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Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking1,2. Here we identify the innate immune kinase TANK-binding kinase 1 (TBK1)3 as a candidate immune-evasion gene in a pooled genetic screen4. Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1 as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1 blockade by decreasing the cytotoxicity threshold to effector cytokines (TNF and IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids and matched patient-derived organoids. Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNF and IFNγ in a JAK-STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.
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Resistencia a Medicamentos Antineoplásicos , Evasão da Resposta Imune , Imunoterapia , Proteínas Serina-Treonina Quinases , Humanos , Evasão da Resposta Imune/genética , Evasão da Resposta Imune/imunologia , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Organoides , Fatores de Necrose Tumoral/imunologia , Interferon gama/imunologia , Esferoides Celulares , Caspases , Janus Quinases , Fatores de Transcrição STATRESUMO
Human pose estimation (HPE) is a technique used in computer vision and artificial intelligence to detect and track human body parts and poses using images or videos. Widely used in augmented reality, animation, fitness applications, and surveillance, HPE methods that employ monocular cameras are highly versatile and applicable to standard videos and CCTV footage. These methods have evolved from two-dimensional (2D) to three-dimensional (3D) pose estimation. However, in real-world environments, current 3D HPE methods trained on laboratory-based motion capture data encounter challenges, such as limited training data, depth ambiguity, left/right switching, and issues with occlusions. In this study, four 3D HPE methods were compared based on their strengths and weaknesses using real-world videos. Joint position correction techniques were proposed to eliminate and correct anomalies such as left/right inversion and false detections of joint positions in daily life motions. Joint angle trajectories were obtained for intuitive and informative human activity recognition using an optimization method based on a 3D humanoid simulator, with the joint position corrected by the proposed technique as the input. The efficacy of the proposed method was verified by applying it to three types of freehand gymnastic exercises and comparing the joint angle trajectories during motion.
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Aprendizado Profundo , Articulações , Postura , Humanos , Postura/fisiologia , Articulações/fisiologia , Imageamento Tridimensional/métodos , Algoritmos , Movimento/fisiologia , Gravação em Vídeo/métodosRESUMO
PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Estudos de Coortes , Risco , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
INTRODUCTION: A previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections. METHODS: This retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae. RESULTS: A total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05-2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae. CONCLUSION: These findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.
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Infecções por Enterobacteriaceae , Infecções Urinárias , Humanos , Estudos Retrospectivos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , beta-Lactamases , Antibacterianos/uso terapêutico , Enterobacteriaceae , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Fatores de Risco , Estudos de CoortesRESUMO
INTRODUCTION: This systematic review and meta-analysis evaluated the available evidence on the risk of metachronous advanced neoplasia (AN) and colorectal cancer (CRC) in patients with 3-4 nonadvanced adenomas (NAAs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases up to January 2021 for studies evaluating metachronous AN and CRC risk by comparing 3 groups (1-2 vs 3-4 vs ≥5 NAAs) at index colonoscopy. The estimates for risk of metachronous AN and CRC were evaluated using random-effects models. RESULTS: Fifteen studies (n = 36,375) were included. The risk of metachronous AN was significantly higher in the 3-4 NAAs group than in the 1-2 NAAs group (relative risk [RR] 1.264, 95% confidence interval [CI] 1.053-1.518, P = 0.012; I2 = 0%); there was no difference between the ≥ 5 NAAs and 3-4 NAAs groups (RR 1.962, 95% CI 0.972-3.958, P = 0.060; I2 = 68%). The risks of metachronous CRC between the 1-2 NAAs and 3-4 NAAs groups (RR 2.663, 95% CI 0.391-18.128, P = 0.317; I2 = 0%) or the 3-4 NAAs and ≥ 5 NAAs groups (RR 1.148, 95% CI 0.142-9.290, P = 0.897; I2 = 0%) were not significantly different. DISCUSSION: Although the risk of metachronous AN was greater in the 3-4 NAAs group than in the 1-2 NAAs group, the risk of metachronous AN and CRC between the 3-4 NAAs and ≥ 5 NAAs groups was not different. This suggests that further studies on metachronous AN and CRC risk in the 3-4 NAAs group are warranted to confirm a firm ≥5-year interval surveillance colonoscopy.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Segunda Neoplasia Primária , Adenoma/epidemiologia , Pólipos do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Segunda Neoplasia Primária/epidemiologia , Fatores de RiscoRESUMO
We use europium doped single crystalline NaYF4nanorods for probing the electric and magnetic contributions to the local density of optical states (LDOS). Reciprocically, we determine intrinsic properties of the emitters (oscillator strength, quantum yield) by comparing their measured and simulated optical responses in front of a mirror. We first experimentally determine the specifications of the nanoprobe (orientation and oscillator strength of the electric and magnetic dipoles moments) and show significant orientation sensitivity of the branching ratios associated with electric and magnetic transitions. In a second part, we measure the modification of the LDOS in front of a gold mirror in a Drexhage's experiment. We discuss the role of the electric and magnetic LDOS on the basis of numerical simulations, taking into account the orientation of the dipolar emitters. We demonstrate that they behave like degenerated dipoles sensitive to polarized partial LDOS.
