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Appelbaum, Limor, Jose Pablo Cambronero, Karla Pollick, et al. "Development and validation of a pancreatic cancer prediction model from electronic health records using machine learning." Journal of Clinical Oncology 38, no. 4_suppl (2020): 679. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.679.
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679 Background: Pancreatic Adenocarcinoma (PDAC) is often diagnosed at an advanced stage. We sought to develop a model for early PDAC prediction in the general population, using electronic health records (EHRs) and machine learning. Methods: We used three EHR datasets from Beth-Israel Deaconess Medical Center (BIDMC) and Partners Healthcare (PHC): 1. “BIDMC-Development-Data” (BIDMC-DD) for model development, using a feed-forward neural network (NN) and L2-regularized logistic regression,randomly split (80:20) into training and test groups. We tuned hyperparameters using cross-validation in training, and report performance on the test split. 2. “BIDMC-Large-Data” (BIDMC-LD) to re-fit and calibrate models. 3. “PHC-Data” for external validation. We evaluate using Area Under the Receiver Operating Characteristic Curve (AUC) and compute 95% CI using empirical bootstrap over test data. PDAC patients were selected using ICD9/-10 codes and validated with tumor registries. In contrast to prior work, we did not predefine feature sets based on known clinical correlates and instead employed data-driven feature selection, specifically importance-based feature pruning, regularization, and manual validation, to identify diagnostic-based features. Results: BIDMC-DD included demographics, diagnoses, labs and medications for 1018 patients (cases = 509; age-sex paired controls). BIDMC-LD included diagnoses for 547,917 patients (cases = 509), and PHC included diagnoses for 160,593 patients (cases = 408). We compared our approach to adapted and re-fitted published baselines. With a 365-day lead-time, NN obtained a BIDMC-DD test AUC of 0.84 (CI 0.79 - 0.90) versus the previous best baseline AUC of 0.70 (CI 0.62 - 0.78). We also validated using BIDMC-DD’s test cancer patients and BIDMC LD controls. The AUC was 0.71 (CI 0.67 - 0.76) at the 365-day cutoff. NN’s external validation AUC on PHC-Data was 0.71 (CI 0.63 - 0.79), outperforming an existing model’s AUC of 0.61 (CI 0.52 - 0.70) (Baecker et al, 2019). Conclusions: Models based on data-driven feature selection outperform models that use predefined sets of known clinical correlates and can help in early prediction of PDAC development.
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Mafi, John N., Roanne Mejilla, Henry Feldman, et al. "Patients learning to read their doctors’ notes: the importance of reminders." Journal of the American Medical Informatics Association 23, no. 5 (2016): 951–55. http://dx.doi.org/10.1093/jamia/ocv167.
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Abstract Objective To examine whether patients invited to review their clinicians’ notes continue to access them and to assess the impact of reminders on whether patients continued to view notes. Materials and methods We followed OpenNotes trial participants for 2 years at Beth Israel Deaconess Medical Center (BIDMC) and Geisinger Health System (GHS). Electronic invitations alerting patients to signed notes stopped at GHS after year 1, creating a natural experiment to assess the impact of reminders. We used generalized linear models to measure whether notes were viewed within 30 days of availability. Results We identified 14 360 patients (49 271 visits); mean age 52.2; 57.8% female. In year 1, patients viewed 57.5% of their notes, and their interest in viewing notes persisted over time. In year 2, BIDMC patients viewed notes with similar frequency. In contrast, GHS patients viewed notes far less frequently, a change starting when invitations ceased (RR 0.29 [0.26–0.32]) and persisting to the end of the study (RR 0.20 [0.17–0.23]). A subanalysis of BIDMC patients revealed that black and other/multiracial patients also continued to view notes, although they were overall less likely to view notes compared with whites (RR 0.75 [0.67–0.83] and 0.93 [0.89–0.98], respectively). Discussion As millions of patients nationwide increasingly gain access to clinicians’ notes, explicit email invitations to review notes may be important for fostering patient engagement and patient-doctor communication. Conclusion Note viewing persists when accompanied by email alerts, but may decline substantially in their absence. Non-white patients at BIDMC viewed notes less frequently than whites, although their interest also persisted.
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Fargnoli, Jessica L., Qi Sun, Deanna Olenczuk, et al. "Resistin is associated with biomarkers of inflammation while total and high-molecular weight adiponectin are associated with biomarkers of inflammation, insulin resistance, and endothelial function." European Journal of Endocrinology 163, no. 2 (2010): 359. http://dx.doi.org/10.1530/eje-09-0555e.
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The authors and the journal apologise for an error in the funding section of this article published in 2010, vol 162, pp 281–288. The grant number that is listed as DK081923 is actually DK081913. The Funding section with the correct grant numbers is published in full below:FundingThis work was supported by the National Institute of Health (grants HL65582, HL60712, HL34594, DK58785, DK081913, DK79929, and DK58845), a discretionary grant from BIDMC, and a grant-in-aid by Tanita Corporation. Dr Hu is a recipient of the American Heart Association Established Investigator Award. Dr Sun is supported by a Postdoctoral Fellowship from the Unilever Corporate Research.
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Nahas, Myrna Rita, Jessica A. Zerillo, Stephen A. Cannistra, and Cheryle Totte. "Raising the safety bar: The hematology/oncology patient safety committee." Journal of Clinical Oncology 32, no. 30_suppl (2014): 144. http://dx.doi.org/10.1200/jco.2014.32.30_suppl.144.
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144 Background: Enhancing patient safety can prevent unintended outcomes arising from defects in healthcare delivery systems. The Hematology/Oncology Patient Safety Committee (HOPSC) at Beth Israel Deaconess Medical Center (BIDMC) is a multidisciplinary team of healthcare providers that meets monthly to review inpatient and outpatient adverse events, near misses, and medical errors that impact patient safety. Methods: Our aim was to quantify and qualify the cases that the HOPSC has reviewed from 2012-2013. In order to identify trends in event reporting, we reviewed the number of events reported to the HOPSC in both the inpatient and outpatient settings. We further subdivided events into two categories: medication-related and non-medication related. Additionally, we delineated which healthcare provider initiated the reporting of each event. Results: Over the two-year period, a total number of 1,061 events were reported to the HOPSC. Of these, 259 were medication-related events. Of the events reported, 40 were by a physician/NP and 1,021 were by a nurse. There was a discrepancy in the type of event reported (24.4% medication vs. 75.6% non-medication related) as well as in the type of reporter (3.8% physician/NP vs. 96.2% nurse). Of all the events reported, 8 were escalated to the Department of Medicine Peer Review Committee. Conclusions: Through review of healthcare provider event reports, the HOPSC has identified several types of adverse events and near misses in the Hematology/Oncology division at BIDMC. The events are mostly reported by inpatient nurses and are primarily medication-related. Given this skewed reporting pattern, we will investigate the reasons why reporting by physicians, especially in the outpatient setting, is limited. Our reported outline of the HOPSC operations may also guide oncology practices elsewhere in their own development of patient safety peer review committees. [Table: see text]
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Khera, Tanvi, Pooja A. Mathur, Valerie M. Banner-Goodspeed, et al. "Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial." BMJ Open 11, no. 3 (2021): e044346. http://dx.doi.org/10.1136/bmjopen-2020-044346.
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IntroductionPostoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored.Methods and analysisThis multicentre, randomised, placebo-controlled, quadruple-blinded trial will include 900 older (>60 years) cardiac surgical patients requiring CPB. Patients meeting the inclusion criteria and not meeting any exclusion criteria will be enrolled at seven centres across the USA with Beth Israel Deaconess Medical Center (BIDMC), Boston, as the central coordinating centre. Additional sites may be included to broaden or speed accrual. The primary outcome measure is the incidence of in-hospital delirium till day 30. Secondary outcomes include the duration and severity of in-hospital delirium, hospital and ICU lengths of stay, postoperative pain scores, postoperative rescue analgesic consumption, postoperative cognitive function and chronic sternal pain. Creation of a biorepository and the use of intraoperative-blinded electroencephalogram (EEG) and cerebral oximetry data will support exploratory endpoints to determine mechanistic predictors of postoperative delirium.Ethics and disseminationThis trial is approved and centrally facilitated by the Institutional Review Board at BIDMC. An independent Data Safety and Monitoring Board is responsible for maintaining safety oversight. Protocol # 2019 P00075, V.1.4 (dated 20 October 2020).Trial registration numberNCT04093219.
