Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.465
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34639259

RESUMO

Intravenous tranexamic acid (TXA) has been administered to reduce intraoperative blood loss in scoliosis surgery. However, the therapeutic effect of TXA on spinal muscular atrophy (SMA) scoliosis surgery is not well demonstrated. Therefore, this study aimed to assess the efficacy of intravenous TXA in SMA scoliosis surgery. From December 1993 to August 2020, 30 SMA patients who underwent scoliosis surgery (posterior fusion with fusion level of thoracic second or third to pelvis) were retrospectively enrolled and divided into the TXA group and non-TXA (control) group, with 15 patients in each group. Survey parameters were the amount of blood loss, blood transfusion, crystalloid transfusion volume, intubation time, and associated pulmonary complications (including pneumonia, pulmonary edema, and pulmonary atelectasis). The TXA group had significantly lesser blood loss than the control group (p = 0.011). Compared with the control group, the TXA group had significantly lower blood transfusion (p < 0.001), crystalloid volume (p = 0.041), and total transfusion volume (p = 0.005). In addition, the TXA group had fewer postoperative pulmonary complications, and patients with pulmonary complications were associated with a higher relative crystalloid volume and relative total transfusion volume (p = 0.003 and 0.022, respectively). In conclusion, TXA can be effective in reducing intraoperative blood loss and crystalloid fluid transfusions during scoliosis surgery in SMA patients, which may aid in reducing postoperative pulmonary complications.

2.
Cell Biol Toxicol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648132

RESUMO

Doxorubicin (DOX) has toxic effects on the heart, causing cardiomyopathy and heart injury, but the underlying mechanisms of these effects require further investigation. This study investigated the role of DOX in promoting ferroptosis to induce myocardial injury. AC16 cardiomyocyte and neonatal rat ventricle cardiomyocytes were used as an in vitro model to study the molecules involved in myocardial injury using gene silencing, ectopic expression, and RNA immunoprecipitation. Messenger RNA and protein level analyses showed that DOX treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. Furthermore, a lack of miR-7-5p expression led to increased levels of transferrin receptor, promoting the uptake of iron and production of lipid reactive oxygen species and demonstrating that DOX-induced ferroptosis occurs in AC16 cells. Additionally, we found that miR-7-5p targets METTL14 in AC16 cells. Meanwhile, the role of METTL14/KCNQ1OT1/miR-7-5p axis in regulating ferroptosis in neonatal rat ventricle cardiomyocytes was also confirmed. Our results indicate that selectively inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34606060

RESUMO

PURPOSE: Precise segmentation of intestinal wall vessels is vital to colonic perforation prevention. However, there are interferences such as gastric juice in the vessel image of the intestinal wall, especially vessels and the mucosal folds are difficult to distinguish, which easily lead to mis-segmentation. In addition, the insufficient feature extraction of intricate vessel structures may leave out information of tiny vessels that result in rupture. To overcome these challenges, an effective network is proposed for segmentation of intestinal wall vessels. METHODS: A global context attention network (GCA-Net) that employs a multi-scale fusion attention (MFA) module is proposed to adaptively integrate local and global context information to improve the distinguishability of mucosal folds and vessels, more importantly, the ability to capture tiny vessels. Also, a parallel decoder is used to introduce a contour loss function to solve the blurry and noisy blood vessel boundaries. RESULTS: Extensive experimental results demonstrate the superiority of the GCA-Net, with accuracy of 94.84%, specificity of 97.89%, F1-score of 73.80%, AUC of 96.30%, and MeanIOU of 76.46% in fivefold cross-validation, exceeding the comparison methods. In addition, the public dataset DRIVE is used to verify the potential of GCA-Net in retinal vessel image segmentation. CONCLUSION: A novel network for segmentation of intestinal wall vessels is developed, which can suppress interferences in intestinal wall vessel images, improve the discernibility of blood vessels and mucosal folds, enhance vessel boundaries, and capture tiny vessels. Comprehensive experiments prove that the proposed GCA-Net can accurately segment the intestinal wall vessels.

