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1.
Clin Rheumatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646447

RESUMO

OBJECTIVE: To compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population METHODS: We identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model. RESULTS: We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16-86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82-10.35, 2.16-12.13, 2.41-6.95, and 2.06-6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk. CONCLUSION: Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide. Key Points • Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD. • Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP. • Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP. • Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33645012

RESUMO

OBJECTIVES: To evaluate PJP infection risk in patients with SLE in Taiwan. METHODS: We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age- and sex-matched non-SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model. RESULTS: The patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person-years and IR ratio of 27.65 (95% CI 17.2-45.3, p < 0.001). Male sex (hazard ratio [HR] 2.42, p < 0.01), end-stage renal disease (ESRD; HR 1.74, p = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, p < 0.001), and average oral dose of >7.5 mg/day prednisolone or equivalent (HR 4.83, p < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, p = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model. CONCLUSIONS: Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, oral prednisolone or equivalent (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

3.
Dis Colon Rectum ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538520

RESUMO

BACKGROUND: The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model). OBJECTIVE: This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer. DESIGN: This was a retrospective study. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n=416) were included. INTERVENTION: A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer using second harmonic generation imaging. A collagen signature was constructed using a LASSO Cox regression model. MAIN OUTCOME MEASURES: Disease-free survival and overall survival. RESULTS: The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%, respectively. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort, respectively. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR=7.17, p<0.001) and overall survival rates (HR=5.03, p<0.001). The new model had a better prognostic value than the clinicopathological model, which included four clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503 .

4.
Artigo em Inglês | MEDLINE | ID: mdl-33537782

RESUMO

BACKGROUND: The diverse risk factors for kidney impairments suggest that kidney function decline is more likely to occur in individuals with a broadly constituted health deficit. Here we conducted a longitudinal cohort study to evaluate the association of baseline frailty status with the risk of estimated glomerular filtration rate (eGFR) decline. METHODS: Overall, 1269 participants aged 70-84 years from Rugao Longevity and Ageing cohort with 3-year follow-up were included. Frailty was measured using a modified Fried frailty assessment. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Associations between baseline frailty status and rapid eGFR decline were examined by multinomial logistic analysis. A linear mixed-effect model was used to determine eGFR decline in mL/min/1.73 m2 over the study period comparing those with frail or prefrail at baseline versus those with robust status. RESULTS: The mean (± standard deviation) age of participants was 75.1 ± 3.8 years. A total of 144 (11%) participants had rapid eGFR decline by at least 10% during the 3-year follow-up. Compared with robust status, baseline frail status was associated with a 2.48-fold [95% confidence interval (CI) 1.24-4.95] increased risk of rapid eGFR decline after multiple adjustments. In multivariate linear mixed model analysis, subjects with frail status but not prefrail status at baseline had a significant coefficient of -1.70 (95% CI -3.35 to -0.04) for the frail × visit term, which indicates an accelerated eGFR decline compared with robust subjects over the study period (P = 0.044). CONCLUSIONS: Frailty may serve as an independent biomarker to predict the decline of kidney function.

5.
Sci Rep ; 11(1): 1612, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452297

RESUMO

The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan's National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose-response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either < 224 or ≥ 224 (hazard ratio [HR]: 2.407, 95% confidence interval [CI] 1.412-7.790; HR: 2.143, 95% CI 1.046-4.393, respectively) increased risk of developing osteonecrosis of the jaw. In conclusion, the risk of BRONJ is significantly higher in patients with pSS compared with the general population.

6.
J Med Chem ; 64(1): 527-542, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33371679

RESUMO

We report the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Inhibitor design entailed the functionalization of lithocholic acid at C(3) and at the cyclopentane ring side chain. Among the series, FCW34 and FCW66 were shown to inhibit MDA-MB-231 cell migration as effectively as ST3GALIII-gene knockdown did. FCW34 was shown to inhibit tumor growth, reduce angiogenesis, and delay cancer cell metastasis in animal models. Furthermore, FCW34 inhibited vessel development and suppressed angiogenic activity in transgenic zebrafish models. Our results provide clear evidence that FCW34-induced sialyltransferase inhibition reduces cancer cell metastasis by decreasing N-glycan sialylation, thus altering the regulation of talin/integrin/FAK/paxillin and integrin/NFκB signaling pathways.