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Babalola, Atinuke, Rebecca A. Miksad, Olubunmi Oladunjoye, et al. "Comparison of Hispanic and non-Hispanic patients with HCC." Journal of Clinical Oncology 32, no. 30_suppl (2014): 294. http://dx.doi.org/10.1200/jco.2014.32.30_suppl.294.
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294 Background: In the U.S., Hispanics have a higher incidence of hepatocellular cancer (HCC) and higher disease-specific mortality. The country of origin for Hispanics varies throughout the U.S. However, little is known about Hispanics with HCC in the Northeast. We compared Hispanic and non-Hispanic patients with HCC at a Boston teaching hospital. Methods: Hispanic patients with HCC seen at Beth Israel Deaconess Medical Center (BIDMC) from 1998-2012 were identified in our database. Ethnicity was determined from demographic and language preference information in electronic medical records and supplemented by comparing surnames with the 1990 Census Spanish Surname List. The comparison group was identified by randomly choosing non-Hispanic patients diagnosed the same years as Hispanic patients. We compared both groups using Chi Squared test. Results: 59 Hispanic and 89 non-Hispanic patients with HCC were included in the analysis. The majority (48%) of Hispanic HCC patients were Puerto Rican. Although the median age at diagnosis was similar (59.1 vs 60.3 years for Hispanics and non-Hispanics), there were more women in the Hispanic cohort (28.8% vs 12.4% p0.012). Hispanics had greater odds of not having private insurance (OR 4.24, 95%CI: 2.101, 8.554). Evaluation of HCC risk factors revealed Hispanics were significantly more likely to have hepatitis C (OR 3.68, 95% CI: 1.830, 7.420). In addition, the incidence of Metabolic Syndrome was significantly higher for Hispanics (44.7% vs. 21.7% p0.025). Although individual components of metabolic syndrome were higher in Hispanics, they were not statistically significant: hypertension (52.5% vs 40.4%), Diabetes Mellitus (39% vs 25%), BMI ≥ 30 (39% vs 27%), hypertrigylceridemia (57% vs 52%) and low HDL levels (50% vs 41%). Hispanics were more likely to have received Transarterial Chemoembolization (TACE) and Radiofrequency ablation (RFA) treatments (OR 2.48, 95% CI: 1.261, 4.858). Conclusions: Hispanic HCC patients at BIDMC were more likely to have hepatitis C, metabolic syndrome and to be female than their non-Hispanic counterparts. Outreach to Hispanic communities to identify patients with hepatitis C and metabolic syndrome, particularly in women, may improve HCC prevention, screening and treatment outcomes.
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Dhahri, Habib, Ines Rahmany, Awais Mahmood, Eslam Al Maghayreh, and Wail Elkilani. "Tabu Search and Machine-Learning Classification of Benign and Malignant Proliferative Breast Lesions." BioMed Research International 2020 (February 28, 2020): 1–10. http://dx.doi.org/10.1155/2020/4671349.
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Breast cancer is the most diagnosed cancer among women around the world. The development of computer-aided diagnosis tools is essential to help pathologists to accurately interpret and discriminate between malignant and benign tumors. This paper proposes the development of an automated proliferative breast lesion diagnosis based on machine-learning algorithms. We used Tabu search to select the most significant features. The evaluation of the feature is based on the dependency degree of each attribute in the rough set. The categorization of reduced features was built using five machine-learning algorithms. The proposed models were applied to the BIDMC-MGH and Wisconsin Diagnostic Breast Cancer datasets. The performance measures of the used models were evaluated owing to five criteria. The top performing models were AdaBoost and logistic regression. Comparisons with others works prove the efficiency of the proposed method for superior diagnosis of breast cancer against the reviewed classification techniques.
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Wang, Ludi, and Xiaoguang Zhou. "Detection of Congestive Heart Failure Based on LSTM-Based Deep Network via Short-Term RR Intervals." Sensors 19, no. 7 (2019): 1502. http://dx.doi.org/10.3390/s19071502.
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Congestive heart failure (CHF) refers to the inadequate blood filling function of the ventricular pump and it may cause an insufficient heart discharge volume that fails to meet the needs of body metabolism. Heart rate variability (HRV) based on the RR interval is a proven effective predictor of CHF. Short-term HRV has been used widely in many healthcare applications to monitor patients’ health, especially in combination with mobile phones and smart watches. Inspired by the inception module from GoogLeNet, we combined long short-term memory (LSTM) and an Inception module for CHF detection. Five open-source databases were used for training and testing, and three RR segment length types (N = 500, 1000 and 2000) were used for the comparison with other studies. With blindfold validation, the proposed method achieved 99.22%, 98.85% and 98.92% accuracy using the Beth Israel Deaconess Medical Center (BIDMC) CHF, normal sinus rhythm (NSR) and the Fantasia database (FD) databases and 82.51%, 86.68% and 87.55% accuracy using the NSR-RR and CHF-RR databases, with N = 500, 1000 and 2000 length RR interval segments, respectively. Our end-to-end system can help clinicians to detect CHF using short-term assessment of the heartbeat. It can be installed in healthcare applications to monitor the status of human heart.
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Chen, Yao-Mei, Yenming J. Chen, Yun-Kai Tsai, Wen-Hsien Ho, and Jinn-Tsong Tsai. "Classification of human electrocardiograms by multi-layer convolutional neural network and hyperparameter optimization." Journal of Intelligent & Fuzzy Systems 40, no. 4 (2021): 7883–91. http://dx.doi.org/10.3233/jifs-189610.
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A multi-layer convolutional neural network (MCNN) with hyperparameter optimization (HyperMCNN) is proposed for classifying human electrocardiograms (ECGs). For performance tests of the HyperMCNN, ECG recordings for patients with cardiac arrhythmia (ARR), congestive heart failure (CHF), and normal sinus rhythm (NSR) were obtained from three PhysioNet databases: MIT-BIH Arrhythmia Database, BIDMC Congestive Heart Failure Database, and MIT-BIH Normal Sinus Rhythm Database, respectively. The MCNN hyperparameters in convolutional layers included number of filters, filter size, padding, and filter stride. The hyperparameters in max-pooling layers were pooling size and pooling stride. Gradient method was also a hyperparameter used to train the MCNN model. Uniform experimental design approach was used to optimize the hyperparameter combination for the MCNN. In performance tests, the resulting 16-layer CNN with an appropriate hyperparameter combination (16-layer HyperMCNN) was used to distinguish among ARR, CHF, and NSR. The experimental results showed that the average correct rate and standard deviation obtained by the 16-layer HyperMCNN were superior to those obtained by a 16-layer CNN with a hyperparameter combination given by Matlab examples. Furthermore, in terms of performance in distinguishing among ARR, CHF, and NSR, the 16-layer HyperMCNN was superior to the 25-layer AlexNet, which was the neural network that had the best image identification performance in the ImageNet Large Scale Visual Recognition Challenge in 2012.
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Nejad, Hadi Chahkandi, Omid Khayat, and Javad Razjouyan. "CHAOTIC FEATURE EXTRACTION AND NEURO-FUZZY CLASSIFIER FOR ECG SIGNAL CHARACTERIZATION." Biomedical Engineering: Applications, Basis and Communications 26, no. 03 (2014): 1450038. http://dx.doi.org/10.4015/s1016237214500380.
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In this paper, a neuro-fuzzy network is employed to classify the ECG beats based on the extracted chaotic features. Six groups of ECG beats (MIT-BIH Normal Sinus rhythm, BIDMC congestive heart failure, CU ventricular tachyarrhythmia, MIT-BIH atrial fibrillation, MIT-BIH Malignant Ventricular Arrhythmia and MIT-BIH supraventricular arrhythmia) are characterized by the six chaotic parameters including the largest Lyapunov exponent and average of the Lyapunov spectrum (related to the chaoticity of the signal), time lag and embedding dimension (related to the phase space reconstruction) and correlation dimension and approximate entropy of the signal (related to the complexity of the signal). Finally, six structures of the neuro-fuzzy network (in terms of the type of fuzzy set, the number of fuzzy sets per variable and the number of learning epochs) were employed to perform the ECG beats classification based on all extracted features for two lengths of the signals. It was found that all respective chaotic features are discriminative and they improve the classification rate of ECG beats. Also, it is shown that a minimum length of the signal is needed for exhibitive feature extraction and for the higher lengths of the signal (in time) no significant improvement is achieved in feature extraction and calculations. The criteria for the classification task are considered as accuracy, specificity and sensitivity which all together comprehensively demonstrate the capability and performance of the classification. Some conclusions are drawn and they are discussed at the end of the paper.
