Scrutinizing high-risk patients from ASC-US cytology via a deep learning model.

BACKGROUND: Atypical squamous cells of undetermined significance (ASC-US) is the most frequent but ambiguous abnormal Papanicolaou (Pap) interpretation and is generally triaged by high-risk human papillomavirus (hrHPV) testing before colposcopy. This study aimed to evaluate the performance of an artificial intelligence (AI)-based triage system to predict ASC-US cytology for cervical intraepithelial neoplasia 2+ lesions (CIN2+). METHODS: More than 60,000 images were used to train this proposed deep learning-based ASC-US triage system, where both cell-level and slide-level information were extracted. In total, 1967 consecutive ASC-US Paps from 2017 to 2019 were included in this study. Histological follow-ups were retrieved to compare the triage performance between the AI system and hrHPV in 622 patients with simultaneous hrHPV testing. RESULTS: In the triage of women with ASC-US cytology for CIN2+, our system attained equivalent sensitivity (92.9%; 95% confidence interval [CI], 75.0%-98.8%) and higher specificity (49.7%; 95% CI, 45.6%-53.8%) than hrHPV testing (sensitivity: 89.3%; 95% CI, 70.6%-97.2%; specificity: 34.3%; 95% CI, 30.6%-38.3%) without requiring additional patient examination or testing. Additionally, the independence of this system from hrHPV testing (κ = 0.138) indicated that these 2 different methods could be used to triage ASC-US as an alternative way. CONCLUSION: This de novo deep learning-based system can triage ASC-US cytology for CIN2+ with a performance superior to hrHPV testing and without incurring additional expenses.

Path Following Control for Underactuated Airships with Magnitude and Rate Saturation.

This paper proposes a reinforcement learning (RL) based path following strategy for underactuated airships with magnitude and rate saturation. The Markov decision process (MDP) model for the control problem is established. Then an error bounded line-of-sight (LOS) guidance law is investigated to restrain the state space. Subsequently, a proximal policy optimization (PPO) algorithm is employed to approximate the optimal action policy through trial and error. Since the optimal action policy is generated from the action space, the magnitude and rate saturation can be avoided. The simulation results, involving circular, general, broken-line, and anti-wind path following tasks, demonstrate that the proposed control scheme can transfer to new tasks without adaptation, and possesses satisfying real-time performance and robustness.

Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injury.

OBJECTIVE: To investigate the clinical efficacy of cefazolin sodium pentahydrate combined with vacuum sealing drainage (VSD) in the treatment of open fracture complicated with soft tissue injury. METHODS: Sixty-three patients with open fracture complicated with soft tissue injury were divided into observation (n = 33) and control (n = 30) groups. After surgical reduction, fixation, and repair of the fractures, the control group was treated with VSD for 10 days, and the observation group was treated with cefazolin sodium pentahydrate based on VSD for 10 days. The infection control time was recorded. After treatment, the pain of patients was evaluated. Before and after treatment, the serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), cortisol, epinephrine, norepinephrine, and glucose were detected. After 6 months of treatment, the total effective rate of the treatment was evaluated. RESULTS: The infection control time and Visual Analogue Scale score after treatment in the observation group were significantly lower than in the control group, respectively (P < 0.05). After the treatment, the serum levels of CRP, IL-6, IL-8, TNF-α, cortisol, epinephrine, norepinephrine, and glucose in each group were significantly lower than before the treatment (P < 0.05), and each index in observation was significantly lower than in the control group (P < 0.05). CONCLUSIONS: In the treatment of open fractures complicated with soft tissue injury, cefazolin sodium pentahydrate combined with VSD can effectively reduce inflammation and stress, thus improving the treatment efficacy.

Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injury

SUMMARY OBJECTIVE To investigate the clinical efficacy of cefazolin sodium pentahydrate combined with vacuum sealing drainage (VSD) in the treatment of open fracture complicated with soft tissue injury. METHODS Sixty-three patients with open fracture complicated with soft tissue injury were divided into observation (n = 33) and control (n = 30) groups. After surgical reduction, fixation, and repair of the fractures, the control group was treated with VSD for 10 days, and the observation group was treated with cefazolin sodium pentahydrate based on VSD for 10 days. The infection control time was recorded. After treatment, the pain of patients was evaluated. Before and after treatment, the serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), cortisol, epinephrine, norepinephrine, and glucose were detected. After 6 months of treatment, the total effective rate of the treatment was evaluated. RESULTS The infection control time and Visual Analogue Scale score after treatment in the observation group were significantly lower than in the control group, respectively (P < 0.05). After the treatment, the serum levels of CRP, IL-6, IL-8, TNF-α, cortisol, epinephrine, norepinephrine, and glucose in each group were significantly lower than before the treatment (P < 0.05), and each index in observation was significantly lower than in the control group (P < 0.05). CONCLUSIONS In the treatment of open fractures complicated with soft tissue injury, cefazolin sodium pentahydrate combined with VSD can effectively reduce inflammation and stress, thus improving the treatment efficacy.

RESUMO OBJETIVO Investigar a eficácia clínica do cefazolin penta-hidrato de sódio combinado com drenagem por vedação a vácuo (VSD) no tratamento da fratura exposta complicada com lesão nos tecidos moles. MÉTODOS Sessenta e três doentes com fratura exposta complicada com lesões nos tecidos moles foram divididos em grupos de observação (n=33) e controle (n=30). Após redução cirúrgica, fixação e reparação da fratura, o grupo de controle foi tratado com VSD durante dez dias e o grupo de observação foi tratado com cefazolina penta-hidrato de sódio com base no VSD durante dez dias. O tempo de controle de infecção foi gravado. Após o tratamento, a dor dos doentes foi avaliada. Antes e após o tratamento, foram detectados os níveis séricos de proteína C-reativa (CRP), interleucina (IL)-6, IL -8, fator de necrose tumoral alfa (TNF-α), cortisol, epinefrina, norepinefrina e glicose. Após seis meses de tratamento, a taxa efetiva total de tratamento foi avaliada. RESULTADOS O tempo de controle da infecção e a pontuação da Escala Visual Analógica após o tratamento no grupo de observação foram significativamente inferiores ao do grupo de controle, respectivamente (P<0,05). Após o tratamento, os níveis séricos de CRP, IL-6, IL-8, TNF-α, cortisol, epinefrina, norepinefrina e glicose em cada grupo foram significativamente menores do que antes do tratamento, respectivamente (P<0,05), e cada índice de observação foi significativamente inferior ao do grupo de controle (P<0,05). CONCLUSÃO No tratamento da fratura exposta complicada com lesões nos tecidos moles, o cefazolin penta-hidrato de sódio combinado com VSD pode efetivamente reduzir a inflamação e o estresse, melhorando assim a eficácia do tratamento.

Estimation of Multi-state Models with Missing Covariate Values Based on Observed Data Likelihood.

Continuous-time multi-state models are commonly used to study diseases with multiple stages. Potential risk factors associated with the disease are added to the transition intensities of the model as covariates, but missing covariate measurements arise frequently in practice. We propose a likelihood-based method that deals efficiently with a missing covariate in these models. Our simulation study showed that the method performs well for both 'missing completely at random' and 'missing at random' mechanisms. We also applied our method to a real dataset, the Einstein Aging Study.

Aß vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aß, and microhemorrhages.

Beta-amyloid (Aß) immunotherapy is a promising intervention to slow Alzheimer's disease. Aging dogs naturally accumulate Aß and show cognitive decline. An active vaccine against fibrillar Aß 1-42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aß. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aß. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11-12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); and (4) ENR/VAC (E/V) and treated for 20 months. VAC decreased brain Aß, pyroglutamate Aß, increased cerebrospinal fluid Aß 42 and brain-derived neurotrophic factor RNA levels but also increased microhemorrhages. ENR reduced brain Aß and prevented microhemorrhages. The combination treatment resulted in a significant maintenance of learning over time, reduced Aß, and increased brain-derived neurotrophic factor mRNA despite increased microhemorrhages; however, there were no benefits to memory. These results suggest that the combination of immunotherapy with behavioral enrichment leads to cognitive maintenance associated with reduced neuropathology that may benefit people with Alzheimer's disease.