Assuntos
Neoplasias da Mama/patologia , Inibidores Enzimáticos/farmacologia , Isoenzimas/antagonistas & inibidores , Metástase Neoplásica/prevenção & controle , Sialiltransferases/antagonistas & inibidores , Animais , Animais Geneticamente Modificados , Catálise , Linhagem Celular Tumoral , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glicoproteínas/metabolismo , Humanos , Integrinas/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Paxilina/metabolismo , Fosforilação , Sialiltransferases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Talina/metabolismo , Peixe-Zebra
7.
J Investig Med ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33229398

RESUMO

Cardiomyocyte hypertrophy is a response to stress or hormone stimulation and is characterized by an increase of cardiomyocyte size. Abnormal long non-coding RNA (lncRNA) expression profile has been identified in various cardiovascular diseases. Though some lncRNAs had been reported to participate in regulation of cardiac hypertrophy, the universal lncRNA profile of cardiomyocyte hypertrophy had not been established. In the present study, we aimed to identify the differentially expressed lncRNA-mRNA network in angiotensin II-stimulated cardiomyocytes, and screen the potential lncRNAs involved in regulation of cardiomyocyte hypertrophy. The hypertrophic cardiomyocytes were induced by angiotensin II (0.1 µmol/L) for 48 hours. High-throughput microarray analysis combined with quantitative real-time PCR assay were then performed to screen the differentially expressed lncRNAs and mRNAs. A total of 1577 lncRNAs and 496 mRNAs transcripts were identified differentially expressed in hypertrophic cardiomyocytes. Among them, 59 transcribed ultraconserved non-coding RNAs (T-UCRs) were found by evolutionary conservation analysis. Subsequently, the lncRNA-mRNA coexpression network was constructed based on Pearson's correlation analysis results, including 4 T-UCRs and 215 mRNAs. The results revealed that uc.242 was positively interacted with prohypertrophic genes (Hgf and Tnc). Functional study showed that inhibition of uc.242 dramatically decreased hypertrophic marker expression levels and cardiomyocyte surface area under the condition of angiotensin II stimulation. The expression of Hgf and Tnc was also decreased in cardiomyocytes after silencing of uc.242. Summarily, the present study provided crucial clues to explore therapeutic targets for pathological cardiac hypertrophy.

8.
Polymers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066199

RESUMO

One of the most effective and renewable utilization methods for lignocellulosic feedstocks is the transformation from solid materials to liquid products. In this work, corn stalk (CS) was liquified with polyethylene glycol 400 (PEG400) and glycerol as the liquefaction solvents, and sulfuric acid as the catalyst. The liquefaction conditions were optimized with the liquefaction yield of 95.39% at the reaction conditions of 150 °C and 120 min. The properties of CS and liquefaction residues (LRs) were characterized using ATR-FTIR, TG, elemental analysis and SEM. The chemical components of liquefied product (LP) were also characterized by GC-MS. The results indicated that the depolymerization and repolymerization reaction took place simultaneously in the liquefaction process. The depolymerization of CS mainly occurred at the temperature of <150 °C, and the repolymerization of biomass derivatives dominated at a higher temperature of 170 °C by the lignin derivatives repolymerization with cellulose derivatives, hemicellulose derivatives and PEG400 and self-condensation of lignin derivatives. The solvolysis liquefaction of CS could be classified into the mechanism of electrophilic substitution reaction attacked by the hydrogen cation.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32982961

RESUMO

In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.