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Bloch, B. Nicolas, Robert E. Lenkinski, and Neil M. Rofsky. "The role of magnetic resonance imaging (MRI) in prostate cancer imaging and staging at 1.5 and 3 Tesla: The Beth Israel Deaconess Medical Center (BIDMC) approach." Cancer Biomarkers 4, no. 4-5 (2008): 251–62. http://dx.doi.org/10.3233/cbm-2008-44-507.
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Olanrewaju, Rashidah Funke, S. Noorjannah Ibrahim, Ani Liza Asnawi, and Hunain Altaf. "Classification of ECG signals for detection of arrhythmia and congestive heart failure based on continuous wavelet transform and deep neural networks." Indonesian Journal of Electrical Engineering and Computer Science 22, no. 3 (2021): 1520. http://dx.doi.org/10.11591/ijeecs.v22.i3.pp1520-1528.
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According to World Health Organization (WHO) report an estimated 17.9 million lives are being lost each year due to cardiovascular diseases (CVDs) and is the top contributor to the death causes. 80% of the cardiovascular cases include heart attacks and strokes. This work is an effort to accurately predict the common heart diseases such as arrhythmia (ARR) and congestive heart failure (CHF) along with the normal sinus rhythm (NSR) based on the integrated model developed using continuous wavelet transform (CWT) and deep neural networks. The proposed method used in this research analyses the time-frequency features of an electrocardiogram (ECG) signal by first converting the 1D ECG signals to the 2D Scalogram images and subsequently the 2D images are being used as an input to the 2D deep neural network model-AlexNet. The reason behind converting the ECG signals to 2D images is that it is easier to extract deep features from images rather than from the raw data for training purposes in AlexNet. The dataset used for this research was obtained from Massachusetts Institute of Technology-Boston's Beth Israel Hospital (MIT-BIH) arrhythmia database, MIT-BIH normal sinus rhythm database and Beth Israel Deaconess Medical Center (BIDMC) congestive heart failure database. In this work, we have identified the best fit parameters for the AlexNet model that could successfully predict the common heart diseases with an accuracy of 98.7%. This work is also being compared with the recent research done in the field of ECG Classification for detection of heart conditions and proves to be an effective technique for the classification.
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Sari, Lydia, Masagus M. Ikhsan Assiddiq U.P., Syah Alam, and Indra Surjati. "Performance Analysis of CRC-Polar Concatenated Codes." JURNAL INFOTEL 12, no. 4 (2020): 123–28. http://dx.doi.org/10.20895/infotel.v12i4.494.
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Polar code has been proven to obtain Shannon capacity for Binary Input Discrete Memoryless Channel (BIDMC) and its use has been proposed as the channel coding in 5G technology. However, its performance is limited in finite block length, compared to Turbo or LDPC codes. This research proposes the use of various CRC codes to complement Polar codes with finite block length and analyses the performance based on Block Error Rate (BLER) to Es/N0 (dB). The CRC codes used are of degrees 11 and 24, with 3 different polynomial generators for each degree. The number of bits in the information sequence is 32. The list sizes used are 1, 2, 4, and 8. Simulation results show that the concatenation of CRC and Polar codes will yield good BLER vs Es/N0 performance for short blocks of codeword, with rates 32/864 and 54/864. Concatenating CRC codes with Polar codes will yield a BLER performance of 10-2 with Es/N0 values of -9.1 to -7.5 dB when CRC codes of degree 11 is used, depending on the SC list used. The use of CRC codes of degree 24 enables a BLER performance of 10-2 with Es/N0 values of -7 to -6 dB when the SC list used is 1 or 2. The use of CRC codes of degree 24 combined with SC list with sizes 4 or 8 will improve the BLER performance to 10-2 with Es/N0 values of -8 to -7.5 dB
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Aseeri, Ahmad O. "Uncertainty-Aware Deep Learning-Based Cardiac Arrhythmias Classification Model of Electrocardiogram Signals." Computers 10, no. 6 (2021): 82. http://dx.doi.org/10.3390/computers10060082.
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Deep Learning-based methods have emerged to be one of the most effective and practical solutions in a wide range of medical problems, including the diagnosis of cardiac arrhythmias. A critical step to a precocious diagnosis in many heart dysfunctions diseases starts with the accurate detection and classification of cardiac arrhythmias, which can be achieved via electrocardiograms (ECGs). Motivated by the desire to enhance conventional clinical methods in diagnosing cardiac arrhythmias, we introduce an uncertainty-aware deep learning-based predictive model design for accurate large-scale classification of cardiac arrhythmias successfully trained and evaluated using three benchmark medical datasets. In addition, considering that the quantification of uncertainty estimates is vital for clinical decision-making, our method incorporates a probabilistic approach to capture the model’s uncertainty using a Bayesian-based approximation method without introducing additional parameters or significant changes to the network’s architecture. Although many arrhythmias classification solutions with various ECG feature engineering techniques have been reported in the literature, the introduced AI-based probabilistic-enabled method in this paper outperforms the results of existing methods in outstanding multiclass classification results that manifest F1 scores of 98.62% and 96.73% with (MIT-BIH) dataset of 20 annotations, and 99.23% and 96.94% with (INCART) dataset of eight annotations, and 97.25% and 96.73% with (BIDMC) dataset of six annotations, for the deep ensemble and probabilistic mode, respectively. We demonstrate our method’s high-performing and statistical reliability results in numerical experiments on the language modeling using the gating mechanism of Recurrent Neural Networks.
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Blattner, M. S., J. August, S. Chopra, et al. "0758 Quantification of Late REM Periods in Patients With Prolonged Sleep Duration." Sleep 43, Supplement_1 (2020): A288. http://dx.doi.org/10.1093/sleep/zsaa056.754.
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Abstract Introduction Evaluation of hypersomnia includes polysomnography followed by mean sleep latency testing (MSLT). As consistent with guidelines as applied in most centers, the overnight portion of the study will be terminated to begin sleep latency testing. For patients with prolonged sleep duration, this interruption could result in REM sleep on nap testing that reflects continuation of their biological night, rather than abnormalities in REM sleep pressure/regulation. Methods We reviewed 42 consecutive extended (unrestricted) sleep studies for patients with a total sleep time greater than 600 minutes. For studies with sleep onset before midnight, we evaluated for REM period onset after 6AM, the number of REM periods after 6AM and 8AM, and the time of the final REM period onset. Results 42 hypnograms were reviewed for patients undergoing evaluation of hypersomnia, median age 32 years (range 19-92) with a median total sleep time of 663 minutes (range 602-832), of these 28/42 (67%) had sleep onset before midnight (12 AM) and were included in the analysis. 27/28 (96%) of hypnograms reviewed had REM sleep after 6 AM, 24/28 (86%) had REM sleep after 8 AM, with the onset of the final REM period ranging from 4:46 AM-12:30 PM for patients with sleep onset time before midnight (12 AM). Conclusion These data suggest that termination of overnight polysomnography to complete mean sleep latency testing, as is standard in most sleep labs, may influence the presence of REM sleep on MSLT for patients with prolonged total sleep duration. These results may have implications for the interpretation of MSLT for patients with long sleep duration, and may explain why a given individual may test as type II narcolepsy or idiopathic hypersomnia unpredictably on repeat testing. Support Sleep Medicine Fellowship at BIDMC
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Maalouf, Elie Azar. "BIDM 2013." Dental News 20, no. 4 (2013): 52–56. http://dx.doi.org/10.12816/0010188.
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Kafadar, Karen, and John W. Tukey. "A Bidec t Table." Journal of the American Statistical Association 83, no. 402 (1988): 532. http://dx.doi.org/10.2307/2288874.
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McKay, Rana R., Wanling Xie, Rosina Lis, et al. "Results of a phase II trial of neoadjuvant abiraterone + prednisone+ enzalutamide + leuprolide (APEL) versus enzalutamide + leuprolide (EL) for patients with high-risk localized prostate cancer (PC) undergoing radical prostatectomy (RP)." Journal of Clinical Oncology 36, no. 6_suppl (2018): 79. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.79.
