Publications by authors named "Fei Ji"

184 Publications

Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III study of baricitinib placebo in patients with moderately to severely active rheumatoid arthritis and an inadequate response to methotrexate therapy: results from the RA-BALANCE study.

Ther Adv Musculoskelet Dis 2021 20;13:1759720X211006964. Epub 2021 Apr 20.

Department of Rheumatology and Immunity, Center of Clinical Immunology, Peking University People's Hospital, Xicheng District, Beijing, P.R. China.

Introduction: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients ( = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity, patient's assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively.

Results: Statistically significant ( ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group.

Conclusion: Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX.Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014.
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http://dx.doi.org/10.1177/1759720X211006964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064513PMC
April 2021

Anthracycline-containing carboplatin-containing neoadjuvant chemotherapy in combination with trastuzumab for HER2-positive breast cancer: the neoCARH phase II randomized clinical trial.

Ther Adv Med Oncol 2021 20;13:17588359211009003. Epub 2021 Apr 20.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, Guangdong 510080, China.

Background: Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockade is unknown. This study aimed to compare the efficacy and safety of epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (EC-TH) with docetaxel/carboplatin/trastuzumab (TCH) neoadjuvant setting for HER2-positive breast cancer under the single HER2 blockade.

Methods: Patients with stage II-IIIC HER2-positive breast cancer were randomly assigned to either eight cycles of EC-TH every 3 weeks during all chemotherapy cycles, or six cycles of TCH every 3 weeks. The primary endpoint was pathological complete response (pCR) (defined as the absence of invasive tumor cells in breast and axilla, ypT0/is ypN0).

Results: From May 2017 to November 2019, 140 patients were randomly assigned, and 135 patients were ultimately found evaluable for the primary endpoint. The pCR was recorded in 25 of 67 patients [37.3%; 95% confidence interval (CI), 25.8-50.0] in the EC-TH group and in 38 of 68 patients (55.9%, 95% CI, 43.3-67.9) in the TCH group ( = 0.032). The most common adverse events (AEs) were neutropenia in 24 of 67 (35.8%) patients in the EC-TH group 27 of 68 (39.7%) in the TCH group ( = 0.642), anemia in 33 of 67 (49.3%) patients in the EC-TH group 34 of 68 (50.0%) in the TCH group ( = 0.931), and thrombocytopenia in five of 67 (7.5%) patients in the EC-TH group 17 of 68 (25.0%) in the TCH group ( = 0.006).

Conclusion: For patients receiving the single HER2 blockade trastuzumab for HER2-positive breast cancer, TCH regimen might be a preferred neoadjuvant therapy.

Trial Registration: This trial was registered with ClinicalTrials.gov identifier: NCT03140553) on 2 May 2017.
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http://dx.doi.org/10.1177/17588359211009003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064510PMC
April 2021

A cyclic peptide antenna ligand for enhancing terbium luminescence.

Analyst 2021 Apr 29. Epub 2021 Apr 29.

Department of Chemistry, University of California, Riverside, Riverside, California 92521, USA.

We present here a cyclic peptide ligand, cy(WQETR), that binds to the terbium ion (Tb3+) and enhances Tb3+ luminescence intensity through the antenna effect. This peptide was identified through screening a cyclic peptide library against Tb3+ with an apparent EC50 of 540 μM. The tryptophan residue from the peptide directly interacts with the Tb3+ ion, which provides access to a low-lying triplet excited state of the tryptophan. Direct excitation of this triplet state enables energy transfer to the Tb3+ ion and enhances Tb3+ luminescence intensity by 150 fold. We further showcase the application of this cy(WQETR)-Tb3+ system by demonstrating the detection of tromethamine with a detection limit of 0.5 mM.
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http://dx.doi.org/10.1039/d1an00530hDOI Listing
April 2021

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients.

Breast 2021 Apr 1;58:10-17. Epub 2021 Apr 1.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Shantou University Medical College, Shantou, 515041, China. Electronic address:

Background: Previous studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.

Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.

Results: A total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59-0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53-0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.

Conclusion: BCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.
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http://dx.doi.org/10.1016/j.breast.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080072PMC
April 2021

SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves.

BMC Neurosci 2021 Mar 22;22(1):18. Epub 2021 Mar 22.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.

Background: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice.

Results: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds.