4.
BMC Musculoskelet Disord ; 22(1): 867, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635092

RESUMO

BACKGROUND: Early versions of spinal muscular atrophy (SMA) scoliosis correction surgery often involved sublaminar devices. Recently, the utilization of pedicle screws has gained much popularity. Pedicle screws are generally believed to provide additional deformity correction, but pedicle size and rotational deformity limit their application in the thoracic spine, resulting in a hybrid construct involving pedicle screws and sublaminar wire. Studies of the efficacy of hybrid instrumentation in SMA scoliosis are often limited by the scarcity of the disease itself. In this study, we aimed to compare the surgical outcomes between hybrid constructs involving pedicle screws and sublaminar wire and sublaminar wire alone in patients with SMA scoliosis. METHODS: We retrospectively reviewed the clinical records and radiographic assessments of patients with SMA scoliosis who underwent corrective surgery between 1993 and 2017. The radiographic assessments included deformity correction and progressive changes in the major curve angle, pelvic tilt (PT) and coronal balance (CB). The correction of deformities was observed postoperatively and at the patient's 2-year follow-up to test the efficacy of each type of construct. RESULTS: Thirty-three patients were included in this study. There were 14 and 19 patients in the wiring and hybrid construct groups, respectively. The hybrid construct group demonstrated a higher major curve angle correction (50.5° ± 11.2° vs. 36.4° ± 8.4°, p < 0.001), a higher apical vertebral rotation correction (10.6° ± 3.9° vs. 4.8° ± 2.6°, p < 0.001), and a reduced progression of the major curve angle at the 2-year follow-up (5.1° ± 2.9° vs. 8.7° ± 4.8°, p < 0.001). A moderate correlation was observed between the magnitude of correction of the apical vertebral rotation angle and the major curve (r = 0.528, p = 0.002). CONCLUSION: This study demonstrated that hybrid instrumentation can provide a greater magnitude of correction in major curve and apical rotation as well as less major curve progression than sublaminar wire instrumentation alone in patients with SMA scoliosis. Level of evidence III.


Assuntos
Atrofia Muscular Espinal , Escoliose , Humanos , Atrofia Muscular Espinal/diagnóstico por imagem , Atrofia Muscular Espinal/cirurgia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Coluna Vertebral , Resultado do Tratamento
5.
Adv Mater ; : e2101413, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480499

RESUMO

The development of reliable and safe high-energy-density lithium-ion batteries is hindered by the structural instability of cathode materials during cycling, arising as a result of detrimental phase transformations occurring at high operating voltages alongside the loss of active materials induced by transition metal dissolution. Originating from the fundamental structure/function relation of battery materials, the authors purposefully perform crystallographic-site-specific structural engineering on electrode material structure, using the high-voltage LiNi0.5 Mn1.5 O4 (LNMO) cathode as a representative, which directly addresses the root source of structural instability of the Fd 3 ¯ m structure. By employing Sb as a dopant to modify the specific issue-involved 16c and 16d sites simultaneously, the authors successfully transform the detrimental two-phase reaction occurring at high-voltage into a preferential solid-solution reaction and significantly suppress the loss of Mn from the LNMO structure. The modified LNMO material delivers an impressive 99% of its theoretical specific capacity at 1 C, and maintains 87.6% and 72.4% of initial capacity after 1500 and 3000 cycles, respectively. The issue-tracing site-specific structural tailoring demonstrated for this material will facilitate the rapid development of high-energy-density materials for lithium-ion batteries.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34477538