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Many studies have explored emotional and mental services that robots can provide for older adults, such as offering them daily conversation, news, music, or health information. However, the ethical issues raised by using sensors for frail older adults to monitor their daily movements or their medication intake, for instance, are still being discussed. In this study, we develop an older adult-guided, caregiver-monitored robot, Dori, which can detect and recognize movement by sensing human poses in accordance with two factors from the human-centered artificial intelligence (HCAI) framework. To design the care robot's services based on sensing movement during daily activities, we conducted focus group interviews with two groups-caregivers and medical staff-on the topic of care robot services not for patients but for prefrail and frail elderly individuals living at home. Based on their responses, we derived the focal service areas of cognitive support, emotional support, physical activity support, medication management, and caregiver management. We also found the two groups differed in their ethical judgments in the areas of dignity, autonomy, controllability, and privacy for services utilizing sensing by care robots. Therefore, the pose recognition technology adopted in the present work uses only joint coordinate information extracted from camera images and thus is advantageous for protecting human dignity and personal information.
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Robótica , Tecnologia Assistiva , Idoso , Inteligência Artificial , Cuidadores/psicologia , Grupos Focais , Humanos , Tecnologia Assistiva/psicologiaRESUMO
PURPOSE: To test the applicability of autofluorescence (AF) spectrum and image in the detection and identification of oral pathogens. METHODS: Oral pathogens (Candida albicans, Porphyromonas gingivalis, Streptococcus mutans) and teeth were used. To induce AF, the 405 nm laser was used as a light source, and AF was obtained and observed using a spectrometer, fluorescence camera, and microscope, respectively. RESULTS: The tested oral pathogens had similar spectral distributions, but their peak intensities and peak ratios were different. Their peak positions and spectral patterns were different from those of the tested sound and carious teeth. These differences were also found from the other referenced oral mucosa. Fluorescence image could localize the existence of oral bacteria. Oral pathogens could be imaged by fluorescence, but identification of each pathogen by image was not probable. CLINICAL SIGNIFICANCE: Oral pathogens can be observed and identified from the lesion if autofluorescence spectrum and fluorescence images are combined.
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Cárie Dentária , Dente , Cárie Dentária/diagnóstico , Cárie Dentária/microbiologia , Fluorescência , Humanos , Lasers , Streptococcus mutans , Dente/patologiaRESUMO
BACKGROUND AND AIM: The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD. METHODS: This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups. RESULTS: In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis. CONCLUSION: Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders.