Conclusions: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.
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http://dx.doi.org/10.1186/s12868-021-00613-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986359PMC
March 2021

RNA m6A reader IMP2/IGF2BP2 promotes pancreatic β-cell proliferation and insulin secretion by enhancing PDX1 expression.

Mol Metab 2021 Mar 9;48:101209. Epub 2021 Mar 9.

Department of Molecular Biology and Diabetes Unit of the Medical Services, Massachusetts General Hospital, Boston, 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Background: Type 2 diabetes (T2D) is a common metabolic disease. Variants in human IGF2 mRNA binding protein 2 (IMP2/IGF2BP2) are associated with increased risk of T2D. IMP2 contributes to T2D susceptibility primarily through effects on insulin secretion. However, the underlying mechanism is not known.

Methods: To understand the role of IMP2 in insulin secretion and T2D pathophysiology, we generated Imp2 pancreatic β-cell specific knockout mice (βIMP2KO) by recombining the Imp2 allele with Cre recombinase driven by the rat insulin 2 promoter. We further characterized metabolic phenotypes of βIMP2KO mice and assessed their β-cell functions.

Results: The deletion of IMP2 in pancreatic β-cells leads to reduced compensatory β-cell proliferation and function. Mechanically, IMP2 directly binds to Pdx1 mRNA and stimulates its translation in an m6A dependent manner. Moreover, IMP2 orchestrates IGF2-AKT-GSK3β-PDX1 signaling to stable PDX1 polypeptides. In human EndoC-βH1 cells, the over-expression of IMP2 is capable to enhance cell proliferation, PDX1 protein level and insulin secretion.

Conclusion: Our work therefore reveals IMP2 as a critical regulator of pancreatic β-cell proliferation and function; highlights the importance of posttranscriptional gene expression in T2D pathology.
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http://dx.doi.org/10.1016/j.molmet.2021.101209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076713PMC
March 2021

Automatic Recognition of Auditory Brainstem Response Characteristic Waveform Based on Bidirectional Long Short-Term Memory.

Front Med (Lausanne) 2020 11;7:613708. Epub 2021 Jan 11.

School of Computer and Communication Engineering, University of Science & Technology Beijing, Beijing, China.

Auditory brainstem response (ABR) testing is an invasive electrophysiological auditory function test. Its waveforms and threshold can reflect auditory functional changes in the auditory centers in the brainstem and are widely used in the clinic to diagnose dysfunction in hearing. However, identifying its waveforms and threshold is mainly dependent on manual recognition by experimental persons, which could be primarily influenced by individual experiences. This is also a heavy job in clinical practice. In this work, human ABR was recorded. First, binarization is created to mark 1,024 sampling points accordingly. The selected characteristic area of ABR data is 0-8 ms. The marking area is enlarged to expand feature information and reduce marking error. Second, a bidirectional long short-term memory (BiLSTM) network structure is established to improve relevance of sampling points, and an ABR sampling point classifier is obtained by training. Finally, mark points are obtained through thresholding. The specific structure, related parameters, recognition effect, and noise resistance of the network were explored in 614 sets of ABR clinical data. The results show that the average detection time for each data was 0.05 s, and recognition accuracy reached 92.91%. The study proposed an automatic recognition of ABR waveforms by using the BiLSTM-based machine learning technique. The results demonstrated that the proposed methods could reduce recording time and help doctors in making diagnosis, suggesting that the proposed method has the potential to be used in the clinic in the future.
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http://dx.doi.org/10.3389/fmed.2020.613708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829202PMC
January 2021

Phenotypic continuum between Waardenburg syndrome and idiopathic hypogonadotropic hypogonadism in humans with SOX10 variants.

Genet Med 2021 Apr 13;23(4):629-636. Epub 2021 Jan 13.

Harvard Reproductive Sciences Center, The Reproductive Endocrine Unit and The Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Purpose: SOX10 variants previously implicated in Waardenburg syndrome (WS) have now been linked to Kallmann syndrome (KS), the anosmic form of idiopathic hypogonadotropic hypogonadism (IHH). We investigated whether SOX10-associated WS and IHH represent elements of a phenotypic continuum within a unifying disorder or if they represent phenotypically distinct allelic disorders.

Methods: Exome sequencing from 1,309 IHH subjects (KS: 632; normosmic idiopathic hypogonadotropic hypogonadism [nIIHH]: 677) were reviewed for SOX10 rare sequence variants (RSVs). The genotypic and phenotypic spectrum of SOX10-related IHH (this study and literature) and SOX10-related WS cases (literature) were reviewed and compared with SOX10-RSV spectrum in gnomAD population.