RESUMO

BACKGROUND: Regulation of glutamate release is crucial for maintaining normal brain function, but excess glutamate release is implicated in many neuropathological conditions. Therefore, the minimum glutamate release from presynaptic nerve terminals is an important neuroprotective mechanism. OBJECTIVE: In this mini-review, we analyze the three B vitamins, namely vitamin B2 (riboflavin), vitamin B6 (pyridoxine), and vitamin B12 (cyanocobalamin), that affect the 4-aminopyridine (4-AP)-evoked glutamate release from presynaptic nerve terminal in rat and discuss their neuroprotective role. METHODS: In this study, the measurements include glutamate release, DiSC3(5), and Fura-2. RESULTS: The riboflavin, pyridoxine, and cyanocobalamin produced significant inhibitory effects on 4-aminopyridine-evoked glutamate release from rat cerebrocortical nerve terminals (synaptosomes) in a dose-dependent relationship. These presynaptic inhibitory actions of glutamate release are attributed to inhibition of physiologic Ca2+-dependent vesicular exocytosis but not Ca2+-independent nonvesicular release. These effects also did not affect membrane excitability, while diminished cytosolic [Ca2+]c through a reduction of direct Ca2+ influx via Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, rather than through indirect Ca2+ induced Ca2+ release from ryanodine-sensitive intracellular stores. Furthermore, their effects were attenuated by GF109203X and Ro318220, two protein kinase C (PKC) inhibitors, suggesting suppression of PKC activity. Taken together, these results suggest that riboflavin, pyridoxine, and cyanocobalamin inhibit presynaptic vesicular glutamate release from rat cerebrocortical synaptosomes, through the depression Ca2+ influx via voltage-dependent Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, and PKC signaling cascade. CONCLUSION: Therefore, these B vitamins may reduce the strength of glutamatergic synaptic transmission and is of considerable importance as potential targets for therapeutic agents in glutamate-induced excitation-related diseases.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34501941

RESUMO

The stigma associated with serious mental illnesses causes a huge burden on patients, their families, and society. In October 2012, in Taiwan, schizophrenia was renamed to reduce the stigma associated with this disease. The aim of this study was to compare the differences of public stigma, self-stigma, and social distance associated with schizophrenia between old and new name of schizophrenia in medical students. A cross-sectional survey was administered to 180 medical students of Taipei Medical University from October 2014 to February 2015. In total, 123 complete questionnaires were included in this study. Participants completed the modified attribution questionnaire, the perceived psychiatric stigma scale, and modified social distance scale to assess public stigma, self-stigma, and social distance, respectively. We also collected basic demographic data and previous experience of contact with people with mental illness. In total, 52 and 71 of the first- and fourth-year medical students, respectively, participated in the study. Among them, there were 51 females and 72 males. A significant difference in age was observed between the first- and fourth-year groups (20.2 ± 1.7 years vs. 22.7 ± 0.9 years, p < 0.001). After renaming schizophrenia, we noted significant differences in the scores in the modified attribution questionnaire, the perceived psychiatric stigma scale, and the modified social distance scale in all participants and the fourth-year students, respectively. Female gender (Beta = 0.230, p = 0.018) was significantly associated with the difference in the score of the modified attribution questionnaire after name change. The difference in the score of the perceived psychiatric stigma scale after the name change (Beta = 0.277, p = 0.004) and age (Beta = -0.186, p = 0.049) were significantly associated with the difference in the score of the modified social distance scale after name change. In conclusion, renaming was associated with the changes in the scores of the modified attribution questionnaire, the perceived psychiatric stigma scale, and the modified social distance scale toward individuals with schizophrenia in medical students of one Taiwan university. Further studies with large sample sizes, diverse participant backgrounds, and that monitor the subsequent behavioral changes are warranted.

