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1.
Vincent K. Lam Hai T. Tran Kimberly C. Banks Richard B. Lanman Waree Rinsurongkawong Nir Peled Jeff Lewis J. Jack Lee Jack Roth Emily B. Roarty Stephen Swisher AmirAli Talasaz P. Andrew Futreal Vassiliki Papadimitrakopoulou John V. Heymach Jianjun Zhang 《Clinical lung cancer》2019,20(1):30-36.e3
Background
Major guidelines do not recommend routine molecular profiling of lung squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next-generation sequencing (NGS), particularly with cell-free circulating tumor DNA, facilitates reevaluation of this premise.Patients and Methods
We retrospectively evaluated the prevalence of actionable alterations in 2 distinct LUSC cohorts totaling 492 patients. A total of 410 consecutive patients with stage 3B or 4 LUSC were tested with a targeted cell-free circulating DNA NGS assay, and 82 patients with LUSC of any stage were tested with a tissue NGS cancer panel.Results
In the overall cohort, 467 patients (94.9%) had a diagnosis of LUSC, and 25 patients (5.1%) had mixed histology with a squamous component. A total of 10.5% of the LUSC subgroup had somatic alterations with therapeutic relevance, including in EGFR (2.8%), ALK/ROS1 (1.3%), BRAF (1.5%), and MET amplification or exon 14 skipping (5.1%). Sixteen percent of patients with mixed histology had an actionable alteration. In the LUSC subgroup, 3 evaluable patients were treated with targeted therapy for an actionable alteration; all of them experienced partial response.Conclusion
In this large, real-world LUSC cohort, we observed a clinically significant prevalence of actionable alterations. Accurate local histopathologic assessment in advanced-stage LUSC can be challenging. Further evaluation of the genomic landscape in this setting is warranted to potentially identify underappreciated treatment options. 相似文献2.
AmirAli Jafarnezhadgero Morteza Madadi Shad Reed Ferber 《Journal of bodywork and movement therapies》2018,22(1):83-89
Introduction
It has been widely postulated that structural and functional misalignments of the foot, such as flat foot, may cause mechanical deviations of the lower limb during walking. The aim of this study was to investigate the effect of foot orthoses on lower extremity joint moment asymmetry during the stance phase of walking in children with asymptomatic flexible flat feet.Methods
Fourteen volunteer male children, clinically diagnosed with flexible flat feet, participated in this study. Subjects completed 12 walking trials at a self-selected walking speed while 3-dimensional kinematic and kinetic data were collected for two conditions: shod with no orthoses, and shod with orthoses. The gait asymmetry index for each variable for each subject was defined as: (1-(lesser moment/greater moment)) × 100.Results
Results reveal no significant differences in ankle or knee joint moment asymmetry. However, the use of foot orthoses decreased asymmetry for the hip abduction moment (P = 0.04) compared to walking without orthoses and also resulted in subtle, non-significant increases in frontal plane subtalar and sagittal plane knee and hip joints moment asymmetry.Conclusion
We conclude that foot orthoses decrease frontal plane hip joint moment asymmetry, but have little effect on ankle and knee joint asymmetry. 相似文献3.
AA Rahsepar A Mirzaee F Moodi M Moohebati S Tavallaie A Eshraghi MS Alavi F Khorashadizadeh H Pourghadamyari R Paydar M Amini R Khojasteh S Mousavi M Sahebi M Ghayour-Mobarhan GA Ferns 《Cardiology》2012,122(4):203-209
Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB. 相似文献
4.
Sara Saffar Soflaei MD PhD Mahmoud Ebrahimi MD Hamid Reza Rahimi MD PhD AmirAli Moodi Ghalibaf MD Maryam Jafari MD Hedieh Alimi MD Nasrin Talkhi MSc Bahram Shahri MD Alireza Heidari-Bakavoli MD Fatemeh Malakouti Mahla Velayati Reza Assaran-Darban PhD Malihehsadat Abedsaeidi MSc Farnoosh Azarian MSc MohammadReza Latifi MSc Mohammad Reza Mohammad Taghizadeh Sarabi MSc Gordon A. Ferns MD PhD Habibollah Esmaily PhD Mohsen Moohebati MD Majid Ghayour-Mobarhan MD PhD 《Annals of noninvasive electrocardiology》2023,28(6):e13086
Background
Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population.Methods
ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS.Results
Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference.Conclusions
Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups. 相似文献5.
Sahar rajabzadeh Karizi Fatemeh Armanmehr Hamideh Ghodrati Azadi Hojjat Shadman Zahroodi AmirAli Moodi Ghalibaf Bibi Sedigheh Fazly Bazzaz Mohammadreza Abbaspour Javad Boskabadi Saeid Eslami Zhila Taherzadeh 《Phytotherapy research : PTR》2023,37(4):1435-1448
The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three–month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events. 相似文献
6.
Next‐Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma 下载免费PDF全文
7.