Results: Thirty-seven SOX10-associated IHH cases were identified as follows: current study: 16 KS; 4 nIHH; literature: 16 KS; 1 nIHH. Twenty-three IHH cases (62%; all KS), had ≥1 known WS-associated feature(s). Moreover, five previously reported SOX10-associated WS cases showed IHH-related features. Four SOX10 missense RSVs showed allelic overlap between IHH-ascertained and WS-ascertained cases. The SOX10-HMG domain showed an enrichment of RSVs in disease states versus gnomAD.

Conclusion: SOX10 variants contribute to both anosmic (KS) and normosmic (nIHH) forms of IHH. IHH and WS represent SOX10-associated developmental defects that lie along a unifying phenotypic continuum. The SOX10-HMG domain is critical for the pathogenesis of SOX10-related human disorders.
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http://dx.doi.org/10.1038/s41436-020-01051-3DOI Listing
April 2021

De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2-Hydroxy-1,4-diones with Nucleophiles.

Chemistry 2021 Mar 22;27(16):5225-5229. Epub 2021 Feb 22.

Jiangsu Key Laboratory of Pesticide Science, and Department of, Chemistry, College of Sciences, Nanjing Agricultural University, 1 Weigang Road, Xuanwu District, Nanjing, 210095, P.R. China.

Herein, a divergent synthesis of a variety of 2α- and 5α-substituted furan derivatives from 2-hydroxy-1,4-diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6-conjugate addition or cyclization/Friedel-Crafts-type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6-conjugate addition for 5α substitution and >20 types for the Friedel-Crafts-type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity-oriented synthesis of α-substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4-hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.
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http://dx.doi.org/10.1002/chem.202005098DOI Listing
March 2021

Comparison of Overall Survival Between Invasive Lobular Breast Carcinoma and Invasive Ductal Breast Carcinoma: A Propensity Score Matching Study Based on SEER Database.

Front Oncol 2020 22;10:590643. Epub 2020 Dec 22.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objective: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most breast cancers. However, the overall survival (OS) differences between ILC and IDC remain controversial. This study aimed to compare nonmetastatic ILC to IDC in terms of survival and prognostic factors for ILC.

Methods: This retrospective cohort study used data from the Surveillance, Epidemiology and End Results (SEER) Cancer Database (www.seer.cancer.gov). Women diagnosed with nonmetastatic ILC and IDC between 2006 and 2016 were included. A propensity score matching (PSM) method was used in our analysis to reduce baseline differences in clinicopathological characteristics and survival outcomes. Kaplan-Meier curves and log-rank test were used for survival analysis.

Results: Compared to IDC patients, ILC patients were diagnosed later in life with poorly differentiated and larger lesions, as well as increased expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). A lower rate of radiation therapy and chemotherapy was observed in ILC. After PSM, ILC, and IDC patients exhibited similar OS (HR=1.017, p=0.409, 95% CI: 0.967-1.069). In subgroup analysis of HR-negative, AJCC stage III, N2/N3 stage patients, or those who received radiotherapy, ILC patients exhibited worse OS compared to IDC patients. Furthermore, multivariate analysis revealed a 47% survival benefit for IDC compared to ILC in HR-negative patients who received chemotherapy (HR=1.47, p=0.01, 95% CI: 1.09-1.97).

Conclusions: Our results demonstrated that ILC and IDC patients had similar OS after PSM. However, ILC patients with high risk indicators had worse OS compared to IDC patients by subgroup analysis.
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http://dx.doi.org/10.3389/fonc.2020.590643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783385PMC
December 2020

Circular RNA circ_ASAP2 promotes cell viability, migration, and invasion of gastric cancer cells by regulating the miR-770-5p/CDK6 axis.

Int J Clin Exp Pathol 2020 1;13(11):2806-2819. Epub 2020 Nov 1.

Department of Cadre/VIP Surgery, The First Affiliated Hospital of Xinjiang Medical University Urumchi 830054, Xinjiang Uygur Autonomous Region, China.

Background: Gastric cancer (GC) is one of the most common causes of cancer death. GSE83521 microarray analysis suggested that circular RNA circ_ASAP2 (hsa_circ_0008768) expression was increased in GC tissues. However, the molecular mechanism of circ_ASAP2 remains unknown.