8.
Light Sci Appl ; 10(1): 190, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535628

RESUMO

This study is the first to explore the potential associations among allergic conjunctivitis (AC), air pollution, and meteorological conditions in Northeast China. Data of meteorology, ambient atmospheric pollutants, and the incidence of allergic conjunctivitis (IAC) in prefecture-level cities between the years 2014 and 2018 are analyzed. The results show an increasing trend in the AC of average growth rate per annum 7.6%, with the highest incidence in the provincial capitals. The IAC is positively correlated with atmospheric pollutants (i.e., PM2.5, PM10, CO, SO2, NO2, and O3) and meteorological factors (i.e., air temperature and wind speed), but negatively correlated with relative humidity. These results suggest that the IAC is directly proportional to pollution level and climatic conditions, and also the precedence of air pollution. We have further obtained the threshold values of atmospheric pollutants concentration and meteorological factors, a turning point above which more AC may be induced. Compared with the air quality standard advised by China and the World Health Organization (WHO), both thresholds of PM10 (70 µg m-3) and PM2.5 (45 µg m-3) are higher than current standards and pose a less environmental risk for the IAC. SO2 threshold (23 µg m-3) is comparable to the WHO standard and significantly lower than that of China's, indicating greater environmental risks in China. Both thresholds of NO2 (27 µg m-3) and O3 (88 µg m-3) are below current standards, indicating that they are major environmental risk factors for the IAC. Our findings highlight the importance of atmospheric environmental protection and reference for health-based amendment.

9.
Comput Med Imaging Graph ; 93: 101974, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34481236

RESUMO

While deep learning models have demonstrated outstanding performance in medical image segmentation tasks, histological annotations for training deep learning models are usually challenging to obtain, due to the effort and experience required to carefully delineate tissue structures. In this study, we propose an unsupervised method, termed as tissue cluster level graph cut (TisCut), for segmenting histological images into meaningful compartments (e.g., tumor or non-tumor regions), which aims at assisting histological annotations for downstream supervised models. The TisCut consists of three modules. First, histological tissue objects are clustered based on their spatial proximity and morphological features. The Voronoi diagram is then constructed based on tissue object clustering. In the last module, morphological features computed from the Voronoi diagram are integrated into a region adjacency graph. Image partition is then performed to divide the image into meaningful compartments by using the graph cut algorithm. The TisCut has been evaluated on three histological image sets for necrosis and melanoma detections. Experiments show that the TisCut could provide a comparative performance with U-Net models, which achieves about 70% and 85% Jaccard index coefficients in partitioning brain and skin histological images, respectively. In addition, it shows the potential to be used for generating histological annotations when training masks are difficult to collect for supervised segmentation models.

10.
Ann Vasc Surg ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34481882

RESUMO

BACKGROUND: To describe a retrograde recanalization for the proximal occluded lesion in right renal artery (RRA) in young patient with fibromuscular dysplasia (FMD). METHODS: A 10-year-old girl presented to our hospital with proximal RRA occlusion and refractory hypertension though she took anti-hypertension medicines. Her renin and aldosterone were beyond the normal level in both base state and excited state. Her glomerular filtration rate at right kidney was only 18.4 ml/min. Angiography revealed proximal RRA occlusion and a compensated collateral artery (CCA) from the infrarenal aorta to the RRA. She was thus diagnosed with focal FMD. A retrograde recanalization was performed through this CCA. RESULTS: Angioplasty and stenting were successfully performed to treat the proximal RRA occlusion. Postoperatively, the glomerular filtration rate in the right kidney improved. One-year follow-up revealed that, the blood pressure maintained at normal range without any antihypertensive agents. No other discomfort was complained. CONCLUSIONS: It is feasible to establish a working pathway with patient's compensated collateral artery to treat the renal artery occlusion.