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79 Background: Patients with high-risk PC have an increased risk of recurrence and mortality despite therapy. Abiraterone, a CYP17 inhibitor, and enzalutamide, a next generation anti-androgen, have demonstrated improved overall survival in metastatic PC. In this multicenter randomized phase II trial, we evaluate the impact of second generation hormone therapy on RP pathologic outcomes. Methods: Eligible patients had biopsy Gleason score ≥4+3=7, PSA >20 ng/mL or cT3 disease (by prostate MRI). Lymph node were require to be <20 mm. Patients were randomized 2:1 to APE:EL for 6 cycles (24 weeks) followed by RP. All RPs underwent central pathology review. The primary endpoint was the rate of pathologic complete response (pCR) or minimum residual disease (MRD, tumor ≤5 mm). Secondary endpoints include PSA response, surgical staging at RP, positive margin rate, and safety. Results: 75 patients were enrolled at four sites: DFCI/BWH (n=55), BIDMC (n=11), UW (n=5), JHU (n=4). Median age was 62 years. Most patients had NCCN high-risk disease [n=66, 88%; cT3 n=21 (28%), Gleason 8-10 n=59 (79%), PSA >20 ng/mL n=17 (23%)]. All patients completed 6 cycles followed by RP. Median PSA nadir was 0.03 and 0.02 ng/mL and time to nadir was 3.7 and 4.6 months in the APEL and EL arms, respectively. The combined pCR or MRD rate was 30% (n=15/50) in the APEL arm and 16% (n=4/25) in the EL arm. The response difference was 14% (80% CI -3%-30%, p=0.263). 15 patients (14 in APEL; 1 in EL) had grade 3 adverse events (AEs). The most common grade 3 AEs were hypertension (n=7) and ALT increase (n=5). No grade 4-5 AEs occurred. Conclusions: Neoadjuvant hormone therapy plus RP in men with high-risk PC resulted in favorable pathologic responses (≤5 mm residual tumor) in 16-30% with a trend towards improved pathologic outcomes with APEL and acceptable safety profile. Follow-up is necessary to evaluate the impact of therapy on recurrence rates. Clinical trial information: NCT02268175. [Table: see text]
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Alam, Mohammad Khursheed. "Management of bilateral impacted maxillary canines (BIMC): open surgical exposure and orthodontic traction." Bangladesh Journal of Medical Science 19, no. 1 (2019): 169–73. http://dx.doi.org/10.3329/bjms.v19i1.43892.
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Background: Patients presenting with BIMC are relatively rare and the aim of the Orthodontist is to create a dentition that is functionally and aesthetically acceptable. The BIMC may result in altered facial appearance with malocclusion and psychological distress in some individuals.
 Case presentation: The present case report describes a 17-year-old female patient with nonsyndromic, BIMC. Clinical and CBCT examinations revealed BIMC. Following open surgical exposure treatment planning, the patient was treated with orthodontic fixed mechanotherapy to correct BIMC and other problems. Slow force mechanics with passive self-ligating MBT 0.022 orthodontic braces were used.
 Results: Open surgical exposure and active orthodontic treatment was completed in 18 months. The management of BIMC requires multidisciplinary approach to achieve better aesthetics and improved occlusal function.
 Conclusion: A combined Open Surgical Exposure-Orthodontic Traction-Orthodontic treatment would help achieve desired aesthetics and functioning occlusion.
 Bangladesh Journal of Medical Science Vol.19(1) 2020 p.169-173
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S. Mohd Sharifuddin, N., N. M. L. Tana, and H. Akagi. "Low-load Efficiency Improvement of a Three-Phase Bidirectional Isolated DC-DC Converter (3P-BIDC) Via Enhanced Switching Strategy." International Journal of Engineering & Technology 7, no. 4.35 (2018): 932. http://dx.doi.org/10.14419/ijet.v7i4.35.28297.
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This paper presents the system design, operation and enhanced switching strategy of a three-phase bidirectional isolated dc-dc converter (3P-BIDC). The paper discusses the operating modes of the 3P-BIDC using phase-shift modulation (PSM), with analysis on its soft-switching characteristics. The phase-shift modulation is the simplest modulation technique that can be applied to the 3P-BIDC. However, it comes with the consequences of low efficiency performance in the low-load conditions. Therefore, this paper investigates the improvement in efficiency of the 3P-BIDC during low-load condition using an enhanced switching strategy combining burst-mode switching and phase-shift modulation. The model of a 700-V, 100-kW, 20-kHz 3P-BIDC and the enhanced switching strategy are verified via simulation using PSCAD. The simulation results shows that the combination of burst-mode and phase-shift modulation technique improves the efficiency of the 3P-BIDC at low-load conditions.
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Atanasiu, Doina, J. Charles Whitbeck, Manuel Ponce de Leon, et al. "Bimolecular Complementation Defines Functional Regions of Herpes Simplex Virus gB That Are Involved with gH/gL as a Necessary Step Leading to Cell Fusion." Journal of Virology 84, no. 8 (2010): 3825–34. http://dx.doi.org/10.1128/jvi.02687-09.
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ABSTRACT Herpes simplex virus (HSV) entry into cells requires four membrane glycoproteins: gD is the receptor binding protein, and gB and gH/gL constitute the core fusion machinery. Crystal structures of gD and its receptors have provided a basis for understanding the initial triggering steps, but how the core fusion proteins function remains unknown. The gB crystal structure shows that it is a class III fusion protein, yet unlike other class members, gB itself does not cause fusion. Bimolecular complementation (BiMC) studies have shown that gD-receptor binding triggers an interaction between gB and gH/gL and concurrently triggers fusion. Left unanswered was whether BiMC led to fusion or was a by-product of it. We used gB monoclonal antibodies (MAbs) to block different aspects of these events. Non-virus-neutralizing MAbs to gB failed to block BiMC or fusion. In contrast, gB MAbs that neutralize virus blocked fusion. These MAbs map to three functional regions (FR) of gB. MAbs to FR1, which contains the fusion loops, and FR2 blocked both BiMC and fusion. In contrast, MAbs to FR3, a region involved in receptor binding, blocked fusion but not BiMC. Thus, FR3 MAbs separate the BiMC interaction from fusion, suggesting that BiMC occurs prior to fusion. When substituted for wild-type (wt) gB, fusion loop mutants blocked fusion and BiMC, suggesting that loop insertion precedes BiMC. Thus, we postulate that each of the gB FRs are involved in different aspects of the path leading to fusion. Upon triggering by gD, gB fusion loops are inserted into target lipid membranes. gB then interacts with gH/gL, and this interaction is eventually followed by fusion.
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Bhowmick, Sourav S., and Hasan M. Jamil. "Biological Data Management (BIDM 2003)." Data & Knowledge Engineering 53, no. 1 (2005): 1–2. http://dx.doi.org/10.1016/j.datak.2004.06.010.
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Mohd Sharifuddin, Nuraina Syahira, Nadia M. L. Tan, and Hirofumi Akagi. "Evaluation of a Three-Phase Bidirectional Isolated DC-DC Converter with Varying Transformer Configurations Using Phase-Shift Modulation and Burst-Mode Switching." Energies 13, no. 11 (2020): 2836. http://dx.doi.org/10.3390/en13112836.
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This paper presents the performance of a three-phase bidirectional isolated DC-DC converter (3P-BIDC) in wye-wye (Yy), wye-delta (Yd), delta-wye (Dy), and delta-delta (Dd) transformer configurations, using enhanced switching strategy that combines phase-shift modulation and burst-mode switching. A simulation verification using PSCAD is carried out to study the feasibility and compare the efficiency performance of the 3P-BIDC with each transformer configuration, using intermittent switching, which combines the conventional phase-shift modulation (PSM) and burst-mode switching, in the light load condition. The model is tested with continuous switching that employs the conventional PSM from medium to high loads (greater than 0.3 p.u.) and with intermittent switching at light load (less than 0.3 p.u), in different transformer configurations. In all tests, the DC-link voltages are equal to the transformer turns ratio of 1:1. This paper also presents the power loss estimation in continuous and intermittent switching to verify the modelled losses in the 3P-BIDC in the Yy transformer configuration. The 3P-BIDC is modelled by taking into account the effects that on-state voltage drop in the insulated-gate bipolar transistor (IGBTs) and diodes, snubber capacitors, and three-phase transformer copper winding resistances will have on the conduction and switching losses, and copper losses in the 3P-BIDC. The intermitting switching improves the efficiency of the DC-DC converter with Yy, Yd, Dy, and Dd connections in light-load operation. The 3P-BIDC has the best efficiency performance using Yy and Dd transformer configurations for all power transfer conditions in continuous and intermittent switching. Moreover, the highest efficiency of 99.6% is achieved at the light power transfer of 0.29 p.u. in Yy and Dd transformer configurations. However, the theoretical current stress in the 3P-BIDC with a Dd transformer configuration is high. Operation of the converter with Dy transformer configuration is less favorable due to the efficiency achievements of lower than 95%, despite burst-mode switching being applied.
