorithm that assigns patients to individualized optimal biological doses. Our design follows a two-stage approach. Initially, patients are enrolled under broad eligibility criteria. Based on the Stage 1 data, we fit a regression model of toxicity and efficacy outcomes on dose and biomarkers to characterize treatment-sensitive patients. In the second stage, we restrict the trial population to sensitive patients, apply a personalized dose allocation algorithm, and choose the recommended dose at the end of the trial. Simulation study shows that the proposed design reliably enriches the trial population, minimizes the number of failures, and yields superior operating characteristics compared to several existing dose-finding designs in terms of both the percentage of correct selection and the number of patients treated at target dose(s).
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Purpose: To analyze adenoma detection rate (ADR) and related quality indicators of colonoscopy among trainees and make recommendations for appropriate colonoscopy training. Methods: ADR and related indicators of colonoscopies performed by 3 trainees and 5 colonoscopy experts between March and November 2022 were analyzed. These indicators were analyzed in both the entire patients and the screening/surveillance group. In addition, the training period of the 3 trainees was divided into 3 sections, and the changes in these indicators were examined. Results: The mean ADR of the 3 trainees was 50.6%. In the screening/surveillance group, the mean ADR of the 3 trainees was 51.8%, showing no significant difference from the experts' ADR (53.4%). When the training period was divided into 3 sections and analyzed in the screening/surveillance group, the mean ADR of the trainees gradually increased to 49.4%, 52.6%, and 53.6%, respectively; however, the difference was insignificant. Analyzing each trainee's ADR, there was a significant difference among the 3 trainees (58.5% vs. 44.7% vs. 50.2%, P=0.008). However, in the third section of the training period, the 3 trainees' ADRs were 53.0%, 49.2%, and 57.3%, respectively, showing no significant difference (P=0.606). Conclusion: In the early stages of training, the ADR was higher than recommended; however, there were variances in ADR between individuals. As the training period passed, the ADR became similar at the expert level, whereas the difference in ADR between trainees decreased. Therefore, efforts to increase ADR should be made actively from the beginning of training and continued during the training period.
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This study was carried out to screen the antifungal activity against Colletotrichum acutatum, Colletotrichum dematium, and Colletotrichum coccodes. Bacterial isolate GP-P8 from pepper soil was found to be effective against the tested pathogens with an average inhibition rate of 70.7% in in vitro dual culture assays. 16S rRNA gene sequencing analysis result showed that the effective bacterial isolate as Bacillus siamensis. Biochemical characterization of GP-P8 was also performed. According to the results, protease and cellulose, siderophore production, phosphate solubilization, starch hydrolysis, and indole-3-acetic acid production were shown by the GP-P8. Using specific primers, genes involved in the production of antibiotics, such as iturin, fengycin, difficidin, bacilysin, bacillibactin, surfactin, macrolactin, and bacillaene were also detected in B. siamensis GP-P8. Identification and analysis of volatile organic compounds through solid phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) revealed that acetoin and 2,3-butanediol were produced by isolate GP-P8. In vivo tests showed that GP-P8 significantly reduced the anthracnose disease caused by C. acutatum, and enhanced the growth of pepper plant. Reverse transcription polymerase chain reaction analysis of pepper fruits revealed that GP-P8 treated pepper plants showed increased expression of immune genes such as CaPR1, CaPR4, CaNPR1, CaMAPK4, CaJA2, and CaERF53. These results strongly suggest that GP-P8 could be a promising biocontrol agent against pepper anthracnose disease and possibly a pepper plant growth-promoting agent.
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Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.