Methods: Expression levels of circ_ASAP2, microRNA-770-5p (miR-770-5p), and the cyclin-dependent kinase 6 (CDK6) were detected by using real time PCR (RT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and transwell assays were applied to explore cell viability, migration, and invasion, respectively. The interactions between miR-770-5p and circ_ASAP2 or CDK6 was predicted by using Starbase software, and then confirmed by luciferase reporter assay. Xenograft tumor model was also used to estimate the effect of circ_ASAP2 on tumor growth .

Results: The expression levels of circ_ASAP2 and CDK6 were increased, and miR-770-5p level was decreased in GC tissues and cells. Furthermore, circ_ASAP2 knockdown inhibited cell viability, migration, and invasion of GC cells. Mechanically, circ_ASAP2 functioned as a sponge of miR-770-5p to regulate CDK6 expression, thereby boosting the progression of GC cells. Circ_ASAP2 silencing hindered the tumor growth of GC .

Conclusion: Circ_ASAP2 knockdown can repress the development of GC cells partly through regulating the miR-770-5p/CDK6 axis, suggesting an underlying circRNA-targeted therapy for GC treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716128PMC
November 2020

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

Adv Ther 2021 01 25;38(1):772-781. Epub 2020 Nov 25.

Eli Lilly and Company, Shanghai, China.

Introduction: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate.

Methods: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively.

Results: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks.

Conclusions: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE.

Trial Registration: ClinicalTrials.gov identifier, NCT02265705.
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http://dx.doi.org/10.1007/s12325-020-01572-yDOI Listing
January 2021

A rolling bearing fault detection method based on compressed sensing and a neural network.

Math Biosci Eng 2020 09;17(5):5864-5882

College of Locomotive and Rolling Stock Engineering, Dalian Jiaotong University, Dalian 116028, China.

The high sampling frequency of traditional Nyquist sampling theory not only puts greater requirements on the sampling equipment, but also generates a large amount of data, which increases the difficulty of information transmission and storage. To this end, this paper proposes a rolling bearing fault signal detection method based on compressed sensing combined with a neural network. Based on the theory of compressed sensing, the observations obtained from compression sampling are divided into two sets of data. Given the one set of data, the predictive ability of the nonlinear time series through the neural network can predict the second set of observed values. The predicted observations are used to reconstruct the signal, thereby reducing the amount of data to be stored and transmitted and realizing secondary compression of the signal.
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http://dx.doi.org/10.3934/mbe.2020313DOI Listing
September 2020

A novel threshold segmentation instantaneous frequency calculation approach for fault diagnosis.

Math Biosci Eng 2020 08;17(5):5395-5413

School of Locomotive and Rolling Stock Engineering, Dalian Jiaotong University, Dalian 116028, China.

Instantaneous frequency can well track and reflect the transient information of signal, so it plays an important role in the analysis and processing of the non-stationary signal. In this paper, the single component signal is compared with the Second Order Differential Equation in polar coordinates. Based on this, a threshold segmentation instantaneous frequency calculation method is proposed. This method is mainly for characteristics of the non-stationary signal, use the change of the area around the signal and the x axis to determine the amplitude mutation point of each single component signal, and perform segmentation. Simulations, mathematical derivations and experimental tests are used to highlight the performance of the proposed method. It is not only simple in calculation, but also can reduce the unnecessary influence of non-stationary signal amplitude mutation on instantaneous frequency, and can effectively judge the fault of rolling bearing in fault diagnosis.
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http://dx.doi.org/10.3934/mbe.2020291DOI Listing
August 2020

A MicroRNA Linking Human Positive Selection and Metabolic Disorders.

Cell 2020 10 14;183(3):684-701.e14. Epub 2020 Oct 14.

Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.

Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.
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http://dx.doi.org/10.1016/j.cell.2020.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092355PMC
October 2020

Effects of High-Dose of Copper Amino Acid Complex on Laying Performance, Hematological and Biochemical Parameters, Organ Index, and Histopathology in Laying Hens.

Biol Trace Elem Res 2020 Oct 12. Epub 2020 Oct 12.

Key Laboratory of Animal Nutrition and Feed in East China of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.