11.
Acta Neurol Taiwan ; 30(2): 63-73, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34549391

RESUMO

PURPOSE: To evaluate the relationship between the severity of clinical symptoms and cognitive function of patients with Parkinson's disease (PD) and the serum vitamin D level and nutrition status. METHODS: Thirty-three adult PD patient were included in the study (November 2016 to October 2018) and their clinical symptom severity (including the Hoehn and Yahr scale and unified Parkinson's disease rating scale (UPDRS)) and cognitive function (mini-mental state examination) were assessed in two visits (at time of enrollment and one year after the enrollment). In the meanwhile, their renal/liver function, serum level of vitamin D, vitamin B12, Folate and high-sensitive C-reactive protein were also measured for clinical correlation and comparisons. RESULTS: From the two visits, we found our patients divided into two group, the well-nourished status group and at risk or malnutrition status group. In both visits, we uncovered patients at risk of malnutrition status had worse clinical severity and more impaired memory. As for hypovitaminosis D, the vitamin D level alone made no significant correlation with the clinical severity and cognitive function. CONCLUSION: This study revealed that PD patient with at risk of malnutrition status has impaired cognitive function but patients with abnormal serum vitamin D level did not have such influence. But PD patients with abnormal vitamin D level have a higher hs-CRP level which has an influence on the cognitive function of PD patients. Therefore, abnormal serum vitamin D level may have an indirect influence on the cognitive function of PD patients through the influence on the hs-CRP level. This study is limited by the small case-number and short follow-up time. Further large scale study and longer observation period are needed for a better delineation of the relationship between the serum vitamin D level and nutritional status with the clinical condition of the PD patients.


Assuntos
Desnutrição , Doença de Parkinson , Deficiência de Vitamina D , Adulto , Cognição , Humanos , Estado Nutricional , Doença de Parkinson/complicações , Deficiência de Vitamina D/complicações
12.
Acta Neurol Taiwan ; 30(1): 11-20, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34549396

RESUMO

OBJECTIVE: No previous study has reported on the clinical characteristics of cryptococcal meningitis (CM) focusing solely on young adults. PATIENTS AND METHODS: Ninety-nine adult patients with CM (64 men and 35 women) were enrolled, of whom 26 were classified into the young adult group (≤ 40 years) and 73 into the non-young adult group (> 40 years). The modified Rankin scale (mRS) was used to evaluate the outcomes of the survivors at the time of discharge and at 1 year of follow-up. The clinical characteristics and laboratory data between 1) the young adult CM patients with and without acquired immunecompromised syndrome and 2) the male and female young adult CM patients were compared. The prognostic factors of the young adult CM patients were also analyzed. RESULTS: The young adult group had a higher incidence of headache as the clinical presentation which may have been due to the higher intracranial pressure in this group. The overall mortality rate of the young adults with CM was high (38.5%, 10/26), but no significant prognostic factors were found. In followup studies of the neurologic deficits, the young adult survivors had better outcomes (mRS scores = 0-2) than the non-young adult group at discharge and 1 year after discharge. CONCLUSION: The young adult CM patients had a higher incidence of headache as the clinical presentation. Although the mortality rate in the young adult CM patients was high, the survivors had better neurologic outcomes.


Assuntos
Meningite Criptocócica , Feminino , Cefaleia/etiologia , Humanos , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Resultado do Tratamento , Adulto Jovem
13.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34548401

RESUMO

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Homeostase , Ferro/metabolismo , Fragmentos de Peptídeos/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética
14.
Prev Med ; 153: 106787, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34506818

RESUMO

A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71-0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77-0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56-0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68-0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55-0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34444167

RESUMO

This study aimed to investigate the factors influencing physicians use of the PharmaCloud system in Taiwan through Technology Continuance Theory (TCT) and to construct a TCT-based structured questionnaire to demonstrate the attitude and behavior of physicians in the Taiwanese medical system. It focused on investigating "confirmation", "perceived usefulness", "perceived ease of use", "attitude", "satisfaction", and "continuance intention" towards the preload-based comparison and manual search in PharmaCloud by attending physicians during their outpatient clinics. Path analysis was used to analyze the cause and effect relationship between variables. This study collected 528 valid questionnaires and the results of path analysis found that factors affecting physicians' continued use of preload-based comparison in PharmaCloud included "perceived usefulness", "satisfaction", and "attitude" (all p < 0.001); however, factors that influenced physicians' continued use of manual search in PharmaCloud were only "satisfaction" and "attitude" (all p < 0.001). Additionally, the effects of "perceived usefulness" and "perceived ease of use" on "satisfaction" could only be seen in preload-based comparison in PharmaCloud. In conclusion, when physicians' actual use of PharmaCloud met their expectations, physicians had higher levels of confirmation and better perceived usefulness, which naturally increased their satisfaction and attitude towards PharmaCloud and positively prompted them to continue using it.


