High concordance of actionable genomic alterations identified between circulating tumor DNA–based and tissue‐based next‐generation sequencing testing in advanced non–small cell lung cancer: The Korean lung liquid versus invasive biopsy program

xloma.fota13 shared this article with you from Inoreader High concordance of actionable genomic alterations identified between circulating tumor DNA–based and tissue‐based next‐generation sequencing testing in advanced non–small cell lung cancer: The Korean lung liquid versus invasive biopsy program Via Cancer Background Because of the growing number of actionable biomarkers in non–small cell lung cancer (NSCLC), sufficient tissue availability for testing is becoming a greater challenge. Liquid biopsy offers a potential solution by complementing standard tissue‐based methods. In this study, the authors analyzed the concordance of actionable genomic alterations sequenced from circulating tumor DNA (ctDNA; Guardant360) and tissue (Oncomine Focus Assay). Methods From September 2015 to May 2018, 421 paired plasma and tissue samples from patients with advanced NSCLC who had previously undergone tissue testing by standard methods were collected. Both types of samples were available for 287 patients (262 in cohort 1 [treatment‐naive] and 25 in cohort 2 [treatment failure]), and only 1 sample type was available for 134 patients (50 in cohort 3 [plasma only] and 84 in cohort 4 [tissue only]). Results In cohort 1, 198 samples (77.6%) showed concordance between tissue and plasma next‐generation sequencing (NGS). Among the discordant cases, plasma testing detected additional genomic alterations in 11 patients (4.2%). In 50 patients without tissue‐based NGS results (cohort 3), the ctDNA‐based test detected genomic alterations in 20 samples (40.0%). The median allele frequency (AF) of mutations identified with ctDNA‐based NGS (0.74%) was lower than that identified with the tissue‐based NGS test (13.90%). Clinical responses to matched targeted therapy occurred, regardless of the ctDNA AF. Upfront ctDNA‐based testing identified 60.4% of patients with genomic alterations. In addition, ctDNA‐based testing uncovered 12.0% more actionable alterations when it was performed after tissue‐based NGS testing. Conclusions The results indicate that a ctDNA‐based test identifies additional patients with actionable genomic alterations and could, therefore, be used to complement traditional tissue‐based testing for NSCLC. Lay Summary Circulating tumor DNA (ctDNA)–based next‐generation sequencing (NGS) testing is becoming essential as the number of actionable genomic biomarker increases for the treatment selection of non–small cell lung cancer. This study demonstrates the additive value of ctDNA‐based testing in addition to tissue‐based NGS and standard of care–based biomarker testing for detecting additional patients with actionable genomic alterations. Clinical responses have also been observed in patients with a low allele frequency detected by ctDNA‐based NGS testing. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical evaluation of p16INK4a immunocytology in cervical cancer screening: A population‐based cross‐sectional study from rural China

xloma.fota13 shared this article with you from Inoreader Clinical evaluation of p16INK4a immunocytology in cervical cancer screening: A population‐based cross‐sectional study from rural China Via Cancer Cytopathology Background Cervical cancer screening with cytology suffers from low sensitivity, whereas the efficiency of human papillomavirus (HPV)‐based screening is limited by low specificity. The authors evaluated a novel p16INK4a immunocytology approach in cervical cancer screening compared with HPV‐based and cytology‐based screening. Methods In total, 2112 women aged 49 to 69 years from Shanxi, China were screened from March to July 2019. HPV testing, liquid‐based cytology (LBC), and p16INK4a immunocytology were performed on samples from all women. Any positive result triggered a referral to colposcopy with biopsy, if indicated. Screening performance for detecting cervical intraepithelial neoplasia grade 2 and 3 or worse (CIN2+/CIN3+) was evaluated using multiple algorithms. Results p16INK4a had a lower positive rate (10.0%) than LBC abnormality (vs 12.1%; P = .004) and a high‐risk HPV positivity (21.4%; P < .001). For the detection of CIN3+, the relative sensitivity of p16INK4a compared with HPV and LBC was 0.93 (95% CI, 0.82‐1.07) and 1.12 (95% CI, 0.95‐1.32), respectively. The specificity of p16INK4a was significantly higher than that for HPV and LBC, with a relative specificity of 1.13 (95% CI, 1.11‐1.16) and 1.02 (95% CI, 1.01‐1.04), respectively. In addition, p16INK4a alone yielded a clinical performance very similar to that of the current mainstream strategy of using HPV16/18 with reflex cytology (ASC‐US+, atypical squamous cells of undetermined significance or worse). The immediate risk of CIN3+ was 14.6% if p16INK4a results were positive and 0.2% if p16INK4a results were negative. Conclusions With minimal colposcopy referrals, p16INK4a screening demonstrated promising utility for risk stratification and yielded a better balance between sensitivity and specificity compared with HPV and LBC primary screening. Moreover, with accuracy and efficiency similar to what is achieved using mainstream cotest algorithms, p16 may simplify the screening practice. More evidence will be required before clinical recommendation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cervical cytology screening facilitated by an artificial intelligence microscope: A preliminary study