The objective of the study was to evaluate the maximum tolerance limit of amino acid copper complex (Cu-Lys-Glu) for laying hens by measuring their laying performance, hematological and serum biochemical parameters, organ index, and histopathology. A total of 450 18-week-old Beijing White layers were randomly allocated to 5 groups (90 birds per group) with 6 replicates of 15 birds each. After a 2-week acclimation on a basal diet (analyzed copper content 8.63 mg/kg), the birds were fed diets supplemented with 0 (control), 15, 75, 150, and 300 mg Cu/kg as Cu-Lys-Glu for 10 weeks. Results showed that, compared with the control group, dietary supplementation with 15, 75, and 150 mg Cu/kg as Cu-Lys-Glu did not affect (P > 0.05) laying performance, whereas hens receiving with 300 mg Cu/kg significantly decreased (P < 0.001) the laying rate as compared with the control. No significant differences (P > 0.05) were observed among the hens receiving 0, 15, 75, and 150 mg Cu/kg as Cu-Lys-Glu in hematological and serum biochemical parameters, organ indexes, and histopathological changes. However, hens receiving 300 mg Cu/kg significantly increased (P < 0.05) the concentrations of mean corpuscular volume (MCV), albumin (ALB), total bilirubin (TBILI), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (UN), and creatinine (CRE), as well as caused severe microscopic histopathological changes in the liver and kidney. In conclusion, 150 mg Cu/kg as Cu-Lys-Glu is identified as no-side-effect supplementation level in laying hens after daily administration for 70 days.
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http://dx.doi.org/10.1007/s12011-020-02406-2DOI Listing
October 2020

Analyzing Stimulus-frequency Otoacoustic Emission Fine Structure Using an Additive Model

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:960-963

A good understanding of the origin of stimulus-frequency otoacoustic emission (SFOAE) fine structure in human ears and its probe level-dependency has potential clinical significance. In this study, we develop a two-component additive model, with total SFOAE unmixed into short- and long-latency components (or reflections) using time windowing method, to investigate the origin of SFOAE fine structure in humans from 40 to 70 dB SPL. The two-component additive model predicts that a spectral notch seen in the amplitude fine structure is produced when short- and long-latency components have opposite phases and comparable magnitudes. And the depth of spectral notch is significantly correlated with the amplitude difference between the two separated components, as well as their degree of opposite phase. Our independent evidence for components contributing to SFOAE fine structure suggests that amplitude, phase and delay fine structure in the human SFOAEs are a construct of the complex addition of two or more internal reflections with different phase slops in the cochlea.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175491DOI Listing
July 2020

The role of adjuvant chemotherapy in stage I-III male breast cancer: a SEER-based analysis.

Ther Adv Med Oncol 2020 20;12:1758835920958358. Epub 2020 Sep 20.

Department of Breast Cancer, Cancer Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou510080, China.

Background And Aims: Male breast cancer is an uncommon disease. The benefit of adjuvant chemotherapy in the treatment of male breast cancer patients has not been determined. The aim of this study was to explore the value of adjuvant chemotherapy in men with stage I-III breast cancer, and we hypothesized that some male patients may safely skip adjuvant chemotherapy.

Methods: Male breast cancer patients between 2010 and 2015 from the Surveillance Epidemiology and End Results database were included. Univariate and multivariate Cox analyses were used to analyse the factors associated with survival. The propensity score matching method was adopted to balance baseline characteristics. Kaplan-Meier curves were used to evaluate the impacts of adjuvant chemotherapy on survival. The primary endpoint was survival.

Results: We enrolled 514 patients for this study, including 257 patients treated with chemotherapy and 257 patients without. There was a significant difference in overall survival (OS) but not in breast cancer-specific survival (BCSS) between the two groups ( < 0.001 for OS and  = 0.128 for BCSS, respectively). Compared with the non-chemotherapy group, the chemotherapy group had a higher 4-year OS rate (97.5% 95.2%,  < 0.001), while 4-year BCSS was similar (98% 98.8%,  = 0.128). The chemotherapy group had longer OS than the non-chemotherapy group among HR+, HER2-, tumour size >2 cm, lymph node-positive male breast cancer patients ( < 0.05). Regardless of tumour size, there were no differences in OS or BCSS between the chemotherapy and non-chemotherapy cohorts for lymph node-negative patients (OS:  > 0.05, BCSS:  > 0.05). Adjuvant chemotherapy showed no significant effects on both OS and BCSS in patients with stage I (OS:  = 0.100, BCSS:  = 0.858) and stage IIA breast cancer (OS:  > 0.05, BCSS:  > 0.05).