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OBJECTIVES: Only a few studies have investigated dietary patterns and intrinsic capacity (IC). This study examined the prospective associations between dietary patterns, IC, and IC sub-domains over 6 years in community-dwelling Korean older adults. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: Data were obtained from participants aged 70-84 years in the Korean Frailty and Aging Cohort Study (2016-2022). The study population included 665 enrollees at baseline who completed IC and dietary data. METHODS: Dietary data were obtained from baseline surveys of the nutritional sub-cohort using two nonconsecutive 24-hour dietary recalls, and dietary patterns were derived using cluster analysis. IC was constructed by measuring cognitive, locomotor, vitality, sensory, and psychological domains. A generalized estimating equation was used to analyze the longitudinal associations between dietary patterns, IC, and IC sub-domain scores. RESULTS: In total, 665 enrollees were included in the analysis. After adjusting for confounders, in older men, the dietary pattern of cluster 1 (variety of healthy foods and alcohols) compared to that of cluster 2 (rice and kimchi) was positively associated with changes in the IC score (ß = 0.41, 95% confidence interval [CI] = 0.04-0.78). In older women, the dietary pattern of cluster 1 (variety of healthy foods) was positively associated with changes in the IC score (ß = 0.30, 95% CI = 0.02-0.58), IC score group (ß = 0.11, 95% CI = 0.02-0.20), and psychological domain (ß = 0.25, 95% CI = 0.11-0.38) compared to that of cluster 3 (rice, vegetables, and kimchi). CONCLUSIONS: Dietary patterns (variety of healthy foods) were positively associated with changes in IC scores and their sub-domains in older adults.
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Dieta , Humanos , Anciano , Masculino , Femenino , Estudios Prospectivos , Anciano de 80 o más Años , Dieta/estadística & datos numéricos , Vida Independiente , República de Corea , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Conducta Alimentaria/psicología , Envejecimiento/psicología , Envejecimiento/fisiología , Fragilidad/epidemiología , Dieta Saludable/estadística & datos numéricos , Patrones DietéticosRESUMEN
The aim of this study was to investigate the additional effects of cerebellar rTMS on the motor recovery of facilitatory rTMS over affected primary motor cortex (M1) in subacute stroke patients. Twenty-eight subacute stroke patients were recruited in this single-blind, randomized, controlled trial. The Cr-Cbll group received Cr-Cbll rTMS stimulation consisting of high-frequency rTMS over affected M1 (10 min), motor training (10 min), and high-frequency rTMS over contralesional Cbll (10 min). The Cr-sham group received sham rTMS instead of high-frequency rTMS over the cerebellum. Ten daily sessions were performed for 2 weeks. A Fugl-Meyer Assessment (FMA) was measured before (T0), immediately after (T1), and 2 months after the intervention (T2). A total of 20 participants (10 in the Cr-Cbll group and 10 in the Cr-sham group) completed the intervention. There was no significant difference in clinical characteristics between the two groups at T0. FMA was significantly improved after the intervention in both Cr-Cbll and Cr-sham groups (p < 0.05). However, there was no significant interaction in FMA between time and group. In conclusion, these results could not demonstrate that rTMS over the contralesional cerebellum has additional effects to facilitatory rTMS over the affected M1 for improving motor function in subacute stroke patients.
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Background: This study aimed to develop an instrument for assessing physical functioning among adults aged 50 years or older living in the community. Methods: Based on a review of various national health surveys and cohort studies, a 144-item bank was constructed for assessing physical functioning. Focus group interviews were conducted among adults aged 50 years or older to investigate their level of understanding of 60 selected items, followed by a pretest of the items on a nationally representative sample (n = 508). The final 25-item questionnaire was tested on an independent sample (n = 259) for validity and reliability based on classical test and item response theories. Predictive validity at the 6-month follow-up was tested in a separate sample (n = 263). Results: The newly developed Life Functioning (LF) scale assessed the dimensions of functional limitations, disabilities, and social activities. The scale satisfied a one-dimensionality assumption with good item fit and demonstrated criterion validity, construct validity, high internal consistency (Cronbach's alpha = 0.93), and test-retest reliability (intra-class correlation coefficient = 0.84; 95% CI, 0.76-0.89). The LF scale comprised 25 items with a total score ranging from 0 to 100. Higher scores indicated higher levels of functioning. The LF score was significantly associated with the physical functioning score at 6 months. Conclusion: The LF scale was developed to assess the physical functioning of people in their late midlife or older. Future studies should test the instrument on a national sample and evaluate its application in diverse population subgroups.