xloma.fota13 shared this article with you from Inoreader Cervical cytology screening facilitated by an artificial intelligence microscope: A preliminary study Via Cancer Cytopathology BACKGROUND Cervical cytology screening is usually laborious with a heavy workload and poor diagnostic consistency. The authors have developed an artificial intelligence (AI) microscope that can provide onsite diagnostic assistance for cervical cytology screening in real time. METHODS A total of 2167 cervical cytology slides were selected from a cohort of 10,601 cases from Shenzhen Maternity and Child Healthcare Hospital, and the training data set consisted of 42,073 abnormal cervical epithelial cells. The recognition results of an AI technique were presented in a microscope eyepiece by an augmented reality technique. Potentially abnormal cells were highlighted with binary classification results in a 10× field of view (FOV) and with multiclassification results according to the Bethesda system in 20× and 40× FOVs. In addition, 486 slides were selected for the reader study to evaluate the performance of the AI microscope. RESULTS In the reader study, which compared manual reading with AI assistance, the sensitivities for the detection of low‐grade squamous intraepithelial lesions and high‐grade squamous intraepithelial lesions were significantly improved from 0.837 to 0.923 (P < .001) and from 0.830 to 0.917 (P < .01), respectively; the κ score for atypical squamous cells of undetermined significance (ASCUS) was improved from 0.581 to 0.637; the averaged pairwise κ of consistency for multiclassification was improved from 0.649 to 0.706; the averaged pairwise κ of consistency for binary classification was improved from 0.720 to 0.798; and the averaged pairwise κ of ASCUS was improved from 0.557 to 0.639. CONCLUSIONS The results of this study show that an AI microscope can provide real‐time assistance for cervical cytology screening and improve the efficiency and accuracy of cervical cytology diagnosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Disability progression in multiple sclerosis is associated with plasma neuroactive steroid profile

xloma.fota13 shared this article with you from Inoreader Disability progression in multiple sclerosis is associated with plasma neuroactive steroid profile Via Latest Results for Neurological Sciences Abstract Background Neuroactive steroids (NASs) exert multiple biological effects on development and inflammation. The effects of NASs on disease progression in multiple sclerosis (MS) are uncertain, prompting analyses of NAS profiles during the transition from clinically isolated syndrome (CIS) to relapsing-remitting (RR) MS. Methods Subjects with CIS or RRMS and healthy controls (HCs) were recruited; demographic and clinical data as well as disability scores measured by the Expanded Disability Status Scale (EDSS) were recorded. Matched plasma NAS and amino acid (AA) concentrations were measured. Results HC (n = 17), CIS (n = 31), and RRMS (n = 33) groups showed similar ages and sex distribution although disability scores were higher in the RRMS group. The conversion rate of CIS to RRMS group was 51.6% (n = 16) during a mean follow-up period of 1.85 years. The RRMS group showed significantly higher mean allopregnanolone, aspartate, and taurine concentrations with lower epiallopregnanolone concentrations than CIS patients, and higher L-serine-O-phosphate and lower alanine, arginine, and glutamine concentrations than the HC group. Among CIS and RRMS groups, multivariate hierarchical regressions revealed that higher concentrations of plasma tetrahydrodeoxycorticosterone (THDOC) may predict disability worsening. Conclusions RRMS and CIS patients exhibited differing concentrations of both NASs and AAs in plasma while both THDOC and pregnanolone might serve as biomarkers of disability worsening. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Potential cost‐effectiveness of using adjunctive dehydrated human amnion/chorion membrane allograft in the management of non‐healing diabetic foot ulcers in the United Kingdom