Conclusion: For stage I and stage IIA patients, adjuvant chemotherapy could not improve OS and BCSS. Therefore, adjuvant chemotherapy might be skipped for stage I and stage IIA male breast cancer patients.
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http://dx.doi.org/10.1177/1758835920958358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509722PMC
September 2020

Air and bone-conducted vestibular evoked myogenic potentials in children with large vestibular aqueduct syndrome.

Acta Otolaryngol 2021 Jan 23;141(1):50-56. Epub 2020 Sep 23.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.

Background: There are few studies focused on vestibular symptoms and function of the children with LVAS.

Objectives: This study aimed to find the characteristics of air and bone-conducted VEMPs among children with LVAS, and to investigate the relationship between VEMPs and vestibular symptoms.

Material And Methods: A total of 44 children with LVAS and 10 healthy children were recruited as the case group and control group. Air and bone-conducted VEMP were performed to the participants.

Results: For air-conducted measurement, there was elevated amplitude of cVEMP in case group than control group. There was no significant difference at oVEMP parameters between the case group and control group. For bone-conducted measurement, significantly longer P1 latency and shorter P1-N1 latency of cVEMP were observed among the case group; there were a series of changes in oVEMP parameters among the case group. Logistic regression model revealed that air-conducted oVEMP asymmetric ratio was valuable to predict vestibular symptoms' development among the kids with LVAS.

Conclusion: Asymmetric ratio of oVEMP could be used as one predictor of developing vestibular symptoms of the children with LVAS. Applying bone-conducted VEMP as one alternative parameter of vestibular syndrome is novel and will certainly remain an area of continued investigation.
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http://dx.doi.org/10.1080/00016489.2020.1815836DOI Listing
January 2021

Adjuvant chemotherapy could benefit early-stage ER/PR positive mucinous breast cancer: A SEER-based analysis.

Breast 2020 Dec 9;54:79-87. Epub 2020 Sep 9.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Purpose: The aim of this study was to explore the value of adjuvant chemotherapy in patients with early-stage ER/PR-positive mucinous carcinoma.

Methods: We identified early-stage ER/PR-positive mucinous carcinoma patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity-score matching (PSM) analysis to eliminate selection bias and differences in baseline characteristics. Univariate and multivariate analyses were performed to identify significant prognostic factors. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS), which were evaluated with the Kaplan-Meier method.

Results: After propensity score matching, 805 pairs were selected. Patients with early-stage ER/PR-positive mucinous adenocarcinoma in the chemotherapy group had a better OS, but not BCSS, than those in the nonchemotherapy group after PSM (OS: p < 0.001; BCSS: p = 0.285). After stratifying by tumor size and lymph node status, adjuvant chemotherapy could significantly improve the OS of early-stage ER/PR-positive patients with tumors larger than 3 cm (p = 0.004) if they had negative lymph nodes (LNs). For patients positive LNs, the OS was significantly different between the chemotherapy group and the non-chemotherapy group when the tumors were larger than 1 cm (T = 1-2.9 cm, p = 0.006; T>3 cm, p = 0.049, respectively).

Conclusion: Adjuvant chemotherapy maybe improves prognosis in patients with negative LNs and tumors larger than 3 cm, or patients with LNs metastasis and tumors larger than 1 cm. We suggest considering clinical characteristics meanwhile when deciding chemotherapy or not. Randomized controlled trials (RCT) are expected to confirm our results in the future.
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http://dx.doi.org/10.1016/j.breast.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502365PMC
December 2020

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

Rheumatol Ther 2020 Dec 2;7(4):851-866. Epub 2020 Sep 2.

Peking University People's Hospital, Beijing, China.

Introduction: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.

Methods: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.

Results: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.

Conclusions: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.

Trial Registration: NCT02265705.
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http://dx.doi.org/10.1007/s40744-020-00231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695798PMC
December 2020

Transcript Profiles of Stria Vascularis in Models of Waardenburg Syndrome.

Neural Plast 2020 1;2020:2908182. Epub 2020 Aug 1.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.

Background: Waardenburg syndrome is an uncommon genetic condition characterized by at least some degree of congenital hearing loss and pigmentation deficiencies. However, the genetic pathway affecting the development of stria vascularis is not fully illustrated.

Methods: The transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pig and mice models. Therefore, GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation.