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OBJECTIVE: We aimed to investigate the changes in aorta size, the factors affecting size changes in patients with acute blunt traumatic aortic injury and to evaluate the adequacy of the current 120% thoracic endovascular aortic repair graft oversizing policy. DESIGN AND METHODS: This retrospective review study was conducted using the prospectively collected medical records of 45 patients (mean age: 53.5 years, male: 39 patients) with blunt traumatic aortic injury treated at a level 1 trauma center between 2012 and 2021. Aortic diameter was measured by computed tomography angiographic images at four different levels [ascending aorta (A), isthmus (B), descending thoracic aorta (C), and infrarenal aorta (D)] on arrival and follow-up (median time interval, 13 days). Associated factors including patient characteristics and hemodynamic parameters on arrival and follow-up were collected to determine their influence on changes in the aorta. RESULTS: The mean diameter of all four aortic levels increased on follow-up computed tomography compared to initial computed tomography (A: + 11.77%, B: + 10.19%, C: + 7.71%, D: + 12.04%). Patient age and injury severity score influenced changes in the diameter of the ascending aorta (P < 0.05). Patient age and blunt traumatic aortic injury grade were significantly associated with changes in the infrarenal aortic diameter (P < 0.05). Three cases of type 1 endoleak were observed at follow-up but all were spontaneously resolved without further intervention at next computed tomography follow-up. CONCLUSIONS: In patients with acute blunt traumatic aortic injury, aortic diameter is significantly smaller by about 10% under shock and is not considered a basis for oversizing the currently implemented 120% thoracic endovascular aortic repair graft sizing. However, in young patients under the age of 40, the change is significantly large and subsequent computed tomography follow-up is required.
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Purpose: Whether to perform surgery or conservatively manage appendicitis in immunosuppressed patients is a concern for clinicians. This study aimed to compare the outcomes of these 2 treatment options for appendicitis in patients with cancer undergoing chemotherapy. Methods: This retrospective study included 206 patients with cancer who were diagnosed with acute appendicitis between August 2001 and December 2021. Among them, patients who received chemotherapy within 1 month were divided into surgical and conservative groups. We evaluated the outcomes, including treatment success within 1 year, 1-year recurrence, and the number of days from the diagnosis of appendicitis to chemotherapy restart, between the 2 groups. Results: Among the 206 patients with cancer who were diagnosed with acute appendicitis, 78 received chemotherapy within 1 month. The patients were divided into surgery (n = 63) and conservative (n = 15) groups. In the surgery group, the duration of antibiotic therapy (7.0 days vs. 16.0 days, P < 0.001) and length of hospital stay (8.0 days vs. 27.5 days, P = 0.002) were significantly shorter than conservative groups. The duration from the diagnosis of appendicitis to the restart of chemotherapy was shorter in the surgery group (20.8 ± 15.1 days vs. 35.2 ± 28.2 days, P = 0.028). The treatment success rate within 1 year was higher in the surgery group (100% vs. 33.3%, P < 0.001). Conclusion: Surgical treatment showed a significantly higher success rate than conservative treatment for appendicitis in patients less than 1 month after chemotherapy. Further prospective studies will be needed to clinically determine treatment options.
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In next-generation neuromorphic computing applications, the primary challenge lies in achieving energy-efficient and reliable memristors while minimizing their energy consumption to a level comparable to that of biological synapses. In this work, hexagonal boron nitride (h-BN)-based metal-insulator-semiconductor (MIS) memristors operating is presented at the attojoule-level tailored for high-performance artificial neural networks. The memristors benefit from a wafer-scale uniform h-BN resistive switching medium grown directly on a highly doped Si wafer using metal-organic chemical vapor deposition (MOCVD), resulting in outstanding reliability and low variability. Notably, the h-BN-based memristors exhibit exceptionally low energy consumption of attojoule levels, coupled with fast switching speed. The switching mechanisms are systematically substantiated by electrical and nano-structural analysis, confirming that the h-BN layer facilitates the resistive switching with extremely low high resistance states (HRS) and the native SiOx on Si contributes to suppressing excessive current, enabling attojoule-level energy consumption. Furthermore, the formation of atomic-scale conductive filaments leads to remarkably fast response times within the nanosecond range, and allows for the attainment of multi-resistance states, making these memristors well-suited for next-generation neuromorphic applications. The h-BN-based MIS memristors hold the potential to revolutionize energy consumption limitations in neuromorphic devices, bridging the gap between artificial and biological synapses.
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The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI.