xloma.fota13 shared this article with you from Inoreader Potential cost‐effectiveness of using adjunctive dehydrated human amnion/chorion membrane allograft in the management of non‐healing diabetic foot ulcers in the United Kingdom Via International Wound Journal Abstract The aim of this study was to estimate the cost‐effectiveness of using dehydrated human amnion/chorion membrane (dHACM) allografts (Epifix) as an adjunct to standard care, compared with standard care alone, to manage non‐healing diabetic foot ulcers (DFUs) in secondary care in the United Kingdom, from the perspective of the National Health Service (NHS). A Markov model was constructed to simulate the management of diabetic lower extremity ulcers over a period of 1 year. The model was used to estimate the cost‐effectiveness of using adjunctive dHACM, compared with standard care alone, to treat non‐healing DFUs in the United Kingdom, in terms of the incremental cost per quality‐adjusted life year (QALY) gained at 2019/2020 prices. The study estimated that at 12 months after the start of treatment, use of adjunctive dHACM instead of standard care alone is expected to lead to a 90% increase in the probability of healing, a 34% reduction in the probability of wound infecti on, a 57% reduction in the probability of wound recurrence, a 6% increase in the probability of avoiding an amputation, and 8% improvement in the number of QALYs. Additionally, if £4062 is spent on dHACM allografts per ulcer, then adjunctive use of dHACM instead of standard care alone is expected to lead to an incremental cost per QALY gain of £20 000. However, if the amount spent on dHACM allografts was ≤£3250 per ulcer, the 12‐month cost of managing an ulcer treated with adjunctive dHACM would break‐even with that of DFUs treated with standard care, and it would have a 0.95 probability of being cost‐effective at the £20 000 per QALY threshold. In conclusion, within the study's limitations, and within a certain price range, adjunctive dHACM allografts afford the NHS a cost‐effective intervention for the treatment of non‐healing DFUs within secondary care among adult patients with type 1 or 2 diabetes mellitus in the United Kingdom. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Differential sensitivity of cinnamaldehyde-evoked calcium fluxes to ruthenium red in guinea pig and mouse trigeminal sensory neurons

xloma.fota13 shared this article with you from Inoreader Differential sensitivity of cinnamaldehyde-evoked calcium fluxes to ruthenium red in guinea pig and mouse trigeminal sensory neurons Via BMC Research Notes Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel expressed on a subset of sensory neurons. TRPA1 is activated by a host of noxious stimuli including pollutants, irritants, oxidative ... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

3D-Printed Screw-Rod Auxiliary System for Unstable Atlas Fractures: A Retrospective Analysis