Assuntos
Troca de Informação em Saúde , Médicos , Atitude do Pessoal de Saúde , Humanos , Programas Nacionais de Saúde , Inquéritos e Questionários , Taiwan
16.
Artigo em Inglês | MEDLINE | ID: mdl-34388099

RESUMO

Almost 25% of COVID-19 patients end up in ICU needing critical mechanical ventilation support. There is currently no validated objective way to predict which patients will end up needing ventilator support, when the disease is mild and not progressed. N=869 patients from two sites (D1: N=822, D2: N=47) with baseline clinical characteristics and chest CT scans were considered for this study. The entire dataset was randomly divided into 70% training, D1 train (N=606) and 30% test-set (D test : D1 test (N=216) + D2 (N=47)). An expert radiologist delineated ground-glass-opacities (GGOs) and consolidation regions on a subset of D1 train, (D1 train_sub, N=88). These regions were automatically segmented and used along with their corresponding CT volumes to train an imaging AI predictor (AIP) on D1 train to predict the need of mechanical ventilators for COVID-19 patients. Finally, top five prognostic clinical factors selected using univariate analysis were integrated with AIP to construct an integrated clinical and AI imaging nomogram (ClAIN). Univariate analysis identified lactate dehydrogenase, prothrombin time, aspartate aminotransferase, %lymphocytes, albumin as top five prognostic clinical features. AIP yielded an AUC of 0.81 on D test and was independently prognostic irrespective of other clinical parameters on multivariable analysis (p<0.001). ClAIN improved the performance over AIP yielding an AUC of 0.84 (p=0.04) on D test. ClAIN outperformed AIP in predicting which COVID-19 patients ended up needing a ventilator. Our results across multiple sites suggest that ClAIN could help identify COVID-19 with severe disease more precisely and likely to end up on a life-saving mechanical ventilation.

17.
J Med Chem ; 64(17): 12537-12547, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34351142

RESUMO

Triple-negative breast cancer (TNBC) has been considered the most aggressive and mortal breast cancer. Thus far, it remains an important challenge to develop TNBC targeted therapy. As revealed from numerous recent studies, ANXA2 may be a potential target to treat TNBC. In the present study, a natural product 5α-epoxyalantolactone (5α-EAL) was discovered as an anti-breast cancer stem cells (BCSCs) lead compound. Furthermore, 5α-EAL was found to be able to notably suppress the function of ANXA2 by covalently targeting cysteine 9 (Cys9) of ANXA2. To the best of our knowledge, 5α-EAL was recognized as the first small molecule functional inhibitor of ANXA2. It could significantly inhibit the formation of the heterotetrameric complex of ANXA2 and S100A10, which is capable of transporting E-cadherin (E-Ca) to the membrane. The above findings may be used as a possible strategy to develop novel anti-TNBC therapies targeting ANXA2.

18.
Sensors (Basel) ; 21(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34451072

RESUMO

Colorectal cancer has become the third most commonly diagnosed form of cancer, and has the second highest fatality rate of cancers worldwide. Currently, optical colonoscopy is the preferred tool of choice for the diagnosis of polyps and to avert colorectal cancer. Colon screening is time-consuming and highly operator dependent. In view of this, a computer-aided diagnosis (CAD) method needs to be developed for the automatic segmentation of polyps in colonoscopy images. This paper proposes a modified SegNet Visual Geometry Group-19 (VGG-19), a form of convolutional neural network, as a CAD method for polyp segmentation. The modifications include skip connections, 5 × 5 convolutional filters, and the concatenation of four dilated convolutions applied in parallel form. The CVC-ClinicDB, CVC-ColonDB, and ETIS-LaribPolypDB databases were used to evaluate the model, and it was found that our proposed polyp segmentation model achieved an accuracy, sensitivity, specificity, precision, mean intersection over union, and dice coefficient of 96.06%, 94.55%, 97.56%, 97.48%, 92.3%, and 95.99%, respectively. These results indicate that our model performs as well as or better than previous schemes in the literature. We believe that this study will offer benefits in terms of the future development of CAD tools for polyp segmentation for colorectal cancer diagnosis and management. In the future, we intend to embed our proposed network into a medical capsule robot for practical usage and try it in a hospital setting with clinicians.