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Dispepsia/complicações , Gastroenterologia/organização & administração , Neurologia/organização & administração , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Sociedades Médicas/organização & administração , Ansiedade , Índice de Massa Corporal , Estudos Transversais , Dispepsia/psicologia , Feminino , Azia , Humanos , Masculino , Prevalência , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
Leveraging the Electronic Health Records (EHR) longitudinal data to produce actionable clinical insights has always been a critical issue for recent studies. Non-forecasted extended hospitalizations account for a disproportionate amount of resource use, the mediocre quality of inpatient care, and avoidable fatalities. The capability to predict the Length of Stay (LoS) and mortality in the early stages of the admission provides opportunities to improve care and prevent many preventable losses. Forecasting the in-hospital mortality is important in providing clinicians with enough insights to make decisions and hospitals to allocate resources, hence predicting the LoS and mortality within the first day of admission is a difficult but a paramount endeavor. The biggest challenge is that few data are available by this time, thus the prediction has to bring in the previous admissions history and free text diagnosis that are recorded immediately on admission. We propose a model that uses the multi-modal EHR structured medical codes and key demographic information to classify the LoS in 3 classes; Short Los (LoS⩽10 days), Medium LoS (10
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Hospitalização , Classificação Internacional de Doenças , Registros Eletrônicos de Saúde , Mortalidade Hospitalar , Humanos , Tempo de InternaçãoRESUMO
BACKGROUND: Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in Asian countries. Individual studies assessing its effects are mostly small, of uneven methodological quality and have unclear results. OBJECTIVES: To assess the effects of ginseng on erectile dysfunction. SEARCH METHODS: We conducted systematic searches on multiple electronic databases, including CENTRAL, MEDLINE, Embase, CINAHL, AMED, and loco-regional databases of east Asia, from their inceptions to 30 January 2021 without restrictions on language and publication status. Handsearches included conference proceedings. SELECTION CRITERIA: We included randomized or quasi-randomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment. DATA COLLECTION AND ANALYSIS: Two authors independently classified studies and three authors independently extracted data and assessed risk of bias in the included studies. We rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: We included nine studies with 587 men with mild to moderate erectile dysfunction, aged from 20 to 70 years old. The studies all compared ginseng to placebo. We found only short-term follow-up data (up to 12 weeks). Primary outcomes Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)-15 instrument (scale: 1 to 30, higher scores imply better function; mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I² = 0%; 3 studies; low certainty evidence) assuming a minimal clinically important difference (MCID) of 4. Ginseng probably also has a trivial effect on erectile function when compared to placebo based on the IIEF-5 instrument (scale: 1 to 25, higher scores imply better function; MD 2.39, 95% CI 0.89 to 3.88; I² = 0%; 3 studies; moderate certainty evidence) assuming a MCID of 5. Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I² = 0%; 7 studies; low certainty evidence). Based on 86 adverse events per 1000 men in the placebo group, this would correspond to 39 more adverse events per 1000 (95% CI 27 fewer to 174 more). Secondary outcomes Ginseng may improve men's self-reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I² = 23%; 6 studies; low certainty evidence). Based on 207 per 1000 men self-reporting the ability to have intercourse in the placebo group, this would correspond to 321 more men (95% CI 158 more to 558 more) per 1000 self-reporting the ability to have intercourse. Ginseng may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF-15 (scale: 0 to 15, higher scores imply greater satisfaction; MD 1.19, 95% CI 0.41 to 1.97; I²=0%; 3 studies; low certainty evidence) based on a MCID of 25% improvement from baseline. It may also have a trivial effect on men's satisfaction with intercourse based on item 5 of the IIEF-5 (scale: 0 to 5, higher scores imply more satisfaction; MD 0.60, 95% CI 0.02 to 1.18; 1 study; low certainty evidence) based on a MCID of 25% improvement from baseline. No study reported quality of life as an outcome. We found no trial evidence to inform comparisons to other treatments for erectile dysfunction, such as phosphodiesterase-5 inhibitors. We were unable to conduct any predefined subgroup analyses. AUTHORS' CONCLUSIONS: Based on mostly low certainty evidence, ginseng may only have trivial effects on erectile function or satisfaction with intercourse compared to placebo when assessed using validated instruments. Ginseng may improve men's self-reported ability to have intercourse. It may have little to no effect on adverse events. We found no trial evidence comparing ginseng to other agents with a more established role in treating erectile dysfunction, such as phosphodiesterase-5 inhibitors.
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Disfunção Erétil/tratamento farmacológico , Panax , Fitoterapia/métodos , Adulto , Idoso , Coito , Intervalos de Confiança , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
Due to the prevalence of globalization and the surge in people's traffic, diseases are spreading more rapidly than ever and the risks of sporadic contamination are becoming higher than before. Disease warnings continue to rely on censored data, but these warning systems have failed to cope with the speed of disease proliferation. Due to the risks associated with the problem, there have been many studies on disease outbreak surveillance systems, but existing systems have limitations in monitoring disease-related topics and internationalization. With the advent of online news, social media and search engines, social and web data contain rich unexplored data that can be leveraged to provide accurate, timely disease activities and risks. In this study, we develop an infectious disease surveillance system for extracting information related to emerging diseases from a variety of Internet-sourced data. We also propose an effective deep learning-based data filtering and ranking algorithm. This system provides nation-specific disease outbreak information, disease-related topic ranking, a number of reports per district and disease through various visualization techniques such as a map, graph, chart, correlation and coefficient, and word cloud. Our system provides an automated web-based service, and it is free for all users and live in operation.