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Pollos , Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Animales , Pollos/virología , Pollos/inmunología , Gripe Aviar/prevención & control , Gripe Aviar/virología , Gripe Aviar/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , América del Norte , Vacunación , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/inmunología , Herpesvirus Meleágrido 1/inmunología , Herpesvirus Meleágrido 1/genéticaRESUMEN
Convolutional neural networks (CNNs) provide flexible function approximations for a wide variety of applications when the input variables are in the form of images or spatial data. Although CNNs often outperform traditional statistical models in prediction accuracy, statistical inference, such as estimating the effects of covariates and quantifying the prediction uncertainty, is not trivial due to the highly complicated model structure and overparameterization. To address this challenge, we propose a new Bayesian approach by embedding CNNs within the generalized linear models (GLMs) framework. We use extracted nodes from the last hidden layer of CNN with Monte Carlo (MC) dropout as informative covariates in GLM. This improves accuracy in prediction and regression coefficient inference, allowing for the interpretation of coefficients and uncertainty quantification. By fitting ensemble GLMs across multiple realizations from MC dropout, we can account for uncertainties in extracting the features. We apply our methods to biological and epidemiological problems, which have both high-dimensional correlated inputs and vector covariates. Specifically, we consider malaria incidence data, brain tumor image data, and fMRI data. By extracting information from correlated inputs, the proposed method can provide an interpretable Bayesian analysis. The algorithm can be broadly applicable to image regressions or correlated data analysis by enabling accurate Bayesian inference quickly.
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Teorema de Bayes , Neoplasias Encefálicas , Imagen por Resonancia Magnética , Método de Montecarlo , Redes Neurales de la Computación , Humanos , Modelos Lineales , Imagen por Resonancia Magnética/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Malaria/epidemiología , AlgoritmosRESUMEN
Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens ranged from approximately 1,000 to 40,000 neurons expressing the mTOR mutant in the somatosensory (SSC) or medial prefrontal (PFC) cortex. Surprisingly, approximately 8,000 to 9,000 neurons expressing the MTOR mutant, which are extrapolated to constitute 0.08-0.09% of total cells or roughly 0.04% of variant allele frequency (VAF) in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.
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Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.
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The gold standard test for diagnosing dysphagia is the videofluoroscopic swallowing study (VFSS). However, the accuracy of this test varies depending on the specialist's skill level. We proposed a VFSS-based artificial intelligence (AI) web application to diagnose dysphagia. Video from the VFSS consists of multiframe data that contain approximately 300 images. To label the data, the server separated them into frames during the upload and stored them as a video for analysis. Then, the separated data were loaded into a labeling tool to perform the labeling. The labeled file was downloaded, and an AI model was developed by training with You Only Look Once (YOLOv7). Using a utility called SplitFolders, the entire dataset was divided according to a ratio of training (70%), test (10%), and validation (20%). When a VFSS video file was uploaded to an application equipped with the developed AI model, it was automatically classified and labeled as oral, pharyngeal, or esophageal. The dysphagia of a person was categorized as either penetration or aspiration, and the final analyzed result was displayed to the viewer. The following labeling datasets were created for the AI learning: oral (n = 2355), pharyngeal (n = 2338), esophageal (n = 1480), penetration (n = 1856), and aspiration (n = 1320); the learning results of the YOLO model, which analyzed dysphagia using the dataset, were predicted with accuracies of 0.90, 0.82, 0.79, 0.92, and 0.96, respectively. This is expected to help clinicians more efficiently suggest the proper dietary options for patients with oropharyngeal dysphagia.
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Recent assessments of the correlations between food and medicine underscore the importance of functional foods in disease prevention and management. Functional foods offer health benefits beyond basic nutrition, with fresh fruits and vegetables being particularly prominent because of their rich polyphenol content. In this study, we elucidated the phytochemicals in ice plant (Mesembryanthemum crystallinum), a globally consumed vegetable, using an LC-QTOF/MS-based untargeted detection method. The phytochemicals were clustered based on their structural similarity using molecular networking and annotated using the in silico tool for network annotation propagation. To identify the bioactive compounds, eight compounds were isolated from ice plant extracts. These compounds were identified using extensive spectroscopic methods, including 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Additionally, we evaluated the antioxidant and anti-inflammatory activities of all the isolates. Among the tested compounds, three showed antioxidant activity and all eight showed anti-inflammatory activity, demonstrating the potential of ice plant as a functional food.