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Alfawzan, Ahmed Ali, and Mohammad Khursheed Alam. "Orthodontic Management of Bilaterally Impacted Maxillary Canines." Bangladesh Journal of Medical Science 20, no. 1 (2021): 212–15. http://dx.doi.org/10.3329/bjms.v20i1.50375.
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Background: Proper diagnosis and treatment planning are the first steps in management of bilateral impacted maxillary canines (BIMC).
 Case Presentation: A 14 years old Saudi female patient with Class II subdivision right molar relationship and BIMC managed by comprehensive orthodontic treatment.
 Conclusion: A well-balanced occlusion by orthodontic management of the case has been done.
 Bangladesh Journal of Medical Science Vol.20(1) 2021 p.212-215
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AhmedAlFarsi, Budour, and Dinesh Kumar Saini. "Business Intelligence Design Model (BIDM) for University." International Journal of Computer Applications 111, no. 14 (2015): 43–49. http://dx.doi.org/10.5120/19609-1492.
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Drummond, D. R., and I. M. Hagan. "Mutations in the bimC box of Cut7 indicate divergence of regulation within the bimC family of kinesin related proteins." Journal of Cell Science 111, no. 7 (1998): 853–65. http://dx.doi.org/10.1242/jcs.111.7.853.
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Members of the bimC family of kinesin related proteins (KRPs) play vital roles in the formation and function of the mitotic spindle. Although they share little amino acid homology outside the highly conserved microtubule motor domain, several family members do contain a ‘bimC box’, a sequence motif around a p34(cdc2) consensus phosphorylation site in their carboxy-terminal ‘tail’ region. One family member, Eg5, requires phosphorylation at this site for association with the mitotic spindle. We show that mutations in the Schizosaccharomyces pombe cut7+ gene that change the bimC box p34(cdc2) consensus phosphorylation site at position 1,011 and a neighbouring MAP kinase consensus phosphorylation site at position 1,020 to non-phosphorylatable residues did not affect the ability of S. pombe cut7 genes to complement temperature sensitive cut7 mutants. Phosphorylation site mutants expressed as fusions to green fluorescent protein associated with the mitotic spindle with a localisation indistinguishable from similarly expressed wild-type Cut7. Cells in which cut7.T1011A replaced the genomic copy of cut7+ were viable and formed normal spindles. Deletion of the entire carboxy-terminal tail region did not affect the ability of Cut7 to associate with the mitotic spindle but did inhibit normal spindle formation. Thus, unlike Eg5, neither the p34(cdc2) consensus phosphorylation site in the bimC box nor the entire tail region of Cut7 are required for association with the mitotic spindle.
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Touitou, I., G. Lhomond, and G. Pruliere. "Boursin, a sea urchin bimC kinesin protein, plays a role in anaphase and cytokinesis." Journal of Cell Science 114, no. 3 (2001): 481–91. http://dx.doi.org/10.1242/jcs.114.3.481.
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We have isolated and characterized Boursin, a kinesin-related protein of the bimC family, from Paracentrotus lividus sea urchin eggs. Boursin is expressed at high levels in eggs and embryos during early cleavage stages. Boursin was found to be associated with different parts of the mitotic spindle from early prophase to telophase. Expression of a form of the protein predicted to act as a dominant negative mutant caused severe defects in cell division and resulted in the formation of embryos with polyploid and multiastral blastomeres. Immunofluorescence analysis indicated that these defects did not arise from failure in either centrosome separation or bipolar spindle formation. Time-lapse observations showed rather that these perturbations in cell division resulted from abnormal anaphase and failure to complete cytokinesis. These phenotypes differ from the phenotype described following perturbation of the function of bimC family members in other organisms. Our study has thus uncovered roles for a bimC kinesin in late stages of cell division.
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Barrett-Connor, Elizabeth, Deborah Goodman-Gruen, and Brad Patay. "Endogenous Sex Hormones and Cognitive Function in Older Men*." Journal of Clinical Endocrinology & Metabolism 84, no. 10 (1999): 3681–85. http://dx.doi.org/10.1210/jcem.84.10.6086.
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Abstract The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59–89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the “World” Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the “World” test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.
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Pandey, Dinesh, and Seema Kothari. "Kinetics and Mechanism of the Oxidation of Dl-Methionine by Benzimidazolium Dichromate." Progress in Reaction Kinetics and Mechanism 34, no. 3 (2009): 199–209. http://dx.doi.org/10.3184/146867809x466221.
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The oxidation of DL-methionine (MT) by benzimidazolium dichromate (BIDC), in dimethyl sulfoxide, leads to the formation of the corresponding sulfoxide. The reaction is first order with respect to BIDC. Michaelis - Menten type kinetics were observed with respect to MT. The reaction is catalysed by hydrogen ions and the dependence is of the form kobs = k‘[H+]. The rate of oxidation of MT was determined in 19 organic solvents. An analysis of the solvent effect by solvatochromic equations indicated that though both the anion- and cation-solvating powers of the solvent contribute to the observed solvent effect, the role of cation-solvation is much the major. A suitable mechanism has been proposed.
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O'Connell, M. J., P. B. Meluh, M. D. Rose, and N. R. Morris. "Suppression of the bimC4 mitotic spindle defect by deletion of klpA, a gene encoding a KAR3-related kinesin-like protein in Aspergillus nidulans." Journal of Cell Biology 120, no. 1 (1993): 153–62. http://dx.doi.org/10.1083/jcb.120.1.153.
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To investigate the relationship between structure and function of kinesin-like proteins, we have identified by polymerase chain reaction (PCR) a new kinesin-like protein in the filamentous fungus Aspergillus nidulans, which we have designated KLPA. DNA sequence analysis showed that the predicted KLPA protein contains a COOH terminal kinesin-like motor domain. Despite the structural similarity of KLPA to the KAR3 and NCD kinesin-like proteins of Saccharomyces cerevisiae and Drosophila melanogaster, which also posses COOH-terminal kinesin-like motor domains, there are no significant sequence similarities between the nonmotor or tail portions of these proteins. Nevertheless, expression studies in S. cerevisiae showed that klpA can complement a null mutation in KAR3, indicating that primary amino acid sequence conservation between the tail domains of kinesin-like proteins is not necessarily required for conserved function. Chromosomal deletion of the klpA gene exerted no observable mutant phenotype, suggesting that in A. nidulans there are likely to be other proteins functionally redundant with KLPA. Interestingly, the temperature sensitive phenotype of a mutation in another gene, bimC, which encodes a kinesin-like protein involved in mitotic spindle function in A. nidulans, was suppressed by deletion of klpA. We hypothesize that the loss of KLPA function redresses unbalanced forces within the spindle caused by mutation in bimC, and that the KLPA and BIMC kinesin-like proteins may play opposing roles in spindle function.
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Bishop, John D., Zhenbo Han, and Jill M. Schumacher. "The Caenorhabditis elegans Aurora B Kinase AIR-2 Phosphorylates and Is Required for the Localization of a BimC Kinesin to Meiotic and Mitotic Spindles." Molecular Biology of the Cell 16, no. 2 (2005): 742–56. http://dx.doi.org/10.1091/mbc.e04-08-0682.
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BimC kinesins are required for mitotic spindle assembly in a variety of organisms. These proteins are localized to centrosomes, spindle microtubules, and the spindle midzone. We have previously shown that the Caenorhabditis elegans Aurora B kinase AIR-2 is required for the localization of the ZEN-4 kinesin protein to midzone microtubules. To determine whether the association of BimC kinesins with spindle microtubules is also dependent on AIR-2, we examined the expression pattern of BMK-1, a C. elegans BimC kinesin, in wild-type and AIR-2–deficient embryos. BMK-1 is highly expressed in the hermaphrodite gonad and is localized to meiotic spindle microtubules in the newly fertilized embryo. In mitotic embryos, BMK-1 is associated with spindle microtubules from prophase through anaphase and is concentrated at the spindle midzone during anaphase and telophase. In the absence of AIR-2, BMK-1 localization to meiotic and mitotic spindles is greatly reduced. This is not a consequence of loss of ZEN-4 localization because BMK-1 is appropriately localized in ZEN-4–deficient embryos. Furthermore, AIR-2 and BMK-1 directly interact with one another and the C-terminal tail domain of BMK-1 is specifically phosphorylated by AIR-2 in vitro. Together with our previous data, these results suggest that at least one function of the Aurora B kinases is to recruit spindle-associated motor proteins to their sites of action.