xloma.fota13 shared this article with you from Inoreader 3D-Printed Screw-Rod Auxiliary System for Unstable Atlas Fractures: A Retrospective Analysis Via pubmed: dysphagia Orthop Surg. 2021 Apr 7. doi: 10.1111/os.13015. Online ahead of print. ABSTRACT OBJECTIVE: To develop and validate the efficacy of a 3D-printed screw-rod auxiliary system for unstable atlas fractures. METHODS: This research is a retrospective analysis, and a total of 14 patients, including 11 males and three females, were enrolled in our hospital from January 2017 to March 2019 who underwent occipitocervical fusion assisted by the 3D-printed screw-rod auxiliary system were reviewed, and with an average age of 53.21 ± 14.81 years, an average body mass index (BMI) of 23.61 ± 1.93 kg/m2 . The operation time, blood loss and radiation times during the operation were recorded. The maximum fracture displacement values of pre- and post-operation were measured based on CT imaging. All screw grades were evaluated after surgery. The occipital-cervical 2 (O-C2 ) angle and occipitocervical inclination (OCI) angle of pre-opera tion, post-operation and the last following-up were measured. The dysphagia scale 3 months after surgery and at the last follow-up, the Neck Disability Index (NDI) 3 months after surgery and at the last follow-up were assessed. RESULTS: All patients were completed the surgery successfully. There was no patient with severe dysphagia or aggravation of nerve injury. The follow-up was from 12 to 14 months, and with an average of 12.5 months. The average surgery time, average blood loss and average radiation times for the 14 patients were 112.14 min, 171.43 mL and 5.07 times, respectively. There was a significant difference in maximum fracture displacement between pre- and post-operation values (P < 0.05). A total of 56 screws were inserted in 14 patients, among them, three screws were classified as grade 1, and the other screws were classified as grade 0. There was a significant difference in the O-C2 between pre-operation and 3 days after operation (P = 0.002); Ther e was a significant difference in OCI angles between pre-operation and 3 days after operation (P < 0.05); there was no significant difference in the O-C2 or OCI angle between 3 days after the operation and the last follow-up (P = 0.079; P = 0.201). The dysphagia scales of two patients were assessed as mild at 3 months after surgery, and the others were assessed as normal at 3 months after surgery. All patients' dysphagia scores returned to normal at the last follow-up. The average NDI and average neck Visual Analogue Scale (VAS) scores at the last follow-up were 2.53 and 8.41, respectively. CONCLUSION: It can objectively restore the OCI to normal with few post-operative complications under the assistance of a screw-rod auxiliary system to perform occipitocervical fusion for unstable atlas fractures and atlantooccipital joint instability. PMID:33826254 | DOI:10.1111/os.13015 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition

xloma.fota13 shared this article with you from Inoreader Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition Via Clinical Cancer Research Online First Articles Epithelial-mesenchymal transition (EMT) has been shown to play a critical role in tumor development from initiation to metastasis. EMT could be regarded as a continuum, with intermediate hybrid epithelial and mesenchymal phenotypes having high plasticity. Classical EMT is characterized by the phenotype change of epithelial cells to cells with mesenchymal properties, but EMT is also associated with multiple other molecular processes, including tumor immune evasion. Some previous studies have shown that EMT is associated with the cell number of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), and the expression of immune checkpoints, such as programmed cell death-ligand 1, in several cancer types. At the molecular level, EMT transcriptional factors, including Snail, Zeb1, and Twist1, produce or attract immunosuppressive cells or promote the expression of immunosuppressive checkpoint molecules via chemokine production, leading to a tum or immunosuppressive microenvironment. In turn, immunosuppressive factors induce EMT in tumor cells. This feedback loop between EMT and immunosuppression promotes tumor progression. For therapy directly targeting EMT has been challenging, the elucidation of the interactive regulation of EMT and immunosuppression is desirable for developing new therapeutic approaches in cancer. The combination of immune checkpoint inhibitors (ICIs) and immunotherapy targeting immunosuppressive cells could be a promising therapy for EMT. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Achyranthes bidentata polypeptide k enhances the survival, growth and axonal regeneration of spinal cord motor neurons in vitro

