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Autologous treatment for ALS with implication for broad neuroprotection

Translational Neurodegeneration 2022年第1期11卷 718-736页

作者： Daehwan Kim Subin Kim Ashley Sung neetika patel Nathan Wong Michael J.Conboy Irina M.Conboy Department of Bioengineering and QB3 Institute University of CaliforniaBerkeleyCA 94720USA

Background: Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor neurons (MNs), leading to paralysis, respiratory failure and death within 2-5 years of diagnosis. The exact mechanisms of sporadic ALS, which comprises 90% of all cases, remain unknown. In familial ALS, mutations in superoxide dismutase (SOD1) cause 10% of cases. Methods: ALS patient-derived human-induced pluripotent stem cells (ALS hiPSCs, harboring the SOD1AV4 mutation), were differentiated to MNs (ALS-MNs). The neuroprotective effects of conditioned medium (CM) of hESCs (H9), wt hiPSCs (WTC-11) and the ALS iPSCs, on MN apoptosis and viability, formation and maintenance of neurites, mitochon-drial activity and expression of inflammatory genes, were examined. For in vivo studies, 200 μl of CM from the ALS iPSCs (CS07 and CS053) was injected subcutaneously into the ALS model mice (transgenic for the human SOD1G93A mutation). Animal agility and strength, muscle innervation and mass, neurological score, onset of paralysis and lifes-pan of the ALS mice were assayed. After observing significant disease-modifying effects, the CM was characterized biochemically by fractionation, comparative proteomics, and epigenetic screens for the dependence on pluripotency. CM of fibroblasts that were differentiated from the wt hiPSCs lacked any neuroprotective activity and was used as a negative control throughout the studies. Results: The secretome of PSCs including the ALS patient iPSCs was neuroprotective in the H2O2 model. In the model with pathogenic SOD1 mutation, ALS iPSC-CM attenuated all examined hallmarks of ALS pathology, rescued human ALS-MNs from denervation and death, restored mitochondrial health, and reduced the expression of inflam-matory genes. The ALS iPSC-CM also improved neuro-muscular health and function, and delayed paralysis and mor-bidity in ALS mice. Compared side by side, cyclosporine (CsA), a mitochondrial membrane blocker that prevents the leakage of mitochondrial DNA, failed to avert the death of ALS-MNs, al

关键词： Neurodegeneration Amyotrophic lateral sclerosis SOD1 mutation Pluripotent stem cells Secretome

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Long-term impact of artificial intelligence on colorectal adenoma detection in high-risk colonoscopy

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World Journal of Gastrointestinal Endoscopy 2024年第6期16卷 335-342页

作者： Kenneth W Chow Matthew T Bell Nicholas Cumpian Maryanne Amour Ryan H Hsu Viktor E Eysselein neetika Srivastava Michael W Fleischman Sofiya Reicher Department of Medicine Harbor-UCLA Medical CenterTorranceCA 90502United States Department of Bioengineering Jacobs School of EngineeringUniversity of CaliforniaSan DiegoLa JollaCA 92093United States Department of Gastroenterology Harbor-UCLA Medical CenterTorranceCA 90502United States

BACKGROUND Improved adenoma detection rate(ADR)has been demonstrated with artificial intelligence(AI)-assisted colonoscopy.However,data on the real-world appli-cation of AI and its effect on colorectal cancer(CRC)screening outcomes is limited.AIM To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or sympt-oms.METHODS AI software(GI Genius,Medtronic)was implemented into the standard proced-ure protocol in November 2022.Data was collected on patient demographics,procedure indication,polyp size,location,and pathology.CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up.RESULTS We evaluated 1008 colonoscopies(278 pre-AI,255 early post-AI,285 established post-AI,and 190 late post-AI).The ADR was 38.1%pre-AI,42.0%early post-AI(P=0.77),40.0%established post-AI(P=0.44),and 39.5%late post-AI(P=0.77).There were no significant differences in polyp detection rate(PDR,baseline 59.7%),advanced ADR(baseline 16.2%),and non-neoplastic PDR(baseline 30.0%)before and after AI introduction.CONCLUSION In patients with an increased pre-test probability of having an abnormal colonoscopy,the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy.Although the potential of AI in colonoscopy is undisputed,current AI technology may not universally elevate screening metrics across all situations and patient populations.Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.