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Heck, M. M., A. Pereira, P. Pesavento, Y. Yannoni, A. C. Spradling, and L. S. Goldstein. "The kinesin-like protein KLP61F is essential for mitosis in Drosophila." Journal of Cell Biology 123, no. 3 (1993): 665–79. http://dx.doi.org/10.1083/jcb.123.3.665.
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We report here that disruption of a recently discovered kinesin-like protein in Drosophila melanogaster, KLP61F, results in a mitotic mutation lethal to the organism. We show that in the absence of KLP61F function, spindle poles fail to separate, resulting in the formation of monopolar mitotic spindles. The resulting phenotype of metaphase arrest with polyploid cells is reminiscent of that seen in the fungal bimC and cut7 mutations, where it has also been shown that spindle pole bodies are not segregated. KLP61F is specifically expressed in proliferating tissues during embryonic and larval development, consistent with a primary role in cell division. The structural and functional homology of the KLP61F, bimC, cut7, and Eg5 kinesin-like proteins demonstrates the existence of a conserved family of kinesin-like molecules important for spindle pole separation and mitotic spindle dynamics.
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PAUL, Ankita, Krithiga SUBRAMANIAN, and Sujitha NACHINARKINIYAN. "PV-based off-board electric vehicle battery charger using BIDC." TURKISH JOURNAL OF ELECTRICAL ENGINEERING & COMPUTER SCIENCES 27, no. 4 (2019): 2850–65. http://dx.doi.org/10.3906/elk-1804-227.
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Panday, Dinesh, Teena Kachawa та Seema Kothari. "Kinetics and Correlation Analysis of Reactivity in the Oxidation of Some α-Hydroxy Acids by Benzimidazolium Dichromate". Progress in Reaction Kinetics and Mechanism 43, № 3-4 (2018): 300–314. http://dx.doi.org/10.3184/146867818x15319903829236.
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Kinetic and mechanistic studies of the oxidation of mandelic acid and nine monosubstituted mandelic acids by benzimidazolium dichromate (BIDC) in dimethyl sulfoxide are discussed with an emphasis on correlation of structure and reactivity. The reactions were of first order with respect to BIDC. However, Michaelis-Menten type kinetics were observed with respect to hydroxy acids. The reactions are catalysed by protons. The deuterium isotope effect for the oxidation of mandelic acid ( kH/ kD = 5.91 at 298 K) indicated an α-C-H bond cleavage in the rate-determining step. An analysis of the solvent effect showed that the role of cationsolvation is major. The reaction showed an excellent correlation with the Hammett σ values, the reaction constant being negative. Based on the kinetic data, analysis of the solvent effect and results of structure-reactivity correlation along with some non-kinetic parameters, a mechanism involving rate-determining oxidative decomposition of the complex through hydride-ion transfer via a cyclic transition state to give the corresponding oxoacid is suggested.
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Pradiptha, I. Dewa Agung Gde Fanji. "HUBUNGAN JENJANG KARIR PERAWAT TERHADAP TURNOVER INTENTION DI RSK BEDAH BIMC SILOAM NUSA DUA." Jurnal Ilmiah PANNMED (Pharmacist, Analyst, Nurse, Nutrition, Midwivery, Environment, Dentist) 15, no. 3 (2020): 536–40. http://dx.doi.org/10.36911/pannmed.v15i3.895.
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Turnover intention is a desire of a person to resign from their job. Career path is one of the factors causing turnover intention. Career path is low and does not clearly influence nurses to make turnover intension. This study aimed to determine the correlation between nurses' career path and turnover intention. The study used a cross-sectional correlation design with a total sampling technique of 45 respondents. Data processing used Spearman Coefficient of Correlation method. The career path of nurses at BIMC Siloam Nusa Dua was PK I = 22 people, PK II = 16 people, and PK III = 7 people. The number of nurses who wanted to make a turnover intention was 60%. Statistical test results p- value = 0,000 which shows there was a correlation between nurses' career levels with turnover intention and the value of r = -0.606 indicates the higher the career path of nurses, the nurse's turnover intention is low. RSK Bedah BIMC Siloam Nusa Dua should provide a clearer career path to prevent turnover intention.
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Li, Hao, Meng Ran Zhou, and Le Zhang. "Study on Data Processing in Optical Fiber Gas Sensing System Based on Membrane Computing." Advanced Materials Research 1044-1045 (October 2014): 1339–42. http://dx.doi.org/10.4028/www.scientific.net/amr.1044-1045.1339.
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Aiming at the problem of multi point (32 and above) EFPI optical fiber gas sensing system in processing data, for instance, weak ability of parallel data processing, low computational efficiency, slow system response etc., this paper utilizing the advantage like maximum concurrent and distributed of membrane computing system studied a method of parallel data processing. This method adopted a algorithm called Bio-inspired Algorithm based on Membrane Computing-BIAMC compared to the commonly used Genetic Algorithm (GA) has less computational cost and higher computational efficiency. Firstly,4 Standard constrained functions was used as test and contrast function and then the improved algorithm is applied to the parallel data processing, to validate the quantitative analysis and effectiveness, in the end, through the simulation to verify the superiority of the algorithm in robustness and accuracy. The experimental results showed that with taking the parallel feature of data input into consideration the BIAMC which applying to EFPI optical fiber gas sensing system have improved the speed of data processing and the utilization rate of hardware system and the response time of whole system compared to the traditional serial processing method, which provided a new method of parallel data processing in multi-channel sensor system.
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Hildebrandt, Emily R., and M. Andrew Hoyt. "Cell Cycle-dependent Degradation of the Saccharomyces cerevisiae Spindle Motor Cin8p Requires APCCdh1 and a Bipartite Destruction Sequence." Molecular Biology of the Cell 12, no. 11 (2001): 3402–16. http://dx.doi.org/10.1091/mbc.12.11.3402.
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Saccharomyces cerevisiae Cin8p belongs to the BimC family of kinesin-related motor proteins that are essential for spindle assembly. Cin8p levels were found to oscillate in the cell cycle due in part to a high rate of degradation imposed from the end of mitosis through the G1 phase. Cin8p degradation required the anaphase-promoting complex ubiquitin ligase and its late mitosis regulator Cdh1p but not the early mitosis regulator Cdc20p. Cin8p lacks a functional destruction box sequence that is found in the majority of anaphase-promoting complex substrates. We carried out an extensive mutagenesis study to define the cis-acting sequence required for Cin8p degradation in vivo. The C terminus of Cin8p contains two elements required for its degradation: 1) a bipartite destruction sequence composed of a KEN-box plus essential residues within the downstream 22 amino acids and 2) a nuclear localization signal. The bipartite destruction sequence appears in other BimC kinesins as well. Expression of nondegradable Cin8p showed very mild phenotypic effects, with an increase in the fraction of mitotic cells with broken spindles.
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Barton, N. R., A. J. Pereira, and L. S. Goldstein. "Motor activity and mitotic spindle localization of the Drosophila kinesin-like protein KLP61F." Molecular Biology of the Cell 6, no. 11 (1995): 1563–74. http://dx.doi.org/10.1091/mbc.6.11.1563.
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The KLP61F gene product is essential for Drosophila development. Mutations in KLP61F display a mitotic arrest phenotype caused by a failure in the proper separation of duplicated centrosomes (Heck et al., 1993). Sequence analysis of KLP61F identified it as a member of the bimC family of kinesin-like microtubule motor proteins. Here we report that KLP61F is distinct from KRP130, a kinesin-like protein recently purified from Drosophila embryos and suggested to be the product of the KLP61F gene (Cole et al., 1994). We also characterized recombinant KLP61F and found that it possesses microtubule-stimulated ATPase and microtubule translocation activities in vitro. In addition, we have used an affinity-purified, KLP61F-specific antiserum to localize native KLP61F and an epitope-tagged KLP61F fusion protein during various stages of mitosis in Drosophila syncytial blastoderm embryos. From early prophase through anaphase, KLP61F is coincident with the distribution of tubulin. Together these results confirm the existence of multiple bimC-like kinesins in Drosophila and suggest that KLP61F function is intrinsic to the mitotic spindle.