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Doenças Transmissíveis , Aprendizado Profundo , Mídias Sociais , Algoritmos , Surtos de Doenças , Humanos , InternetRESUMO
BACKGROUND: The personality traits of endoscopists have been suggested to affect the adenoma detection rate (ADR). We thus evaluated the relationship between endoscopists' personality traits and the ADR during colonoscopy using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). METHODS: In total, 1230 patients (asymptomatic and aged 50-80 years) who underwent screening or surveillance (≥ 5 years) colonoscopy were recruited from 13 university hospitals by 20 endoscopists between September 2015 and December 2017. We retrospectively measured the ADR, polyp detection rate (PDR), and number of adenomas per colonoscopy (APC). All 20 endoscopists completed all 567 true/false MMPI-2 items. RESULTS: The overall mean colonoscopy withdrawal time, PDR, ADR, and APC were 7.3 ± 2.8 min, 55%, 45.3%, and 0.97 ± 1.58, respectively. No significant difference was observed in the MMPI-2 clinical scales (e.g., hypochondriasis and psychasthenia), content scales (e.g., obsessiveness and type A character), or supplementary scales (e.g., dominance and social responsibility) between the high ADR group (ADR ≥45%, n = 10) and the low ADR group (ADR < 45%, n = 10). In multivariate logistic regression analysis, the ADR was associated significantly with patient age and sex. The ADR was related significantly to endoscopists' colonoscopy experience and the per-minute increase in the colonoscopy withdrawal time (OR 1.21, 95% CI 1.06-1.38, p = 0.005). In a logistic regression analysis adjusted for patient factors, the ADR was associated significantly with ego strength (OR 1.04, 95% CI 1.00-1.09, p = 0.044), as measured by the MMPI-2. CONCLUSIONS: With the exception of ego strength, the endoscopists' personality traits were not associated with adenoma or polyp detection.
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Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/estatística & dados numéricos , Gastroenterologistas/psicologia , Idoso , Colonoscopia/psicologia , Feminino , Humanos , MMPI , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Appropriate colonoscopy withdrawal times for individual colonic segments are not well known. The relationship between withdrawal time and adenoma detection rate (ADR)/polyp detection rate (PDR) in individual colonic segments was examined in this study. METHODS: This was a prospective observational study involving 724 patients who underwent colonoscopy screening or surveillance colonoscopy from October 2015 to February 2017 at 10 university hospitals. RESULTS: In the right side of the colon, the ADR (33.2% vs 13.7%, P < .001), PDR, serrated polyp detection rate, and number of adenomas per colonoscopy (APC) were significantly higher when the colonoscopy withdrawal time was ≥2 minutes compared with <2 minutes. When the withdrawal time was ≥4 minutes in the proximal colon and ≥3 minutes in the left segment of the colon, the ADR, PDR, and APC were significantly higher compared with withdrawal times of <4 minutes and <3 minutes, respectively. Multivariate analyses showed that the ADR was significantly associated with withdrawal times of ≥2 minutes in the right side of the colon (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.72-5.15; P < .001), ≥4 minutes in the proximal colon (OR, 4.48; 95% CI, 3.15-6.36; P < .001), and ≥3 minutes in the left segment of the colon (OR, 2.92; 95% CI, 1.74-4.91; P < .001). CONCLUSIONS: The PDR and ADR appeared to be significantly increased when the withdrawal time was ≥2 minutes in the right-sided colon segment, ≥4 minutes in the proximal colon, and ≥3 minutes in the left-sided colon segment compared with shorter withdrawal times.
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Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Adenocarcinoma/patologia , Adenoma/patologia , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/patologia , Assistência ao Convalescente , Idoso , Colo Ascendente/patologia , Colo Descendente/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Fatores de TempoRESUMO
Despite recent advances in targeted drugs and immunotherapy, cancer remains "the emperor of all maladies" due to almost inevitable emergence of resistance. Drug resistance is thought to be driven by genetic alterations and/or dynamic plasticity that deregulate pathway activities and regulatory programs of a highly heterogeneous tumour. In this study, we propose a modelling framework to simulate population dynamics of heterogeneous tumour cells with reversible drug resistance. Drug sensitivity of a tumour cell is determined by its internal states, which are demarcated by coordinated activities of multiple interconnected oncogenic pathways. Transitions between cellular states depend on the effects of targeted drugs and regulatory relations between the pathways. Under this framework, we build a simple model to capture drug resistance characteristics of BRAF-mutant melanoma, where two cell states are determined by two mutually inhibitory - main and alternative - pathways. We assume that cells with an activated main pathway are proliferative yet sensitive to the BRAF inhibitor, and cells with an activated alternative pathway are quiescent but resistant to the drug. We describe a dynamical process of tumour growth under various drug regimens using the explicit solutions of mean-field equations. Based on these solutions, we compare efficacy of three treatment strategies from simulated data: static treatments with continuous and constant dosages, periodic treatments with regular intermittent active phases and drug holidays, and treatments derived from optimal control theory (OCT). Periodic treatments outperform static treatments with a considerable margin, while treatments based on OCT outperform the best periodic treatment. Our results provide insights regarding optimal cancer treatment modalities for heterogeneous tumours, and may guide the development of optimal therapeutic strategies to circumvent plastic drug resistance. They can also be used to evaluate the efficacy of suboptimal treatments that may account for side effects of the treatment and the cost of its application.