关键词： Artificial intelligence Colonoscopy Adenoma detection rate Screening Colorectal adenoma

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A machine learning pipeline for fuel-economical driving model

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International Journal of Intelligent Computing and Cybernetics 2022年第4期15卷 473-496页

作者： neetika Jain Sangeeta Mittal Jaypee Institute of Information Technology NoidaIndia

Purpose-A cost-effective way to achieve fuel economy is to reinforce positive driving behaviour.Driving behaviour can be controlled if drivers can be alerted for behaviour that results in poor fuel economy.Fuel consumption must be tracked and monitored instantaneously rather than tracking average fuel economy for the entire trip duration.A single-step application of machine learning(ML)is not sufficient to model prediction of instantaneous fuel consumption and detection of anomalous fuel economy.The study designs an ML pipeline to track and monitor instantaneous fuel economy and detect anomalies.Design/methodology/approach-This research iteratively applies different variations of a two-step ML pipeline to the driving dataset for hatchback cars.The first step addresses the problem of accurate measurement and prediction of fuel economy using time series driving data,and the second step detects abnormal fuel economy in relation to contextual information.Long short-term memory autoencoder method learns and uses the most salient features of time series data to build a regression model.The contextual anomaly is detected by following two approaches,kernel quantile estimator and one-class support vector machine.The kernel quantile estimator sets dynamic threshold for detecting anomalous behaviour.Any error beyond a threshold is classified as an anomaly.The one-class support vector machine learns training error pattern and applies the model to test data for anomaly detection.The two-step ML pipeline is further modified by replacing long short term memory autoencoder with gated recurrent network autoencoder,and the performance of both models is compared.The speed recommendations and feedback are issued to the driver based on detected anomalies for controlling aggressive behaviour.Findings-A composite long short-term memory autoencoder was compared with gated recurrent unit autoencoder.Both models achieve prediction accuracy within a range of 98%-100%for prediction as a first step.Recall and accuracy metrics for anomaly det

关键词： Eco-driving Fuel economy Contextual model Naturalistic driving Deep learning Anomaly detection Long short term memory Gated recurrent unit

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Evaluating Partitioning Based Clustering Methods for Extended Non-negative Matrix Factorization (NMF)

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Intelligent Automation & Soft Computing 2023年第2期35卷 2043-2055页

作者： neetika Bhandari Payal Pahwa Guru Gobind Singh Indraprastha University DelhiIndia Bhagwan Parshuram Institute of Technology DelhiIndia

Data is humongous today because of the extensive use of World WideWeb, Social Media and Intelligent Systems. This data can be very important anduseful if it is harnessed carefully and correctly. Useful information can beextracted from this massive data using the Data Mining process. The informationextracted can be used to make vital decisions in various industries. Clustering is avery popular Data Mining method which divides the data points into differentgroups such that all similar data points form a part of the same group. Clusteringmethods are of various types. Many parameters and indexes exist for the evaluationand comparison of these methods. In this paper, we have compared partitioningbased methods K-Means, Fuzzy C-Means (FCM), Partitioning AroundMedoids (PAM) and Clustering Large Application (CLARA) on secure perturbeddata. Comparison and identification has been done for the method which performsbetter for analyzing the data perturbed using Extended NMF on the basis of thevalues of various indexes like Dunn Index, Silhouette Index, Xie-Beni Indexand Davies-Bouldin Index.

关键词： Clustering CLARA Davies-Bouldin index Dunn index FCM intelligent systems K-means non-negative matrix factorization(NMF) PAM privacy preserving data mining Silhouette index Xie-Beni index

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Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients

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World Journal of Transplantation 2023年第5期13卷 239-249页

作者： Pavithra Ramakrishnan neetika Garg Samantha Pabich Didier A Mandelbrot Kurtis J Swanson Department of Medicine University of MinnesotaMinneapolisMN 55455United States Department of Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States

Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are novel oral hypoglycemic agents garnering much attention for their substantial benefits.These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease(CKD)and heart failure management.SGLT2i use post-kidney transplant is an emerging area of research.Highlights from this mini review include the following:Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients(KTRs),median time from transplant to initiation was 3 years(range:0.88-9.6 years).Median baseline estimated glomerular filtration rate(eGFR)was 66.7 mL/min/1.73 m2(range:50.4-75.8).Median glycohemoglobin(HgbA1c)at initiation was 7.7%(range:6.9-9.3).SGLT2i were demonstrated to be effective short-term impacting HgbA1c,eGFR,hemoglobin/hematocrit,serum uric acid,and serum magnesium levels.They are shown to be safe in KTRs with low rates of infections,hypoglycemia,euglycemic diabetic ketoacidosis,and stable tacrolimus levels.More data is needed to demonstrate long-term outcomes.SGLT2i appear to be safe,effective medications for select KTRs.Our present literature,though limited,is founded on precedent robust research in CKD patients with diabetes.Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient,graft and cardiovascular outcomes of these agents,but also to augment management in KTRs.