Results: There were 113 genes in tyrosine metabolism, melanin formation, and ion transportations showed significant changes in pig models and 191 genes in mice models. In addition, there were some spice's specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19, and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1, and Col11a2 genes were higher, and the expression of Col8a2, Cd34, and Ncam genes were lower in the porcine models compared to mouse models.

Conclusions: Our data suggests that there is a significant difference on the gene expression and function between these two models.
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http://dx.doi.org/10.1155/2020/2908182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416267PMC
August 2020

The lysine demethylase KDM4A controls the cell-cycle expression of replicative canonical histone genes.

Biochim Biophys Acta Gene Regul Mech 2020 10 13;1863(10):194624. Epub 2020 Aug 13.

Massachusetts General Hospital, Cancer Center and Harvard Medical School, Department of Medicine, 13th street bldg. 149, Charlestown, MA 02129, United States of America; Fox Chase Cancer Center, 333 Cottman Avenue West 260, Philadelphia, PA 19111, United States of America. Electronic address:

Chromatin modulation provides a key checkpoint for controlling cell cycle regulated gene networks. The replicative canonical histone genes are one such gene family under tight regulation during cell division. These genes are most highly expressed during S phase when histones are needed to chromatinize the new DNA template. While this fact has been known for a while, limited knowledge exists about the specific chromatin regulators controlling their temporal expression during cell cycle. Since histones and their associated mutations are emerging as major players in diseases such as cancer, identifying the chromatin factors modulating their expression is critical. The histone lysine tri-demethylase KDM4A is regulated over cell cycle and plays a direct role in DNA replication timing, site-specific rereplication, and DNA amplifications during S phase. Here, we establish an unappreciated role for the catalytically active KDM4A in directly regulating canonical replicative histone gene networks during cell cycle. Of interest, we further demonstrate that KDM4A interacts with proteins controlling histone expression and RNA processing (i.e., hnRNPUL1 and FUS/TLS). Together, this study provides a new function for KDM4A in modulating canonical histone gene expression.
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http://dx.doi.org/10.1016/j.bbagrm.2020.194624DOI Listing
October 2020

Multiparametric MRI-based radiomics analysis for the prediction of breast tumor regression patterns after neoadjuvant chemotherapy.

Transl Oncol 2020 Nov 3;13(11):100831. Epub 2020 Aug 3.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. Electronic address:

Objectives: Breast cancers show different regression patterns after neoadjuvant chemotherapy. Certain regression patterns are associated with more reliable margins in breast-conserving surgery. Our study aims to establish a nomogram based on radiomic features and clinicopathological factors to predict regression patterns in breast cancer patients.

Methods: We retrospectively reviewed 144 breast cancer patients who received neoadjuvant chemotherapy and underwent definitive surgery in our center from January 2016 to December 2019. Tumor regression patterns were categorized as type 1 (concentric regression + pCR) and type 2 (multifocal residues + SD + PD) based on pathological results. We extracted 1158 multidimensional features from 2 sequences of MRI images. After feature selection, machine learning was applied to construct a radiomic signature. Clinical characteristics were selected by backward stepwise selection. The combined prediction model was built based on both the radiomic signature and clinical factors. The predictive performance of the combined prediction model was evaluated.

Results: Two radiomic features were selected for constructing the radiomic signature. Combined with two significant clinical characteristics, the combined prediction model showed excellent prediction performance, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval 0.8343-0.9701) in the primary cohort and 0.826 (95% confidence interval 0.6774-0.9753) in the validation cohort.

Conclusions: Our study established a unique model combining a radiomic signature and clinicopathological factors to predict tumor regression patterns prior to the initiation of NAC. The early prediction of type 2 regression offers the opportunity to modify preoperative treatments or aids in determining surgical options.
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http://dx.doi.org/10.1016/j.tranon.2020.100831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399245PMC
November 2020

Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss.

Neural Plast 2020 12;2020:6235948. Epub 2020 Jun 12.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.

The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-B (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-B (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss.
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http://dx.doi.org/10.1155/2020/6235948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306080PMC
June 2020

Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function.

Sci Adv 2020 Apr 22;6(17):eaax9856. Epub 2020 Apr 22.

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important "indirect effects" are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical "indirect effects" in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.
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http://dx.doi.org/10.1126/sciadv.aax9856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176434PMC
April 2020

Baricitinib in patients with rheumatoid arthritis with inadequate response to methotrexate: results from a phase 3 study.