10.
Ann Palliat Med ; 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32787381

RESUMO

Tracheomegaly and tracheoesophageal fistula (TEF) may be complicated within 12­200 days (with a mean of 43 days) of mechanical ventilation but rare in short-term intubation. Here we present a case of TEF secondary to post-intubation tracheomegaly in a tetanus patient. A 49-year-old male was admitted to the emergency room (ER) and diagnosed with tetanus. He became intubated and mechanically ventilated, but showed over-inflation of the endotracheal tube cuff on X-ray and chest computed tomography since the 8th day. After extubation, the patient had severe coughing during eating. Fiberoptic bronchoscopy and gastroscopy demonstrated a TEF located at the anterior wall of the esophagus. Esophageal exclusion and jejunostomy were performed to heal the fistula. The recurrent and uncontrollable muscular rigidity and spasms might be the main cause early tracheomegaly and TEF. Short-term intubation induced TEF should be aware of in specific patients. Both cuff pressure and cuff volume should be monitored to minimize tracheoesophageal injuries in such cases.

11.
Front Oncol ; 10: 1050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714867

RESUMO

Objectives: The present study aimed to explore the association between spleen density and post-operative outcomes of patients after curative gastrectomy. Methods: From June 2014 to December 2015, we conducted a retrospective study to analyze pertinent clinical data from gastric cancer patients who underwent gastrectomy at the First and the Second Affiliated Hospital of Wenzhou Medical University. Spleen density was determined via computed tomography scans. Univariate and multivariate analyses were performed to determine the risk factors associated with post-operative outcomes after gastric cancer surgery. Results: Three hundred and ninety five patients were included, of whom 98 (24.8%) were defined as having a diffuse reduction of spleen density based on diagnostic cutoff values (spleen density ≤43.89 HU). Multivariate analysis revealed diffuse reduction of spleen density as an independent risk factor for post-operative complications and long-term overall survival. Conclusions: Spleen density can predict severe postoperative complications and long-term overall survival in gastric cancer patients. As an imaging evaluation method, spleen density is a novel tool can be used in clinical as a prognostic predictor for patients with gastric cancer.

12.
J Diabetes Res ; 2020: 7058145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509882

RESUMO

Background: Postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy imposes significant social and economic burdens. We aimed to investigate the relationship between preoperative blood glucose level and PGS and develop a nomogram for individualized prediction. Patients and Methods. We retrospectively analyzed 633 patients with gastric cancer who underwent subtotal gastrectomy. Preoperative blood glucose levels were evaluated via receiver operating characteristic (ROC) curve analysis. Chi-squared tests and multivariable logistic regression analyses were used to develop a predictive model for PGS, presented as a nomogram, which was assessed for its clinical usefulness. Results: Thirty-eight of 633 patients were diagnosed with PGS. Based on the ROC curve analysis, the preoperative blood glucose cutoff value for PGS was 6.25 mmol/L. The predictors of PGS included preoperative hyperglycemia (odds ratio (OR) 2.3, P = 0.03), body mass index (BMI; OR 0.21, P = 0.14 for BMI < 18.5 and OR 3.0, P = 0.004 for BMI > 24), and the anastomotic method (OR 7.3, P = 0.001 for Billroth II and OR 5.9, P = 0.15 for Roux-en-Y). The predictive model showed good discrimination ability, with a C-index of 0.710, and was clinically useful. Conclusions: Preoperative hyperglycemia effectively predicts PGS. We present a nomogram incorporating the preoperative blood glucose level, BMI, anastomotic method, and tumor size, for individualized prediction of PGS.