关键词： Sodium glucose cotransporter-2 Sodium glucose cotransporter-2 inhibitor Kidney transplantation Diabetes Post-transplant diabetes mellitus New onset diabetes after transplant

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Resuscitative cardiac arrest during a Caesarean section-When every second counts:A case report

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Journal of Acute Disease 2022年第1期11卷 42-44页

作者： Rabi Narayan Hota Shalendra Singh Priyanka Rathore neetika Tripathi Priya Taank 无 Dept of Anaesthesiology&Critical Care Armed Forces Medical CollegePune 411040India Dept of Obstetric and Gynaecology Armed Forces Medical CollegePune 411040India Dept of Ophthalmology Armed Forces Medical CollegePune 411040India

Rationale:Cardiac pulmonary arrest is the most challenging and dreaded complication of neuraxial blockade.Patient’s concern:A 21-year-old patient at 37 weeks of gestation,with previous lower segment Caesarean section pregnancy presented for elective Caesarean section.Diagnosis:Cardiac arrest after performing a subarachnoid block.Intervention:Maternal resuscitation.Outcome:Return of spontaneous circulation was achieved within 4-5 min of cardiopulmonary resuscitation.A single live healthy male baby was delivered.Lesson:A careful preoperative evaluation,adequate preload,constant vigilant monitoring to recognize vasovagal response at the earliest,and immediate initiation of resuscitative measures play the most important role in saving the precious lives in case of pregnant patients undergoing Caesarean section under subarachnoid block.

关键词： Cardiac arrest Pregnancy Neuraxial blockade Subarachnoid block

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Role of novel biomarkers in kidney transplantation

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World Journal of Transplantation 2020年第9期10卷 230-255页

作者： Kurtis J Swanson Fahad Aziz neetika Garg Maha Mohamed Didier Mandelbrot Arjang Djamali Sandesh Parajuli Department of Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States Department of Surgery University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States

Clinical application of biomarkers is an integral component of transplant care.Clinicians and scientists alike are in search of better biomarkers than the current serologic(serum creatinine,donor-specific antibodies),urine-derived(urinalysis,urine protein),and histologic ones we now use.The science behind recent biomarker discovery spans across multiple molecular biologic disciplines,including transcriptomics,proteomics,and metabolomics.Innovative methodology and integration of basic and clinical approaches have allowed researchers to unearth molecular phenomena preceding clinical disease.Biomarkers can be classified in several ways.In this review,we have classified them via their origin and outcome:Primarily immunologic,i.e.,representative of immune regulation and dysfunction and non-immunologic,pertaining to delayed graft function,cardiovascular events/mortality,infection,malignancy,posttransplant diabetes,graft,and patient survival.Novel biomarker uses to guide the diagnosis and management of transplant-related outcomes is a promising area of research.However,the use of biomarkers to predict outcomes after kidney transplantation is not well studied.In this review,we summarize the recent studies illustrating biomarker use and transplant outcomes.

关键词： Biomarkers Kidney Transplantation Rejection Infection Mortality Graft survival

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Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression

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World Journal of Transplantation 2019年第6期9卷 123-133页

作者： Sandesh Parajuli Fahad Aziz neetika Garg Sarah E Panzer Emily Joachim Brenda Muth Maha Mohamed Justin Blazel Weixiong Zhong Brad C Astor Didier A Mandelbrot Arjang Djamali Division of Nephrology Department of MedicineUniversity of WisconsinMadisonWI 53705United States Department of Pathology University of WisconsinMadisonWI 53705United States Department of Population Health Sciences University of WisconsinMadisonWI 53705United States Division of Transplantation Department of SurgeryUniversity of WisconsinMadisonWI 53705United States

BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.AIM To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.METHODS In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.RESULTS We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy(IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy(TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR(40%),TG(17%), and IFTA(13%). Most grafts failed within two years of post-transplant(36%). Subsequently, approximately 10%-15% of grafts failed every two years: >2-4 years(16%), > 4-6 years(13%), > 6-8 years(11%), > 8-10 years(9%) and > 10 years(16%). AR was the most common cause of graft failure in the first six years(48%), whereas TG was the most prevalent cause of graft failure after 6 years(32%) of transplant.CONCLUSION In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

关键词： Kidney biopsy Acute rejection Graft failure Transplant glomerulopathy Interstitial fibrosis and tubular atrophy

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