xloma.fota13 shared this article with you from Inoreader Achyranthes bidentata polypeptide k enhances the survival, growth and axonal regeneration of spinal cord motor neurons in vitro Via NeuroReport - Current Issue Achyranthes bidentata polypeptide k (ABPPk), a powerful active component from a traditional Chinese medicinal herb-Achyranthes bidentata Bl., has exhibited promising neuroprotective activity due to its multiple-targeting capability. However, the effect of ABPPk on the survival, growth and axonal regeneration of spinal cord motor neurons remains unclear. Here, a modified method, which is more optimized for embryonic cells in ambient carbon dioxide levels, was used for acquisition of rat embryonic spinal cord motor neurons with high survival and purity. ABPPk concentration-dependently enhanced the neuronal viabilit y and promoted the neurite outgrowth. Co-culture of motor neurons and skeletal myocytes model indicated that ABPPk enhanced the neuromuscular junction development and maturation. A microfluidic axotomy model was further established for the axonal disconnection, and ABPPk significantly accelerated the axonal regeneration of motor neurons. Furthermore, we demonstrated that the upregulation of three neurofilament protein subunits in motor neurons might be relevant to the mechanisms of the growth-promoting effect of ABPPk. Our findings provide an experimental and theoretical basis for the development of ABPPk as a potential application in the development of treatment strategy for nerve injury diseases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of functional MRI signal complexity based on permutation fuzzy entropy in bipolar disorder

xloma.fota13 shared this article with you from Inoreader Analysis of functional MRI signal complexity based on permutation fuzzy entropy in bipolar disorder Via NeuroReport - Current Issue Bipolar disorder is a manifestation of an emotional disease and is associated with emotional and cognitive dysfunction. The entropy-based method has been widely used to study the complexity of resting-state functional MRI (rs-fMRI) signals in mental diseases; however, alterations in the brain rs-fMRI signal complexities in bipolar disorder patients remain unclear, and previously used entropy methods are sensitive to noise. Here, we performed a work using permutation fuzzy entropy (PFEN), which has better performance than previously used methods, to analyze the brain complexity of bipolar disorder p atients. Based on PFEN research, we obtained brain entropy maps of 49 bipolar disorder patients and 49 normal control, extracted the regions of interest to analyze the complexity of abnormal brain regions and further analyzed the correlation between the PFEN values of abnormal brain regions and the clinical measurement scores. Compared with the values in the normal control group, we found that significantly increased PFEN values mainly appeared in the middle temporal gyrus, angular gyrus, superior occipital gyrus and medial superior frontal gyrus, and the decreased PFEN values were found in the inferior temporal gyrus in bipolar disorder patients. In addition, the PFEN values of the angular gyrus was significantly negatively correlated with clinical scores. These findings improve our understanding of the pathophysiology of bipolar disorder patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ischemic-time associated reductions in equol monosulfate plasma levels in a mouse model of ischemic stroke: support the existence of a ‘brain–gut axis’

xloma.fota13 shared this article with you from Inoreader Ischemic-time associated reductions in equol monosulfate plasma levels in a mouse model of ischemic stroke: support the existence of a 'brain–gut axis' Via NeuroReport - Current Issue Background Interest is growing in the role played by intestinal flora in the pathogeneses of diseases and in the possibility of treating disease by altering intestinal flora compositions. Recent studies have focused on the relationship between the intestinal microbiome and brain function as proposed by the brain–gut axis hypothesis. Objectives To investigate the relation between ischemic stroke and plasma equol monosulfate levels (a soy isoflavone metabolite) in a middle cerebral artery occlusion (MCAO) mouse model. Methods Mice (C57BL/6) were subjected to MCAO for various times (30 min to 24 h), and degrees of cerebral damage were assessed using total infarction volumes, brain edema severities and neurological deficit scores. Hematoxylin and eosin and cresyl violet staining were used to observe morphological changes in ischemic brains. Levels of equol monosulfate in plasma and the relationships between these and degree of brain injury were investigated. Results Infarction volumes, brain edema severity and neurological deficit scores were significantly correlated with ischemic time, and morphological deteriorations of brain neuronal cells also increased with ischemic duration. Equol monosulfate contents were ischemic-time dependently lower in MCAO treated animals than in sham-operated controls. Conclusion Ischemic stroke may time-dependently reduce plasma levels of equol monosulfate by lowering the metabolic rate of equol in MCAO-induced mice. This study provides indirect support of the brain–gut axis hypothesis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.