13.
Ann Clin Transl Neurol ; 7(7): 1072-1082, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32478484

RESUMO

OBJECTIVES: The data concerning the association between Tx and ADs remain unclear and are scarce. This study was undertaken to investigate whether people with Tx are more likely to develop ADs, compared to those without Tx. METHODS: Individuals who received Tx between 2002 and 2015 were identified and matched on age and sex with individuals without Tx. We performed multivariate and stratified analysis using the Kaplan-Meier method and Cox proportional hazards models in order to estimate the association between Tx and the risk of developing ADs. RESULTS: A total of 2550 thymectomized (Txd) patients and 24,664.941 non-Txd comparison subjects were selected from NHIRD. Tx-MG (myasthenia gravis) as compared with general population (nonTx-nonMG), adjusted hazard ratio (aHR) were higher for incident Addison disease (aHR = 10.40, 95% CI 1.01-107), autoimmune hemolytic anemia (aHR = 21.54, 95% CI 2.06-14.8), Hashmoto thyroiditis (aHR = 5.52, 95% CI 1.34-34.7), ankylosing spondylitis (aHR = 2.73, 95% CI 1.09-6.84), rheumatoid arthritis (aHR = 5.25, 95% CI 1.79-15.47), primary Sjogren syndrome (pSS) (aHR = 3.77, 95% CI 1.30-11.0), and systemic lupus erythemtoasus (aHR = 10.40). Tx-nonMG as compared with general population, aHR were higher for incident autoimmune hemolytic anemia (aHR = 25.50), Hashmoto thyroiditis (aHR = 6.75) and systemic lupus erythematosus (SLE) (aHR = 13.38). NonTx-MG as compared with general population, aHR were higher for incident Hashmoto thyroiditis (aHR = 6.57), pSS (aHR = 4.50), SLE (aHR = 17.29), and systemic vasculitis (aHR = 25.86). INTERPRETATION: In conclusion, based on a retrospective cohort study throughout Taiwan, patients with Tx have a higher risk of new onset ADs than patients without Tx.

14.
J Med Genet ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381727

RESUMO

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

15.
Kidney Int ; 98(4): 1020-1030, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32450157

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUTs) are the most common cause of chronic kidney disease in children. Human 16p11.2 deletions have been associated with CAKUT, but the responsible molecular mechanism remains to be illuminated. To explore this, we investigated 102 carriers of 16p11.2 deletion from multi-center cohorts, among which we retrospectively ascertained kidney morphologic and functional data from 37 individuals (12 Chinese and 25 Caucasian/Hispanic). Significantly higher CAKUT rates were observed in 16p11.2 deletion carriers (about 25% in Chinese and 16% in Caucasian/Hispanic) than those found in the non-clinically ascertained general populations (about 1/1000 found at autopsy). Furthermore, we identified seven additional individuals with heterozygous loss-of-function variants in TBX6, a gene that maps to the 16p11.2 region. Four of these seven cases showed obvious CAKUT. To further investigate the role of TBX6 in kidney development, we engineered mice with mutated Tbx6 alleles. The Tbx6 heterozygous null (i.e., loss-of-function) mutant (Tbx6+/‒) resulted in 13% solitary kidneys. Remarkably, this incidence increased to 29% in a compound heterozygous model (Tbx6mh/‒) that reduced Tbx6 gene dosage to below haploinsufficiency, by combining the null allele with a novel mild hypomorphic allele (mh). Renal hypoplasia was also frequently observed in these Tbx6-mutated mouse models. Thus, our findings in patients and mice establish TBX6 as a novel gene involved in CAKUT and its gene dosage insufficiency as a potential driver for kidney defects observed in the 16p11.2 microdeletion syndrome.

16.
IEEE Trans Cybern ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32310813

RESUMO

In this article, a robust adaptive learning control strategy for uncertain single-input-single-output systems in strict-feedback form and controllability canonical form (CCF) is studied. For the strict-feedback system, the dynamic surface control is introduced while for the controllability canonical system, sliding-mode control is further constructed. The finite-time design is introduced for fast convergence. Under the switching mechanism, the intelligent design and the robust technique work together to obtain robust tracking performance. Once the states run out of the domain of intelligent control, the robust item will pull the states back while inside the neural working domain, the composite learning is developed to achieve higher approximation precision by building the prediction error for the weight update. The closed-loop system stability is analyzed via the Lyapunov approach. Especially for the CCF, the finite-time convergence is achieved while the system signals are globally uniformly ultimately bounded. Simulation studies on the general nonlinear systems and the flight dynamics show that the new design scheme obtains better tracking performance with higher precision and stronger robustness.