Multi-state models and missing covariate data: Expectation-Maximization algorithm for likelihood estimation.

Multi-state models have been widely used to analyze longitudinal event history data obtained in medical and epidemiological studies. The tools and methods developed recently in this area require completely observed data. However, missing data within variables of interest is very common in practice, and it has been an issue in applications. We propose a type of EM algorithm, which handles missingness within multiple binary covariates efficiently, for multi-state model applications. Simulation studies show that the EM algorithm performs well for both missing completely at random (MCAR) and missing at random (MAR) covariate data. We apply the method to a longitudinal aging and cognition study dataset, the Klamath Exceptional Aging Project (KEAP), whose data were collected at Oregon Health & Science University and integrated into the Statistical Models of Aging and Risk of Transition (SMART) database at the University of Kentucky.

A comparison of time-homogeneous Markov chain and Markov process multi-state models.

Time-homogeneous Markov models are widely used tools for analyzing longitudinal data about the progression of a chronic disease over time. There are advantages to modeling the true disease progression as a discrete time stationary Markov chain. However, one limitation of this method is its inability to handle uneven follow-up assessments or skipped visits. A continuous time version of a homogeneous Markov process multi-state model could be an alternative approach. In this article, we conduct comparisons of these two methods for unevenly spaced observations. Simulations compare the performance of the two methods and two applications illustrate the results.

Transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: a retrospective study of a 5-year experience in a single institution.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is the mainstay of management for patients with unresectable hepatocellular carcinoma (HCC). The aim of this study is to evaluate the survival rates of patients with unresectable HCC following TACE performed in a single center. METHODOLOGY: The authors retrospectively assessed the electronic medical records of 512 patients in whom HCC was newly diagnosed from January 2008 to December 2012 at a single tertiary medical center. Patients with decompensated hepatic function were excluded. Hepatic artery infusion chemotherapy was performed using one drug or combinations of oxaliplatin, fluorouracil and doxorubicin. The primary endpoint of the study was overall survival (OS). Survival rates were calculated using Kaplan-Meier method. RESULTS: A total of 512 HCC patients (425 men and 87 women; mean age, 58.9 years; age range, 38.3-86.1 years) were treated with TACE in a single center. The overall survival rates at 1, 2, and 3 years were 62%, 43%, and 37%, respectively. The overall median survival time from the start of TACE treatment was 15 months. CONCLUSIONS: TACE is an effective minimally invasive therapy option for palliative treatment of HCC patients.

Chaperone-dependent Neurodegeneration: A Molecular Perspective on Therapeutic Intervention.

Maintenance of cellular homeostasis is regulated by the molecular chaperones. Under pathogenic conditions, aberrant proteins are triaged by the chaperone network. These aberrant proteins, known as "clients," have major roles in the pathogenesis of numerous neurological disorders, including tau in Alzheimer's disease, α-synuclein and LRRK2 in Parkinson's disease, SOD-1, TDP-43 and FUS in amyotrophic lateral sclerosis, and polyQ-expanded proteins such as huntingtin in Huntington's disease. Recent work has demonstrated that the use of chemical compounds which inhibit the activity of molecular chaperones subsequently alter the fate of aberrant clients. Inhibition of Hsp90 and Hsc70, two major molecular chaperones, has led to a greater understanding of how chaperone triage decisions are made and how perturbing the chaperone system can promote clearance of these pathogenic clients. Described here are major pathways and components of several prominent neurological disorders. Also discussed is how treatment with chaperone inhibitors, predominately Hsp90 inhibitors which are selective for a diseased state, can relieve the burden of aberrant client signaling in these neurological disorders.