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Resistencia a Medicamentos Antineoplásicos , Melanoma , Modelos Biológicos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf , Humanos , Melanoma/tratamento farmacológico , Melanoma/enzimologia , Melanoma/genética , Melanoma/patologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismoRESUMO
INTRODUCTION AND HYPOTHESIS: This study evaluated the effects of using a heating pad during cystoscopy on anxiety, pain, and distress in female patients. METHODS: Seventy-four female patients who underwent rigid cystoscopy between January 2017 and August 2017 were randomized to either the experimental group using a heating pad (n = 37) or the control group using a pad without heat (n = 37). In the experimental group, a heating pad was applied to the patient's sacrum during cystoscopy. All patients completed the State-Trait Anxiety Inventory-S (STAI-S, 20-80) before and after the procedure and assessed their degree of pain and distress after the procedure using a visual analog scale (0-10). Systolic and diastolic blood pressure and pulse rate were also measured before and after the procedure. RESULTS: Demographic characteristics, mean age, procedure duration, and pre- and post-procedural systolic and diastolic blood pressures and pulse rate were statistically similar between the experimental and control groups. The mean STAI-S score of the experimental group was significantly lower than that in the control group (33.1 ± 10.1 vs 48.2 ± 11.1, p < 0.001). The experimental group had significantly lower pain and distress scores (visual analog scale, 3.8 ± 1.6 and 3.8 ± 1.8 respectively,) than the control group (6.4 ± 1.9 and 6.3 ± 2.1 respectively, both p < 0.001). CONCLUSIONS: Using a heating pad during cystoscopy significantly reduced female patients' anxiety, pain, and distress. We found this to be a safe, simple, and effective tool to use during cystoscopy.
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Cistoscopia/efeitos adversos , Temperatura Alta/uso terapêutico , Dor Processual/prevenção & controle , Idoso , Ansiedade/etiologia , Ansiedade/prevenção & controle , Cistoscopia/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Dor Processual/etiologiaRESUMO
This study was performed to evaluate what percentage of urinary tract infections (UTIs) caused by extended spectrum ß-lactamase (ESBL)-producing strains recurs with ESBL-producing strains during follow up and to assess the risk factors for recurrence with ESBL-producing Escherichia coli strains on subsequent first recurrence episode. We enrolled female patients with UTIs caused by ESBL-producing E. coli between May 2012 and December 2015, who were longitudinally followed up for at least 24 months. Among the 206 patients with ESBL positive UTI, 180 completed the study. 60 (60/180, 33.3%) of patient with first episode of UTI caused by ESBL-producing E. coli experienced recurrent UTIs during follow up. Of 60 patients, 43 (43/60, 71.7%) recurred with ESBL-producing E. coli on the first UTI recurrence episode. On multivariate analysis, the time to recurrence and history of cephalosporin usage in the last 6 months were identified as risk factors for recurrence with ESBL-producing E. coli per se (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.8-1.0, p = 0.030 and OR = 27.0, 95% CI 2.4-299.8, p = 0.007, respectively). These findings show that high proportion of patient with UTI caused by ESBL-producing E. coli recurs with ESBL-producing E. coli on subsequent recurrence episode. While result of antibiotic susceptibility cannot be identified on the visit day empirical treatment should be referred to the antecedent antibiotic resistance profile in patients whose previous UTIs were due to ESBL-producing strains.