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Dewar, Rajan, Julia Friedman, Daniel Xia, et al. "Systematic Analysis of Cell-of-Origin, Sequencing and Genomic Imbalances Identifies a Distinct Subset of Rituximab Treated Diffuse Large B-Cell Lymphoma with an Inferior Survival." Blood 126, no. 23 (2015): 3910. http://dx.doi.org/10.1182/blood.v126.23.3910.3910.
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Abstract Introduction: Diffuse Large B-cell Lymphoma (DLBCL), exhibits a wide range of clinical and biological heterogeneity. While initially responsive to rituximab based therapy, more than 70% of patients relapse within 5 years. Two distinct subtypes of DLBCLs were previously identified by gene expression profiling, that correlated to the cell of origin (COO); currently an immunohistochemistry (IHC) surrogate (Hans algorithm) is used to identify this COO. However, the value of COO identification by IHC is being questioned in patients treated with rituximab based regimen. As such there is a need for the identification of additional prognostication markers. The purpose of the present study is to systematically characterize a cohort of patients with DLBCL using a variety of methods including COO by IHC, copy number changes by array-based comparative genomic hybridization, and single gene mutations by next generation sequencing. The goal is to identify prognostic molecular biomarkers that predict survival better than current methods such as COO in DLBCL patients treated with rituximab. Methods: Patients diagnosed between 2003 and 2011 and treated with R-CHOP/R-EPOCH at BIDMC were identified. IPI/R-IPI, ECOG performance status, overall survival data were collected from retrospective chart review. Molecular and immunohistochemical studies were performed on formalin-fixed paraffin embedded tissue (FFPE), which was obtained prior to initiation of therapy (at the time of diagnosis). aCGH: Using a previously developed assay for aCGH to detect genomic gain/loss from archival FFPE, we characterized each DLBCL sample for the presence or absence of 50 copy number variations (CNVs) from 32 common regions of overlapping genomic imbalances comprising 36 minimal common regions. The calling criteria were based on GISTIC defined peaks based on copy number data from three publicly available datasets: IS-172, IS-51HR, EMEXP-3463. Gene panels: Next Generation Sequencing (NGS) was performed using a targeted hybrid capture panel and run on a Miseq (Illumina, Inc.). Gene selection for the panel was based on frequently mutated genes reported in DLBCL, Follicular lymphoma (FL), and Mantle Cell Lymphoma (MCL). Also selected for the panel were genes involved in known dysregulated pathways, therapeutic targets, and genes mapped to sites of genomic gains or losses. Cell of Origin: Immunostains were performed for BCL6, CD10, MUM1, FOXP1, GCET and LMO2. The immunostains were blindly scored by three different pathologists. For this study, GCB vs ABC determination was made using the Hans algorithm (CD10, BCL6 and MUM1 expression). Statistics: Kaplan-Meier (KM) survival analysis was performed using R (version 3.2.1). Results: Data on an initial subset of 49 patients with comprehensive molecular, COO and clinical information is presented (and an additional ~100 case analysis is in progress). Average age of patients at the time of diagnosis was 63, with 23 males and 26 females. By univariate analysis, the COO was not significantly associated with survival in the patients treated with rituximab based regimen (KM p=0.678). By contrast, three of the CNVs were associated with survival by Kaplan Meier analysis (Table 1). Also four, gene mutations were significantly associated with poor survival by univariate analysis (Table 1). Table 1.Markers significantly associated with survival in rituximab treated patients with DLBCL. Ab28 predicted for better survival, whereas the presence of the other mutations or CNVs predicted for poor survival.Gene / CRp value (KM)Ab29 (D1p13.1)0.00787PIK3C2G0.00126PIM10.00499CD79B0.00567DTX10.0102Ab3(A1q21.1-q25.1(3))0.0193Ab28 (D1p36.32-p36.31)0.0211 Conclusions: Our systematic analysis of DLBCLs using multiple immunohistochemical and molecular methods identified mutational and copy number biomarkers predictive of survival in DLBCL patients, treated with rituximab in univariate analysis. Multivariate analysis and data from additional cases will reveal whether these molecular biomarkers can better predict patient survival, compared to current methods (such as COO by IHC). Disclosures Friedman: Cancer Genetics Inc.,: Employment, Equity Ownership. Guttapalli:Cancer Genetics, Inc.: Employment, Equity Ownership. Thodima:Cancer Genetics, Inc.: Employment, Equity Ownership. Kamalakaran:Cancer Genetics, Inc.: Employment, Equity Ownership. Houldsworth:Cancer Genetics Inc.,: Employment, Equity Ownership.
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Manier, Salomon, Erica N. Boswell, Siobhan Glavey, et al. "Mirna Expression Profiling and Proteomic Analysis Of Circulating Exosomes From Multiple Myeloma Patients." Blood 122, no. 21 (2013): 3086. http://dx.doi.org/10.1182/blood.v122.21.3086.3086.
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Abstract Introduction Exosomes are small vesicles (50-100 nm) of endocytic origin, which are released in the extra-cellular milieu by several cell types. It is known that cell-to-cell communication is partially mediated by exosomes. Exosomes play a role in tumor progression where they have been shown to carry and transfer microRNAs (miRNAs) and proteins to the recipient cells. In this study, we sought to characterize circulating exosomes in terms of their ability to modulate the microenvironment, leading to Multiple Myeloma (MM) progression. Method Exosomes were collected from peripheral blood obtained from healthy individuals (n=5), MGUS patients (n=5) and MM patients (n=10), using ultracentrifugation. Further characterization was carried out using electron microscopy and immunogold labeling for the detection of CD63 and CD81 and for the size using Nanosight® analysis. MiRNA were isolated using miRNeasy mini kit (Qiagen®) and profiling has been performed using nCounter miRNA expression assay (Nanostring® Technologies, Seattle WA). Bioinformatic software tools (TargetScan, MIRDB) were used to predict the target genes of identified miRNA to define their function. Proteins were isolated from exosomes following lysis and precipitated by acetone before in-solution trypsin digestion and ZipTip® purification. Proteomic analysis was performed using mass spectrometry (BIDMC Mass Spectrometry, ObiTrap Elite®). Spectral count numbers were determined with a false discovery rate (FDR) less than 0.5%. Results Circulating exosomes were studied at ultrastructural level showing positivity for CD81 and CD63, as demonstrated by immunogold labeling and electron microscopy. Exosome number and size did not differ based on clinical stage on Nanosight® analysis. We identified 16 miRNAs differentially expressed in circulating exosomes obtained from MGUS patients compared to healthy subjects (FC >2 or <-2; p<0.05): specifically, higher expression of miR-450a, -30e, -125a, -300 and lower expression of miR-185, -150, -98 were observed in MGUS- compared to healthy individual-derived circulating exosomes. Interestingly, miR-30e and -150 modulate NK cell activity by targeting perforin and c-Myb, respectively. We found 96 miRNAs differentially expressed in circulating exosomes from MM patients as compared to healthy donors: specifically lower expression of Let-7 family members, miR-150, -15a and higher expression of miR-125b, -144 and -363 were observed. Interestingly, miR-15a is involved in angiogenesis regulating VEGFA and FGF2. Let-7 family members are tumor suppressors targeting k-Ras and c-Myc and miR-150 regulates CXCR-4 expression. Moreover, these patterns have been described in MM cells suggesting that circulating exosomes in MM are mainly released from MM cells and could play a role in modulating the tumor micro-environment. The mass spectrometry analysis was performed on protein derived from circulating exosomes from 5 healthy donors, 5 MGUS and 10 MM patients. 272 proteins were identified in circulating exosomes including proteins highly associated with exosomes such as CD9, HSP70, Rab proteins (Rab7a; Rab5; Rab27b) and annexins. Comparing MM exosomal proteins to healthy donor exosomal proteins, we found significantly distinctive peptide counts for fibronectin (FC=3.5; p=0.002), AMBP protein (FC=3; p=0.001) and Ig gamma-1 chain C region (FC=2.5; p=0.006). Interestingly, fibronectin expression level in the microenvironment has been reported to be associated with tumor proliferation and drug resistance in MM. Conclusion These findings indicate that circulating exosomes differ between normal, MGUS and MM patients in terms of miRNA and protein content. Circulating exosomes could potentially be involved in modulating the host microenvironment for specific homing of clonal plasma cells to the bone marrow; thus providing a better understanding of the epigenetic changes responsible for the transition to MM stage. Disclosures: Leleu: CELGENE: Honoraria; JANSSEN: Honoraria. Ghobrial:Onyx: Advisoryboard Other; BMS: Advisory board, Advisory board Other, Research Funding; Noxxon: Research Funding; Sanofi: Research Funding.