Talasaz AH Nemat-Gorgani M Liu Y Ståhl P Dutton RW Ronaghi M Davis RW 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(40):14773-14778
We report on a rapid simulation method for predicting protein orientation on a surface based on electrostatic interactions. New methods for predicting protein immobilization are needed because of the increasing use of biosensors and protein microarrays, two technologies that use protein immobilization onto a solid support, and because the orientation of an immobilized protein is important for its function. The proposed simulation model is based on the premise that the protein interacts with the electric field generated by the surface, and this interaction defines the orientation of attachment. Results of this model are in agreement with experimental observations of immobilization of mitochondrial creatine kinase and type I hexokinase on biological membranes. The advantages of our method are that it can be applied to any protein with a known structure; it does not require modeling of the surface at atomic resolution and can be run relatively quickly on readily available computing resources. Finally, we also propose an orientation of membrane-bound cytochrome c, a protein for which the membrane orientation has not been unequivocally determined. 相似文献
8.
Guru Sonpavde MD Neeraj Agarwal MD Gregory Russell Pond PhD Rebecca J. Nagy MSc Roberto H. Nussenzveig PhD Andrew W. Hahn MD Oliver Sartor MD Theodore Stewart Gourdin MD Lakshminarayanan Nandagopal MD Elisa M. Ledet PhD Gurudatta Naik MPH Andrew J. Armstrong MD MSc Jue Wang MD Mehmet Asim Bilen MD Shilpa Gupta MD Petros Grivas MD PhD Sumanta K. Pal MD Richard B. Lanman MD AmirAli Talasaz PhD Michael B. Lilly MD 《Cancer》2019,125(9):1459-1469
9.
Seung Tae Kim Won Suk Lee Richard B. Lanman Stefanie Mortimer Oliver A. Zill Kyoung-Mee Kim Kee Taek Jang Seok-Hyung Kim Se Hoon Park Joon Oh Park Young Suk Park Ho Yeong Lim Helmy Eltoukhy Won Ki Kang Woo Yong Lee Hee-Cheol Kim Keunchil Park Jeeyun Lee AmirAli Talasaz 《Oncotarget》2015,6(37):40360-40369
Sequencing of the mutant allele fraction of circulating cell-free DNA (cfDNA) derived from tumors is increasingly utilized to detect actionable genomic alterations in cancer.We conducted a prospective blinded study of a comprehensive cfDNA sequencing panel with 54 cancer genes. To evaluate the concordance between cfDNA and tumor DNA (tDNA), sequencing results were compared between cfDNA from plasma and genomic tumor DNA (tDNA). Utilizing next generation digital sequencing technology (DST), we profiled approximately 78,000 bases encoding 512 complete exons in the targeted genes in cfDNA from plasma. Seventy-five patients were prospectively enrolled between February 2013 and March 2014, including 61 metastatic cancer patients and 14 clinical stage II CRC patients with matched plasma and tissue samples. Using the 54-gene panel, we detected at least one somatic mutation in 44 of 61 tDNA (72.1%) and 29 of 44 (65.9%) cfDNA. The overall concordance rate of cfDNA to tDNA was 85.9%, when all detected mutations were considered. We collected serial cfDNAs during cetuximab-based treatment in 2 metastatic KRAS wild-type CRC patients, one with acquired resistance and one with primary resistance. We demonstrate newly emerged KRAS mutation in cfDNA 1.5 months before radiologic progression. Another patient had a newly emerged PIK3CA H1047R mutation on cfDNA analysis at progression during cetuximab/irinotecan chemotherapy with gradual increase in allele frequency from 0.8 to 2.1%. This blinded, prospective study of a cfDNA sequencing showed high concordance to tDNA suggesting that the DST approach may be used as a non-invasive biopsy-free alternative to conventional sequencing using tumor biopsy. 相似文献
10.
AmirAli Jafarnezhadgero Morteza Madadi-Shad Fatemeh Salari Esker D.G.E. Robertson 《Journal of bodywork and movement therapies》2018,22(3):741-746
Gait asymmetry is defined as a loss of perfect agreement between the dominant and non-dominant lower limbs. Conflicting results from gait asymmetry studies may be due to different definitions of asymmetry, different research methods, and/or different variables and formulas used for asymmetry calculation. As a result, this makes it difficult to compare joint asymmetry values between studies. An accurate and precise understanding of asymmetry during human walking is an important step towards developing enhanced rehabilitation protocols for pathological gait. This study examined bilateral lower extremity joint moment asymmetry during the stance phase of walking using three different methods. Fourteen male children (with flat feet) aged 8–14 years participated in this study. The three-dimensional lower limb kinetics was evaluated during a comfortable gait. Then, right and left lower limb joint moments were used to calculate the joint moment asymmetry via three different methods (Lathrop-Lambach method: equation used by Lathrop-Lambach et al. (2014); Su method: equation used by Su et al. (2015); Nigg method: equation used by Nigg et al. (2013)). Repeated-measures ANOVAs (α = 0.05) were used to compare the values of net joint moment asymmetry calculated by the three methods. The results of the statistical analyses found that the amounts of moment symmetry between limbs calculated by the first two methods were significantly greater than that of using the Nigg method (except for the values of the frontal ankle moment computed by the Lathrop-Lambach method). Furthermore, in comparison of the first two methods, using the Su method showed a reduction in moment asymmetry for all joints and for all moments (p < 0.05). We conclude that, although all of three common methods for determining asymmetry between limbs have documented merit, they sometimes differ dramatically in results. 相似文献