17.
Front Aging Neurosci ; 12: 77, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296326

RESUMO

Identifying patients with mild cognitive impairment (MCI) who are at high risk of progressing to Alzheimer's disease (AD) is crucial for early treatment of AD. However, it is difficult to predict the cognitive states of patients. This study developed an extreme learning machine (ELM)-based grading method to efficiently fuse multimodal data and predict MCI-to-AD conversion. First, features were extracted from magnetic resonance (MR) images, and useful features were selected using a feature selection method. Second, multiple modalities of MCI subjects, including MRI, positron emission tomography, cerebrospinal fluid biomarkers, and gene data, were individually graded using the ELM method. Finally, these grading scores calculated from different modalities were fed into a classifier to discriminate subjects with progressive MCI from those with stable MCI. The proposed approach has been validated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, and an accuracy of 84.7% was achieved for an AD prediction within 3 years. Experiments on predicting AD conversion from MCI within different periods showed similar results with the 3-year prediction. The experimental results demonstrate that the proposed approach benefits from the efficient fusion of four modalities, resulting in an accurate prediction of MCI-to-AD conversion.

18.
J Cell Mol Med ; 24(9): 4931-4943, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32277576

RESUMO

Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs.

19.
Clin Rheumatol ; 39(10): 2999-3007, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32240432

RESUMO

OBJECTIVE: This study assessed the risk of Parkinson disease (PD) in patients with primary Sjögren's syndrome (pSS) using a nationwide, population-based cohort during a 15-year follow-up period. METHOD: We identified 17,028 patients with pSS by using the catastrophic illness registry in the Taiwan National Health Insurance Research Database, and 68,094 matched non-pSS controls. RESULTS: The pSS cohort showed a higher incidence of PD development than did the non-pSS cohort (1.60% vs. 1.17%, p = 0.0001). The adjusted hazard ratio (aHR) of developing PD was 1.23 times greater in the pSS group than in the non-pSS group. When stratified by sex, age, and comorbidities, the female patients with pSS and patients aged between 61 and 70 years were associated with a higher PD risk (aHR 1.28 and aHR 1.30, respectively). Patients with pSS with no other comorbidity had a higher risk of PD (aHR: 2.17), compared with the non-pSS patients with no other comorbidity. When comparing non-pSS patients without or with comorbidity with pSS without or with comorbidity, pSS patients with comorbidity had highest risk of PD (aHR: 3.814). CONCLUSIONS: All of the above findings suggested that pSS is an independent risk factor for the development of PD. Key Points •The patients with pSS had 1.23 times risk of Parkinson disease than the non-pSS group. •The female patients with pSS and patients aged between 61 and 70 years were associated with a higher PD risk (aHR 1.28 and aHR 1.30, respectively). •The pSS patients with comorbidity had highest risk of PD (aHR: 3.814).

20.
Biomed Res Int ; 2020: 1852070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190653

RESUMO

Background: Percutaneous endoscopic transforaminal discectomy (PETD) is regarded as a viable alternative option for upper lumbar disc herniation (LDH). However, few studies have evaluated PETD for upper LDH, and no study has compared the advantages of endoscopic procedures versus conventional surgery. The present study was aimed at comparing the surgical outcome and safety of PETD versus conventional open lumbar discectomy in the treatment of upper LDH. Methods: Data from 42 patients treated for upper LDH from July 2015 to July 2018 were retrospectively analyzed, including 21 patients treated with PETD (PETD group) and 21 patients treated with conventional posterior lumbar discectomy (open group). The two groups were compared regarding demographic information, physical examination, radiological evaluations, and perioperative indicators. The clinical outcomes were assessed in accordance with the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified MacNab criteria. Results: The postoperative ODI and VAS scores were significantly improved in both groups compared with the preoperative baseline values (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (. Conclusions: PETD has a similar outcome to the conventional surgical method for the treatment of upper LDH but provides the typical advantages of minimally invasive procedures such as reduced iatrogenic injury, minimal activity restrictions, and accelerated ambulation recovery postoperatively.

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