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Liu, Yuliang, Michael S. Lee, Mark A. Olson, and Ronald N. Harty. "Bimolecular Complementation to Visualize Filovirus VP40-Host Complexes in Live Mammalian Cells: Toward the Identification of Budding Inhibitors." Advances in Virology 2011 (2011): 1–10. http://dx.doi.org/10.1155/2011/341816.
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Virus-host interactions play key roles in promoting efficient egress of many RNA viruses, including Ebola virus (EBOV or “e”) andMarburg virus(MARV or “m”). Late- (L-) domains conserved in viral matrix proteins recruit specific host proteins, such as Tsg101 and Nedd4, to facilitate the budding process. These interactions serve as attractive targets for the development of broad-spectrum budding inhibitors. A major gap still exists in our understanding of the mechanism of filovirus budding due to the difficulty in detecting virus-host complexes and mapping their trafficking patterns in the natural environment of the cell. To address this gap, we used a bimolecular complementation (BiMC) approach to detect, localize, and follow the trafficking patterns of eVP40-Tsg101 complexes in live mammalian cells. In addition, we used the BiMC approach along with a VLP budding assay to test small molecule inhibitors identified byin silicoscreening for their ability to block eVP40 PTAP-mediated interactions with Tsg101 and subsequent budding of eVP40 VLPs. We demonstrated the potential broad spectrum activity of a lead candidate inhibitor by demonstrating its ability to block PTAP-dependent binding of HIV-1 Gag to Tsg101 and subsequent egress of HIV-1 Gag VLPs.
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Yin, Hongwei, Liru You, Danielle Pasqualone, Kristen M. Kopski та Tim C. Huffaker. "Stu1p Is Physically Associated with β-Tubulin and Is Required for Structural Integrity of the Mitotic Spindle". Molecular Biology of the Cell 13, № 6 (2002): 1881–92. http://dx.doi.org/10.1091/mbc.01-09-0458.
Full textAbstract:
Formation of the bipolar mitotic spindle relies on a balance of forces acting on the spindle poles. The primary outward force is generated by the kinesin-related proteins of the BimC family that cross-link antiparallel interpolar microtubules and slide them past each other. Here, we provide evidence that Stu1p is also required for the production of this outward force in the yeast Saccharomyces cerevisiae. In the temperature-sensitive stu1–5mutant, spindle pole separation is inhibited, and preanaphase spindles collapse, with their previously separated poles being drawn together. The temperature sensitivity of stu1–5 can be suppressed by doubling the dosage of Cin8p, a yeast BimC kinesin–related protein. Stu1p was observed to be a component of the mitotic spindle localizing to the midregion of anaphase spindles. It also binds to microtubules in vitro, and we have examined the nature of this interaction. We show that Stu1p interacts specifically with β-tubulin and identify the domains required for this interaction on both Stu1p and β-tubulin. Taken together, these findings suggest that Stu1p binds to interpolar microtubules of the mitotic spindle and plays an essential role in their ability to provide an outward force on the spindle poles.
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Kashina, A. S., G. C. Rogers, and J. M. Scholey. "The bimC family of kinesins: essential bipolar mitotic motors driving centrosome separation." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1357, no. 3 (1997): 257–71. http://dx.doi.org/10.1016/s0167-4889(97)00037-2.
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Khairallah, Carlos. "BIDM 2016 : Beirut International Dental Meeting, October 13 - 15 / 2016, Biel, Beirut, Lebanon." Dental News 23, no. 4 (2016): 60–66. http://dx.doi.org/10.12816/0033909.
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Dalakas, Vassilis, Stylianos Papaharalabos, P. Takis Mathiopoulos, E. Alberto Candreva, Giovanni E. Corazza, and Alessandro Vanelli-Coralli. "BICMC and TD Comparative Performance Study of 16-APSK Signal Variants for DVB-S2 Systems." IEEE Communications Letters 19, no. 5 (2015): 723–26. http://dx.doi.org/10.1109/lcomm.2015.2411660.
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Le Guellec, R., J. Paris, A. Couturier, C. Roghi, and M. Philippe. "Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein." Molecular and Cellular Biology 11, no. 6 (1991): 3395–98. http://dx.doi.org/10.1128/mcb.11.6.3395.
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By differential screening of a Xenopus egg cDNA library, we selected nine clones (Eg1 to Eg9) corresponding to mRNAs which are deadenylated and released from polysomes soon after fertilization. The sequence of one of these clones (Eg5) revealed that the corresponding protein has the characteristic features of a kinesin-related protein. More specifically, Eg5 was found to be nearly 30% identical to a kinesin-related protein encoded by bimc, a gene involved in nuclear division in Aspergillus nidulans.
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Le Guellec, R., J. Paris, A. Couturier, C. Roghi, and M. Philippe. "Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein." Molecular and Cellular Biology 11, no. 6 (1991): 3395–98. http://dx.doi.org/10.1128/mcb.11.6.3395-3398.1991.
Full textAbstract:
By differential screening of a Xenopus egg cDNA library, we selected nine clones (Eg1 to Eg9) corresponding to mRNAs which are deadenylated and released from polysomes soon after fertilization. The sequence of one of these clones (Eg5) revealed that the corresponding protein has the characteristic features of a kinesin-related protein. More specifically, Eg5 was found to be nearly 30% identical to a kinesin-related protein encoded by bimc, a gene involved in nuclear division in Aspergillus nidulans.
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Soardi, Gian Alberto, Simone Perandini, Anna Rita Larici, et al. "Multicentre external validation of the BIMC model for solid solitary pulmonary nodule malignancy prediction." European Radiology 27, no. 5 (2016): 1929–33. http://dx.doi.org/10.1007/s00330-016-4538-5.
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Wilson, Patricia G. "BimC motor protein KLP61F cycles between mitotic spindles and fusomes in Drosophila germ cells." Current Biology 9, no. 16 (1999): 923—S3. http://dx.doi.org/10.1016/s0960-9822(99)80400-x.
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Putra, Putu Wira Kusuma, I. Kadek Agus Widiantara, and AA Nara Kusuma. "Effectiveness of the Use of Acupressure Wristband at Neiguan Point (P6) Towards Postoperative Nausea Vomiting (PONV) in Orthopedic Surgical Patients." Journal of Holistic Nursing Science 8, no. 1 (2021): 31–38. http://dx.doi.org/10.31603/nursing.v8i1.3814.
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Postoperative nausea and vomiting (PONV) is one of the most common causes of patient discomfort after undergoing surgery. The emergence of PONV allows the emergence of various complications including dehydration, electrolyte imbalance, slowing the wound healing process, the emergence of problems related to nutritional fulfillment to pneumonia aspiration. Pharmacological treatment has been done but it has not been effective and there are side effects of drugs used so that we need a complementary therapy that works synergistically with antiemetic therapy, namely acupressure. This study aimed at determine the effectiveness of the use of acupressure wristband at neiguan point (p6) towards postoperative nausea vomiting (ponv) in orthopedic surgical patients at BIMC Hospital Kuta. The study design was a pre-experimental with non-randomized uncontrolled trial with pretest-posttest without control group design, with a total of 19 research subjects included in the inclusion criteria. The research instrument consisted of two questionnaires namely the patient information form and the RINVR questionnaire (Rhodes Index of Nausea Vomiting and Retching). The results showed that the incidence of PONV before being given an intervention was obtained by 12 people (63.2%) had mild nausea and vomiting 7 people (36, 8%) experience moderate nausea and vomiting. Whereas after being given the intervention obtained as many as 6 people (31.6%) did not experience nausea, vomiting, 12 people (63.2%) experienced mild nausea, and 1 (5.3%) experienced moderate nausea and vomiting. Wilcoxon test results showed there is the effect of the use of acupressure wristband at neiguan point (p6) towards postoperative nausea vomiting (PONV) in orthopedic surgical patients at BIMC Hospital Kuta