Assuntos
Cistite/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/fisiologia , Infecções Urinárias/microbiologia , Resistência beta-Lactâmica , Doença Aguda/terapia , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Cistite/tratamento farmacológico , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Estudos Longitudinais , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Recidiva , Infecções Urinárias/tratamento farmacológicoRESUMO
INTRODUCTION: This study aimed to analyze the characteristics, etiology, and treatment of a series of patients with spontaneous perirenal hemorrhage (Wunderlich syndrome [WS]). METHODS: We retrospectively reviewed the records of 26 patients hospitalized for WS in a tertiary urological center between 2011 and 2018. All patients were evaluated for perirenal hemorrhage observed on computed tomography (CT) in the emergency department. Clinical variables (age, underlying diseases, symptoms, shock, and hospitalization period), laboratory test results, and radiological and pathological results were reviewed. RESULTS: The series included 28 events from 26 patients with a mean follow-up period of 20.2⯱â¯18.0â¯months. Flank pain was most common symptoms (92%). Twelve patients (46%) had visible renal lesions and associated hematoma and 14 only showed perirenal hematoma. In six patients with shock (systolic blood pressureâ¯<â¯90â¯mmâ¯Hg), 2 underwent emergency angioembolization. Twelve patients (46%) underwent exploration and total nephrectomy. In the final diagnosis, 4 cases of renal cell carcinoma, 3 of angiomyolipoma, 4 of simple renal cyst, 2 of acquired cystic kidney disease, 4 of sarcoma or other malignancy, 4 of chronic pyelonephritis, and 5 of idiopathic WS were observed. Patient age was associated with prediction of renal cell carcinoma in the patients with WS. CONCLUSION: Renal masses are the main cause of WS, and CT is the diagnostic procedure of choice. Old age is a possible risk factor for renal cell carcinoma in etiology of WS. Surgical treatment is preferred in patients diagnosed with renal malignancy and in cases of hemodynamic instability.
Assuntos
Dor no Flanco/patologia , Hemorragia/patologia , Nefropatias/patologia , Adulto , Fatores Etários , Idoso , Feminino , Dor no Flanco/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Nefropatias/complicações , Nefropatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nefrectomia , Estudos Retrospectivos , Choque , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: We assessed the association between metabolic health status and incidence of prostate cancer using the National Health Check-ups (NHC) database of Korea. METHODS: A total of 11,771,252 men who participated in the NHC between 2009 and 2012 and 56,552 men who were newly diagnosed with prostate cancer were analyzed. Normal-weight and obesity were defined as body mass index (BMI) < 25 kg/m2 and ≥ 25 kg/m2, respectively. Metabolic obesity was defined as the presence ≥ 3 components of the metabolic syndrome. Participants were stratified into 4 groups: metabolically healthy, normal-weight; metabolically obese, normal-weight (MONW); metabolically healthy, obese (MHO); and metabolically obese, obese. Multivariate Cox regression analysis was performed to examine the relationship between metabolic health status and incidence of prostate cancer. RESULTS: During a mean 5.4 ± 1.1 years of follow-up, 56,552 patients were registered with a diagnosis of prostate cancer. When analyzed according to metabolic health status classification, the multivariable-adjusted hazard ratio (HR) was 1.143 for the MONW group, 1.097 for the MHO group, showing the HR for the MONW group was higher than that for the MHO group. As the number of metabolic syndrome components increased, HR increased significantly. When stratified based on BMI, metabolically obese patients showed significantly higher HR than metabolically healthy patients in all BMI groups. CONCLUSION: This population-based nationwide study revealed an association between metabolic health status and the incidence of prostate cancer, and the risk increased according to the number of components of the metabolic syndrome.
Assuntos
Síndrome Metabólica/diagnóstico , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Bases de Dados Factuais , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
Indoor positioning technology has attracted the attention of researchers due to the increasing pervasiveness of smartphones and the development of sensor technology, along with the increase of indoor time. Sensor technology, which is one of the most commonly used data sources for indoor positioning, has the advantage that sensors can receive data from a smartphone without installing any additional device. However, the readings of built-in sensors are easily affected by the surrounding environment and are even occasionally different from each other which adversely influence the accuracy of indoor positioning. Moreover, once an error occurs, it can accumulate because there is not any reference point in the sensor, only in indoor positioning. In this paper, we present an accurate indoor positioning technology, which uses smartphone built-in sensors and Bluetooth beacon-based landmarks. Our proposed algorithm chooses proper one between values of sensors alternately based on their characteristics. It exploits landmarks as the reference points of indoor positioning. It also allows individuals to add the location where they repeatedly detect the same and special beacon received signal strength indicator values as a crowdsourced landmark. Extensive experimental results show that our proposed algorithm facilitates the acquisition of accurate heading direction and coordinates of the user.