Clin Exp Rheumatol 2020 Jul-Aug;38(4):732-741. Epub 2020 May 20.

CEPIC - Centro Paulista de Investigação Clinica e Serviços Médicos, Ipiranga São Paulo, Brazil.

Objectives: This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy.

Methods: In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28-joint counts (DAS28)-high-sensitivity C-reactive protein (hsCRP), Simplified Disease Activity Index (SDAI) score ≤3.3, mean duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS 0-10), worst tiredness NRS, and worst joint pain NRS at week 12.

Results: Most patients (approximately 80%) were from China. More patients achieved ACR20 response at week 12 with baricitinib than with placebo (58.6% vs. 28.3%; p<0.001). Statistically significant improvements were also seen in HAQ-DI, DAS28-hsCRP, morning joint stiffness, worst tiredness, and worst joint pain in the baricitinib group compared to placebo at week 12. Through week 24, rates of treatment-emergent adverse events, including infections, were higher for baricitinib compared to placebo, while serious adverse event rates were similar between baricitinib and placebo.

Conclusions: In patients with RA who had an inadequate response to MTX, baricitinib was associated with significant clinical improvements as compared with placebo.
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September 2020

A nomogram to predict non-sentinel lymph node metastasis in patients with initial cN+ breast cancer that downstages to cN0 after neoadjuvant chemotherapy.

J Surg Oncol 2020 Sep 20;122(3):373-381. Epub 2020 May 20.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.

Background And Objectives: This study mainly explored the factors that influence non-sentinel lymph node (NSLN) metastasis in patients with breast cancer (BC) whose axillary lymph nodal status changed from clinically node positive (cN+) to clinically node negative (cN0) after neoadjuvant chemotherapy (NAC).

Methods: We retrospectively analyzed the clinicopathological factors affecting NSLN metastasis in a total of 179 patients with cN+ BC downstaged to cN0 (120 in the training set and 59 in the validation set) who underwent both sentinel lymph node (SLN) biopsy and axillary lymph node dissection following NAC.

Results: Among 179 patients enrolled, the overall NSLN metastatic rate was 24.0% (95% confidence interval [CI]: 17.7%-30.3%). In multivariate logistic regression analysis, the number of positive SLNs achieving a pathological complete remission of the breast and clinical node staging was independent predictors of NSLN metastasis. A nomogram was established based on these factors and displayed a good discriminatory capability, with an area under the curve of 0.919 (95% CI: 0.865-0.973) for the training set and 0.900 (95% CI: 0.812-0.988) for the validation set and its clinical utility was confirmed by the decision curve analysis.

Conclusions: The nomogram established showed the ability to predict NSLN metastases in patients with initial cN+ BC that downstaged to cN0 after NAC.
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http://dx.doi.org/10.1002/jso.25989DOI Listing
September 2020

S-phase Enriched Non-coding RNAs Regulate Gene Expression and Cell Cycle Progression.

Cell Rep 2020 05;31(6):107629

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Many proteins that are needed for progression through S-phase are produced from transcripts that peak in the S-phase, linking temporal expression of those proteins to the time that they are required in cell cycle. Here, we explore the potential roles of long non-coding RNAs in cell cycle progression. We use a sensitive click-chemistry approach to isolate nascent RNAs in a human cell line, and we identify more than 900 long non-coding RNAs (lncRNAs) whose synthesis peaks during the S-phase. More than 200 of these are long intergenic non-coding RNAs (lincRNAs) with S-phase-specific expression. We characterize three of these lincRNAs by knockdown and find that all three lincRNAs are required for appropriate S-phase progression. We infer that non-coding RNAs are key regulatory effectors during the cell cycle, acting on distinct regulatory networks, and herein, we provide a large catalog of candidate cell-cycle regulatory RNAs.
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http://dx.doi.org/10.1016/j.celrep.2020.107629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954657PMC
May 2020

Erratum: Analysis of Tau Protein Expression in Predicting Pathological Complete Response to Neoadjuvant Chemotherapy in Different Molecular Subtypes of Breast Cancer.

J Breast Cancer 2020 Apr 5;23(2):230-231. Epub 2020 Mar 5.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

[This corrects the article on p. 47 in vol. 23, PMID: 32140269.].
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http://dx.doi.org/10.4048/jbc.2020.23.e19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192745PMC
April 2020