Assuntos
Colonoscopia , Redes Neurais de Computação , Bases de Dados Factuais , Diagnóstico por Computador , Processamento de Imagem Assistida por Computador , Projetos de Pesquisa
19.
JMIR Med Inform ; 9(8): e23230, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463639

RESUMO

BACKGROUND: The International Classification of Diseases (ICD) code is widely used as the reference in medical system and billing purposes. However, classifying diseases into ICD codes still mainly relies on humans reading a large amount of written material as the basis for coding. Coding is both laborious and time-consuming. Since the conversion of ICD-9 to ICD-10, the coding task became much more complicated, and deep learning- and natural language processing-related approaches have been studied to assist disease coders. OBJECTIVE: This paper aims at constructing a deep learning model for ICD-10 coding, where the model is meant to automatically determine the corresponding diagnosis and procedure codes based solely on free-text medical notes to improve accuracy and reduce human effort. METHODS: We used diagnosis records of the National Taiwan University Hospital as resources and apply natural language processing techniques, including global vectors, word to vectors, embeddings from language models, bidirectional encoder representations from transformers, and single head attention recurrent neural network, on the deep neural network architecture to implement ICD-10 auto-coding. Besides, we introduced the attention mechanism into the classification model to extract the keywords from diagnoses and visualize the coding reference for training freshmen in ICD-10. Sixty discharge notes were randomly selected to examine the change in the F1-score and the coding time by coders before and after using our model. RESULTS: In experiments on the medical data set of National Taiwan University Hospital, our prediction results revealed F1-scores of 0.715 and 0.618 for the ICD-10 Clinical Modification code and Procedure Coding System code, respectively, with a bidirectional encoder representations from transformers embedding approach in the Gated Recurrent Unit classification model. The well-trained models were applied on the ICD-10 web service for coding and training to ICD-10 users. With this service, coders can code with the F1-score significantly increased from a median of 0.832 to 0.922 (P<.05), but not in a reduced interval. CONCLUSIONS: The proposed model significantly improved the F1-score but did not decrease the time consumed in coding by disease coders.

20.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445342

RESUMO

Epigenetic regulation by histone deacetylase (HDAC) is associated with synaptic plasticity and memory formation, and its aberrant expression has been linked to cognitive disorders, including Alzheimer's disease (AD). This study aimed to investigate the role of class IIa HDAC expression in AD and monitor it in vivo using a novel radiotracer, 6-(tri-fluoroacetamido)-1-hexanoicanilide ([18F]TFAHA). A human neural cell culture model with familial AD (FAD) mutations was established and used for in vitro assays. Positron emission tomography (PET) imaging with [18F]TFAHA was performed in a 3xTg AD mouse model for in vivo evaluation. The results showed a significant increase in HDAC4 expression in response to amyloid-ß (Aß) deposition in the cell model. Moreover, treatment with an HDAC4 selective inhibitor significantly upregulated the expression of neuronal memory-/synaptic plasticity-related genes. In [18F]TFAHA-PET imaging, whole brain or regional uptake was significantly higher in 3xTg AD mice compared with WT mice at 8 and 11 months of age. Our study demonstrated a correlation between class IIa HDACs and Aßs, the therapeutic benefit of a selective inhibitor, and the potential of using [18F]TFAHA as an epigenetic radiotracer for AD, which might facilitate the development of AD-related neuroimaging approaches and therapies.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Inibidores de Histona Desacetilases/farmacocinética , Histona Desacetilases/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/fisiologia , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacocinética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/química , Histona Desacetilases/classificação , Histona Desacetilases/genética , Humanos , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Células Tumorais Cultivadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...